Cardiology (all articles)
Meta-analysis: Hemodiafiltration Reduces Mortality in Kidney Failure Patients Compared to Hemodialysis
7 Nov, 2024 | 12:19h | UTCBackground: Kidney failure patients undergoing hemodialysis face high mortality rates, with approximately 50% dying within five years of initiating treatment. Hemodiafiltration, a convection-based therapy that removes a broader spectrum of uraemic toxins, has been proposed to improve survival outcomes. Previous studies have shown mixed results regarding its efficacy, and uncertainties remain about its effects on specific patient subgroups, dose-response relationships with convection volume, and cause-specific mortality.
Objective: To compare the effects of online hemodiafiltration versus standard hemodialysis on all-cause and cause-specific mortality in patients with kidney failure.
Methods: An individual patient data meta-analysis of five randomized controlled trials was conducted, encompassing 4,153 patients (2,083 on hemodiafiltration and 2,070 on hemodialysis). Databases including MEDLINE, Embase, and the Cochrane Central Register were searched up to July 17, 2024. The primary outcome was all-cause mortality. Subgroup analyses based on patient characteristics and dose–response analyses using convection volume were performed.
Results: Over a median follow-up of 30 months, all-cause mortality occurred in 477 patients (23.3%) receiving hemodiafiltration and 559 patients (27.0%) receiving hemodialysis. Hemodiafiltration significantly reduced all-cause mortality (hazard ratio [HR] 0.84, 95% CI 0.74–0.95) compared to hemodialysis. Cardiovascular mortality was also lower in the hemodiafiltration group (HR 0.78, 95% CI 0.64–0.96), particularly deaths due to cardiac causes (HR 0.67, 95% CI 0.50–0.89). No differential effects were observed across predefined patient subgroups. A dose-dependent relationship was found between higher convection volumes and reduced mortality risk.
Conclusions: Hemodiafiltration significantly reduces all-cause and cardiovascular mortality in patients with kidney failure compared to standard hemodialysis. The mortality benefit is dose-dependent, with higher convection volumes associated with greater risk reductions.
Implications for Practice: These findings support the adoption of online hemodiafiltration as a superior alternative to conventional hemodialysis. Clinicians should consider implementing high-dose hemodiafiltration to improve survival outcomes in patients with kidney failure.
Study Strengths and Limitations: Strengths include the large sample size and use of individual patient data, allowing for comprehensive subgroup and dose–response analyses. Limitations involve heterogeneity among the included studies and potential biases due to open-label designs. The lack of blinding may have influenced outcome reporting.
Future Research: Further studies are needed to evaluate the long-term benefits of hemodiafiltration on patient-reported outcomes, cost-effectiveness, and environmental impacts. Investigations into the optimal convection volumes and the mechanisms underlying the observed mortality reductions are also warranted.
News Release: CLEAR SYNERGY Trial Finds No Cardiovascular Benefit of Colchicine Post-Myocardial Infarction
7 Nov, 2024 | 11:55h | UTCIntroduction: The international CLEAR SYNERGY (OASIS 9) trial investigated the long-term cardiovascular effects of colchicine in patients undergoing percutaneous coronary intervention (PCI) following acute myocardial infarction (MI). Colchicine, an anti-inflammatory agent, had previously shown promise in reducing cardiovascular events in patients with coronary artery disease. This study aimed to evaluate whether colchicine could improve outcomes in a high-risk post-MI population.
Highlights:
- Study Design: Over 7,000 patients with acute MI (95% with STEMI) were enrolled and randomized to receive either colchicine 0.5 mg daily or placebo, in addition to standard care. The trial featured a 2×2 factorial design, also assessing spironolactone versus placebo.
- Primary Outcome: After a median follow-up of 3.5 years, the primary endpoint—a composite of cardiovascular death, MI, stroke, or ischemia-driven revascularization—occurred in 9.1% of the colchicine group and 9.3% of the placebo group (Hazard Ratio [HR] 0.99; 95% Confidence Interval [CI] 0.85-1.16; p=0.93), indicating no significant difference.
- Secondary Outcomes: There were no significant differences in individual components of the primary endpoint, including cardiovascular death (3.3% vs. 3.2%), MI (2.9% vs. 3.1%), or ischemia-driven revascularization (4.6% vs. 4.7%). All-cause mortality was slightly lower in the colchicine group but not statistically significant.
- Safety Profile: Colchicine was associated with a higher incidence of diarrhea (10.2% vs. 6.6%; p<0.001). Serious infections were similar between groups.
- Comparison with Previous Studies: The findings contrast with earlier trials like COLCOT and LoDoCo2, which reported cardiovascular benefits with colchicine in similar patient populations. Possible reasons for the discrepancy include differences in patient characteristics, study design, and the impact of external factors such as the COVID-19 pandemic.
Conclusion: The CLEAR SYNERGY trial concludes that routine use of colchicine following PCI for acute MI does not reduce the risk of major adverse cardiovascular events. These results suggest reevaluating the role of colchicine in post-MI management and may influence future guideline recommendations. Clinicians should consider these findings when prescribing colchicine, balancing the lack of cardiovascular benefit against the potential for gastrointestinal side effects.
Source: This research was conducted by the Population Health Research Institute and presented at the Transcatheter Cardiovascular Therapeutics (TCT) conference on October 29, 2024. Detailed results are available through the American College of Cardiology (https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2024/10/25/04/34/clear-synergy) and TCTMD (https://www.tctmd.com/news/colchicine-surprise-no-help-post-mi-large-clear-synergy-trial-shows).
RCT: Lipoprotein(a) and LDL-C as Independent Cardiovascular Risk Factors in Statin Trials
5 Nov, 2024 | 17:50h | UTCBackground: Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] are both known risk factors for atherosclerotic cardiovascular disease (ASCVD). However, the interaction between Lp(a) and LDL-C levels in relation to ASCVD risk, especially in the context of LDL-C-lowering treatments like statins, remains unclear. This study aimed to clarify if LDL-C reduction impacts Lp(a)-associated ASCVD risk.
Objective: This meta-analysis examined whether LDL-C reduction with statins affects ASCVD risk mediated by elevated Lp(a) levels.
Methods: Data from 27,658 participants across six statin trials were analyzed, including both placebo and statin groups. ASCVD risk was assessed using multivariable Cox proportional hazards models with adjustments for various cardiovascular risk factors. The study evaluated continuous associations between Lp(a) levels, LDL-C levels, and ASCVD risk.
Results: Elevated Lp(a) levels were associated with higher ASCVD risk across all LDL-C levels, even among patients with the lowest LDL-C achieved through statin therapy. Statin-treated patients with Lp(a) >50 mg/dL exhibited a significantly higher ASCVD risk, even in the lowest quartile of achieved LDL-C (HR 1.38, 95% CI 1.06–1.79). The highest risk was observed in individuals with both elevated Lp(a) and LDL-C levels (HR 1.90, 95% CI 1.46–2.48).
Conclusions: Lp(a) and LDL-C are independent risk factors for ASCVD, with LDL-C lowering alone insufficient to mitigate the risk associated with elevated Lp(a).
Implications for Practice: These findings underscore the need for distinct strategies to manage patients with elevated Lp(a), particularly as LDL-C reduction alone does not fully address the associated ASCVD risk.
Study Strengths and Limitations: This study’s strength lies in its large participant pool and robust statistical analysis; however, variability in Lp(a) measurement methods across trials may limit precision.
Future Research: Investigations into therapies specifically targeting Lp(a) may offer additional ASCVD risk reduction beyond LDL-C lowering alone.
Cohort Study: Late Ventricular Arrhythmias After Primary PCI for STEMI Are Rare but Increase Mortality
5 Nov, 2024 | 15:24h | UTCBackground: Ventricular tachycardia (VT) and ventricular fibrillation (VF) are critical complications following ST-segment elevation myocardial infarction (STEMI). While early VT/VF typically occurs before or shortly after reperfusion, contemporary data on the incidence of late VT/VF post-primary percutaneous coronary intervention (PCI) are limited. Understanding the risk of late VT/VF is essential for optimizing in-hospital monitoring and discharge timing.
Objective: To assess the risk of late VT and VF after primary PCI in patients with STEMI, identify associated factors, and evaluate their impact on in-hospital mortality.
Methods: This cohort study analyzed data from 174,126 adults with STEMI treated with primary PCI between January 1, 2015, and December 31, 2018, using the National Cardiovascular Data Registry Chest Pain–MI Registry. Late VT/VF was defined as events occurring one or more days after PCI. Multivariable logistic regression was employed to identify factors associated with late VT/VF and its association with in-hospital mortality.
Results: Among the patients, 8.9% experienced VT or VF after primary PCI. Late VT/VF occurred in 2.4% of patients overall and 1.7% of those with uncomplicated STEMI. Late VT/VF associated with cardiac arrest was rare, occurring in 0.4% of all patients and 0.1% of patients with uncomplicated STEMI. Decreased left ventricular ejection fraction (LVEF) was the most significant factor associated with late VT/VF with cardiac arrest (adjusted odds ratio [AOR] for every 5-unit decrease ≤40%: 1.67; 95% CI, 1.54–1.85). Late VT/VF was linked to increased odds of in-hospital mortality (AOR, 6.40; 95% CI, 5.63–7.29).
