Internal Medicine
RCT: High-Intensity NPPV Reduced Criteria for Intubation in Acute COPD Exacerbations
16 Sep, 2024 | 16:50h | UTCBackground: Acute exacerbations of chronic obstructive pulmonary disease (COPD) often lead to hypercapnic respiratory failure requiring ventilatory support. Noninvasive positive pressure ventilation (NPPV) is standard care, commonly delivered at low intensity with lower inspiratory pressures. However, approximately 15% of patients still require endotracheal intubation despite low-intensity NPPV. High-intensity NPPV, using higher inspiratory pressures to achieve greater reductions in PaCO₂, has shown benefits in stable hypercapnic COPD patients, but its effect during acute exacerbations is unclear.
Objective: To determine whether high-intensity NPPV reduces the need for endotracheal intubation in patients with acute COPD exacerbations and persistent hypercapnia compared to low-intensity NPPV.
Methods: In a multicenter, randomized clinical trial conducted at 30 respiratory wards in China from January 2019 to January 2022, 300 patients with acute COPD exacerbations and PaCO₂ greater than 45 mm Hg after 6 hours of low-intensity NPPV were enrolled. Participants were randomized 1:1 to receive either high-intensity NPPV (inspiratory positive airway pressure [IPAP] adjusted to achieve tidal volumes of 10–15 mL/kg predicted body weight, typically IPAP 20–30 cm H₂O) or to continue low-intensity NPPV (IPAP adjusted for tidal volumes of 6–10 mL/kg, maximum IPAP 20 cm H₂O). Patients in the low-intensity group meeting prespecified criteria for intubation were allowed to crossover to high-intensity NPPV. The primary outcome was the need for endotracheal intubation during hospitalization, defined by prespecified clinical and gas exchange criteria. Secondary outcomes included actual endotracheal intubation rates, mortality, length of hospital stay, and adverse events.
Results: Of the 300 patients (mean age 73 years; 68% male), the primary outcome occurred in 4.8% of the high-intensity group versus 13.7% of the low-intensity group (absolute difference –9.0%; 95% CI, –15.4% to –2.5%; one-sided P = .004; adjusted risk ratio [RR], 0.35; 95% CI, 0.14–0.76). However, actual endotracheal intubation rates did not differ significantly between groups (3.4% vs 3.9%; absolute difference –0.5%; 95% CI, –4.8% to 3.7%; P = .81). The high-intensity group had greater reductions in PaCO₂ levels over 72 hours (mean PaCO₂ at 72 hours: 53 mm Hg vs 64 mm Hg; P < .001) and higher rates of achieving normocapnia (21.8% vs 4.6%; P < .001). Abdominal distension occurred more frequently in the high-intensity group (37.4% vs 25.5%; absolute difference 11.9%; 95% CI, 1.5%–22.4%; P = .03), but other adverse events and serious adverse events were similar between groups.
Conclusions: High-intensity NPPV reduced the proportion of patients meeting criteria for endotracheal intubation compared to low-intensity NPPV in patients with acute COPD exacerbations and persistent hypercapnia. However, actual intubation rates did not differ, possibly due to crossover from low- to high-intensity NPPV in patients meeting intubation criteria.
Implications for Practice: High-intensity NPPV may be considered for patients with acute COPD exacerbations who remain hypercapnic after initial low-intensity NPPV, as it may reduce progression to severe respiratory failure requiring intubation criteria. Clinicians should monitor for abdominal distension and potential alkalosis, although these did not significantly affect overall tolerance or safety.
Study Strengths and Limitations: Strengths include the multicenter randomized design, clear enrollment criteria, and standardized protocols. Limitations include early trial termination, unblinded interventions, potential bias due to allowed crossover, and lack of power to detect differences in mortality or actual intubation rates.
Future Research: Further large-scale trials are needed to confirm these findings, assess the impact on actual intubation rates and mortality, and explore the efficacy of high-intensity NPPV in different clinical settings and patient populations, including those without prior NPPV exposure or with more severe respiratory distress.
RCT: Tenecteplase Noninferior to Alteplase in Acute Ischemic Stroke
14 Sep, 2024 | 20:03h | UTCBackground: Acute ischemic stroke (AIS) is a leading cause of morbidity and mortality globally, with a particularly high burden in China. Intravenous thrombolysis with alteplase, administered within 4.5 hours of symptom onset, is the current standard of care. Tenecteplase, a genetically modified variant of alteplase with greater fibrin specificity and a longer half-life, allows for single-bolus administration, potentially simplifying and expediting treatment. Prior studies suggest tenecteplase may be as effective as alteplase in AIS, but data specific to Chinese patients are limited.
Objective: To determine whether tenecteplase is noninferior to alteplase in achieving excellent functional outcomes in Chinese patients with AIS treated within 4.5 hours of symptom onset.
Methods:
- Design: Multicenter, randomized, open-label, blinded-endpoint, noninferiority trial conducted at 55 centers in China between July 2021 and July 2023.
- Participants: 1,489 Chinese adults aged ≥18 years with AIS, National Institutes of Health Stroke Scale (NIHSS) scores of 1–25, measurable neurological deficits, and symptom onset within 4.5 hours.
- Interventions: Patients were randomized 1:1 to receive either:
- Tenecteplase: 0.25 mg/kg intravenous single bolus (maximum 25 mg).
- Alteplase: 0.9 mg/kg intravenous (maximum 90 mg), with 10% as an initial bolus and the remainder infused over 1 hour.
- Outcomes:
- Primary Outcome: Proportion of patients achieving a modified Rankin Scale (mRS) score of 0 or 1 at 90 days (indicating no symptoms or no significant disability).
- Secondary Outcomes: Major neurological improvement at 24 hours, mRS scores of 0–2 at 90 days, change in NIHSS score at 90 days, Barthel Index score ≥95 at 90 days.
- Safety Outcomes: Symptomatic intracerebral hemorrhage (sICH) per ECASS III definition and all-cause mortality at 90 days.
