Rivaroxaban, Aspirin Benefit CAD/PAD Patients Despite Number of Comorbidities

Thomas Vanassche, MD, PhD

A recent study showed the addition of low-dose rivaroxaban to patients with coronary artery disease (CAD) or peripheral arterial disease (PAD) to aspirin reduced cardiovascular (CV) events and mortality.

Investigators, led by Thomas Vanassche, MD, PhD, Department of Cardiovascular Sciences, University Hospitals Leuven, found the addition of low-dose rivaroxaban to aspirin exhibited benefit regardless of the number of concomitant drugs or comorbidities in patients with vascular disease.

Study

Investigators performed an analysis of the COMPASS study, a double-blind, randomized placebo-controlled that compared aspirin alone, low-dose rivaroxaban with aspirin, or rivaroxaban alone in patients with stable vascular disease.

The COMPASS study included patients with CAD and/or PAD without requirements for therapeutic anticoagulation or dual antiplatelet therapy.

Patients with CAD under 65 years required ≥2 affected vascular beds, ≥2 additional CV risk factors, such as smoking, diabetes, estimated glomerular filtration rate <60 mL per minute, heart failure, or prior non-lacunar ischemic stroke.

At randomization, baseline use of drugs for CV condition or prevention was collected.

Investigators also collected info on the presence of concomitant medical conditions in the categories of cancer, gastrointestinal disease, cardiometabolic risk conditions, respiratory disease, renal and genitourinary disease, liver disease, neurocognitive disease, cardiovascular disease other than CAD/PAD, and musculoskeletal disease.

The primary efficacy outcome included a composite of myocardial infarction, stroke, or CV death, while the primary safety outcome was major bleeding.

The team used univariate Cox proportional hazards regression models to compare study outcomes by number of cardiovascular medications, any medications, and number of concomitant conditions.

Further, they used stratified cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the comparison of rivaroxaban plus aspirin vs aspirin alone

Results

Data on medication including non-cardiovascular drugs was available for 27,388 (99.7%), with a mean follow-up of 23 months.

Investigators noted on top of aspirin treatment and rivaroxaban and placebo, 74.8% of patients took ≥3 additional CV drugs and 16.9% took ≥5 CV drugs.

Further, 59.4% of participants had ≥3 concomitant medical conditions, with 11.6% having ≥5 comorbidities.

Data show that the risk of the primary endpoint increased with a higher number of CV drugs.

Patients taking ≥5 CV drugs had a 74% higher incidence rate of combination of stroke, myocardial infarction, or CV death (HR 1.74; 95% CI, 1.47 - 2.05, P <.0001).

In addition, data show the risk of major bleeding did not increase with the number of CV medications (HR 1.17; 95% CI, 0.93 - 1.46).

The team observed the higher number of comorbidities was associated with an increased risk for both primary efficacy outcome and major bleeding.

In comparison to a patient with ≤1 comorbidities, patients with ≥4 comorbidities had a two-fold risk of stroke, myocardial infarction, or CV death (HR 2.45, 95%CI 2.01 - 2.99, P <0.0001), as well as major bleeding (HR 2.34, 95%CI 1.79 - 2.06, P <0.0001).

Data show event rates were lower in patients receiving rivaroxaban plus aspirin compared with aspirin alone with a 20 - 30% relative risk reduction.

Investigators noted the efficacy, safety, and clinical benefit of rivaroxaban was not affected by the number of drugs or comorbidities.

They also observed patients taking more concomitant medications had the largest reduction in net clinical outcome with added rivaroxaban (1.1% vs 0.4% reduction with >4 vs 0 - 2 cardiovascular drugs).

Conclusion

Investigators concluded that patients receiving multiple drugs with multimorbidity had a higher risk of CV events.

However, they noted the efficacy, safety, and net clinical benefits from the addition of low-dose rivaroxaban to aspirin in patients with stable vascular diseases were not affected by the number of drugs or comorbidities.

“The presence of multiple comorbidities or the need for several drugs should not dissuade the addition of low-dose rivaroxaban to aspirin in otherwise eligible patients,” investigators wrote.

The study, “Low-dose rivaroxaban plus aspirin in patients with polypharmacy and multimorbidity: an analysis from the COMPASS trial,” was published online in European Heart Journal.