Conclusions: Late VT/VF after primary PCI for STEMI is infrequent, particularly in patients with uncomplicated presentations. However, when late VT/VF occurs, it is associated with a significantly higher risk of in-hospital mortality.
Implications for Practice: While vigilant monitoring remains crucial, patients with uncomplicated STEMI may be candidates for earlier discharge through shared decision-making. Identifying high-risk patients for late VT/VF can enable tailored monitoring strategies to improve outcomes.
Study Strengths and Limitations: Strengths include a large, contemporary cohort and detailed data on in-hospital VT/VF events. Limitations involve the observational design, potential unmeasured confounders, and the inability to differentiate between VT and VF due to registry definitions.
Future Research: Further studies are warranted to develop precise risk prediction models for late VT/VF and to explore effective out-of-hospital monitoring strategies post-STEMI.
Multisociety Guidelines for Perioperative Management of GLP-1 Receptor Agonists
3 Nov, 2024 | 14:27h | UTCIntroduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of metabolic diseases such as type 2 diabetes, obesity, and heart failure by enhancing glycemic control and promoting satiety. However, their effect of delaying gastric emptying has raised perioperative safety concerns due to the risk of residual gastric contents leading to pulmonary aspiration during anesthesia. Reports of aspiration incidents and gastrointestinal side effects like nausea and vomiting have prompted the need for unified clinical guidance. This multisociety clinical practice guideline aims to provide recommendations for safely managing patients on GLP-1RAs during the perioperative period, balancing metabolic benefits with procedural risks.
Key Recommendations:
- Shared Decision-Making:
- Collaborative Approach: The continuation or discontinuation of GLP-1RAs should involve shared decision-making among the patient, surgical team, anesthesia providers, and prescribing clinicians.
- Risk Assessment: Evaluate factors that elevate the risk of delayed gastric emptying and aspiration, including:
- Dose Escalation Phase: Higher risk during dose escalation compared to maintenance.
- Higher Dosage: Increased gastrointestinal side effects with higher doses.
- Weekly Formulations: Greater side effects with weekly dosing compared to daily formulations.
- Gastrointestinal Symptoms: Presence of nausea, vomiting, abdominal pain, dyspepsia, or constipation.
- Comorbid Conditions: Conditions like gastroparesis, bowel dysmotility, or neurological disorders affecting gastric motility.
- Timing: Conduct risk assessments well in advance of surgery to allow for appropriate preoperative planning.
- Management of GLP-1RA Therapy:
- Continuation in Low-Risk Patients: GLP-1RAs may be continued preoperatively in patients without elevated risk factors.
- Balancing Risks in High-Risk Patients:
- Metabolic vs. Procedural Risks: Weigh the risks of aspiration against potential metabolic complications like hyperglycemia if GLP-1RAs are withheld.
- Avoiding Bias: Decisions should not be based solely on obesity status to prevent bias.
- Discontinuation Guidelines:
- Daily Formulations: Hold on the day of surgery.
- Weekly Formulations: Discontinue one week prior to surgery.
- Day-of-Surgery Assessment: All patients should be evaluated for symptoms of delayed gastric emptying on the day of the procedure, regardless of GLP-1RA usage.
- Minimizing Aspiration Risk:
- Preoperative Dietary Modifications:
- Liquid Diet: Implement a liquid diet for at least 24 hours before surgery, similar to protocols for colonoscopy and bariatric procedures.
- Gastric Content Assessment:
- Point-of-Care Ultrasound: Use gastric ultrasound to assess residual gastric contents when there is concern for delayed emptying, acknowledging potential limitations in resources and expertise.
- Anesthesia Plan Adjustments:
- Rapid Sequence Induction: Consider rapid sequence induction with tracheal intubation to minimize aspiration risk in patients with confirmed or suspected delayed gastric emptying.
- Procedure Continuation vs. Cancellation: Engage in shared decision-making to weigh the benefits of proceeding with the procedure against the risks, aiming to avoid unnecessary cancellations.
- Preoperative Dietary Modifications:
Conclusion: By adopting these recommendations, healthcare providers can enhance patient safety during the perioperative period for those receiving GLP-1RA therapy. The guidelines emphasize individualized care through shared decision-making, considering both metabolic benefits and procedural risks. Implementing these practices is expected to reduce aspiration incidents, optimize surgical outcomes, and ensure equitable care without bias against patients with obesity or metabolic disorders. As new evidence and medications emerge, these guidelines may be updated to reflect best practices.
Reference: Kindel TL, Wang AY, Wadhwa A, et al. Multisociety clinical practice guidance for the safe use of glucagon-like peptide-1 receptor agonists in the perioperative period. Surgery for Obesity and Related Diseases. 2024; In Press. https://doi.org/10.1016/j.soard.2024.08.033
Clinical Trial Follow-up: Empagliflozin Continues to Reduce Cardiorenal Risks Post-Discontinuation in CKD Patients
3 Nov, 2024 | 13:08h | UTCBackground: Chronic kidney disease (CKD) progression leads to end-stage kidney disease, adversely affecting quality of life, increasing cardiovascular morbidity and mortality, and imposing high economic costs. Previous trials, including the EMPA-KIDNEY trial, demonstrated that empagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, provides cardiorenal benefits in CKD patients at risk of progression. The persistence of these benefits after discontinuation of the drug remains uncertain.
Objective: To assess how the effects of empagliflozin on kidney disease progression and cardiovascular outcomes evolve after discontinuation in patients with CKD.
Methods: In this randomized, double-blind, placebo-controlled trial, 6,609 patients with CKD were assigned to receive empagliflozin 10 mg daily or placebo and followed for a median of 2 years during the active trial period. Eligible patients had an estimated glomerular filtration rate (eGFR) between 20 and less than 45 ml/min/1.73 m², or between 45 and less than 90 ml/min/1.73 m² with a urinary albumin-to-creatinine ratio of at least 200 mg/g. After the active trial, 4,891 surviving patients consented to a 2-year post-trial follow-up without the trial drug, during which local practitioners could prescribe open-label SGLT2 inhibitors. The primary composite outcome was kidney disease progression or cardiovascular death from the start of the active trial to the end of the post-trial period.
Results: During the combined active and post-trial periods, a primary outcome event occurred in 26.2% of patients in the empagliflozin group and 30.3% in the placebo group (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.72–0.87). During the post-trial period alone, the HR was 0.87 (95% CI, 0.76–0.99), indicating continued benefit after drug discontinuation. The risk of kidney disease progression was 23.5% in the empagliflozin group versus 27.1% in the placebo group (HR, 0.79; 95% CI, 0.72–0.87). Cardiovascular death occurred in 3.8% and 4.9% of patients, respectively (HR, 0.75; 95% CI, 0.59–0.95). No significant effect was observed on death from noncardiovascular causes (5.3% in both groups).
Conclusions: In patients with CKD at risk for progression, empagliflozin continued to confer cardiorenal benefits for up to 12 months after discontinuation. These findings suggest that short-term treatment with empagliflozin has lasting effects on kidney and cardiovascular outcomes.
Implications for Practice: Empagliflozin should be considered for a broad range of CKD patients to slow disease progression and reduce cardiovascular risk, with benefits extending beyond active treatment. Clinicians should initiate empagliflozin therapy in eligible CKD patients to maximize long-term cardiorenal protection.
Study Strengths and Limitations: Strengths include the large sample size, broad eligibility criteria, and high follow-up rates. Limitations involve the exclusion of certain regions during post-trial follow-up and reliance on local eGFR measurements during this period.
Future Research: Further studies are needed to understand the mechanisms behind the sustained benefits of empagliflozin after discontinuation and to explore the long-term effects of extended treatment durations.
RCT: No Significant Difference Between Intraosseous and Intravenous Vascular Access in Out-of-Hospital Cardiac Arrest Outcomes
3 Nov, 2024 | 12:58h | UTCBackground: Out-of-hospital cardiac arrest (OHCA) is a major global health concern, resulting in high mortality rates despite advancements in emergency care. In Denmark alone, approximately 5,000 cases occur annually, with a 30-day survival rate of only about 14%. Rapid vascular access during cardiopulmonary resuscitation (CPR) is crucial for administering medications like epinephrine, as recommended by international guidelines. Both intraosseous (IO) and intravenous (IV) routes are routinely used, but their comparative effectiveness remains unclear. Current guidelines favor IV access for initial attempts, yet this recommendation is based on very low-certainty evidence, highlighting the need for well-designed clinical trials.
Objective: To compare the effectiveness of initial intraosseous versus intravenous vascular access on sustained return of spontaneous circulation (ROSC) in adults experiencing nontraumatic OHCA.