Results:
- Participants: 1,465 patients were included in the full analysis set (732 tenecteplase; 733 alteplase). Median age was 66 years, median NIHSS score was 6, and 30.4% were female.
- Primary Outcome:
- 72.7% in the tenecteplase group achieved mRS 0 or 1 at 90 days compared to 70.3% in the alteplase group.
- Adjusted risk ratio (RR): 1.03 (95% CI, 0.97–1.09), meeting the predefined noninferiority margin (RR ≥0.937).
- Secondary Outcomes:
- Major Neurological Improvement at 24 Hours: 48.0% (tenecteplase) vs. 45.0% (alteplase); RR, 1.07 (95% CI, 0.96–1.19).
- mRS 0–2 at 90 Days: 80.9% (tenecteplase) vs. 79.9% (alteplase); RR, 1.01 (95% CI, 0.96–1.06).
- Change in NIHSS Score at 90 Days: Mean change of –3.70 (tenecteplase) vs. –3.02 (alteplase); adjusted difference, –0.45 (95% CI, –1.40 to 0.50).
- Barthel Index ≥95 at 90 Days: 75.7% (tenecteplase) vs. 73.9% (alteplase); RR, 1.02 (95% CI, 0.96–1.08).
- Safety Outcomes:
- sICH: Occurred in 1.2% of patients in both groups; RR, 1.01 (95% CI, 0.37–2.70).
- 90-Day Mortality: 4.6% (tenecteplase) vs. 5.8% (alteplase); RR, 0.80 (95% CI, 0.51–1.23).
Conclusions: Tenecteplase was noninferior to alteplase in achieving excellent functional outcomes (mRS 0 or 1) at 90 days in Chinese patients with AIS treated within 4.5 hours of symptom onset. Safety profiles, including rates of sICH and mortality, were similar between the two treatments. These findings support tenecteplase as a suitable alternative to alteplase for intravenous thrombolysis in AIS.
Implications for Practice:
- Administration Advantage: Tenecteplase’s single-bolus administration could streamline treatment workflows and reduce door-to-needle times.
- Efficacy and Safety: Comparable efficacy and safety profiles suggest tenecteplase can be confidently used in place of alteplase.
- Patient Selection: Results are applicable to a broad range of AIS patients, including those with varying stroke severities and ages.
Study Strengths and Limitations:
- Strengths: Large sample size, multicenter design, and inclusion of a real-world patient population enhance the generalizability of findings.
- Limitations: Open-label design may introduce bias despite blinded endpoint assessments. The relatively low proportion of patients undergoing thrombectomy limits conclusions about combined therapy.
Future Research:
- Further studies could explore the effectiveness of tenecteplase in specific subgroups, such as patients with large vessel occlusions or those requiring endovascular interventions.
- Investigations into long-term outcomes beyond 90 days and real-world implementation strategies may provide additional insights.
RCT: PCI Reduces Major Adverse Cardiac Events in Patients Undergoing TAVI with Significant Coronary Artery Disease
14 Sep, 2024 | 19:09h | UTCBackground:
Severe aortic stenosis and coronary artery disease (CAD) frequently coexist, particularly in the elderly population. Approximately 50% of patients undergoing transcatheter aortic valve implantation (TAVI) have concurrent CAD. The optimal management of significant coronary lesions in patients undergoing TAVI remains uncertain, with guidelines providing no clear recommendations. Understanding whether percutaneous coronary intervention (PCI) improves outcomes in this setting is crucial for guiding clinical practice.
Objective:
To evaluate whether routine PCI of physiologically significant coronary lesions improves clinical outcomes compared to conservative management in patients with stable CAD undergoing TAVI.
Methods:
- Design: International, multicenter, open-label, randomized controlled trial (NOTION-3).
- Participants: 455 patients with severe symptomatic aortic stenosis scheduled for TAVI and at least one significant coronary lesion (defined as fractional flow reserve [FFR] ≤0.80 or diameter stenosis ≥90%).
- Interventions:
- PCI Group (n=227): Underwent PCI of all eligible lesions followed by TAVI.
- Conservative Treatment Group (n=228): Received TAVI without prior PCI.
- Primary Endpoint: Major adverse cardiac events (MACE), a composite of death from any cause, myocardial infarction (MI), or urgent revascularization.
- Secondary Endpoints: Included individual components of the primary endpoint, bleeding events, stroke, hospital admissions for heart failure, and procedural complications.
- Follow-Up: Median of 2 years (interquartile range, 1 to 4 years).
Results:
- Baseline Characteristics: Median age was 82 years; 67% were men; median Society of Thoracic Surgeons–Procedural Risk of Mortality (STS-PROM) score was 3%.
- Primary Endpoint (MACE):
- Occurred in 26% of patients in the PCI group versus 36% in the conservative group.
- Hazard Ratio (HR): 0.71 (95% Confidence Interval [CI], 0.51 to 0.99; P=0.04), indicating a 29% relative risk reduction with PCI.
- Components of MACE:
- Myocardial Infarction:
- Lower incidence in the PCI group.
- Urgent Revascularization:
- Reduced need in the PCI group.
- Myocardial Infarction:
- All-Cause Mortality:
- No significant difference between groups.
- Bleeding Events:
- Higher in the PCI group (28% vs. 20%; HR, 1.51; 95% CI, 1.03 to 2.22).
- Bleeding assessed according to Valve Academic Research Consortium–2 criteria.
- Procedural Complications:
- PCI-related complications occurred in 3% of patients in the PCI group.
- Safety Endpoints:
- Similar rates of stroke and stent thrombosis between groups.
- Acute kidney injury was less frequent in the PCI group (5% vs. 11%; HR, 0.45; 95% CI, 0.23 to 0.89).
Conclusions:
In patients with stable CAD and severe symptomatic aortic stenosis undergoing TAVI, performing PCI on significant coronary lesions resulted in a statistically significant reduction in MACE over a median follow-up of 2 years compared to conservative management. The benefit was primarily due to reductions in myocardial infarction and urgent revascularization rates. However, this advantage was accompanied by an increased risk of bleeding events.
