Comparing Ticagrelor Versus Clopidogrel in Patients With a History of Cerebrovascular Disease

The PLATO trial was a phase 3, randomized, double-blind, parallel-group, multinational, clinical study comparing the efficacy of ticagrelor (formerly known as AZD6140, marketed as Brilinta) versus standard care treatment with clopidogrel. Patients (n=18624) with moderate- to high-risk acute coronary syndrome undergoing coronary intervention or medically managed were randomized to ticagrelor 180mg loading dose followed by 90mg twice daily thereafter, or clopidogrel 300 to 600mg loading dose followed by 75mg once daily for 6 to 12 months.1 The primary end point was the time of the first event of death from vascular causes, myocardial infarction or stroke, and occurred in 11.7% of patients treated with clopidogrel, versus 9.8% of patients randomized to ticagrelor, representing a highly significant benefit (hazard ratio [HR]=0.84; CI=0.77–0.92; P <0.001) for ticagrelor.1 Importantly, the benefit of ticagrelor was driven equally by the reduction of vascular death ( P <0.001), and myocardial infarction ( P <0.005) with 89 events favoring ticagrelor each, but not stroke ( P =0.22) with 19 less events in the clopidogrel arm.1 Moreover, the original PLATO data indicated a 17% increase in stroke (19 extra events; number needed to harm 491) with ticagrelor versus clopidogrel (125/9333 [1.5%] versus 106/9291 [1.3%]; HR=1.17 [0.91–1.52]; P =0.22) (Table 1).1 However, the Food and Drug Administration complete response review indicates an even greater risk of stroke (24% increase) with ticagrelor versus …