Methods: This randomized, parallel-group superiority trial was conducted across all five regions of Denmark, covering 5.9 million inhabitants. Adults aged 18 years or older with nontraumatic OHCA requiring vascular access during CPR were randomized to receive either initial IO or IV access. The IO group was further randomized to humeral or tibial access for a secondary comparison. The primary outcome was sustained ROSC, defined as no need for chest compressions for at least 20 minutes. Key secondary outcomes included 30-day survival and survival with favorable neurologic outcome (modified Rankin scale score of 0–3). Procedural outcomes such as success rates of vascular access within two attempts, time to successful access, and time to first epinephrine administration were also assessed.
Results: Among 1,479 patients included in the primary analysis (731 in the IO group and 748 in the IV group), successful vascular access within two attempts was achieved in 92% of the IO group versus 80% of the IV group. Despite the higher success rate with IO access, the time to first successful access and time to first epinephrine dose were similar between groups. Sustained ROSC occurred in 30% of patients in the IO group and 29% in the IV group (risk ratio [RR], 1.06; 95% confidence interval [CI], 0.90–1.24; P=0.49). At 30 days, survival rates were 12% in the IO group and 10% in the IV group (RR, 1.16; 95% CI, 0.87–1.56), with favorable neurologic outcomes observed in 9% and 8% of patients, respectively (RR, 1.16; 95% CI, 0.83–1.62). No significant differences were found in procedural times, adverse events, or quality-of-life measures among survivors.
Conclusions: In adults with nontraumatic OHCA, initial intraosseous vascular access did not result in a significant difference in sustained ROSC compared to intravenous access. Both methods yielded comparable survival rates and neurologic outcomes at 30 days, suggesting that the choice of vascular access route may not critically impact immediate resuscitation success.
Implications for Practice: These findings indicate that emergency medical services can opt for either intraosseous or intravenous vascular access during resuscitation based on provider expertise, patient anatomy, and situational considerations without adversely affecting patient outcomes. Emphasizing flexibility in vascular access approach may facilitate quicker access and streamline resuscitation efforts in the prehospital setting.
Study Strengths and Limitations: Strengths include the randomized design, large sample size, and nationwide implementation, enhancing generalizability. Limitations involve potential crossover between groups, lack of blinding among clinicians, and the study being underpowered to detect small differences in long-term outcomes.
Future Research: Further studies are needed to assess long-term survival and neurologic outcomes, and to explore whether specific patient subgroups may benefit more from one vascular access method over the other during cardiac arrest resuscitation.
Reference: Vallentin MF, Granfeldt A, Klitgaard TL, et al. Intraosseous or Intravenous Vascular Access for Out-of-Hospital Cardiac Arrest. New England Journal of Medicine. 2024 Oct 31; DOI: http://doi.org/10.1056/NEJMoa2407616
RCT: Intraosseous vs. Intravenous Drug Administration in Out-of-Hospital Cardiac Arrest Shows No Difference in 30-Day Survival
3 Nov, 2024 | 12:48h | UTCBackground: Out-of-hospital cardiac arrest requires rapid drug administration, with medications like epinephrine being highly time-dependent. Intravenous access can be challenging prehospital due to environmental and patient factors, potentially delaying treatment. Intraosseous access may offer faster drug delivery, but its impact on clinical outcomes is unclear.
Objective: To compare the effectiveness of an intraosseous-first versus intravenous-first vascular access strategy on 30-day survival in adults experiencing out-of-hospital cardiac arrest requiring drug therapy.
Methods: In this multicenter, open-label, randomized trial across 11 UK emergency medical systems, 6,082 adults were assigned to receive either intraosseous-first or intravenous-first vascular access during resuscitation. The primary outcome was survival at 30 days. Secondary outcomes included return of spontaneous circulation and favorable neurologic function at hospital discharge (modified Rankin scale score ≤3).
Results: At 30 days, survival was 4.5% in the intraosseous group and 5.1% in the intravenous group (adjusted odds ratio [OR], 0.94; 95% confidence interval [CI], 0.68–1.32; P=0.74). Favorable neurologic outcome at discharge was similar between groups (2.7% vs. 2.8%; adjusted OR, 0.91; 95% CI, 0.57–1.47). Return of spontaneous circulation was lower in the intraosseous group (36.0% vs. 39.1%; adjusted OR, 0.86; 95% CI, 0.76–0.97).
Conclusions: An intraosseous-first vascular access strategy did not improve 30-day survival compared to an intravenous-first strategy in adults with out-of-hospital cardiac arrest. The intraosseous route was associated with a lower rate of return of spontaneous circulation.
Implications for Practice: Paramedics should consider that intraosseous access may not offer a survival advantage over intravenous access and may be linked to a reduced return of spontaneous circulation. This finding may influence decisions on vascular access during resuscitation efforts.
Study Strengths and Limitations: Strengths include a large, multicenter randomized design; limitations involve early termination reducing statistical power and inability to blind prehospital providers.
Future Research: Further studies should investigate why intraosseous access is associated with lower return of spontaneous circulation and assess if specific intraosseous techniques or sites affect outcomes.
RCT: Transcatheter Tricuspid-Valve Replacement Improves Symptoms and Quality of Life in Severe Tricuspid Regurgitation
3 Nov, 2024 | 12:37h | UTCBackground: Severe tricuspid regurgitation is associated with debilitating symptoms and increased mortality. Surgical intervention is infrequently performed due to high operative risks and late patient presentation, leading to poor outcomes. Transcatheter tricuspid-valve replacement offers a less invasive alternative versus surgical intervention, but data on its efficacy are limited.
Objective: To compare the safety and effectiveness of transcatheter tricuspid-valve replacement plus medical therapy versus medical therapy alone in patients with severe symptomatic tricuspid regurgitation.
Methods: In this international, multicenter randomized controlled trial, 400 patients with severe symptomatic tricuspid regurgitation despite optimal medical therapy were randomized in a 2:1 ratio to receive transcatheter tricuspid-valve replacement plus medical therapy (valve-replacement group, n=267) or medical therapy alone (control group, n=133). The primary outcome was a hierarchical composite of death from any cause, implantation of a right ventricular assist device or heart transplantation, postindex tricuspid-valve intervention, hospitalization for heart failure, and improvements in the KCCQ-OS score by at least 10 points, NYHA functional class by at least one class, and 6-minute walk distance by at least 30 meters.
Results: At one year, the win ratio favoring valve replacement was 2.02 (95% confidence interval [CI], 1.56 to 2.62; P<0.001), indicating superiority over medical therapy alone. Patients in the valve-replacement group had significant improvements in quality of life, with 66.4% achieving an increase of at least 10 points in the KCCQ-OS score compared to 36.5% in the control group. Improvement of at least one NYHA class was observed in 78.9% of the valve-replacement group versus 24.0% of the control group. Reduction of tricuspid regurgitation to mild or less was achieved in 95.2% of patients in the valve-replacement group, compared to 2.3% in the control group. Severe bleeding occurred more frequently in the valve-replacement group (15.4% vs. 5.3%; P=0.003), as did new permanent pacemaker implantation (17.8% vs. 2.3%; P<0.001).
Conclusions: Transcatheter tricuspid-valve replacement significantly improved clinical outcomes, symptoms, functional capacity, and quality of life in patients with severe tricuspid regurgitation compared to medical therapy alone, despite higher risks of severe bleeding and pacemaker implantation.
Implications for Practice: Transcatheter tricuspid-valve replacement offers a promising therapeutic option for patients with severe symptomatic tricuspid regurgitation who are at high surgical risk. Clinicians should consider this intervention to improve patient symptoms and quality of life, while carefully weighing the procedural risks, particularly bleeding and arrhythmias requiring pacemaker implantation.
Study Strengths and Limitations: Strengths of the study include its randomized controlled design and comprehensive evaluation of both clinical and patient-reported outcomes. Limitations involve the smaller control group due to the 2:1 randomization and a one-year follow-up period that may not capture long-term benefits or risks.
Future Research: Further studies with longer follow-up are needed to assess the durability of transcatheter tricuspid-valve replacement, its long-term impact on survival and hospitalization rates, and strategies to minimize procedural complications.
Review: Chronic Low-Level Lead Poisoning
3 Nov, 2024 | 01:15h | UTCIntroduction: Lead poisoning, historically known as plumbism, remains a significant health concern despite reductions in lead use. Chronic low-level lead exposure has been identified as a critical risk factor for cardiovascular disease in adults and cognitive deficits in children, even at blood lead concentrations previously deemed safe. This review by Lanphear et al. explores the multifaceted effects of chronic, low-level lead poisoning, emphasizing its impact on neurodevelopment, kidney function, and cardiovascular health, and underscores the urgent need for effective prevention strategies.
Key Findings:
- Exposure and Absorption: Lead exposure occurs primarily through ingestion and inhalation, with children absorbing lead more readily than adults. Absorption is enhanced in the presence of iron or calcium deficiency. Once absorbed, lead is predominantly stored in the skeleton, and factors altering bone metabolism can mobilize lead back into the bloodstream.