Clinical Implications:
- Patient Selection: PCI should be considered in patients with physiologically significant coronary lesions (FFR ≤0.80 or diameter stenosis ≥90%) undergoing TAVI.
- Risk–Benefit Analysis: Clinicians should balance the reduction in MACE against the increased bleeding risk when deciding on PCI.
- Treatment Strategy: The findings support a strategy of routine revascularization in this patient population to improve cardiovascular outcomes.
- Future Considerations: Further research is needed to determine the optimal timing of PCI relative to TAVI and to identify which patient subgroups may derive the most benefit.
Recommendations:
- Guideline Update: The results may inform future guidelines to provide clearer recommendations on managing CAD in patients undergoing TAVI.
- Individualized Care: Decisions regarding PCI should be individualized, considering patient comorbidities, anatomical complexity, and bleeding risk.
- Antithrombotic Therapy: Attention to antiplatelet and anticoagulation strategies is important to mitigate bleeding risks.
Study Limitations:
- Exclusion of patients with recent acute coronary syndromes and left main coronary artery disease limits the generalizability.
- Changes in antithrombotic regimens over the study period reflect evolving clinical practice but may affect outcomes.
- Majority of patients had low to intermediate SYNTAX scores, so results may not apply to those with more complex CAD.
Final Note:
The NOTION-3 trial provides valuable evidence supporting the use of PCI in patients with significant CAD undergoing TAVI, emphasizing the importance of comprehensive cardiovascular care in this high-risk population.
Polled Analysis: Semaglutide Reduces Heart Failure Events in Obese Patients with HFpEF
12 Sep, 2024 | 13:39h | UTCStudy Design and Population: This post-hoc pooled analysis combined data from four randomized, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) involving 3,743 participants with heart failure and preserved or mildly reduced ejection fraction (HFpEF). The participants had various comorbidities including obesity, diabetes, and atherosclerotic cardiovascular disease. They were randomized to receive either semaglutide or placebo.
Main Findings: Semaglutide significantly reduced the risk of the composite endpoint of cardiovascular death or worsening heart failure events compared to placebo (HR 0.69, 95% CI 0.53–0.89, p=0.0045). It also reduced worsening heart failure events alone (HR 0.59, 95% CI 0.41–0.82, p=0.0019). However, no significant reduction in cardiovascular death alone was observed (HR 0.82, 95% CI 0.57–1.16, p=0.25). Semaglutide was generally well tolerated, with fewer serious adverse events compared to placebo.
Implications for Practice: These findings suggest semaglutide may be an effective therapy to reduce heart failure-related events in obese patients with HFpEF. Although semaglutide did not reduce cardiovascular death, its ability to lower the risk of heart failure hospitalizations makes it a potential therapeutic option for managing HFpEF in this population, a condition with limited treatment choices.
RCT: 24-Hour Oxygen Therapy Does Not Reduce Hospitalization or Mortality Compared to 15-Hour Therapy in Severe Hypoxemia
12 Sep, 2024 | 13:21h | UTCStudy Design and Population: This multicenter, registry-based randomized controlled trial compared the effects of 24-hour versus 15-hour daily oxygen therapy in 241 patients with chronic, severe hypoxemia. Patients, recruited between 2018 and 2022, were assigned to either 24 hours (117 patients) or 15 hours (124 patients) of oxygen therapy daily. The study’s primary outcome was the composite of hospitalization or death from any cause within 1 year.
Main Findings: After 12 months, the results showed no significant difference between the two groups in the primary outcome. The event rates for hospitalization or death were similar in the 24-hour and 15-hour groups (124.7 vs. 124.5 events per 100 person-years, hazard ratio 0.99, 95% CI, 0.72-1.36). Secondary outcomes, including individual rates of hospitalization and mortality, also showed no meaningful differences, and adverse event rates were comparable between groups.
Implications for Practice: These findings suggest that increasing oxygen therapy from 15 to 24 hours per day does not reduce hospitalization or mortality in patients with severe hypoxemia. Therefore, the less burdensome 15-hour regimen may be preferable in clinical practice, as it is equally effective while reducing patient burden.
RCT: Once-Weekly Insulin Efsitora Non-Inferior to Insulin Degludec for HbA1c Control but Increases Hypoglycemia in Adults with Type 1 Diabetes
12 Sep, 2024 | 13:06h | UTCStudy Design and Population: This 52-week, randomized, open-label non-inferiority trial included 692 adults with type 1 diabetes from 82 global sites. Participants were randomly assigned to receive once-weekly insulin efsitora (n=343) or once-daily insulin degludec (n=349), both in combination with insulin lispro. The primary objective was to assess the change in HbA1c from baseline to week 26, with a non-inferiority margin of 0.4%.
Main Findings: HbA1c reduction was similar between the groups at 26 weeks (–0.51% for efsitora vs. –0.56% for degludec; p=0.43). However, participants on efsitora experienced higher rates of level 2 or 3 hypoglycemia (14.03 vs. 11.59 events per patient year, p=0.016) and a greater incidence of severe hypoglycemia (10% for efsitora vs. 3% for degludec). Overall, the safety profile was similar, with no treatment-related deaths.
Implications for Practice: Once-weekly insulin efsitora offers comparable glycemic control to daily degludec, but its association with increased hypoglycemia, especially during dose titration, indicates that closer monitoring and optimization are necessary. This treatment could reduce the burden of daily injections, but its hypoglycemia risks must be managed carefully.
RCT: Transcatheter Repair Noninferior to Mitral-Valve Surgery for Secondary Mitral Regurgitation
12 Sep, 2024 | 12:13h | UTCStudy Design and Population: This noninferiority trial, conducted in Germany, enrolled 210 patients with heart failure and secondary mitral regurgitation who remained symptomatic despite medical therapy. Patients were randomized to undergo either transcatheter edge-to-edge repair or mitral-valve surgery, with outcomes assessed over a one-year period.
