Coronary Insufficiency
RCT: Routine Spironolactone Post-MI Does Not Reduce Cardiovascular Events
20 Nov, 2024 | 18:03h | UTCBackground: Mineralocorticoid receptor antagonists (MRAs), such as spironolactone, have demonstrated mortality benefits in patients with heart failure following myocardial infarction (MI). However, the efficacy of routine spironolactone use in all patients post-MI, regardless of heart failure status, remains uncertain.
Objective: To evaluate whether routine administration of spironolactone reduces cardiovascular events in patients after MI who have undergone percutaneous coronary intervention (PCI).
Methods: In a multicenter, double-blind, placebo-controlled trial with a 2-by-2 factorial design, 7,062 patients with MI undergoing PCI were randomized to receive spironolactone (25 mg daily) or placebo, and colchicine or placebo. The two primary outcomes were: (1) a composite of death from cardiovascular causes or new or worsening heart failure, assessed as the total number of events; and (2) a composite of the first occurrence of MI, stroke, new or worsening heart failure, or death from cardiovascular causes. Median follow-up was 3 years.
Results: No significant differences were observed between the spironolactone and placebo groups in the primary outcomes. For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group versus 220 events (2.1 per 100 patient-years) in the placebo group (hazard ratio [HR] adjusted for competing risk, 0.91; 95% confidence interval [CI], 0.69–1.21; P=0.51). For the second primary outcome, events occurred in 280 patients (7.9%) in the spironolactone group and 294 patients (8.3%) in the placebo group (HR adjusted for competing risk, 0.96; 95% CI, 0.81–1.13; P=0.60). Serious adverse events were similar between groups.
Conclusions: Routine use of spironolactone after MI did not reduce cardiovascular mortality or new or worsening heart failure compared to placebo.
Implications for Practice: These findings suggest that routine prescription of spironolactone for all patients after MI may not be beneficial and should be reconsidered. Clinicians should carefully evaluate the indication for MRAs post-MI, particularly in patients without heart failure, and remain cautious about routine use without clear evidence of benefit.
Study Strengths and Limitations: Strengths of the study include its large sample size, multicenter international design, and long follow-up period, enhancing the generalizability of the findings. However, limitations include lower-than-expected event rates, potentially reducing statistical power to detect significant differences. The high rate of discontinuation of the trial regimen and underrepresentation of women and certain racial and ethnic groups may also limit the applicability of the results. Additionally, the possibility of a type II error due to reduced power cannot be excluded.
Future Research: Further studies are warranted to identify specific subgroups of patients who may benefit from spironolactone post-MI and to explore alternative therapies that effectively reduce cardiovascular events after MI.
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).
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.
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.
Meta-analysis: Perioperative Colchicine Reduced Postoperative Atrial Fibrillation After CABG
18 Sep, 2024 | 13:33h | UTCBackground: Coronary artery disease (CAD) remains a leading cause of mortality worldwide. Inflammation is a key factor in the development and progression of CAD, and anti-inflammatory therapies have shown potential in improving cardiovascular outcomes. Colchicine, traditionally used to treat gout, has demonstrated efficacy in reducing cardiovascular events in patients with chronic CAD. Previous individual studies have suggested that perioperative colchicine may decrease the incidence of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass grafting (CABG), but a comprehensive analysis is needed to confirm these findings.
Objective: To evaluate the effect of perioperative colchicine administration on the incidence of POAF in patients undergoing isolated CABG surgery through a meta-analysis of randomized controlled trials (RCTs).
Methods: A systematic search was conducted across MEDLINE, Web of Science, and The Cochrane Library to identify RCTs comparing perioperative colchicine administration with standard care in patients undergoing CABG. Inclusion criteria encompassed studies involving isolated CABG patients randomized to receive colchicine or standard care without colchicine. The primary outcome was the incidence of POAF during short-term follow-up.
Results: Five RCTs published between 2014 and 2022 met the inclusion criteria, including a total of 839 patients undergoing isolated CABG. Perioperative colchicine administration was associated with a significant reduction in POAF rates compared to standard care (relative risk [RR], 0.54; 95% confidence interval [CI], 0.40–0.73; p < 0.01). Other outcomes, such as graft patency, myocardial infarction, or long-term mortality, were not uniformly reported and, therefore, not analyzed.
Conclusions: Perioperative administration of colchicine is associated with a significant reduction in the incidence of POAF in patients undergoing CABG surgery.