- Neurodevelopmental Effects: Lead exposure is linked to preterm birth, cognitive deficits, attention deficit–hyperactivity disorder (ADHD), and behavioral disorders in children. Notably, cognitive deficits are proportionately larger at lower blood lead levels, with significant IQ reductions observed even at the lowest measurable concentrations.
- Kidney Disease: Chronic lead exposure is a risk factor for chronic kidney disease. Higher blood lead levels are associated with reduced glomerular filtration rates and an increased risk of developing chronic kidney conditions.
- Cardiovascular Disease: Lead induces hypertension and atherosclerosis through mechanisms such as oxidative stress and endothelial dysfunction. It is a leading risk factor for mortality from cardiovascular disease, with substantial risk increases even at low blood lead concentrations. Studies indicate that lead exposure may have contributed to historical trends in coronary heart disease mortality.
- Global Burden: In 2019, lead exposure accounted for approximately 5.5 million deaths from cardiovascular disease and the loss of 765 million IQ points in children globally. The economic cost associated with lead-related health outcomes is estimated at $6 trillion annually, representing about 7% of the global gross domestic product.
- Screening and Treatment: Screening high-risk populations is recommended, including children in older housing and workers in certain industries. While chelation therapy can reduce body lead burden, its effects on health outcomes are inconsistent, highlighting the importance of primary prevention.
- Prevention Strategies: Eliminating environmental sources of lead through government-funded population strategies is essential. This includes replacing lead-containing infrastructure like water service lines, banning leaded aviation fuel, reducing lead in consumer products, and remediating contaminated soils and older housing with lead-based paints.
Conclusion: Chronic low-level lead poisoning continues to pose a significant global health threat, contributing to cardiovascular disease and neurodevelopmental deficits. The disproportionate effects at even the lowest exposure levels underscore the necessity for robust, population-wide prevention strategies. Implementing stringent regulatory actions to eliminate sources of lead exposure is imperative to reduce the substantial morbidity, mortality, and economic burdens associated with lead poisoning.
RCT: Early TAVR Improves Clinical Outcomes in Asymptomatic Severe Aortic Stenosis
29 Oct, 2024 | 13:04h | UTCBackground: Severe aortic stenosis is prevalent among adults aged 65 and older. Current guidelines recommend aortic-valve replacement for symptomatic patients or asymptomatic patients with specific high-risk features. For other asymptomatic patients, routine clinical surveillance is standard due to limited evidence supporting early intervention, particularly with transcatheter aortic-valve replacement (TAVR).
Objective: To determine whether early TAVR reduces the incidence of death, stroke, or unplanned cardiovascular hospitalization compared to standard clinical surveillance in patients with asymptomatic severe aortic stenosis.
Methods: In this prospective, multicenter, randomized controlled trial, 901 asymptomatic patients aged ≥65 years with severe aortic stenosis and preserved left ventricular ejection fraction were randomized 1:1 to undergo early TAVR or to receive guideline-directed clinical surveillance. The mean age was 75.8 years, and the mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 1.8%, indicating low surgical risk. The primary endpoint was a composite of death from any cause, stroke, or unplanned hospitalization for cardiovascular causes.
Results: Over a median follow-up of 3.8 years, the primary endpoint occurred in 26.8% of the TAVR group compared to 45.3% of the surveillance group (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.40–0.63; P<0.001). Individual components showed lower rates in the TAVR group: death (8.4% vs. 9.2%), stroke (4.2% vs. 6.7%), and unplanned cardiovascular hospitalizations (20.9% vs. 41.7%). Early TAVR patients also maintained better quality of life, with 86.6% achieving favorable outcomes at 2 years compared to 68.0% in the surveillance group (P<0.001). By 2 years, 87.0% of patients in the surveillance group underwent aortic-valve replacement, many presenting with advanced symptoms and cardiac damage. Procedural complications and periprocedural adverse events were similar between groups.
Conclusions: Early TAVR significantly reduced death, stroke, and unplanned cardiovascular hospitalizations in asymptomatic patients with severe aortic stenosis compared to clinical surveillance. Early intervention preserved quality of life and cardiac function, suggesting that early TAVR may benefit this patient population.
Implications for Practice: These findings support considering early TAVR in asymptomatic patients with severe aortic stenosis to improve clinical outcomes and quality of life. This may challenge current guidelines that recommend surveillance over early intervention.
Study Strengths and Limitations: Strengths include the randomized design, large sample size, and multicenter participation. Limitations involve the study population being predominantly low surgical risk patients aged ≥65 years with anatomy suitable for transfemoral TAVR, which may limit generalizability to younger patients, those with higher surgical risk, or those unsuitable for TAVR.
Future Research: Further research is needed to assess long-term valve durability, outcomes in diverse patient populations, and comparisons with surgical aortic-valve replacement. Studies on cost-effectiveness and the impact on guidelines are also warranted.
RCT: Vitamin K2 Reduces Nocturnal Leg Cramps in Older Adults
28 Oct, 2024 | 18:59h | UTCBackground Nocturnal leg cramps (NLCs) affect 50% to 60% of adults, causing significant discomfort, sleep disturbances, and reduced quality of life. Current treatments lack robust evidence for efficacy and safety, with quinine no longer recommended due to severe adverse effects. Vitamin K2 has shown promise in reducing muscle cramps in dialysis patients, suggesting potential benefits for managing NLCs.
Objective To evaluate whether vitamin K2 supplementation reduces the frequency, duration, and severity of nocturnal leg cramps in older adults compared with placebo.
Methods In this multicenter, double-blind, placebo-controlled randomized clinical trial conducted in China from September 2022 to December 2023, 199 community-dwelling individuals aged 65 years or older with at least two episodes of NLCs over a two-week screening period were enrolled. Participants were randomly assigned in a 1:1 ratio to receive daily oral vitamin K2 (menaquinone-7, 180 μg) or placebo for eight weeks. The primary outcome was the mean number of NLCs per week. Secondary outcomes included cramp duration and severity, measured on a 1 to 10 analog scale.
Results Of the 199 participants (mean age 72.3 ± 5.5 years; 54.3% female), 103 received vitamin K2 and 96 received placebo. Baseline weekly cramp frequency was similar between groups (vitamin K2: 2.60 ± 0.81; placebo: 2.71 ± 0.80). Over eight weeks, the vitamin K2 group experienced a significant reduction in mean weekly cramps to 0.96 ± 1.41, while the placebo group increased to 3.63 ± 2.20 (between-group difference: −2.67; 95% CI, −2.86 to −2.49; P < .001). The vitamin K2 group also showed greater reductions in cramp severity (mean decrease of 2.55 ± 2.12 points vs 1.24 ± 1.16 points in placebo) and duration (mean decrease of 0.90 ± 0.88 minutes vs 0.32 ± 0.78 minutes in placebo). No adverse events related to vitamin K2 were reported.
Conclusions Vitamin K2 supplementation significantly reduced the frequency, severity, and duration of nocturnal leg cramps in older adults, demonstrating both efficacy and safety.
Implications for Practice Vitamin K2 may offer an effective and safe therapeutic option for managing NLCs in older individuals, addressing a significant unmet clinical need in primary care.
Study Strengths and Limitations Strengths include the randomized, double-blind design and focus on an older population; limitations involve the relatively mild symptoms of participants and lack of assessment of quality of life or sleep improvements.
Future Research Further studies should assess the impact of vitamin K2 on sleep quality and quality of life in patients with more severe NLCs and explore the underlying mechanisms of its muscle-relaxing effects.
RCT: Early DOACs Safe and Non-Inferior to Delayed Initiation Post-Stroke with Atrial Fibrillation
28 Oct, 2024 | 17:52h | UTCBackground: Atrial fibrillation increases ischaemic stroke risk, and patients are prone to recurrence. Prompt anticoagulation post-stroke is critical, but optimal timing is unclear due to bleeding concerns. Guidelines often delay DOAC initiation without strong evidence.
Objective: To determine if early DOAC initiation (≤4 days) is non-inferior to delayed initiation (7–14 days) in preventing recurrent ischaemic events without increasing intracranial haemorrhage risk in patients with acute ischaemic stroke and atrial fibrillation.
Methods: In this multicentre, open-label, blinded-endpoint, phase 4 randomised controlled trial at 100 UK hospitals, 3,621 adults with atrial fibrillation and acute ischaemic stroke were randomised to early or delayed DOAC initiation. Eligibility required physician uncertainty about timing. Participants and clinicians were unmasked; outcomes were adjudicated by a masked committee. The primary outcome was a composite of recurrent ischaemic stroke, symptomatic intracranial haemorrhage, unclassifiable stroke, or systemic embolism within 90 days.