Main Findings: Transcatheter repair was found to be noninferior to mitral-valve surgery regarding the primary efficacy outcome—a composite of death, heart failure hospitalization, mitral-valve reintervention, assist device implantation, or stroke at one year (16.7% in the transcatheter group vs. 22.5% in the surgery group; mean difference, -6%; 95% CI, -17 to 6; P<0.001 for noninferiority). The transcatheter group experienced fewer major adverse events within 30 days (14.9% vs. 54.8%; mean difference, -40%; 95% CI, -51 to -27; P<0.001).
Implications for Practice: Transcatheter edge-to-edge repair offers a similar efficacy to mitral-valve surgery at one year with a lower rate of short-term adverse events, suggesting it may be a suitable alternative, particularly for patients with higher surgical risk.
Cohort Study: Lower Risk of Cardiovascular Complications in Post–COVID-19 Vaccine Myocarditis Compared to Conventional Etiologies
7 Sep, 2024 | 20:36h | UTCStudy Design and Population: This French nationwide cohort study included 4,635 individuals aged 12-49 hospitalized for myocarditis between December 2020 and June 2022. The cohort was divided into three groups: 558 patients with post–COVID-19 mRNA vaccine myocarditis, 298 with post–COVID-19 infection myocarditis, and 3,779 with conventional myocarditis.
Main Findings: At 18 months of follow-up, the frequency of cardiovascular events was significantly lower in the postvaccine myocarditis group (5.7%) compared to conventional myocarditis (13.2%) with a weighted hazard ratio (wHR) of 0.55 (95% CI, 0.36-0.86). Hospital readmission for myopericarditis occurred in 3.2% of postvaccine cases, 4.0% of post–COVID-19 cases, and 5.8% of conventional cases. The all-cause mortality rate was 0.2% for postvaccine myocarditis, 1.3% for post–COVID-19 myocarditis, and 1.3% for conventional myocarditis.
Implications for Practice: Postvaccine myocarditis patients, primarily young males, experience fewer complications compared to conventional myocarditis, but long-term follow-up is still needed. These findings should guide future mRNA vaccine recommendations and clinical management for myocarditis patients.
Reference: Semenzato L. et al. (2024). Long-term Prognosis of Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2, or Conventional Etiologies. JAMA, Online. DOI: http://doi.org/10.1001/jama.2024.16380
Link: https://jamanetwork.com/journals/jama/fullarticle/2822933
RCT: Olanzapine Improves Nausea and Vomiting Control in Moderately Emetogenic Chemotherapy but Increases Somnolence
7 Sep, 2024 | 19:28h | UTCStudy Design and Population: This phase 3, multicenter, open-label randomized clinical trial involved 560 chemotherapy-naive patients aged 18 years or older with solid malignant tumors. The trial, conducted at three institutes in India, compared the efficacy of adding olanzapine to standard antiemetic therapy in patients receiving moderately emetogenic chemotherapy (MEC) based on oxaliplatin, carboplatin, or irinotecan.
Main Findings: The group receiving olanzapine in addition to standard antiemetic therapy showed significantly higher complete response (CR) rates (91% vs 82%, P = .005) compared to the observation group. The olanzapine group also demonstrated superior control of nausea (96% vs 87%, P < .001) and chemotherapy-induced nausea and vomiting (CINV) (96% vs 91%, P = .02). The use of rescue medications was significantly lower in the olanzapine group. Grade 1 somnolence occurred in 10% of patients receiving olanzapine but was absent in the observation group.
Implications for Practice: The results support the inclusion of olanzapine in antiemetic regimens for MEC to improve CINV outcomes. However, mild somnolence should be considered when prescribing olanzapine as part of antiemetic prophylaxis. Further research could explore dose optimization to minimize adverse effects.
Reference: Ostwal, V. et al. (2024). Olanzapine as antiemetic prophylaxis in moderately emetogenic chemotherapy: a phase 3 randomized clinical trial. JAMA Network Open. DOI: http://doi.org/10.1001/jamanetworkopen.2024.26076
Link: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2822027
RCT: Pulmonary Vein Isolation Reduces Atrial Fibrillation Burden and Improves Quality of Life vs. Sham Procedure
7 Sep, 2024 | 17:24h | UTCStudy Design and Population: This double-blind, randomized clinical trial (SHAM-PVI) compared pulmonary vein isolation (PVI) via cryoablation to a sham procedure in 126 patients with symptomatic paroxysmal or persistent atrial fibrillation (AF). The study, conducted in two UK tertiary centers, enrolled patients between January 2020 and March 2024. Major exclusions included long-standing persistent AF, prior left atrial ablation, and ejection fraction below 35%. Patients were monitored using implantable loop recorders.
Main Findings: At 6 months, the PVI group demonstrated a significant reduction in AF burden (60.31%) compared to the sham group (35.0%), with a geometric mean difference of 0.25 (95% CI, 0.15-0.42; P < .001). Quality-of-life scores also improved more in the PVI group, with an 18.39-point difference (95% CI, 11.48-25.30). Symptom improvement was also marked, with a reduction in the Mayo AF-Specific Symptom Inventory frequency score of −6.36 points (95% CI, −8.46 to −4.26).
Implications for Practice: PVI significantly reduces AF burden and improves both symptoms and quality of life in patients with symptomatic AF, compared to a sham procedure. These findings support the efficacy of PVI beyond a placebo effect, making it a compelling option for managing AF in patients not responsive to antiarrhythmic drugs.
