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Daily Cardiology Research Analysis

3 papers

Three practice-informing studies stood out today. An individual patient data meta-analysis found clopidogrel monotherapy superior to aspirin for secondary prevention in coronary artery disease without increasing major bleeding. Two Lancet randomized trials in peripheral and coronary interventions reported that paclitaxel-coated devices did not improve quality of life in claudication and showed a five-year mortality signal, and that immediate complete revascularization in STEMI was not non-inferi

Summary

Three practice-informing studies stood out today. An individual patient data meta-analysis found clopidogrel monotherapy superior to aspirin for secondary prevention in coronary artery disease without increasing major bleeding. Two Lancet randomized trials in peripheral and coronary interventions reported that paclitaxel-coated devices did not improve quality of life in claudication and showed a five-year mortality signal, and that immediate complete revascularization in STEMI was not non-inferior to staged revascularization during the index admission.

Research Themes

  • Antiplatelet monotherapy optimization in secondary prevention
  • Safety and effectiveness of drug-coated devices in peripheral artery disease
  • Timing of complete revascularization in STEMI with multivessel disease

Selected Articles

1. Clopidogrel versus aspirin for secondary prevention of coronary artery disease: a systematic review and individual patient data meta-analysis.

88.5Level IMeta-analysisLancet (London, England) · 2025PMID: 40902613

Across 28,982 patients with established CAD, clopidogrel monotherapy reduced MACCE versus aspirin (HR 0.86) without increasing major bleeding or mortality over long-term follow-up. These data support preferential use of clopidogrel for secondary prevention after DAPT cessation.

Impact: This high-quality IPD meta-analysis directly challenges aspirin’s entrenched role in secondary prevention, showing superior efficacy of clopidogrel without a bleeding penalty.

Clinical Implications: Clinicians should consider clopidogrel monotherapy as the default single antiplatelet strategy for secondary prevention in CAD patients after DAPT, especially in post-PCI or prior ACS populations.

Key Findings

  • MACCE was lower with clopidogrel than aspirin (2.61 vs 2.99 per 100 patient-years; HR 0.86, 95% CI 0.77–0.96; p=0.0082).
  • Major bleeding rates were similar between clopidogrel and aspirin (HR 0.94, 95% CI 0.74–1.21; p=0.64).
  • Mortality did not differ between groups over follow-up.
  • Findings were derived from seven randomized trials using one-stage IPD frailty models.

Methodological Strengths

  • Individual patient data meta-analysis across seven randomized trials with standardized one-stage frailty modeling
  • Large sample size (n=28,982) and extended follow-up enabling robust efficacy and safety assessment

Limitations

  • Heterogeneity in trial designs and populations; not a single protocol RCT
  • Some trials included initial DAPT phases; potential variability in monotherapy initiation timing

Future Directions: Head-to-head RCTs comparing clopidogrel vs aspirin in specific subgroups (e.g., diabetes, elderly, CKD) and pharmacogenomic-guided strategies (e.g., CYP2C19) could refine personalized antiplatelet monotherapy.

2. Paclitaxel-coated versus uncoated devices for infrainguinal endovascular revascularisation in patients with intermittent claudication (SWEDEPAD 2): a multicentre, participant-masked, registry-based, randomised controlled trial.

87Level IRCTLancet (London, England) · 2025PMID: 40902614

In a pragmatic, participant-masked RCT of 1,136 claudication patients, paclitaxel-coated infrainguinal devices did not improve 1-year disease-specific quality of life and showed a higher 5-year mortality signal versus uncoated devices. Routine use for intermittent claudication is not supported.

Impact: This large registry-based RCT addresses patient-centered endpoints and long-term safety, challenging widespread use of paclitaxel-coated devices for claudication.

Clinical Implications: For intermittent claudication, prioritize symptom-guided care and supervised exercise; if endovascular therapy is chosen, consider uncoated devices given lack of QoL benefit and mortality signal with paclitaxel-coated devices.

Key Findings

  • No difference in 1-year VascuQoL-6 between paclitaxel-coated and uncoated devices (mean difference −0.02; 95% CI −0.66 to 0.62; p=0.96).
  • Overall all-cause mortality was not different over a median 7.1 years (HR 1.18; 95% CI 0.94–1.48), but 5-year mortality incidence was higher with paclitaxel-coated devices (HR 1.47; 95% CI 1.09–1.98).
  • Femoropopliteal interventions comprised 96% of cases; most patients had Rutherford category 3 claudication.

Methodological Strengths

  • Nationwide, pragmatic, participant-masked, registry-based randomized design
  • High external validity with long-term follow-up and patient-centered primary endpoint

Limitations

  • Device heterogeneity and evolving technology may influence generalizability
  • Trial powered for QoL primary endpoint; mortality analyses may be exploratory

Future Directions: Mechanistic and device-level studies to understand mortality signals; head-to-head comparisons with alternative technologies and stratified analyses by lesion and patient risk.

3. Immediate versus staged complete revascularisation during index admission in patients with ST-segment elevation myocardial infarction and multivessel disease (OPTION-STEMI): a multicentre, non-inferiority, open-label, randomised trial.

84Level IRCTLancet (London, England) · 2025PMID: 40902612

In OPTION-STEMI, immediate complete revascularization during the index procedure did not achieve non-inferiority versus staged complete revascularization during the index admission for the 1-year composite of death, non-fatal MI, or unplanned revascularization. Fractional flow reserve was used to guide treatment of intermediate non-culprit lesions.

Impact: This randomized trial informs a common clinical decision in STEMI with multivessel disease and suggests caution against routine immediate multivessel PCI in the index procedure.

Clinical Implications: For STEMI with multivessel disease, staged complete revascularization during index admission remains a prudent strategy; routine immediate complete revascularization should be individualized rather than adopted broadly.

Key Findings

  • Primary composite endpoint at 1 year occurred in 13% (immediate) vs 11% (staged); HR 1.24 (95% CI 0.86–1.79), not meeting non-inferiority.
  • Non-culprit lesions with 50–69% stenosis were evaluated by FFR to guide revascularization.
  • Randomized 994 STEMI patients across 14 centers; ongoing long-term follow-up.

Methodological Strengths

  • Randomized, multicenter design with pre-specified non-inferiority margin and blinded endpoint adjudication
  • Use of FFR for intermediate lesions enhances physiologic guidance

Limitations

  • Open-label design may introduce performance bias
  • Single-country setting and modest event rates may limit power and generalizability

Future Directions: Assessment of longer-term outcomes, subgroup effects (e.g., shock, complex anatomy), and integration with physiology-guided staged strategies to refine timing decisions.