Results: Among 3,621 patients (mean age 78.5; 45% female), the primary outcome occurred in 59 patients (3.3%) in both early and delayed groups (adjusted risk difference 0.0%, 95% CI –1.1 to 1.2%). Upper confidence limit below the 2% non-inferiority margin (p=0.0003) confirmed non-inferiority. Symptomatic intracranial haemorrhage rates were similar (0.6% early vs 0.7% delayed; p=0.78). No significant differences in mortality or heterogeneity across subgroups.
Conclusions: Early DOAC initiation within 4 days is non-inferior to delayed initiation in preventing recurrent events without increasing intracranial haemorrhage risk. Findings challenge guidelines advising delayed anticoagulation and support early initiation regardless of stroke severity.
Implications for Practice: Clinicians should consider starting DOACs within 4 days post-stroke in atrial fibrillation patients. Early initiation is safe and effective, potentially improving outcomes and suggesting guidelines may need revision.
Study Strengths and Limitations: Strengths include large sample size and masked outcome adjudication. Limitations include exclusion of patients with very severe strokes and low event rates, potentially limiting detection of rare adverse events.
Future Research: Further studies should explore optimal DOAC timing within 4 days and assess safety in patients with severe strokes or extensive haemorrhagic transformation.
Post-trial Follow-up: Empagliflozin Shows Sustained Benefits Post-Discontinuation in Chronic Kidney Disease
25 Oct, 2024 | 20:29h | UTCBackground: Chronic kidney disease (CKD) progression leads to end-stage kidney disease, affecting quality of life and increasing cardiovascular morbidity and mortality. Empagliflozin, an SGLT2 inhibitor, has shown renal and cardiovascular benefits during active treatment. The persistence of these effects post-discontinuation is uncertain.
Objective: To evaluate how the cardiorenal benefits of empagliflozin evolve after stopping the medication, by assessing the composite outcome of kidney disease progression or cardiovascular death during both the active trial and a subsequent post-trial follow-up.
Methods: In the EMPA-KIDNEY trial, 6609 patients with CKD were randomized to receive empagliflozin 10 mg daily or placebo and were followed for a median of 2 years during the active trial. Eligible patients had an eGFR of 20–45 ml/min/1.73 m² or an eGFR of 45–90 ml/min/1.73 m² with a urinary albumin-to-creatinine ratio ≥200 mg/g. After the active trial, 4891 surviving patients (74%) consented to a 2-year post-trial follow-up without the trial medication, although open-label SGLT2 inhibitors could be prescribed by local practitioners. The primary outcome was a composite of kidney disease progression or cardiovascular death assessed from the start of the active trial to the end of the post-trial period.
Results: During the combined active and post-trial periods, a primary outcome event occurred in 26.2% of patients in the empagliflozin group and 30.3% in the placebo group (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.72–0.87). During the post-trial period alone, the HR was 0.87 (95% CI, 0.76–0.99), indicating sustained benefits after discontinuation. The risk of kidney disease progression was 23.5% with empagliflozin versus 27.1% with placebo. Cardiovascular death occurred in 3.8% of the empagliflozin group and 4.9% of the placebo group (HR, 0.75; 95% CI, 0.59–0.95). There was no significant difference in noncardiovascular mortality.
Conclusions: Empagliflozin continued to confer cardiorenal benefits for up to 12 months after discontinuation in patients with CKD at risk for progression. The sustained reduction in kidney disease progression and cardiovascular death suggests long-term advantages of empagliflozin beyond active treatment, supporting its role in CKD management.
Implications for Practice: These findings support the early initiation and continued use of empagliflozin in patients with CKD to maximize long-term cardiorenal benefits. Clinicians should consider empagliflozin as part of standard care for a broad range of CKD patients, regardless of diabetes status, to slow disease progression and reduce cardiovascular risk.
Study Strengths and Limitations: While the study’s large, diverse CKD population and extended follow-up enhance its generalizability, reliance on local creatinine measurements and lack of hospitalization data during post-trial follow-up are limitations.
Future Research: Further studies should explore the mechanisms underlying the sustained benefits of empagliflozin after discontinuation and assess long-term effects on hospitalization and quality of life in CKD patients.
Systematic Review: Intensive Blood Pressure Targets Do Not Reduce Mortality or Cardiovascular Events in Hypertensive Patients with Chronic Kidney Disease
20 Oct, 2024 | 17:50h | UTCBackground: Chronic kidney disease (CKD) is a significant independent risk factor for cardiovascular disease and mortality, affecting approximately 10% of the global population. Hypertension is prevalent in CKD patients, ranging from 22% to 80% depending on disease stage. While lowering blood pressure is essential in managing CKD, the optimal blood pressure targets remain uncertain, particularly whether lower-than-standard targets provide additional benefits.
Objective: To compare the effects of standard versus lower-than-standard blood pressure targets on mortality and morbidity outcomes in hypertensive patients with CKD.
Methods: A systematic review and meta-analysis of six randomized controlled trials (RCTs) involving 7348 participants were conducted. Studies included adults with hypertension and CKD randomized to lower blood pressure targets (≤130/80 mmHg) versus standard targets (≤140–160/90–100 mmHg) with at least 12 months of follow-up. Primary outcomes were total mortality, total serious adverse events, total cardiovascular events, cardiovascular mortality, and progression to end-stage renal disease (ESRD). Data were analyzed using GRADE methodology to assess the certainty of evidence.
Results: Over a mean follow-up of 3.6 years, lower blood pressure targets likely resulted in little to no difference in total mortality (risk ratio [RR] 0.90; 95% confidence interval [CI], 0.76 to 1.06; moderate-certainty evidence), total serious adverse events (RR 1.01; 95% CI, 0.94 to 1.08; moderate-certainty), and total cardiovascular events (RR 1.00; 95% CI, 0.87 to 1.15; moderate-certainty) compared to standard targets. Lower targets may result in little to no difference in cardiovascular mortality (RR 0.90; 95% CI, 0.70 to 1.16; low-certainty) and progression to ESRD (RR 0.94; 95% CI, 0.80 to 1.11; low-certainty). Participants in the lower target groups achieved greater reductions in systolic and diastolic blood pressure but required more antihypertensive medications.
Conclusions: Intensive blood pressure targets probably do not reduce total mortality, serious adverse events, or cardiovascular events compared to standard targets in hypertensive patients with CKD, and may have little to no effect on cardiovascular mortality or progression to ESRD.
Implications for Practice: Clinicians should consider that lowering blood pressure below standard targets in hypertensive CKD patients may not provide additional benefit in reducing mortality or cardiovascular events. The increased medication burden and potential for adverse effects with intensive targets should be weighed against the lack of demonstrated benefit.
Study Strengths and Limitations: Strengths include the use of individual participant data from six RCTs and a comprehensive analysis using GRADE methodology. Limitations involve the open-label design of the included studies, potential risk of bias, heterogeneity in blood pressure targets and CKD definitions, and limited adverse event reporting.
Future Research: Further high-quality RCTs are needed to determine optimal blood pressure targets in hypertensive CKD patients, including those with varying levels of proteinuria and using out-of-office blood pressure monitoring. Ongoing studies may provide additional evidence in the near future.
Review: Endovascular Management of Acute Stroke
20 Oct, 2024 | 14:43h | UTCIntroduction: Stroke due to large vessel occlusion (LVO) remains a leading cause of disability and mortality worldwide. Endovascular therapy has revolutionized acute ischemic stroke management by enhancing recanalization rates and improving patient outcomes. This review outlines the evolution of endovascular treatments, expansion of therapeutic indications, current best practices, and ongoing research in the endovascular management of acute stroke.
Key Recommendations:
- Early Time Window Therapy (0–6 Hours): Robust evidence from randomized controlled trials demonstrates that mechanical thrombectomy significantly improves functional outcomes in patients with anterior circulation LVO presenting within 6 hours of symptom onset. Patients are selected based on moderate-to-severe neurological deficits and small infarct cores identified via imaging.
- Extended Time Window Therapy (6–24 Hours): Trials such as DAWN and DEFUSE3 have extended thrombectomy benefits to patients up to 24 hours after symptom onset. Advanced imaging techniques, like CT perfusion and MRI, identify patients with substantial penumbral tissue, indicating potential for recovery.
- Large Ischemic Core Infarcts: Recent studies (e.g., SELECT2, ANGEL-ASPECT) suggest that patients with large core infarcts can benefit from endovascular therapy, challenging previous contraindications. Individualized patient selection is crucial to balance risks and benefits.
- Basilar Artery Occlusion: New evidence supports thrombectomy for basilar artery occlusions, especially in patients with moderate-to-severe symptoms. This intervention improves outcomes in a condition historically associated with high morbidity and mortality.
- Bridging Thrombolysis: The necessity of intravenous thrombolysis before thrombectomy in patients directly admitted to endovascular centers is under debate. Meta-analyses indicate that omitting thrombolysis may not adversely affect outcomes, although it remains standard for patients at non-thrombectomy centers.
- Simplified Imaging for Patient Selection: The use of non-contrast CT and CT angiography alone has proven effective for patient selection, reducing treatment delays and expanding access to thrombectomy, particularly in resource-limited settings.