Implications for Practice: Colchicine may be considered as a prophylactic strategy to reduce POAF in patients undergoing CABG, potentially improving both short- and long-term outcomes. Given the association of POAF with increased perioperative morbidity and long-term adverse events, implementing colchicine could have substantial clinical benefits in this high-risk population.
Study Strengths and Limitations: Strengths of this meta-analysis include the exclusive inclusion of randomized controlled trials and the use of rigorous statistical methods, including sensitivity analysis, which confirmed the robustness of the results. Limitations involve the small number of studies (five RCTs), potential variability in colchicine dosing regimens, and the lack of data on other clinically relevant outcomes.
Future Research: Large-scale, multicenter RCTs are warranted to further assess the effects of colchicine on other important outcomes in CABG patients, such as graft patency, myocardial infarction rates, and long-term mortality. Future studies should also evaluate the risk-benefit profile of colchicine in this patient population to establish its full role in clinical practice.
Reference: Kirov H., Caldonazo T., Runkel A., et al. (2024). Colchicine in Patients with Coronary Disease Undergoing Coronary Artery Bypass Surgery – A Meta-Analysis of Randomized Controlled Trials. The American Journal of Cardiology. DOI: http://doi.org/10.1016/j.amjcard.2024.09.003
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.
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: 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.
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.
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.
Meta-Analysis: 1-Month Dual Antiplatelet Therapy Reduces Major Bleeding Without Increasing Stent Thrombosis After PCI with DES – Am J Cardiol
17 Aug, 2024 | 19:29h | UTCMain Findings: The analysis found that 1-month DAPT significantly reduced the risk of major bleeding (OR 0.66, 95% CI 0.45-0.97, p = 0.03) compared to >1-month DAPT. Additionally, there was no significant difference in stent thrombosis rates between the groups (OR 1.08, 95% CI 0.81-1.44, p = 0.60). Secondary outcomes, including all-cause mortality, cardiovascular death, myocardial infarction, stroke, and major adverse cardiovascular or cerebrovascular events were also similar between the groups.
Implications for Practice: The findings support the use of 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor as a safer alternative to longer-term DAPT in patients undergoing PCI with DES. This strategy may help reduce bleeding risks without increasing the likelihood of thrombotic events, making it a viable option for routine clinical practice, particularly in patients at high risk for bleeding.
Study: Novel Point-of-Care hs-cTnI Test Shows High Diagnostic Accuracy and Predictive Values for Myocardial Infarction – J Am Coll Cardiol
17 Aug, 2024 | 19:00h | UTCStudy Design and Population: This international, multicenter diagnostic study assessed the clinical and analytical performance of the new high-sensitivity cardiac troponin I (hs-cTnI)-SPINCHIP point-of-care (POC) test. The study involved 1,102 adult patients presenting with acute chest discomfort in emergency departments, with myocardial infarction (MI) diagnoses adjudicated by two independent cardiologists.
Main Findings: The hs-cTnI-SPINCHIP test exhibited strong diagnostic accuracy with an area under the receiver-operating characteristic curve of 0.94, similar to established central laboratory assays. The 0/1-hour algorithm of the test identified 51% of patients as low risk for MI with a sensitivity and negative predictive value of 100%, while it confirmed MI in 27% of patients with a specificity of 90.9% and a positive predictive value of 72.9%. Consistency was observed across different sample types.
Implications for Practice: The SPINCHIP hs-cTnI POC test provides a rapid and accurate option for diagnosing MI in emergency settings, aiding quicker decision-making for ruling out or confirming MI.
RCT: Intravenous Amino Acids Reduce AKI Incidence in Cardiac Surgery Patients – N Engl J Med
3 Aug, 2024 | 19:12h | UTCStudy Design and Population: In this multinational, double-blind, randomized clinical trial, 3511 adult patients scheduled for cardiac surgery with cardiopulmonary bypass were recruited from 22 centers across three countries. Patients were randomly assigned to receive an intravenous infusion of either a balanced mixture of amino acids (2 g/kg/day) or a placebo (Ringer’s solution) for up to three days.
Main Findings: The primary outcome, occurrence of acute kidney injury (AKI), was significantly lower in the amino acid group (26.9%) compared to the placebo group (31.7%) with a relative risk of 0.85 (95% CI, 0.77 to 0.94; P=0.002). The incidence of severe AKI (stage 3) was also reduced in the amino acid group (1.6% vs. 3.0%; relative risk, 0.56; 95% CI, 0.35 to 0.87). There were no substantial differences between the groups regarding secondary outcomes such as the use and duration of kidney-replacement therapy or all-cause 30-day mortality.