Reference: Dulai, R., Sulke, N., Freemantle, N., Lambiase, P. D., Farwell, D., Srinivasan, N. T., et al. (2024). Pulmonary vein isolation vs sham intervention in symptomatic atrial fibrillation: The SHAM-PVI randomized clinical trial. JAMA. http://doi.org/10.1001/jama.2024.17921
Link: https://jamanetwork.com/journals/jama/fullarticle/2823283
Meta-Analysis: Ticagrelor Monotherapy Reduces Bleeding Without Increasing Ischemic Risk in Coronary Stent Patients
7 Sep, 2024 | 15:06h | UTCStudy Design and Population: This systematic review and individual patient-level meta-analysis pooled data from six randomized trials, comparing ticagrelor monotherapy after short-term dual antiplatelet therapy (DAPT) with standard 12-month DAPT in patients who underwent percutaneous coronary intervention with drug-eluting stents. The analysis included 23,256 patients in the per-protocol population and 24,407 in the intention-to-treat population, excluding those requiring long-term anticoagulants.
Main Findings: Ticagrelor monotherapy was found to be noninferior to 12-month DAPT for major adverse cardiovascular or cerebrovascular events (MACCE), with a hazard ratio (HR) of 0.91 (95% CI 0.78-1.07). It also reduced the risk of major bleeding (HR 0.43, p<0.0001) and all-cause mortality (HR 0.76, p=0.034). Subgroup analyses suggested possible benefits in women for mortality and in patients with acute coronary syndrome (ACS) for bleeding reduction.
Implications for Practice: Ticagrelor monotherapy may offer a safer alternative to prolonged DAPT by reducing bleeding risks without increasing ischemic events, particularly in ACS patients. Further research is needed to fully explore potential survival benefits, especially in women.
Reference: Valgimigli M, Hong S-J, Gragnano F, et al. (2024). De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: a systematic review and individual patient-level meta-analysis of randomised trials. Lancet. http://doi.org/10.1016/S0140-6736(24)01616-7
Link: https://www.sciencedirect.com/science/article/pii/S0140673624016167
RCT: Renal Denervation Reduces Blood Pressure in Chinese Patients With Uncontrolled Hypertension
7 Sep, 2024 | 14:57h | UTCStudy Design and Population: This was a prospective, multicenter, randomized, sham-controlled trial investigating the efficacy and safety of catheter-based radiofrequency renal denervation (RDN) in Chinese patients with uncontrolled hypertension despite standardized triple antihypertensive therapy. A total of 217 patients (mean age 45.3 years, 21% female) were randomized 1:1 to receive RDN or a sham procedure.
Main Findings: At 6 months, patients who underwent RDN showed a significantly greater reduction in 24-hour ambulatory systolic blood pressure (−13.0 mm Hg) compared to the sham group (−3.0 mm Hg), with a baseline-adjusted difference of −9.4 mm Hg (P<0.001). Significant reductions were also observed in 24-hour diastolic BP and office systolic and diastolic BP. One access site complication occurred in the RDN group but resolved without further issues.
Implications for Practice: This trial demonstrates that RDN is an effective and safe option for reducing blood pressure in patients with uncontrolled hypertension, offering a potential adjunct to antihypertensive therapy in this population. Further research may solidify its role in managing resistant hypertension.
Reference: Jiang X et al. (2024). Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.124.069215
Link: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.069215
RCT: Invasive Strategy Does Not Significantly Improve Cardiovascular Outcomes Over Conservative Management in Older Adults with NSTEMI
7 Sep, 2024 | 13:25h | UTCStudy Design and Population: This was a prospective, multicenter, randomized trial conducted across 48 sites in the UK, enrolling 1,518 patients aged 75 years or older with non-ST-segment elevation myocardial infarction (NSTEMI). Patients were randomly assigned to receive either the best available medical therapy alone (conservative strategy) or in combination with invasive treatment (coronary angiography and revascularization). The population included individuals who were frail or had high comorbidities, with a mean age of 82 years.
Main Findings: Over a median follow-up of 4.1 years, the primary outcome (a composite of cardiovascular death or nonfatal myocardial infarction) occurred in 25.6% of the invasive-strategy group and 26.3% of the conservative-strategy group (HR, 0.94; 95% CI, 0.77–1.14; P=0.53), showing no significant difference. Cardiovascular death rates were similar between the two groups, but nonfatal myocardial infarction was lower in the invasive group (11.7% vs. 15.0%; HR, 0.75; 95% CI, 0.57–0.99). Procedural complications were rare, affecting less than 1% of patients.
Implications for Practice: This trial suggests that in older adults with NSTEMI, an invasive strategy does not significantly reduce the risk of cardiovascular death or nonfatal myocardial infarction compared to a conservative approach. The findings support the consideration of conservative management in frail elderly patients or those with significant comorbidities, given the minimal additional benefit of invasive treatment.
Reference: Kunadian, V., Mossop, H., Shields, C., Bardgett, M., Watts, P., Teare, M. D., Pritchard, J., et al. (2024). Invasive treatment strategy for older patients with myocardial infarction. New England Journal of Medicine. http://doi.org/10.1056/NEJMoa2407791
Link: https://www.nejm.org/doi/10.1056/NEJMoa2407791
RCT: Edoxaban Monotherapy Reduces Bleeding Events in Atrial Fibrillation with Stable CAD Compared to Dual Therapy
7 Sep, 2024 | 13:03h | UTCStudy Design and Population: This multicenter, open-label, adjudicator-masked randomized trial enrolled 1,040 patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) across 18 sites in South Korea. Patients were randomly assigned to receive either edoxaban monotherapy (n=524) or dual antithrombotic therapy (edoxaban plus a single antiplatelet agent; n=516). The mean age was 72.1 years, with a mean CHA2DS2-VASc score of 4.3, reflecting a moderate to high stroke risk.
Main Findings: At 12 months, the primary composite outcome occurred in fewer patients in the edoxaban monotherapy group (6.8%) than in the dual therapy group (16.2%) (HR, 0.44; 95% CI, 0.30–0.65; P<0.001). The reduction was largely driven by a significantly lower incidence of major bleeding or clinically relevant non-major bleeding (4.7% vs. 14.2%; HR, 0.34; 95% CI, 0.22–0.53). In contrast, the incidence of major ischemic events was similar between the two groups.