Conclusion: Advancements in endovascular therapy have markedly improved outcomes for patients with acute ischemic stroke due to LVO. Expanded treatment indications and simplified imaging protocols have broadened patient eligibility for thrombectomy. Ongoing research into adjunctive therapies and optimization of management strategies holds promise for further reducing stroke-related disability and mortality.
Cohort Study: Ondansetron Initiation Linked to Increased 10-Day Sudden Cardiac Death Risk in Hemodialysis Patients
20 Oct, 2024 | 14:05h | UTCBackground: Individuals undergoing maintenance hemodialysis have a markedly elevated risk of sudden cardiac death, attributed to structural heart disease, electrolyte imbalances, and polypharmacy. Ondansetron, a commonly used antiemetic known to prolong the QT interval, has been associated with fatal arrhythmias when administered intravenously in the general population. However, its cardiac safety profile in the hemodialysis population remains unclear.
Objective: To assess whether initiation of oral ondansetron, compared to antiemetics with lesser QT-prolonging potential, is associated with a higher 10-day risk of sudden cardiac death among patients receiving maintenance hemodialysis.
Methods: This new-user, active-comparator cohort study analyzed data from the United States Renal Data System between 2012 and 2019. A total of 119,254 patients receiving in-center hemodialysis who initiated either oral ondansetron or comparator antiemetics (promethazine, metoclopramide, or prochlorperazine) were included. Inverse probability of treatment-weighted survival models estimated adjusted hazard ratios (aHR) and risk differences (aRD), using an intention-to-treat approach with non-sudden cardiac death as a competing event.
Results: Among the patients, 64,978 (55%) initiated ondansetron, while 54,276 (45%) initiated comparator antiemetics. Ondansetron initiation was associated with a higher 10-day risk of sudden cardiac death compared to comparator drugs (aHR 1.44; 95% CI, 1.08–1.93; aRD 0.06%; 95% CI, 0.01%–0.11%). The number needed to harm was 1,688. Secondary analyses of additional cardiac outcomes, including ventricular arrhythmias and cardiovascular mortality, yielded consistent findings.
Conclusions: Initiation of oral ondansetron is associated with an increased short-term risk of sudden cardiac death among patients on maintenance hemodialysis compared to initiation of antiemetics with lesser QT-prolonging potential.
Implications for Practice: Clinicians should exercise caution when prescribing ondansetron to hemodialysis patients and consider alternative antiemetics with lower QT-prolonging risks. If ondansetron is necessary, monitoring for cardiac arrhythmias and performing electrocardiograms may be advisable to mitigate potential risks.
Study Strengths and Limitations: Strengths include a large, nationally representative cohort and an active-comparator design that minimizes confounding. Limitations involve potential residual confounding inherent in observational studies, possible misclassification of outcomes, and inability to assess dose-response relationships due to power constraints.
Future Research: Further studies are warranted to confirm these findings, elucidate the underlying mechanisms of increased cardiac risk, and evaluate the safety of ondansetron across different dosages and patient subgroups within the hemodialysis population.
Guideline: SCAI Expert Consensus on Management of STEMI Patients Undergoing Primary PCI
13 Oct, 2024 | 12:44h | UTCIntroduction: ST-elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality, requiring rapid diagnosis and timely reperfusion. While primary percutaneous coronary intervention (PCI) is the preferred reperfusion method, existing guidelines lack detailed procedural and technical recommendations for the cardiac catheterization laboratory (CCL). The Society for Cardiovascular Angiography & Interventions (SCAI) presents this expert consensus statement to provide best practices for CCL team readiness, optimal angiography and intervention techniques, management of special circumstances and anatomical subsets, and strategies to improve quality of care in STEMI patients undergoing primary PCI.
Key Recommendations:
- CCL Team Readiness:
- Prehospital notification and ECG transmission expedite care.
- Implement emergency department (ED) bypass when feasible.
- Perform a focused cardiovascular assessment prior to PCI.
- Arterial Access:
- Prefer transradial access over femoral to reduce complications.
- Use ultrasound guidance and contemporary techniques for femoral access when necessary.
- Diagnostic Assessment:
- Conduct complete coronary angiography during the index procedure.
- Measure left ventricular end-diastolic pressure (LVEDP) to guide management.
- Managing Thrombus:
- Assess thrombus burden after wire crossing.
- Use bail-out aspiration thrombectomy selectively for large thrombus burden.
- Consider parenteral or intracoronary antiplatelet agents for refractory thrombus.
- Managing No-Reflow:
- Administer intracoronary vasodilators to the distal bed.
- Enhance coronary perfusion pressure by augmenting mean arterial pressure and reducing LVEDP.
- Intracoronary Imaging:
- Encourage routine use of IVUS or OCT to guide PCI.
- Employ intracoronary imaging to investigate stent thrombosis or suspected nonatherosclerotic causes.
- Special Circumstances:
- In cardiogenic shock, perform right heart catheterization and consider mechanical circulatory support.
- After failed fibrinolysis, proceed with immediate catheterization and rescue PCI.
- In multivessel disease, complete revascularization is recommended.
- Anatomical Subsets:
- Use plaque modification techniques for calcified lesions.
- Prefer a provisional one-stent strategy in bifurcation lesions.
- Focus on restoring flow in coronary aneurysms.
- Nonatherosclerotic STEMI Causes:
- Administer intracoronary nitroglycerin to identify epicardial vasospasm.
- Manage spontaneous coronary artery dissection conservatively if flow is preserved.
- Use thrombectomy for coronary embolism.
- Investigate MINOCA with additional imaging and testing.
- Quality Improvement:
- Track all STEMI cases to assess treatment times and outcomes for continuous improvement.
Conclusion: Adherence to these recommendations is expected to enhance patient outcomes by optimizing procedural strategies, reducing complications, and improving survival in STEMI patients undergoing primary PCI.
Meta-analysis: Colchicine Reduces Ischemic Stroke and MACE in Patients with Prior Stroke or Coronary Disease
13 Oct, 2024 | 12:10h | UTCBackground: Colchicine is recommended for secondary prevention in cardiovascular disease, but its efficacy in preventing ischemic stroke and benefits in key patient subgroups remain uncertain. Inflammation plays a significant role in stroke and cardiovascular events, and colchicine’s anti-inflammatory properties may confer additional protective effects.
Objective: To evaluate the efficacy of colchicine for secondary prevention of ischemic stroke and major adverse cardiovascular events (MACE) in patients with prior stroke or coronary disease, and to assess its safety profile across key clinical subgroups.
Methods: A trial-level meta-analysis was conducted, including six randomized controlled trials with a total of 14,934 patients with prior stroke or coronary disease. Trials comparing colchicine with placebo or no colchicine for at least three months were included. The primary efficacy outcomes were ischemic stroke and MACE, defined as a composite of ischemic stroke, myocardial infarction, coronary revascularization, or cardiovascular death. Secondary outcomes included serious safety events and mortality.
Results: Colchicine reduced the risk of ischemic stroke by 27% (1.8%] vs. 186 events [2.5%]; RR 0.73, 95% CI 0.58–0.90; P = .004) and MACE by 27% (505 events [6.8%] vs. 693 events [9.4%]; RR 0.73, 95% CI 0.65–0.81; P < .001). The efficacy was consistent across key subgroups, including sex, age (<70 vs. ≥70 years), diabetes status, and statin use at baseline. Colchicine was not associated with an increase in serious safety outcomes, all-cause mortality (201 deaths [2.7%] vs. 181 deaths [2.4%]; RR 1.09, 95% CI 0.89–1.33; P = .39), cardiovascular death, or non-cardiovascular death.
Conclusions: In patients with prior stroke or coronary disease, colchicine significantly reduces the risk of ischemic stroke and MACE without increasing serious adverse events or mortality. These findings support the use of low-dose colchicine as an effective secondary prevention therapy in a broad cardiovascular patient population.
Implications for Practice: Clinicians should consider incorporating low-dose colchicine into secondary prevention regimens for patients with prior stroke or coronary disease, given its demonstrated efficacy and acceptable safety profile. Its affordability and widespread availability make it a practical option for diverse healthcare settings, including low- and middle-income countries.
Study Strengths and Limitations: Strengths include a large pooled sample size and inclusion of multiple trials across various patient populations, enhancing generalizability. Limitations involve potential performance bias in non-placebo-controlled trials, differences in stroke outcome definitions among studies, and the inability to perform individual patient data analyses.
Future Research: Further studies are needed to evaluate the long-term effects of colchicine on vascular events and cognitive decline in stroke patients, assess safety in patients with renal impairment, and explore its impact on non-cardiovascular mortality.
RCT: Nonstandard Arm Positions Overestimate Blood Pressure Readings in Adults
12 Oct, 2024 | 22:55h | UTCBackground: Accurate blood pressure (BP) measurement is crucial for the diagnosis and management of hypertension, a leading cause of cardiovascular disease and mortality worldwide. Guidelines recommend measuring BP with the arm supported on a desk at heart level. However, in clinical practice, nonstandard arm positions—such as resting the arm on the lap or having it unsupported at the side—are commonly used, potentially leading to inaccurate readings.