Implications for Practice: The infusion of amino acids in adult patients undergoing cardiac surgery appears to reduce the incidence of AKI, indicating a potential protective renal effect. However, this intervention did not significantly impact other secondary outcomes, including mortality and the use of kidney-replacement therapy. These findings suggest that amino acids could be considered as a strategy to mitigate AKI risk in this patient population, although further research is needed to explore long-term benefits and other clinical outcomes.
Cohort Study: Late ventricular arrhythmias are rare in STEMI patients without left ventricular dysfunction post-primary PCI – JAMA Netw Open
11 May, 2024 | 14:15h | UTCStudy Design and Population: This cohort study analyzed data from the US National Cardiovascular Data Registry Chest Pain–MI Registry, involving 174,126 adults with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) from 2015 to 2018. The population included a broad demographic with a focus on those experiencing late ventricular tachycardia (VT) or ventricular fibrillation (VF) post-PCI, specifically examining occurrences one day or more after the intervention.
Main Findings: The study found that 8.9% of the patients developed VT or VF after PCI, with 2.4% experiencing these arrhythmias late in the hospitalization period. Among patients with uncomplicated STEMI, late VT or VF with cardiac arrest was exceedingly rare, occurring in only 0.1%. Notably, reduced left ventricular ejection fraction was strongly associated with an increased risk of late VT or VF with cardiac arrest. The presence of late VT or VF significantly correlated with higher in-hospital mortality rates.
Implications for Practice: The findings suggest that late VT or VF after primary PCI in STEMI patients is infrequent, particularly among those without complications. This data supports the potential for safe earlier hospital discharge in uncomplicated cases. However, vigilance is advised due to the significant mortality risk associated with late VT or VF events. Clinicians should consider patient-specific risk factors such as left ventricular function when making discharge decisions.
Reference (link to free full-text):
RCT: Beta-blockers post myocardial infarction showed no benefit in patients with preserved ejection fraction
30 Apr, 2024 | 13:40h | UTCThis randomized, open-label clinical trial conducted across 45 centers in Sweden, Estonia, and New Zealand examined the impact of long-term beta-blocker treatment in patients with acute myocardial infarction (AMI) who had undergone coronary angiography and had a preserved left ventricular ejection fraction (LVEF ≥ 50%). The study involved 5020 patients, predominantly from Sweden, with a median follow-up of 3.5 years. Participants were randomly assigned to receive either a beta-blocker (metoprolol or bisoprolol) or no beta-blocker. The primary endpoint was a composite of death from any cause or new myocardial infarction. The results showed no significant difference in the primary endpoint between the beta-blocker group (7.9%) and the no–beta-blocker group (8.3%) with a hazard ratio of 0.96 (95% CI, 0.79 to 1.16; P=0.64). Additionally, no significant differences were observed in secondary endpoints such as death from cardiovascular causes, myocardial infarction, or hospitalizations for atrial fibrillation and heart failure. Safety endpoints were also comparable between the groups. Overall, long-term beta-blocker treatment did not confer a reduction in risk for the primary composite endpoint or improve secondary outcomes in this patient population.
Commentary on X:
Original Article: Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction (REDUCE-AMI trial) https://t.co/z1NNeAK9Mm
Editorial: Routine Beta-Blockers in Secondary Prevention — On Injured Reserve https://t.co/NzlExH0LZm #ACC24 pic.twitter.com/8Jqpj2dM6E
— NEJM (@NEJM) April 17, 2024
Reference (link to abstract – $ for full-text):
RCT: Post-1 month ticagrelor monotherapy vs. dual antiplatelet therapy significantly reduces bleeding events in acute coronary syndromes
30 Apr, 2024 | 13:26h | UTCIn this randomized, placebo-controlled, double-blind clinical trial, 3400 patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI) were assessed to compare the effects of ticagrelor alone versus ticagrelor plus aspirin from 1 to 12 months post-PCI. The study aimed to determine if ticagrelor alone could reduce bleeding without increasing major adverse cardiovascular or cerebrovascular events (MACCE). The primary findings indicated that ticagrelor alone resulted in significantly lower clinically relevant bleeding (2.1% vs. 4.6%, p<0.0001) and demonstrated non-inferiority in MACCE rates compared to the dual therapy group (3.6% vs. 3.7%, pnon-inferiority<0.0001). These outcomes suggest that ticagrelor monotherapy, starting one month post-PCI, may be an effective alternative to standard dual antiplatelet therapy in reducing bleeding risks without compromising safety.
