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Analyses identify candidates for rivaroxaban-aspirin therapy
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Two new analyses based on the COMPASS trial identified patients at high vascular risk and with enrichment criteria that may benefit from combination rivaroxaban-aspirin therapy.
As Cardiology Today previously reported, in the main results of COMPASS, among patients with stable atherosclerotic vascular disease, those assigned low-dose rivaroxaban (Xarelto, Janssen/Bayer) plus aspirin had better CV outcomes than those assigned aspirin alone.
High-risk patients
In one of the new analyses, Sonia S. Anand, MD, PhD, FRCPC, professor of medicine, associate chair of equity and diversity in the department of medicine and director of the Population Genomics Program at McMaster University in Ontario, Canada, and colleagues identified subgroups of patients at high risk for recurrent vascular events who may benefit from combination rivaroxaban-aspirin therapy.
The researchers stratified patients from the COMPASS cohort according to the REACH score and CART analysis. Outcomes of interest included a composite of CV death, MI, stroke, acute limb ischemia or vascular amputation; severe bleeding; and net clinical benefit at 30 months.
Using the REACH score, the following patients were classified as high risk: those with disease in at least two vascular beds, those with a history of HF and those with renal insufficiency. Using the CART analysis, the following patients were classified as high risk: those with disease in at least two vascular beds, those with a history of HF and those with diabetes.
Compared with aspirin alone, rivaroxaban plus aspirin reduced risk for serious vascular events (HR = 0.75; 95% CI, 0.66-0.85) and prevented 23 events per 1,000 patients over 30 months while nonsignificantly increasing risk for severe bleeding (HR = 1.34; 95% CI, 0.95-1.88), which caused two events per 1,000 patients over 30 months, according to the researchers.
In the REACH score, the high-risk cohort accounted for 50.2% of patients and 66.5% of vascular events, whereas in the CART analysis, the high-risk cohort accounted for 59.6% of patients and 74.7% of vascular events, the researchers wrote.
In patients with at least one high-risk feature from the CART analysis, rivaroxaban plus aspirin prevented 33 serious vascular events per 1,000 patients at 30 months, whereas in patients at lower risk, the combination therapy prevented 10 serious vascular events per 1,000 patients at 30 months, Anand and colleagues wrote.
Enrichment criteria
In the second analysis, Arthur Darmon, MD, from French Alliance for Cardiovascular Trials, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Assistance Publique–Hôpitaux de Paris, and colleagues analyzed 16,875 patients from the REACH registry who met criteria for inclusion in COMPASS.
The goal was to assess ischemic and bleeding risks according to the presence of at least one enrichment criterion, defined as age older than 65 years, diabetes, moderate renal failure, peripheral artery disease, current smoking, HF, ischemic stroke and asymptomatic carotid stenosis.
The ischemic outcome was CV death, MI or stroke. The bleeding outcome was hemorrhagic stroke, hospitalization for bleeding or transfusion.
Each enrichment criterion was associated with increased risk for ischemic and bleeding outcomes, with no group having a favorable trade-off, according to the researchers.
Compared with patients with no enrichment criteria, patients with at least one had elevated risk for ischemic events (one criterion, 7%; 95% CI, 5.6-8.7; two criteria, 12.5%; 95% CI, 11.1-14.1; three criteria, 16.6%; 95% CI, 14.7-18.6; four or more criteria, 21.8%; 95% CI, 19.9-23.9), Darmon and colleagues wrote.
Patients with at least one enrichment criterion also had elevated risk for bleeding compared with patients with none, but to a lesser degree than seen for ischemic events (one criterion, 1.5%; 95% CI, 0.9-2.1; two criteria, 1.8%; 95% CI, 1.3-2.2; three criteria, 2%; 95% CI, 1.5-2.6; four or more criteria, 3.2%; 95% CI, 2.6-3.9), according to the researchers.
Help with personalization
In a related editorial, William R. Hiatt, MD, professor of medicine and president of the Colorado Prevention Center at the University of Colorado School of Medicine, and colleagues wrote, “Both papers indicate that simple clinical features can be very useful in identifying high-risk patients with cardiovascular disease, where the absolute risk benefit of rivaroxaban plus aspirin is particularly robust.”
They concluded that: “These analyses will likely help clinicians personalize the COMPASS approach, as applied to their patients, where individual high-risk patient characteristics should inform the clinical decision to add low-dose rivaroxaban to background aspirin therapy in an otherwise stable patient. Future studies that more critically focus on the drivers of cardiac and limb ischemic risk within the PAD population are needed to support clinical translation of therapies to this high-risk and undertreated population.” – by Erik Swain
References:
Anand SS, et al. J Am Coll Cardiol. 2019;doi:10.1016/j.jacc.2019.02.079.
Darmon A, et al. J Am Coll Cardiol. 2019;doi:10.1016/j.jacc.2019.04.046.
Hiatt WA, et al. J Am Coll Cardiol. 2019;doi:10.1016/j.jacc.2019.05.007.
Disclosures: The analysis by Anand and colleagues was funded by Bayer. Anand reports she has received speaking honoraria and consultant fees from Bayer. The analysis by Darmon and colleagues was partially funded by Bayer. The REACH registry was initially funded in part by Bristol-Myers Squibb and Sanofi. Darmon reports he has received research grants from Abbott and travel fees from Alvi Medica and Bayer. Hiatt reports he has received research grant support from Abbott, Bayer and Janssen. Please see the studies and editorial for all other authors’ relevant financial disclosures.