Implications for Practice: Edoxaban monotherapy provides a safer antithrombotic option for patients with AF and stable CAD by significantly reducing bleeding without increasing ischemic events compared to dual therapy. These findings suggest that monotherapy could be a preferable long-term treatment strategy in this population.
RCT: Interruption of Oral Anticoagulation during TAVI Reduces Bleeding Without Increasing Thromboembolic Events
7 Sep, 2024 | 12:43h | UTCStudy Design and Population: This international, open-label, randomized noninferiority trial examined 858 patients undergoing transcatheter aortic-valve implantation (TAVI) who had an indication for oral anticoagulation due to concomitant diseases. Patients were randomized 1:1 to either continue or interrupt their oral anticoagulation during the procedure, with the primary outcome being a composite of cardiovascular death, stroke, myocardial infarction, major vascular complications, or major bleeding within 30 days.
Main Findings: Primary outcome events occurred in 16.5% of the continuation group and 14.8% of the interruption group, showing a non-significant risk difference of 1.7 percentage points (95% CI, -3.1 to 6.6). Thromboembolic events were similar between groups (8.8% in continuation vs. 8.2% in interruption). However, bleeding events were significantly higher in the continuation group (31.1% vs. 21.3%; risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6).
Implications for Practice: Interrupting oral anticoagulation during TAVI significantly reduces bleeding without increasing thromboembolic risks, suggesting it may be a safer strategy for patients undergoing TAVI. These findings could influence clinical decision-making regarding anticoagulation management in this population.
Reference: van Ginkel, D.J. et al. (2024). Continuation versus Interruption of Oral Anticoagulation during TAVI. The New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2407794
RCT: Continuing Aspirin vs. Antiplatelet Cessation Before Surgery Did Not Reduce Ischemic Events in Patients With Coronary Stents Over 1 Year Post-Implantation
7 Sep, 2024 | 12:29h | UTCStudy Design and Population: This randomized controlled trial (ASSURE-DES) investigated the perioperative management of antiplatelet therapy in 926 patients with coronary drug-eluting stents (DES) undergoing low-to-intermediate-risk noncardiac surgery. The patients, at least one year post-stent implantation, were randomized to continue aspirin monotherapy or stop all antiplatelet therapy five days prior to surgery.
Main Findings: The study found no significant difference in the primary composite outcome (death, myocardial infarction, stent thrombosis, or stroke) between the aspirin monotherapy group (0.6%) and the no antiplatelet group (0.9%). However, minor bleeding was more frequent in the aspirin group (14.9% vs 10.1%, P=0.027), with no difference in major bleeding.
Implications for Practice: These results suggest that for stable patients with DES undergoing noncardiac surgery, temporarily discontinuing aspirin may be a safe option, as continuing aspirin did not reduce ischemic events but did increase minor bleeding risk. Further research is needed to assess outcomes in higher-risk surgical settings.
RCT: Azithromycin Increases Asthma Remission Rates in Adults With Persistent Uncontrolled Asthma
6 Sep, 2024 | 22:35h | UTCStudy Design and Population: This secondary analysis stems from the Asthma and Macrolides: Azithromycin Efficacy and Safety (AMAZES) trial, a randomized, double-anonymized, placebo-controlled trial. The study involved 335 adults with persistent uncontrolled asthma, who were treated with either azithromycin (500 mg, 3 times weekly) or placebo for 12 months. The goal was to evaluate azithromycin’s impact on asthma remission, defined through clinical and lung function measures.
Main Findings: Azithromycin significantly increased the rate of clinical remission compared to placebo (50.6% vs. 38.9%; P = .032). Clinical remission combined with lung function criteria was also higher in the azithromycin group (50.8% vs. 37.1%; P = .029). Although the complete remission rate (including sputum eosinophil count <3%) trended higher, it did not reach statistical significance (23% vs. 13.7%; P = .058).
Implications for Practice: This secondary analysis suggests that azithromycin, when added to standard asthma therapy, could significantly increase remission rates in adults with persistent uncontrolled asthma, including both eosinophilic and noneosinophilic subtypes.
RCT: AF Screening Does Not Reduce Stroke Hospitalizations in Elderly Patients
6 Sep, 2024 | 22:18h | UTCStudy Design and Population: The GUARD-AF trial was a prospective, randomized controlled trial conducted across 149 primary care sites in the U.S. It enrolled 11,905 participants aged 70 and older, with a median age of 75 years, 56.6% of whom were female. Participants were randomized 1:1 to either screening for atrial fibrillation (AF) using a 14-day continuous electrocardiographic patch monitor or usual care. The primary outcome was all-cause stroke hospitalization, with bleeding as a key safety outcome.
Main Findings: After a median follow-up of 15.3 months, AF diagnosis was higher in the screening group (5%) compared to the usual care group (3.3%), and anticoagulation initiation was also more frequent (4.2% vs. 2.8%). However, the risk of stroke hospitalization was not significantly different between the screening and usual care groups (0.7% vs. 0.6%; HR: 1.10, 95% CI: 0.69-1.75). Similarly, there was no significant difference in bleeding risk (1.0% vs. 1.1%; HR: 0.87, 95% CI: 0.60-1.26).
Implications for Practice: The findings suggest that screening for AF using continuous electrocardiographic monitoring in elderly patients does not reduce stroke hospitalizations despite an increased detection of AF. Given the low event rates and premature termination of enrollment due to COVID-19, further studies are needed to confirm these results and explore alternative strategies for stroke prevention in this population.
RCT: Finerenone Reduces Worsening Heart Failure Events in Patients with Mildly Reduced or Preserved Ejection Fraction
6 Sep, 2024 | 22:03h | UTCStudy Design and Population: This international, double-blind, randomized clinical trial included 6,001 patients with heart failure and a left ventricular ejection fraction of 40% or greater. Patients were randomly assigned to receive either finerenone (20 mg or 40 mg daily) or placebo in addition to standard therapy, with a median follow-up period of 32 months.