Objective: To determine the effect of commonly used nonstandard arm positions on BP measurements compared to the standard, recommended position.
Methods: In a crossover randomized clinical trial from August 2022 to June 2023, 133 adults aged 18 to 80 years were recruited. Participants were randomly assigned to receive sets of triplicate BP measurements with the arm in three positions: (1) supported on a desk with the midcuff at heart level (desk 1; reference), (2) hand supported on the lap (lap), and (3) arm unsupported at the side (side). To account for intrinsic BP variability, all participants underwent a fourth set of BP measurements with the arm supported on a desk (desk 2). The primary outcomes were the difference in differences in mean systolic BP (SBP) and diastolic BP (DBP) between the reference BP (desk 1) and the two nonstandard arm positions (lap and side).
Results: Among 133 participants (mean age 57 years; 53% female), 36% had SBP ≥130 mm Hg, and 41% had a body mass index ≥30 kg/m². Compared to the reference position, the lap and side positions resulted in significantly higher BP readings. The difference in differences for the lap position was an increase in SBP of 3.9 mm Hg (95% CI, 2.5-5.2) and DBP of 4.0 mm Hg (95% CI, 3.1-5.0). For the side position, the increases were SBP 6.5 mm Hg (95% CI, 5.1-7.9) and DBP 4.4 mm Hg (95% CI, 3.4-5.4). These patterns were consistent across subgroups.
Conclusions: Commonly used nonstandard arm positions during BP measurements, such as resting the arm on the lap or having it unsupported at the side, significantly overestimate BP readings compared to the standard recommended position. This overestimation may lead to misdiagnosis and overestimation of hypertension.
Implications for Practice: Clinicians should adhere to guideline-recommended arm positioning during BP measurements to ensure accurate readings. Proper arm support with the midcuff at heart level is necessary to avoid overestimation of BP, which can result in unnecessary follow-up and overtreatment due to hypertension overdiagnosis.
Study Strengths and Limitations: Strengths include the randomized crossover design ideal for studying BP differences, a larger sample size than previous studies, and focus on arm positions commonly used in clinical practice with an automated BP device. Limitations include unequal randomization due to the randomization function used, small sample sizes in some subgroups, and uncertain generalizability to other settings or devices.
Future Research: Further studies are needed to investigate strategies to improve adherence to guideline-recommended arm positions in clinical practice, assess the impact of educational interventions on BP measurement accuracy, and explore the effects of arm position on BP readings using different devices or in diverse populations.
Review: Management of Atrial Fibrillation in Older Adults
12 Oct, 2024 | 19:52h | UTCIntroduction: Atrial fibrillation (AF) predominantly affects adults over 65 years old and often coexists with multiple chronic conditions, polypharmacy, and geriatric syndromes such as frailty. Despite this, most randomized controlled trials and guidelines do not tailor recommendations specifically for older adults with these complexities. This review addresses the gap by synthesizing evidence and applying aging science principles to AF management, aiming to provide a framework that prioritizes patients’ goals across the spectrum of older adults—from fit individuals to those who are frail or at the end of life.
Key Recommendations:
- Individualized Care Approach: Clinicians should tailor AF management by considering patients’ comorbidities, frailty, and personal health goals. Tools like the Clinical Frailty Scale and comprehensive geriatric assessment can aid in assessing fitness and frailty.
- Screening for AF: Systematic population-level screening for AF in older adults has not conclusively shown a reduction in stroke incidence. Decisions regarding screening should be individualized, weighing the potential benefits and burdens.
- Lifestyle Interventions: For functional older adults, lifestyle modifications such as weight loss, moderate physical activity, blood pressure control, and alcohol avoidance are recommended to prevent and manage AF.
- Symptom Management: Use validated patient-reported outcome measures to assess and manage AF symptoms effectively, aligning treatment with patients’ experiences and quality of life goals.
- Rate and Rhythm Control:
- Fit Older Adults: Early rhythm control is preferred, with catheter ablation showing superiority over anti-arrhythmic drugs in maintaining sinus rhythm and improving quality of life.
- Multimorbid/Frail Older Adults: Treatment should be individualized, balancing the risks and benefits of anti-arrhythmic drugs versus catheter ablation.
- Heart Failure Coexistence: Catheter ablation is recommended over medical therapy for patients with AF and heart failure with reduced ejection fraction.
- Anticoagulation Therapy:
- General Recommendation: Direct oral anticoagulants (DOACs) are preferred over warfarin due to similar efficacy and lower bleeding risk.
- Multimorbid/Frail Older Adults: Apixaban is favored for its lower bleeding risk. Decisions should consider life expectancy and patient preferences.
- End-of-Life Care: De-escalation of anticoagulation may be appropriate when risks outweigh benefits or when it aligns with the patient’s comfort-focused goals.
- Left Atrial Appendage Closure (LAAC):
- Indications: LAAC is considered for patients with contraindications to long-term anticoagulation.
- Considerations: Procedural risks should be weighed against potential benefits, especially in frail older adults.
Conclusion: Implementing an individualized, goal-directed approach to AF management in older adults can enhance patient care by aligning treatments with patients’ health priorities and improving clinical outcomes. Recognizing the heterogeneity among older adults with AF, clinicians should adopt strategies that consider fitness, frailty, comorbidities, and patient preferences to optimize care across the aging spectrum.
Meta-Analysis: Oral Anticoagulant Monotherapy Reduced Bleeding Without Increasing Ischemic Events in AF and Stable CAD
9 Oct, 2024 | 11:13h | UTCBackground: Atrial fibrillation (AF) patients with stable coronary artery disease (CAD) often require both oral anticoagulants (OACs) for stroke prevention and antiplatelet therapy for CAD management. However, dual antithrombotic therapy (DAT) increases bleeding risk. The optimal antithrombotic regimen in this population remains unclear.
Objective: To evaluate whether OAC monotherapy reduces major bleeding without increasing ischemic events compared to DAT in patients with AF and stable CAD.
Methods: This meta-analysis followed PRISMA guidelines, pooling data from three randomized controlled trials (RCTs) involving 3,945 patients with AF and stable CAD. The trials included used various OACs (rivaroxaban, edoxaban, or warfarin/DOAC) and compared them with DAT. The primary outcomes were all-cause death, cardiovascular death, and major bleeding. Secondary outcomes included stroke (ischemic and hemorrhagic) and myocardial infarction (MI).
Results: OAC monotherapy significantly reduced the risk of major bleeding compared to DAT (3.4% vs 5.8%; RR: 0.55; 95% CI: 0.32–0.95; p=0.03). There were no significant differences between groups in all-cause death (4.2% vs 5.4%; RR: 0.85; 95% CI: 0.49–1.48; p=0.57), cardiovascular death (2.4% vs 3.0%; RR: 0.84; 95% CI: 0.50–1.41; p=0.50), any stroke event (2.2% vs 3.1%; RR: 0.74; 95% CI: 0.46–1.18; p=0.21), or myocardial infarction (RR: 1.57; 95% CI: 0.79–3.12; p=0.20).
Conclusions: In patients with AF and stable CAD, OAC monotherapy significantly reduces major bleeding risk compared to DAT without increasing the risk of ischemic events or mortality.
Implications for Practice: OAC monotherapy may be a preferable antithrombotic strategy in patients with AF and stable CAD, balancing effective thromboembolic protection with a lower bleeding risk. Clinicians should consider OAC monotherapy to simplify antithrombotic regimens and reduce bleeding complications, especially beyond one year after coronary events or interventions.
Study Strengths and Limitations: Strengths include the inclusion of recent large-scale RCTs and the focus on a clinically relevant patient population. Limitations involve reliance on study-level data, limited number of trials, and potential heterogeneity among included studies. The duration of DAT was not consistently available, and individual patient data meta-analysis may provide more detailed insights.
Future Research: Additional large-scale RCTs and individual patient data meta-analyses are needed to confirm these findings and to determine the optimal duration and type of antithrombotic therapy in patients with AF and stable CAD.
Aspirin vs. Clopidogrel Monotherapy After PCI: 1-Year Follow-Up of the STOPDAPT-3 Trial
6 Oct, 2024 | 16:51h | UTCBackground: Following percutaneous coronary intervention (PCI) with drug-eluting stents (DES), patients are typically managed with dual antiplatelet therapy (DAPT). Recent evidence suggests that monotherapy with a P2Y12 inhibitor may reduce bleeding risks compared to aspirin monotherapy, but no prior trials have directly compared these regimens beyond one month of DAPT. The STOPDAPT-3 trial aimed to evaluate the cardiovascular and bleeding outcomes of aspirin versus clopidogrel monotherapy following a short duration of DAPT.
Objective: To compare the efficacy and safety of aspirin monotherapy with clopidogrel monotherapy from 1 month to 1 year after PCI with DES, focusing on cardiovascular and bleeding outcomes.
