How to reduce risk in secondary prevention: First of all address the basics!

Cardiovascular diseases are still the leading cause of mortality globally, even if in high-income countries other causes such as cancer are becoming more important. It might be uncertain if the latter findings are caused by improved control of cardiovascular risk factors. However, recent data indicate that most non-fatal and fatal cardiovascular events around the world are preventable and can be attributed to a small number of common modifiable risk factors. Despite increasing therapeutic options to target cardiovascular risk, most patients with established cardiovascular disease remain at an increased risk of major cardiovascular events. Several large randomised trials such as COMPASS, PEGASUS or DAPT have shown that intensified antithrombotic treatment strategies beyond the setting of acute myocardial infarction and/or coronary intervention are associated with a significant reduction of cardiovascular events. In contrast to dual antiplatelet strategies, the COMPASS trial did demonstrate that the combination of low-dose rivaroxaban with aspirin, as compared to aspirin alone, was even associated with a reduced all-cause mortality. However, each of these treatment approaches was also associated with an increase in bleeding, which significantly reduced the net clinical benefit depending on how bleeding was weighted or what type of bleeding was included in these analyses. As bleeding is associated with a worse prognosis beyond the initial bleeding event, current guidelines recommend a thoughtful weighting of ischaemic and bleeding risk before initiating such an intensified long-term anticoagulatory treatment. 4 However, the identification of patients with a presumed net clinical benefit from such intensified treatment strategies can be challenging. The present analysis by Vanassche et al. provides additional insights into this difficult matter. In this secondary analysis of the COMPASS trial, patients were stratified according to the number of insufficiently controlled and potentially modifiable cardiovascular risk factors. These were blood pressure (systolic 140mmHg and/or diastolic 90mmHg), active smoker, total cholesterol ( 150mg/dL), diabetes mellitus, body mass index ( 25 or <20 kg/m) and level of physical activity (<150 minutes/week). Despite the widespread use of secondary prevention therapies in this trial, the number of risk factors at baseline was still a powerful predictor of subsequent vascular events. Patients with a lower number of cardiovascular risk factors showed a lower annual incidence of cardiovascular events. Even if the relative risk reduction of major vascular events associated with low-dose rivaroxaban and aspirin was similar across different strata, the absolute risk reduction increased with the rising number of risk factors. The authors have to be congratulated for this comprehensive presentation of modifiable options that are associated with altered risk levels. As prospective and well-designed interventional studies targeting multiple modifiable risk factors are sparse, the present data provide important insights into how the day to day care of patients with established atherosclerotic disease might be affected and improved. There are three items that should be highlighted: