The protective effect of rivaroxaban against stroke in people with cardiovascular disease greatly outweighs the bleeding risk, especially in high-risk patients, a new analysis of the landmark COMPASS study shows.
In 2017 the rivaroxaban trial in people with stable cardiovascular disease was stopped early because of “overwhelming efficacy” in reducing the risk of stroke, myocardial infraction and cardiovascular death by 24% compared to aspirin monotherapy.
However the additional finding of a 70% relative increase in the broad definition of ‘major bleeding’ events led to the perception that the risks of adding the DOASC to aspirin therapy may outweigh the benefits.
But in a new analysis of prespecified outcomes, the COMPASS study investigators used a composite outcome of ‘net clinical benefit’ to show that there a was substantial reduction in major efficacy events, particularly stroke and cardiovascular mortality, whereas severe bleeding events were less frequent and had less impact.
In the study that involved more than 18,000 patients randomised to aspirin with or without rivaroxavan, they showed that the net clinical benefit outcome was a reduction in major adverse events of 20% (Hazard Ratio 0.80). This outcome encompassed stroke, MI, cardiovascular death, fatal bleeding and symptomatic bleeding into a critical organ.
In absolute terms this represented 19.5 fewer serious or fatal events per 1000 patients at 30 months compared to aspirin alone, with a number needed to treat (NNT) of 52.
For individual outcomes, the rivaroxaban treatment arm had an average of 10.6 fewer strokes, 4.8 fewer MI events and 8.2 fewer cardiovascular deaths compared to aspirin monotherapy, at a cost of 0.4 more fatal bleeds and 2.8 more cases of symptomatic bleeding into critical organ.
The absolute risk reductions of the DOAC were greater in high risk populations such as people with polyvascular disease (≥2 vascular beds affected with atherosclerosis), impaired renal function (eGFR ≤60 ml/min), heart failure, and diabetes.
For example in people with eGFR ≤60 ml/min the NNT to prevent one serious or fatal event was 31 compared to 57 in people with eGFR >60 ml/min.
The study investigators also noted that the excess in major and severe bleeding events was mainly confined to the first year of treatment whereas the net clinical benefit became increasingly favourable over time due to the ongoing cardioprotection offered by the anticoagulant against chronic cardiovascular events.
“Our data may hence help clinicians and patients in their shared decision making process of choosing the optimal antithrombotic therapy,” they study authors wrote in Circulation.
“This is particularly true for high-risk patients, who are frequently undertreated due to the fear of severe bleeding events.”