Daily Cardiology Research Analysis
Three rigorously conducted clinical studies reshape cardiology practice: a double-blind RCT shows that adding aspirin to oral anticoagulation in chronic coronary syndrome increases ischemic events, death, and major bleeding; an RCT supports P2Y12 inhibitor monotherapy after 1 month in low-risk AMI PCI patients with lower bleeding; and an individual participant data meta-analysis indicates transcatheter aortic valve implantation reduces 1-year death or stroke versus surgery in low–intermediate ri
Summary
Three rigorously conducted clinical studies reshape cardiology practice: a double-blind RCT shows that adding aspirin to oral anticoagulation in chronic coronary syndrome increases ischemic events, death, and major bleeding; an RCT supports P2Y12 inhibitor monotherapy after 1 month in low-risk AMI PCI patients with lower bleeding; and an individual participant data meta-analysis indicates transcatheter aortic valve implantation reduces 1-year death or stroke versus surgery in low–intermediate risk severe aortic stenosis.
Research Themes
- Antithrombotic optimization in coronary disease
- Bleeding risk reduction through de-escalation strategies post-PCI
- Structural heart intervention selection (TAVI vs SAVR) in severe aortic stenosis
Selected Articles
1. Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation.
In a multicenter, double-blind RCT of 872 chronic coronary syndrome patients already on long-term oral anticoagulation, adding daily aspirin increased the composite of cardiovascular events, all-cause mortality, and major bleeding versus placebo, prompting early trial termination. Results argue against routine aspirin on top of oral anticoagulation in this high-risk group.
Impact: This double-blind RCT provides definitive evidence that aspirin on top of oral anticoagulation harms high-risk CCS patients, challenging common additive strategies and informing guideline updates.
Clinical Implications: Avoid routine aspirin addition to oral anticoagulation in chronic coronary syndrome with prior stenting and high atherothrombotic risk; prioritize OAC monotherapy unless a compelling short-term indication exists, and re-evaluate bleeding risk regularly.
Key Findings
- Primary composite endpoint occurred in 16.9% with aspirin vs 12.1% with placebo (adjusted HR 1.53).
- All-cause mortality was higher with aspirin: 13.4% vs 8.4% (adjusted HR 1.72).
- Major bleeding tripled with aspirin: 10.2% vs 3.4% (adjusted HR 3.35); trial stopped early for excess deaths.
Methodological Strengths
- Multicenter, double-blind, randomized, placebo-controlled design
- Hard clinical endpoints with adjudication and prespecified analyses
Limitations
- Early termination may inflate effect estimates and limits long-term assessment
- Conducted in France; generalizability to other health systems requires caution
Future Directions: Define subgroups (e.g., recent stenting, complex PCI) where short-term aspirin may still be warranted; evaluate alternative strategies (e.g., OAC plus P2Y12 inhibitor) and personalized bleeding/ischemia risk tools.
BACKGROUND: The appropriate antithrombotic regimen for patients with chronic coronary syndrome who are at high atherothrombotic risk and receiving long-term oral anticoagulation remains unknown. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial in France involving patients with chronic coronary syndrome who had undergone a previous stent implantation (>6 months before enrollment) and were at high atherothrombotic risk and currently receiving long-term oral anticoagulation. The patients were randomly assigned in a 1:1 ratio to receive aspirin (100 mg once daily) or placebo; all the patients continued to receive their current oral anticoagulation therapy. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia. The key safety outcome was major bleeding. RESULTS: A total of 872 patients underwent randomization; 433 were assigned to the aspirin group, and 439 to the placebo group. The trial was stopped early at the advice of the independent data and safety monitoring board after a median follow-up of 2.2 years because of an excess of deaths from any cause in the aspirin group. A primary efficacy outcome event occurred in 73 patients (16.9%) in the aspirin group and in 53 patients (12.1%) in the placebo group (adjusted hazard ratio, 1.53; 95% confidence interval [CI], 1.07 to 2.18; P = 0.02). Death from any cause occurred in 58 patients (13.4%) in the aspirin group and in 37 (8.4%) in the placebo group (adjusted hazard ratio, 1.72; 95% CI, 1.14 to 2.58; P = 0.01). Major bleeding occurred in 44 patients (10.2%) in the aspirin group and in 15 patients (3.4%) in the placebo group (adjusted hazard ratio, 3.35; 95% CI, 1.87 to 6.00; P<0.001). A total of 467 and 395 serious adverse events were reported in the aspirin group and placebo group, respectively. CONCLUSIONS: Among patients with chronic coronary syndrome at high atherothrombotic risk who were receiving an oral anticoagulant, the addition of aspirin led to a higher risk of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia than placebo, as well as higher risks of death from any cause and major bleeding. (Funded by the French Ministry of Health and Bayer Healthcare; ClinicalTrials.gov number, NCT04217447.).