Commentary on X:
Ticagrelor, in combination with #aspirin for 1 month, followed by ticagrelor alone,
after #PCI (GLOBAL LEADERS): a randomised superiority trial https://t.co/Bo8gfHIZLeRegister now to freely access #ESCCongress #LancetCardiology content up to Sept 10! https://t.co/6wOSrV9yXM pic.twitter.com/8EV5d8s1c8
— The Lancet (@TheLancet) August 27, 2018
Reference (link to abstract – $ for full-text):
RCT: Efficacy and safety of microaxial flow pump in STEMI-related cardiogenic shock
28 Apr, 2024 | 20:17h | UTCThis randomized clinical trial assessed the impact of a microaxial flow pump (Impella CP) on mortality in 355 patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock. Patients were randomly assigned to receive either the microaxial flow pump plus standard care or standard care alone. The primary outcome was mortality at 180 days. Results showed a significant reduction in death rates in the microaxial flow pump group (45.8%) compared to the standard care group (58.5%) with a hazard ratio of 0.74 (95% CI, 0.55 to 0.99; P=0.04). However, the incidence of severe adverse events was notably higher in the microaxial flow pump group, including severe bleeding and device-related complications.
Reference (link to abstract – $ for full-text):
RCT: Reduction in cardiac events through preventive PCI in vulnerable atherosclerotic coronary plaques
28 Apr, 2024 | 17:39h | UTCThis multicenter, open-label, randomized controlled trial assessed the effectiveness of preventive percutaneous coronary intervention (PCI) versus optimal medical therapy alone in treating patients with non-flow-limiting vulnerable coronary plaques identified by intracoronary imaging. Conducted across 15 research hospitals in four countries, the trial enrolled 1,606 patients, with 803 in each treatment group. After 2 years, major adverse cardiac events were significantly lower in the PCI group (0.4%) compared to the medical therapy group (3.4%), with a p-value of 0.0003. These results suggest that preventive PCI can effectively reduce cardiac events in patients with high-risk vulnerable plaques, supporting the expansion of PCI indications to these patients.
Reference (link to abstract – $ for full-text):
RCT: Intravascular ultrasound guidance improves outcomes in percutaneous coronary intervention for acute coronary syndrome
28 Apr, 2024 | 17:22h | UTCThis randomized clinical trial evaluated 3505 acute coronary syndrome (ACS) patients across 58 centers in China, Italy, Pakistan, and the UK, comparing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) with angiography-guided PCI. The study’s primary endpoint was target vessel failure—comprising cardiac death, myocardial infarction, or revascularisation—after 1 year. The IVUS-guided group showed significantly lower rates of the primary endpoint (4.0%) compared to the angiography-guided group (7.3%), with a hazard ratio of 0.55. This outcome was primarily driven by reductions in myocardial infarction and revascularisation, with similar safety profiles between the two groups.
Reference (link to abstract – $ for full-text):
M-A Proportional increase in new-onset diabetes with different intensities of statin therapy
27 Apr, 2024 | 15:41h | UTCStudy Design and Population:
This research is a meta-analysis of individual participant data from large, long-term, randomized, double-blind controlled trials involving statins. The study encompasses 19 trials comparing statin use to placebo and four trials comparing varying intensities of statin therapy, involving a total of 154,664 participants over periods ranging from 4.3 to 4.9 years. Participants were adults enrolled in statin trials with a scheduled duration of at least two years and a participant count of at least 1000.
Main Findings:
The study revealed a dose-dependent increase in the incidence of new-onset diabetes when using statins. Participants receiving low to moderate-intensity statin therapy showed a 10% increase in new-onset diabetes annually compared to placebo, while those on high-intensity statin therapy exhibited a 36% increase. The absolute increases in new-onset diabetes were significantly influenced by the extent of HbA1c measurement. Notably, a large portion of new-onset diabetes cases occurred among participants with baseline glycaemic levels nearing the diabetes diagnostic threshold. Furthermore, the study found a moderate rise in mean glucose levels and HbA1c among those without baseline diabetes, and a significant worsening of glycemia among those with existing diabetes.
Implications for Practice:
The findings highlight a moderate, dose-dependent risk of new-onset diabetes associated with statin therapy, especially in individuals close to the diagnostic threshold for diabetes. These results should be considered in the clinical management of statin therapy, balancing the small increases in glycemia against the substantial benefits of statins in reducing cardiovascular risk. Healthcare providers should monitor glycaemic control in patients on statin therapy, particularly those prescribed high-intensity doses.
