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February 2, 2026European Heart Journal - Cardiovascular Pharmacotherapy0 citations

Net Clinical Benefit of Extended Dual Pathway Inhibition in Chronic Coronary Syndrome as Classified by the 2024 ESC Criteria: a COMPASS Substudy

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MWMorten WürtzKOKevin Kris Warnakula OlesenQYQilong Yi

Key Result

Dual pathway inhibition provided similar net clinical benefit in low-risk and high-risk patients (high-risk HR 0.80; 95% CI 0.69-0.93), indicating 2024 ESC criteria perform poorly for guiding DPI.

Key Points

  • This research aims to evaluate the clinical benefits of extended dual pathway inhibition in chronic coronary syndrome patients based on the 2024 ESC criteria.
  • Randomized CCS patients to receive either aspirin alone or dual pathway inhibition (DPI) with aspirin and rivaroxaban.
  • Risk stratified patients according to 2024 ESC criteria.
  • Measured endpoints included major adverse cardiovascular events (MACE), all-cause death, and bleeding complications.
  • High-risk patients exhibited greater incidences of MACE and composite adverse events.
  • DPI significantly reduced MACE and all-cause death in both low- and high-risk groups.
  • 2024 ESC criteria showed limitations in effectively distinguishing between high and low ischemic risk.

Study Design

Type

RCT (n=15,429)

Randomization

randomized

Structured PICO

Does dual pathway inhibition with aspirin and rivaroxaban improve net clinical benefit compared to aspirin alone in patients with chronic coronary syndrome stratified by 2024 ESC criteria?

P
Population
15,429 patients with chronic coronary syndrome randomized to aspirin alone or dual pathway inhibition, followed for 30 months.
I
Intervention
Dual pathway inhibition (DPI) with aspirin and rivaroxaban
C
Comparator
Aspirin alone
O
Outcome
Net clinical benefit (30-month absolute risk difference combining MACE and bleeding)composite

The 2024 ESC criteria for chronic coronary syndrome perform poorly in distinguishing ischemic risk, as dual pathway inhibition provides similar net clinical benefit regardless of risk classification.

Main Result

Hazard Ratio: 0.8 (95% CI 0.69–0.93)

Absolute Risk Reduction: 2.06%

Abstract

Abstract Background and Aims Extended dual pathway inhibition (DPI) with aspirin and rivaroxaban is recommended in high-risk patients with chronic coronary syndrome (CCS). In the 2024 update of the European Society of Cardiology guidelines on CCS, the high-risk criteria were revised. In the COMPASS cohort, we evaluated net clinical benefit of DPI according to baseline risk as defined by the ESC criteria in CCS patients. Methods CCS patients randomized to aspirin alone or DPI (n=15,429) were risk stratified using the 2024 ESC criteria. Endpoints included major adverse cardiovascular events (MACE), all-cause death, fatal/critical organ bleeding, and composite adverse events (MACE and bleeding). Net clinical benefit was the 30-month absolute risk difference combining MACE and bleeding. Results High-risk status was associated with higher 30-month incidences of MACE (6.4% vs. 5.0%, HR 1.33, 95% CI 1.09−1.63) and composite adverse events (7.1% vs. 5.7%, HR 1.31 1.09–1.58), but not all-cause death or bleeding. DPI reduced MACE (low-risk: HR 0.66 0.45−0.95; high-risk: HR 0.77 0.66.−0.91; p-value for interaction 0.42) and all-cause death (low-risk: 0.78 0.53−1.14; high-risk: HR 0.78 0.64−0.94, p-value for interaction 0.99). DPI provided similar net clinical benefit in low-risk (30-month risk difference -1.77% -3.88−0.33, HR 0.79 0.56−1.11) and high-risk patients (30-month risk difference -2.06% -3.20−-0.91, HR 0.80 0.69−0.93; p-value for interaction 0.94). Conclusions In CCS patients, DPI reduced all-cause death and MACE while increasing major bleeding. The 2024 ESC criteria performed poorly in terms of distinguishing patients at high vs. low ischemic risk, making them inadequate to provide guidance for DPI use.

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Cite This Study

Würtz et al. (2026) conducted an RCT in Chronic coronary syndrome (n=15,429). Extended dual pathway inhibition (DPI) with aspirin and rivaroxaban vs. Aspirin alone was evaluated on Net clinical benefit (composite of MACE and bleeding) in high-risk patients (HR 0.80, 95% CI 0.69-0.93). Dual pathway inhibition provided similar net clinical benefit in low-risk and high-risk patients (high-risk HR 0.80; 95% CI 0.69-0.93), indicating 2024 ESC criteria perform poorly for guiding DPI.

synapsesocial.com/papers/6980fe35c1c9540dea810077https://doi.org/10.1093/ehjcvp/pvag008
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