Main Findings: The finerenone group experienced a 16% reduction in the composite primary outcome of worsening heart failure events and death from cardiovascular causes compared to placebo (rate ratio, 0.84; 95% CI, 0.74 to 0.95; P=0.007). Specifically, total worsening heart failure events were lower in the finerenone group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P=0.006), but cardiovascular mortality did not significantly differ between the groups (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was linked to an increased risk of hyperkalemia.
Implications for Practice: Finerenone reduces worsening heart failure events in patients with mildly reduced or preserved ejection fraction, making it a viable addition to standard heart failure therapy. However, clinicians should monitor for hyperkalemia, a known side effect, and the lack of significant mortality benefit highlights the need for further investigation into long-term cardiovascular outcomes.
2024 ESC Guidelines for the Management of Chronic Coronary Syndromes
1 Sep, 2024 | 18:49h | UTCIntroduction: The 2024 guidelines were developed by the European Society of Cardiology (ESC) with the endorsement of the European Association for Cardio-Thoracic Surgery (EACTS). These guidelines provide updated recommendations for the management of chronic coronary syndromes (CCS), focusing on the diagnosis, treatment, and long-term care of patients with stable coronary artery disease (CAD).
Key Points:
1 – History and Risk Assessment:
– Detailed assessment of cardiovascular risk factors, medical history, and symptom characteristics is essential in patients with suspected CCS.
– Symptoms like chest pain triggered by emotional stress, dyspnea on exertion, or fatigue should be considered potential angina equivalents.
2 – Diagnostic Testing:
– Coronary Computed Tomography Angiography (CCTA): Recommended as a first-line diagnostic tool for patients with low to moderate pre-test likelihood of obstructive CAD.
– Stress Imaging: Stress echocardiography, SPECT, PET, or cardiac MRI is recommended for those with moderate to high pre-test likelihood to diagnose myocardial ischemia and estimate the risk of major adverse cardiovascular events (MACE).
3 – Revascularization Indications:
– Symptom Relief: Revascularization is recommended for patients with obstructive CAD who have significant symptoms despite optimal medical therapy.
– Prognostic Benefit: Indicated in patients with left main coronary artery disease, severe three-vessel disease, or two-vessel disease including proximal left anterior descending artery stenosis, particularly if associated with reduced left ventricular function.
– High-Risk Anatomical Features: Revascularization is advised when significant stenosis is present in patients with high-risk anatomical features identified by imaging, especially if non-invasive testing shows a large area of ischemia.
4 – Lifestyle and Risk Management:
– A comprehensive approach to cardiovascular risk reduction, including lifestyle changes (e.g., smoking cessation, diet, and physical activity) and guideline-directed medical therapy, is strongly recommended.
– Home-based cardiac rehabilitation and digital health interventions are suggested to improve long-term adherence to healthy behaviors.
5 – Antianginal and Antithrombotic Therapy:
– Tailoring antianginal therapy based on individual patient characteristics, comorbidities, and local drug availability is recommended.
– Long-term antithrombotic therapy with aspirin or clopidogrel is recommended for patients with prior myocardial infarction or revascularization.
Conclusion: The 2024 ESC guidelines emphasize a patient-centered approach, integrating advanced diagnostic tools and personalized therapeutic strategies to optimize outcomes for patients with chronic coronary syndromes. The guidelines highlight the importance of detailed risk assessment, appropriate use of diagnostic imaging, clear criteria for revascularization, and a strong focus on lifestyle interventions alongside pharmacological management.
Updated ESC Hypertension Guidelines 2024: Intensified Blood Pressure Targets and New Categories – Eur Heart J
31 Aug, 2024 | 19:54h | UTCIntroduction:
The 2024 ESC Guidelines for managing elevated blood pressure (BP) and hypertension were developed by the European Society of Cardiology (ESC) and endorsed by the European Society of Endocrinology (ESE) and the European Stroke Organisation (ESO). These guidelines introduce significant updates to BP management, including more intensive treatment targets and the introduction of a new category for “Elevated BP.”
Key Points:
1 – New Intensive BP Target: For most patients receiving BP-lowering medication, the guidelines now recommend a systolic BP treatment target range of 120-129 mmHg. This marks a significant shift from previous guidelines, which suggested a less aggressive initial target.
2 – New ‘Elevated BP’ Category: The guidelines introduce a new category, “Elevated BP,” defined as a systolic BP of 120-139 mmHg and/or diastolic BP of 70-89 mmHg. This aims to identify more patients at risk of cardiovascular events, such as heart attacks and strokes, before they meet the traditional threshold for hypertension.
3 – Pragmatic BP Management: For patients who cannot tolerate the intensive BP target, the guidelines recommend aiming for a BP that is “as low as reasonably achievable” (ALARA), particularly in frail or older individuals.
4 – Lifestyle Modifications: The guidelines emphasize lifestyle interventions, including dietary changes like potassium supplementation and new exercise recommendations, as first-line strategies for managing BP.
5 – Renal Denervation: For the first time, the guidelines include recommendations on the use of renal denervation—a procedure for patients with resistant hypertension that has not responded to standard treatments. This is not recommended as a first-line treatment but may be considered in specific high-risk cases.
Conclusion:
These new guidelines represent a major update in the management of hypertension, particularly in promoting more aggressive BP targets to reduce cardiovascular risks. The inclusion of a new BP category and recommendations for renal denervation highlight the guidelines’ focus on early intervention and advanced treatment options.
2024 ESC Guidelines for the Management of Atrial Fibrillation – Eur Heart J
31 Aug, 2024 | 19:34h | UTCIntroduction: The 2024 guidelines for the management of atrial fibrillation (AF) were developed by the European Society of Cardiology (ESC) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) and other specialized associations. These guidelines aim to provide evidence-based recommendations for the diagnosis, treatment, and management of AF, with a focus on improving patient outcomes through a multidisciplinary approach.