2. Transcatheter or Surgical Treatment of Patients With Aortic Stenosis at Low to Intermediate Risk: An Individual Participant Data Meta-Analysis.
An IPD meta-analysis of 4 investigator-initiated RCTs (n=2873), augmented by aggregate data from industry trials, showed TAVI reduced 1‑year all-cause death or any stroke versus SAVR in low–intermediate risk severe AS (overall HR ~0.76). Results support TAVI as an alternative in this population, while underscoring the need for long-term durability and safety data.
Impact: Pooled patient-level evidence strengthens external validity beyond single trials, informing heart teams when selecting TAVI vs SAVR in low–intermediate risk patients.
Clinical Implications: For suitable low–intermediate risk AS patients, TAVI can be considered to reduce 1-year death/stroke; decisions should integrate anatomy, frailty, coronary/access considerations, and valve durability until longer-term outcomes mature.
Key Findings
- IPD meta-analysis of 4 RCTs (n=2873) showed TAVI reduced 1‑year death or any stroke vs SAVR (1‑stage HR 0.73; 95% CI 0.56–0.95).
- Overall 2-stage meta-analysis across 8 RCTs confirmed benefit (HR 0.76; 95% CI 0.60–0.97).
- Secondary outcomes included signals favoring TAVI (e.g., less new-onset atrial fibrillation), while pacemaker needs remain a consideration.
Methodological Strengths
- Individual participant data pooled from investigator-initiated RCTs with harmonized endpoints
- Complemented by aggregate data to increase power and generalizability
Limitations
- Primary analyses focused on 1-year outcomes; long-term valve durability and complications unresolved
- Heterogeneity in devices, surgical techniques, and periprocedural care across trials
Future Directions: Extended follow-up IPD analyses to evaluate durability, structural valve deterioration, conduction disturbance, and valve-in-valve feasibility; assessment of subgroups (e.g., bicuspid valves, younger patients).
IMPORTANCE: Mounting evidence suggests transcatheter aortic valve implantation (TAVI) as preferred treatment for patients at low to intermediate surgical risk. However, limitations in study design and statistical power raise concerns about the generalizability of individual randomized clinical trials (RCTs) comparing TAVI and surgical aortic valve replacement (SAVR) to routine clinical practice. OBJECTIVE: To compare 1-year outcomes of TAVI vs SAVR in patients with severe symptomatic aortic stenosis at low to intermediate surgical risk applying a 2-stage individual participant data (IPD) and aggregate meta-analyses. DATA SOURCES: MEDLINE databases were searched for RCTs comparing TAVI and SAVR in patients with aortic stenosis until June 15, 2025. STUDY SELECTION: RCTs were selected comparing TAVI vs SAVR in patients with severe symptomatic aortic stenosis at low or intermediate surgical risk with 1-year follow-up. DATA EXTRACTION AND SYNTHESIS: IPD were obtained from all investigator-initiated RCTs (DEDICATE, NOTION, NOTION-2, and UK TAVI) and analyzed in 1- and 2-stage IPD meta-analyses. An overall meta-analysis was performed by adding aggregate data from industry-sponsored RCTs. MAIN OUTCOMES AND MEASURES: The primary end point was all-cause death or any stroke 1 year after randomization. Secondary end points included all-cause death, any stroke, disabling stroke, cardiovascular death, rehospitalization for cardiovascular cause, myocardial infarction, new-onset atrial fibrillation, new permanent pacemaker implantation, and aortic valve reintervention. RESULTS: The IPD meta-analysis included 4 RCTs comprising 2873 patients (mean [SD] age, 76.7 [5.5] years; 805 [56.1%] male) at low to intermediate surgical risk randomly assigned to TAVI (n = 1439) or SAVR (n = 1434). At 1 year, the hazard ratio (HR) for the primary end point for TAVI compared to SAVR was 0.73 (95% CI, 0.56-0.95) in the 1-stage and 0.79 (95% CI, 0.49-1.27) in the 2-stage IPD meta-analysis. In the 2-stage overall meta-analysis the HR for the primary end point was 0.76 (95% CI, 0.60-0.97). CONCLUSIONS AND RELEVANCE: In this IPD meta-analysis of 4 RCTs, and an overall meta-analysis of 8 RCTs of patients with severe symptomatic AS at low to intermediate risk, TAVI was associated with a reduction in the 1-year incidence of all-cause death or any stroke. These findings emphasize TAVI as alternative option in patients at low to intermediate risk. Long-term follow-up is warranted to evaluate sustainability of these findings.
