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Net clinical benefit of extended dual pathway inhibition according to baseline risk in patients with chronic coronary
Morten Würtz1,2, Kevin Kris Warnakula Olesen1,2, Deepak L Bhatt3
1Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200, Aarhus, Denmark.
Insights
Dual pathway inhibition (DPI) with aspirin and rivaroxaban offers similar net clinical benefit for both low/moderate and high-risk patients with chronic coronary syndrome (CCS). This treatment effectively reduces major adverse cardiovascular events and all-cause death across risk strata.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Clinical Trials
Background:
- Current guidelines recommend extended dual pathway inhibition (DPI) using aspirin and rivaroxaban for patients with chronic coronary syndrome (CCS) who are at high ischemic risk.
- The CHADS-P2A2RC score is a validated tool for predicting cardiovascular risk and guiding antithrombotic therapy allocation in CCS patients.
Purpose of the Study:
- To evaluate the net clinical benefit of DPI treatment in patients with CCS.
- To assess whether the benefit of DPI varies based on baseline cardiovascular risk, as determined by the CHADS-P2A2RC score.
- To analyze DPI's impact on major adverse cardiovascular events (MACE), all-cause death, and bleeding events within the COMPASS trial population.
Main Methods:
- The study analyzed data from 14,670 CCS patients in the COMPASS trial, randomized to aspirin alone or DPI.
- Patients were stratified into low/moderate-risk (CHADS-P2A2RC < 4) and high-risk (CHADS-P2A2RC ≥ 4) groups.
- Net clinical benefit was defined as the 30-month risk difference between MACE and bleeding events. Key outcomes included MACE, all-cause death, and fatal/critical organ bleeding.
Main Results:
- High-risk patients exhibited higher 30-month incidences of MACE (7.9% vs. 3.9%) and fatal/critical organ bleeding (1.2% vs. 0.8%) compared to low/moderate-risk patients.
- DPI significantly reduced MACE and all-cause death in both low/moderate-risk (MACE HR 0.62, death HR 0.65) and high-risk groups (MACE HR 0.82, death HR 0.81).
- The increase in fatal/critical organ bleeding with DPI was not substantial across risk groups (low/moderate risk HR 1.35, high risk HR 1.18).
Conclusions:
- Patients with CCS, stratified by the CHADS-P2A2RC score, derived similar net clinical benefit from DPI treatment, regardless of their baseline risk level.
- DPI therapy led to a comparable reduction in all-cause death for both low/moderate-risk and high-risk CCS patients.
- The findings support the use of DPI in a broader range of CCS patients, guided by risk stratification using the CHADS-P2A2RC score.
Aims:
Guidelines recommend extended dual pathway inhibition (DPI) with aspirin and rivaroxaban in patients with chronic coronary syndrome (CCS) at high ischaemic risk. The CHADS-P2A2RC score improves risk prediction and enables antithrombotic treatment allocation in these patients. This study evaluated the net clinical benefit of DPI treatment according to baseline risk as classified by the CHADS-P2A2RC score in patients with CCS included in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial.
Methods And Results:
COMPASS patients with CCS (n = 14 670), randomized to aspirin alone or DPI, were stratified according to cardiovascular risk using the CHADS-P2A2RC score. Endpoints were 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 risk difference of MACE and bleeding. Thirty-month incidences of MACE [7.9% vs. 3.9%, hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.83-2.18] and fatal/critical organ bleeding (1.2% vs. 0.8%, HR 1.49, 95% CI 1.06-1.92) were higher in high-risk (CHADS-P2A2RC ≥ 4) than in low/moderate-risk (CHADS-P2A2RC < 4) patients. DPI reduced MACE (low/moderate risk: HR 0.62, 95% CI 0.47-0.82; high risk: HR 0.82, 95% CI 0.68-0.99, P for interaction 0.09) and all-cause death (low/moderate risk: HR 0.65, 95% CI 0.46-0.91; high risk: HR 0.81, 95% CI 0.65-1.00, P for interaction 0.29), without substantially increasing fatal/critical organ bleeding (low/moderate risk: HR 1.35, 95% CI 0.72-2.53; high risk: HR 1.18, 95% CI 0.73-1.90, P for interaction 0.73). DPI provided net clinical benefit of similar magnitude in low/moderate-risk (-1.81%, 95% CI -3.00 to -0.62) and high-risk (-1.96%, 95% CI -3.60 to -0.33) CCS patients.
Conclusion:
As classified by the CHADS-P2A2RC score, low/moderate- and high-risk patients with CCS derived similar net clinical benefit and reduction in all-cause death from DPI treatment.
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