Key Points:
1 – Patient-Centered Care and Education:
– Education directed at patients, caregivers, and healthcare professionals is essential for optimizing shared decision-making. This approach ensures that treatment options are discussed openly, considering both the benefits and risks.
2 – Comorbidity and Risk Factor Management:
– Diuretics are recommended for patients with AF, heart failure (HF), and congestion to alleviate symptoms and improve AF management.
– Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are recommended for patients with AF and HF, regardless of left ventricular ejection fraction (LVEF), to reduce the risk of hospitalization and cardiovascular death.
3 – Stroke Prevention and Anticoagulation:
– Oral anticoagulation is recommended for all patients with clinical AF and elevated thromboembolic risk, particularly those with a CHA2DS2-VA score of 2 or more.
– Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists (VKAs) in eligible patients undergoing cardioversion.
4 – Rate and Rhythm Control:
– Beta-blockers, diltiazem, verapamil, or digoxin are recommended as first-choice drugs for heart rate control in patients with AF and LVEF >40%.
– Catheter ablation is recommended as a first-line treatment option in patients with paroxysmal AF to reduce symptoms and prevent AF progression.
Conclusion: The 2024 ESC guidelines emphasize a patient-centered, multidisciplinary approach to AF management, with a strong focus on the early identification and management of comorbidities and risk factors. The guidelines also advocate for the use of DOACs in stroke prevention and recommend specific strategies for rate and rhythm control to enhance patient outcomes.
Updated Guidelines for Potentially Inappropriate Medication Use in Older Adults (2023 AGS Beers Criteria®) – J Am Geriatr Soc
31 Aug, 2024 | 19:20h | UTCIntroduction:
The American Geriatrics Society (AGS) has released the 2023 update to the AGS Beers Criteria®, a critical tool for healthcare professionals aimed at improving the safety of medication prescribing in adults aged 65 and older. The guidelines identify potentially inappropriate medications (PIMs) that should generally be avoided in older adults due to the heightened risk of adverse effects.
Key Points:
1 – Anticholinergic Drugs: First-generation antihistamines (e.g., diphenhydramine) should be avoided due to their high anticholinergic activity, which can lead to confusion, dry mouth, constipation, and other serious side effects, including increased risk of falls and dementia.
2 – Nitrofurantoin: Should be avoided in individuals with a creatinine clearance less than 30 mL/min due to the risk of pulmonary toxicity, hepatotoxicity, and peripheral neuropathy.
3 – Cardiovascular Drugs: Aspirin for primary prevention of cardiovascular disease is not recommended in older adults due to the increased risk of bleeding and lack of clear benefit. Similarly, warfarin is discouraged as an initial treatment for nonvalvular atrial fibrillation or venous thromboembolism in favor of Direct Oral Anticoagulants (DOACs) unless DOACs are contraindicated.
4 – Central Nervous System (CNS) Medications: Benzodiazepines and non-benzodiazepine receptor agonist hypnotics (“Z-drugs”) are associated with increased risks of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults and should generally be avoided.
5 – Antipsychotics: Should be avoided for the treatment of behavioral problems in dementia or delirium due to the increased risk of stroke and greater rates of cognitive decline and mortality unless required for specific psychiatric conditions like schizophrenia or bipolar disorder.
Conclusion:
The 2023 AGS Beers Criteria® continues to serve as an essential guide for minimizing the risks associated with medication use in older adults. It emphasizes the need for individualized care and the importance of weighing the benefits and risks of medications, particularly in vulnerable populations.
RCT: No Difference in Postoperative Complications Between Continuation and Discontinuation of Renin-Angiotensin System Inhibitors Before Major Surgery – JAMA
31 Aug, 2024 | 19:12h | UTCStudy Design and Population: This multicenter randomized clinical trial included 2,222 patients who had been treated with renin-angiotensin system inhibitors (RASIs) for at least 3 months and were scheduled for major noncardiac surgery at 40 hospitals in France between January 2018 and April 2023. The participants were randomly assigned to either continue RASIs until the day of surgery or to discontinue them 48 hours before surgery.
Main Findings: The trial found no significant difference in the primary outcome—a composite of all-cause mortality and major postoperative complications within 28 days—between the continuation and discontinuation groups (22% in both groups, RR 1.02, 95% CI 0.87-1.19). However, the continuation group experienced a higher incidence of intraoperative hypotension (54% vs. 41%, RR 1.31, 95% CI 1.19-1.44).
Implications for Practice: Continuation of RASIs before major noncardiac surgery does not increase the risk of postoperative mortality or major complications, but it does elevate the risk of intraoperative hypotension. Clinicians should weigh these risks when deciding whether to continue or discontinue RASIs before surgery.
RCT: Beta-Blocker Interruption Post-Myocardial Infarction Increases Cardiovascular Events Without Improving Quality of Life – N Engl J Med
31 Aug, 2024 | 19:04h | UTCStudy Design and Population: This multicenter, open-label, randomized, noninferiority trial included 3,698 patients across 49 sites in France. Participants had a history of myocardial infarction, a left ventricular ejection fraction of at least 40%, and had not experienced a cardiovascular event in the past six months. The study compared outcomes between patients who either interrupted or continued long-term beta-blocker therapy, with a minimum follow-up of one year.
Main Findings: Interruption of beta-blocker treatment resulted in a higher incidence of adverse cardiovascular events (23.8%) compared to continuation (21.1%), with a hazard ratio of 1.16 (95% CI, 1.01 to 1.33). The difference did not meet the criteria for noninferiority (P=0.44). Additionally, there was no significant improvement in quality of life among patients who discontinued beta-blockers.
Implications for Practice: The findings suggest that in patients with a history of myocardial infarction and stable cardiovascular health, continuing beta-blocker therapy is preferable to interruption. Discontinuation may increase the risk of adverse cardiovascular outcomes without offering quality of life benefits, supporting the ongoing use of beta-blockers in this population.