3. Early Discontinuation of Aspirin after PCI in Low-Risk Acute Myocardial Infarction.
In low-risk AMI patients with early complete revascularization and 1 month of event-free DAPT, switching to P2Y12 inhibitor monotherapy was noninferior to continuing DAPT for 11 months for the composite of death, MI, stent thrombosis, stroke, or major bleeding, and halved clinically relevant bleeding. Stent thrombosis was rare in both arms.
Impact: Provides high-quality randomized evidence supporting DAPT de-escalation in a clearly defined low-risk AMI PCI population, enabling bleeding reduction without ischemic penalty.
Clinical Implications: For selected low-risk AMI patients with complete revascularization and event-free first month, consider stopping aspirin at 1 month and continuing P2Y12 inhibitor monotherapy to reduce bleeding risk; apply careful patient selection and contrast with data from earlier aspirin withdrawal trials.
Key Findings
- Primary composite event: 2.1% with P2Y12 monotherapy vs 2.2% with continued DAPT (noninferior; difference -0.09 percentage points; P=0.02).
- Clinically relevant bleeding (BARC 2/3/5) reduced: 2.6% vs 5.6% (HR 0.46; 95% CI 0.29–0.75).
- Stent thrombosis infrequent and similar between groups; serious adverse events comparable.
Methodological Strengths
- Multicenter randomized design with prespecified noninferiority margin and clinically relevant composite endpoint
- Contemporary practice: complete revascularization, modern DES, and standardized follow-up
Limitations
- Open-label design may introduce performance bias (though hard endpoints mitigate this)
- Generalizability limited to low-risk AMI with complete revascularization and event-free first month
Future Directions: Evaluate de-escalation in broader or higher-risk AMI populations, optimal P2Y12 agent choice, and integration with anticoagulation in atrial fibrillation after PCI.
BACKGROUND: An appropriate duration of dual antiplatelet therapy after percutaneous coronary intervention for acute myocardial infarction that has been treated with guideline-recommended complete revascularization and a contemporary drug-eluting stent remains unclear. METHODS: We conducted a multicenter, open-label, randomized trial at 40 European sites. Adults with acute myocardial infarction who had undergone successful complete revascularization within 7 days after the infarction and had subsequently completed 1 month of dual antiplatelet therapy with no ischemic or major bleeding events were randomly assigned to transition to a P2Y12 inhibitor as monotherapy or to continue dual antiplatelet therapy for an additional 11 months. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, stroke, or major bleeding (defined by the Bleeding Academic Research Consortium [BARC] as a bleeding event of type 3 or 5) at 11 months after randomization (tested for noninferiority with a margin of 1.25 percentage points). The main secondary outcome was BARC type 2, 3, or 5 bleeding (clinically relevant bleeding) at 11 months after randomization (tested for superiority). RESULTS: Among the 2246 enrolled patients, 1942 underwent randomization: 961 to receive P2Y12-inhibitor monotherapy and 981 to continue dual antiplatelet therapy. A primary-outcome event occurred in 20 patients (2.1%) in the P2Y12-inhibitor monotherapy group and in 21 patients (2.2%) in the dual antiplatelet therapy group (difference, -0.09 percentage points; 95% confidence interval [CI], -1.39 to 1.20; P = 0.02 for noninferiority). BARC type 2, 3, or 5 bleeding occurred in 2.6% of the patients in the P2Y12-inhibitor monotherapy group and in 5.6% of those in the dual antiplatelet therapy group (hazard ratio, 0.46; 95% CI, 0.29 to 0.75; P = 0.002 for superiority). Stent thrombosis was infrequent, and the incidence was similar in the two groups. The incidence of serious adverse events appeared to be similar in the two groups. CONCLUSIONS: Among low-risk patients with acute myocardial infarction who had undergone early complete revascularization and had completed 1 month of dual antiplatelet therapy without complications, P2Y12-inhibitor monotherapy was noninferior to continued dual antiplatelet therapy with respect to the occurrence of adverse cardiovascular and cerebrovascular events and resulted in a lower incidence of bleeding events. (Funded by MicroPort [France]; TARGET-FIRST ClinicalTrials.gov number, NCT04753749.).