Anticoagulation in Atherosclerotic Disease

Abstract

The prevention of atherothrombotic events is an essential therapeutic goal in the treatment of patients with arteriosclerotic diseases. After plaque rupture, a rapidly growing thrombus can lead to acute vascular occlusion and thus heart attack, stroke or limb ischaemia. The acute therapy combines anticoagulation and platelet inhibition. However, the only available therapy so far in the primary and secondary prevention of stable patients is the platelet inhibitors aspirin and clopidogrel. Despite the use of antiplatelet therapies, including aspirin and P2Y₁₂-receptor antagonists, some patients with artery disease continue to experience recurrent cardiovascular ischaemic events due to excessive thrombin generation beyond the acute period. As a result, studies have tested non-vitamin K antagonist oral anticoagulants (NOACs), specifically the factor Xa inhibitors, either alone or in combination with antiplatelet therapy, in the management of arterial disease. For the first time, the COMPASS study investigated low-dose anticoagulation in stable coronary heart disease or peripheral arterial disease. The addition of 2 × 2.5 mg rivaroxaban to long-term aspirin therapy not only prevented cardiovascular death, myocardial infarction and stroke, but even reduced all-cause mortality by a relative 18% after a mean follow-up of 23 months. This benefit came at the expense of more gastrointestinal bleeding, which might be reduced by the addition of a proton pump inhibitor (investigations are ongoing). Interestingly, however, there was no increase in fatal or intracranial haemorrhages. Therefore, a new standard therapy for high-risk patients with atherosclerotic disease may become available in the near future.