Is it time to replace acetylsalicylic acid monotherapy in secondary prevention with a more effective treatment?
Abstract
For more than 20 years, pharmacological treatments have been known to be more effective than the still most widely used monotherapy with acetylsalicylic acid (ASA) alone in the secondary prevention of atherosclerosis complications (coronary or peripheral). These long-established treatments include the combination of ASA with warfarin and clopidogrel monotherapy (without ASA).
In the first case, this combination did not make it into practice because of the increased incidence of major bleeding, which counteracted the positive effect on reducing ischaemic events and resulted in the absence of any difference in mortality. In the second case, clopidogrel monotherapy proved to be both slightly more effective and safer than ASA, but the difference was so small that this change did not make it into routine practice, probably because clopidogrel was much more expensive than ASA at the time.
The combination of antiplatelet and anticoagulant therapy (which failed in the case of warfarin with ASA) was tried again after the discovery of new oral anticoagulants, which have a lower incidence of bleeding complications compared with warfarin. One of the largest studies in cardiovascular pharmacotherapy, the COMPASS trial, compared 3 treatments: monotherapy with ASA, combination of ASA with low-dose rivaroxaban, and rivaroxaban alone.
The combination proved to be the most effective treatment and reduced not only the primary combined end-point but also overall mortality (at the cost of a higher risk of non-fatal bleeding). This review article summarizes the results of a number of studies looking at pharmacological secondary prevention of complications of coronary and peripheral atherosclerosis, and demonstrates that monotherapy with ASA alone might perhaps still have a place in the lowest-risk individuals, but in intermediate- or high-risk patients, modern cardiology has considerably more effective treatments available - and prominent among these is the combination of ASA with low-dose rivaroxaban.