Evolving Approaches to Antithrombotics in Stroke Prevention and Treatment

Vijayakumar Javalkar, MD, MCh; Okkes Kuybu, MD; Abdallah Amireh, MD; Roger E. Kelley, MD


South Med J. 2020;113(11):585-592. 

In This Article

Long-term Dual Antiplatelet Therapy

The results of the MATCH (Management of Atherothrombosis With Clopidogrel in High-Risk Patients), CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance), and SPS3 (Secondary Prevention of Small Subcortical Strokes) trials[43–45] provided guidance against the combination of aspirin and clopidogrel, often referred to as DAPT, in the longer-term prevention of vascular events, including deaths, in patients with ischemic stroke and transient ischemic attack (TIA); however, the benefit of shorter-term DAPT is now recognized and is discussed below. Of interest, a recent study of cilostazol, released for peripheral vascular disease, may hold some promise for longer-term DAPT.

Cilostazol is a quinolinone derivative with antiplatelet and vasodilator properties. A multicenter Japanese study[46] explored the role of DAPT with the use of cilostazol for secondary prevention in patients at higher risk for ischemic stroke. In this trial, patients with a higher risk of noncardioembolic ischemic strokes were included. Patients received monotherapy with either aspirin, 81 or 100 mg/day, or clopidogrel, 50 to 75 mg/day, alone or in combination with cilostazol at 100 mg twice per day. The patients were required to meet certain criteria indicative of a higher risk for stroke recurrence.

The trial medication was continued for ≥6 months, for a maximum of 3.5 years. Ischemic stroke recurred in 3% (annualized rate 2.2%) on dual therapy, whereas the recurrence rate was 7% (annualized rate 4.5%) on monotherapy. Treatment was favorable toward DAPT, with the HR 0.49, 95% CI 0.31–0.76, and P = 0.001. There also was no evidence of a higher risk of severe or life-threatening bleeding with DAPT compared with monotherapy (HR 0.66, 95% CI 0.27–1.6, P = 0.35)