Reference (free full-text):
PCI vs. CABG in left main coronary disease patients with and without diabetes—a pooled analysis of 4 trials
22 Mar, 2024 | 11:41h | UTCStudy Design and Population: This research pooled individual patient data from four randomized clinical trials (SYNTAX, PRECOMBAT, NOBLE, and EXCEL), comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in 4393 patients with left main coronary artery disease. The trials included both patients with and without diabetes, allowing for a comparative analysis of outcomes based on the revascularization method and the presence of diabetes.
Main Findings: Patients with diabetes exhibited higher rates of 5-year mortality, spontaneous myocardial infarction (MI), and repeat revascularization compared to those without diabetes. However, mortality rates following PCI vs. CABG were similar in diabetic (15.3% vs. 14.1%, respectively) and non-diabetic patients (9.7% vs. 8.9%, respectively). PCI was associated with a lower risk of stroke within the first year post-operation across all patients. Notably, diabetic patients underwent higher rates of spontaneous MI and repeat revascularization after PCI compared to CABG, with a more significant absolute excess risk observed beyond the first year compared to non-diabetic patients.
Implications for Practice: For patients with left main disease deemed suitable for either PCI or CABG, diabetes status significantly influences long-term outcomes, including death and cardiovascular events. While PCI offers a lower early risk of stroke, it is associated with increased risks of spontaneous MI and repeat revascularization, particularly in diabetic patients. These findings underscore the importance of considering patient-specific factors, such as diabetes status, in choosing between PCI and CABG for left main coronary artery disease revascularization.
Reference
Prakriti Gaba et al. (2024). Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main Disease With or Without Diabetes: Findings From a Pooled Analysis of 4 Randomized Clinical Trials. Circulation, 0. DOI: 10.1161/CIRCULATIONAHA.123.065571. Access the study here: Link
Meta-Analysis: No mortality benefit of early vs. delayed/selective coronary angiography in out-of-hospital cardiac arrest without ST-elevation
21 Mar, 2024 | 11:40h | UTCStudy Design and Population: This article presents a systematic review and meta-analysis of five randomized controlled trials comparing early/immediate versus delayed/selective coronary angiography (CAG) in 1512 patients who experienced out-of-hospital cardiac arrest (OHCA) without ST-segment elevation. The population had a mean age of 67 years, with 26% female and 23% having a prior myocardial infarction. Follow-up duration was at least 30 days across included studies.
Main Findings: The analysis revealed no significant difference in the odds of all-cause death between early/immediate and delayed/selective CAG strategies (Odds Ratio [OR] 1.12, 95% CI 0.91–1.38). Similar results were found for the composite outcome of all-cause death or neurological deficit (OR 1.10, 95% CI 0.89–1.36). Subgroup analysis showed no significant effect modification based on age, initial cardiac rhythm, history of coronary artery disease, the presumed ischemic cause of arrest, or time to return of spontaneous circulation. Interestingly, a trend toward increased odds of death was observed in women receiving early CAG compared to men, although this finding approached but did not reach statistical significance.
Implications for Practice: The findings suggest that for OHCA patients without ST-segment elevation, an early/immediate CAG strategy does not confer a mortality benefit over a delayed/selective approach across major subgroups. Notably, the potential for increased mortality risk in women with early CAG warrants further investigation. Clinicians should consider these results when deciding on the timing of CAG in this patient population, keeping in mind the overall lack of mortality benefit and the nuanced differences among subgroups.
Reference: Fardin Hamidi et al. (2023). Early versus delayed coronary angiography in patients with out-of-hospital cardiac arrest and no ST-segment elevation: a systematic review and meta-analysis of randomized controlled trials. Clinical Research in Cardiology, 113(561–569). Access the study here: [Link]
2023 AHA/ACC Guideline for chronic coronary disease – B-blockers downgraded in patients without recent MI or low ejection fraction
21 Jul, 2023 | 13:52h | UTCKey Perspectives: 2023 Multisociety Guideline for Managing Chronic Coronary Disease – American College of Cardiology
Top things to know: 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease – American Heart Association
News Releases:
Commentary: New Chronic Heart Disease Guidelines Update Roles of GDMT, Imaging, and Revascularization – TCTMD
Commentary on Twitter with key points (thread – click for more)
?2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients w/ Chronic Coronary Disease aims to provide recommendations for diagnostic evaluation, symptom relief, improvement in QoL & reduction of future #ASCVD-related events & #heartfailure in patients w/ CCD.
— American College of Cardiology (@ACCinTouch) July 20, 2023