Methods: The STOPDAPT-3 trial was a prospective, multicenter, open-label, randomized clinical trial conducted in Japan. A total of 6002 patients with acute coronary syndrome (ACS) or high bleeding risk (HBR) were randomized to either a 1-month DAPT regimen followed by aspirin monotherapy (aspirin group, n=2920) or 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group, n=2913). The primary endpoints were a composite of cardiovascular events (cardiovascular death, myocardial infarction, stent thrombosis, or ischemic stroke) and major bleeding (Bleeding Academic Research Consortium 3 or 5).
Results: At the 1-year follow-up, both the aspirin and clopidogrel groups had comparable cardiovascular outcomes (4.5% incidence in both groups; HR 1.00, 95% CI 0.77–1.30, P=0.97). Bleeding rates were also similar between groups (aspirin: 2.0%; clopidogrel: 1.9%; HR 1.02, 95% CI 0.69–1.52, P=0.92). No significant differences were observed in secondary outcomes, including all-cause mortality, myocardial infarction, stent thrombosis, or revascularization. Additionally, adherence to the assigned monotherapy at 1 year was high in both groups (87.5% for aspirin; 87.2% for clopidogrel).
Conclusions: Aspirin monotherapy, compared to clopidogrel monotherapy, resulted in similar cardiovascular and bleeding outcomes during the 1-year follow-up after PCI with DES. Both therapies appear equally effective and safe for use following short-duration DAPT.
Implications for Practice: These findings suggest that either aspirin or clopidogrel monotherapy could be safely used following a short course of DAPT, with similar clinical outcomes. In regions where more potent P2Y12 inhibitors are not widely used, aspirin monotherapy remains a cost-effective and safe alternative.
Study Strengths and Limitations: The study’s strengths include a large sample size and a well-structured, multicenter design. Limitations include the lack of randomization after 1 month and the high prescription of proton pump inhibitors, which may have affected bleeding outcomes. Additionally, the follow-up period of 1 year may be too short to detect long-term differences.
Future Research: Longer-term studies are needed to confirm the findings, particularly regarding cardiovascular outcomes beyond 1 year. Further research is also required to evaluate the impact of aspirin versus more potent P2Y12 inhibitors in diverse populations and clinical settings.
RCT: Early Surgical AVR Improved Outcomes in Asymptomatic Severe Aortic Stenosis
6 Oct, 2024 | 16:29h | UTCBackground: Severe aortic stenosis (AS) is a prevalent valvular heart disease requiring intervention in symptomatic patients. The optimal timing for surgical aortic valve replacement (AVR) in truly asymptomatic patients with severe AS and normal left ventricular (LV) systolic function remains uncertain and is under investigation.
Objective: To determine whether early surgical AVR improves clinical outcomes compared to conservative management with watchful waiting in asymptomatic patients with severe AS and normal LV ejection fraction (LVEF ≥50%).
Methods: The AVATAR trial was a multicenter, randomized controlled trial involving 157 low-risk, asymptomatic patients (mean age 67 years, 57% men) with severe AS and normal LVEF. Patients were randomized to early surgical AVR (n=78) or conservative treatment (n=79). All participants had negative exercise stress tests to confirm asymptomatic status. The primary composite endpoint included all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure (HF). Secondary outcomes encompassed individual components of the primary endpoint, cardiovascular death, serious adverse events, and procedural metrics.
Results: Over a median follow-up of 63 months, the primary composite endpoint occurred in 23.1% of the early surgery group versus 46.8% of the conservative group (hazard ratio [HR] 0.42; 95% confidence interval [CI], 0.24–0.73; P=0.002). All-cause mortality was significantly lower in the early surgery group (16.7% vs. 34.2%; HR 0.44; 95% CI, 0.23–0.85; P=0.012). Unplanned HF hospitalizations were also reduced (4.0% vs. 17.0%; HR 0.21; 95% CI, 0.06–0.73; P=0.007). There were no significant differences in stroke rates between the groups. Serious adverse events occurred less frequently in the early surgery group (26.4% vs. 49.4%; P=0.013). Sudden cardiac death was less common in the early surgery group, though not statistically significant (5.1% vs. 11.4%; P=0.17).
Conclusions: Early surgical AVR in asymptomatic patients with severe AS and normal LVEF significantly improved clinical outcomes, including reductions in all-cause mortality and HF hospitalizations, compared to conservative management.
Implications for Practice: These findings support considering early surgical AVR in truly asymptomatic patients with severe AS and normal LV function to reduce the risk of adverse events and improve long-term outcomes. Clinicians should weigh the benefits of early intervention against surgical risks, emphasizing careful patient selection and monitoring.
Study Strengths and Limitations: Strengths of the study include its randomized design, extended follow-up period, and strict inclusion of truly asymptomatic patients confirmed by negative exercise testing. Limitations involve a smaller sample size than initially projected, potential impacts of the COVID-19 pandemic on follow-up and healthcare access, and early termination of enrollment, which may affect the generalizability of the results.
Future Research: Further large-scale randomized trials are needed to validate these findings and explore the role of early intervention strategies, including transcatheter aortic valve implantation (TAVI), in asymptomatic patients with severe AS.
Guideline Summary: Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors for Adults with Chronic Kidney Disease
4 Oct, 2024 | 11:14h | UTCIntroduction
A recent clinical practice guideline published in The BMJ titled “Sodium-glucose cotransporter-2 (SGLT-2) inhibitors for adults with chronic kidney disease” provides evidence-based recommendations on the use of SGLT-2 inhibitors in adults with chronic kidney disease (CKD), regardless of diabetes status. The guideline aims to assist clinicians in making informed decisions to improve patient outcomes in CKD management.
Key Recommendations and Patient Care Implications
- Risk Stratification
- Assessment: Patients with CKD should be stratified based on their risk of disease progression and complications using estimated glomerular filtration rate (eGFR) and albuminuria levels, following the Kidney Disease Improving Global Outcomes (KDIGO) classification.
- Clinical Implication: Proper risk stratification guides the intensity of treatment and monitoring.
- Use of SGLT-2 Inhibitors
- Low to Moderate Risk Patients: For adults at low or moderate risk, the guideline suggests administering SGLT-2 inhibitors (weak recommendation in favor).
- Patient Care Impact: Clinicians should discuss potential benefits and risks with patients, considering individual preferences.
- High to Very High Risk Patients: For adults at high or very high risk, a strong recommendation is made to administer SGLT-2 inhibitors.
- Patient Care Impact: Clinicians should prioritize initiating SGLT-2 inhibitors in these patients to reduce risks of mortality and progression to kidney failure.
- Low to Moderate Risk Patients: For adults at low or moderate risk, the guideline suggests administering SGLT-2 inhibitors (weak recommendation in favor).
- Benefits of SGLT-2 Inhibitors
- Outcomes: Reduction in all-cause mortality, cardiovascular mortality, hospitalization for heart failure, kidney failure, non-fatal myocardial infarction, and non-fatal stroke.
- Clinical Implication: SGLT-2 inhibitors provide significant protective effects on cardiovascular and kidney health in CKD patients.
- Potential Harms and Monitoring
- Adverse Effects: Minimal increase in risks of acute kidney injury requiring dialysis, bone fractures, lower limb amputations, ketoacidosis, genital infections, or symptomatic hypovolemia.
- Patient Counseling: Patients should be informed about possible side effects and advised on when to seek medical attention.
- Monitoring: Routine laboratory monitoring is not generally necessary, except in high-risk individuals.
- Practical Considerations for Prescribing
- Initiation: Start SGLT-2 inhibitors in patients with eGFR ≥20 mL/min/1.73 m².
- Continuation: Medications can be continued even if eGFR falls below 20 mL/min/1.73 m² until dialysis is initiated.
- Dosage: Initiate at the highest possible dose without the need for titration.
- Drug Selection: Canagliflozin, dapagliflozin, and empagliflozin are suitable options.
- Concurrent Medications: Review and adjust diuretics to prevent volume depletion.
- Patient Education and Self-Management
- Sick Day Rules: Advise patients to temporarily discontinue SGLT-2 inhibitors during acute illnesses causing dehydration.
- Lifestyle Modifications: Encourage adherence to medication and healthy lifestyle changes to enhance treatment efficacy.
- Applicability and Exceptions
- Applicable Populations: Recommendations apply broadly to adults with CKD, with or without type 2 diabetes.
- Exceptions: Caution or alternative approaches may be necessary for patients:
- Receiving kidney replacement therapy.
- With kidney transplants, polycystic kidney disease, rare kidney diseases.
- With eGFR <20 mL/min/1.73 m² not on replacement therapy.
Conclusion
The guideline underscores the importance of incorporating SGLT-2 inhibitors into the management plan for adults with CKD to improve survival and reduce cardiovascular and kidney-related complications. Clinicians should evaluate each patient’s risk profile and engage in shared decision-making to optimize treatment outcomes.