Ticagrelor useful in clopidogrel non-responders

The RESPOND Study by Gurbel PA et al (Circulation. 2010;121:1188-1199)has found that ticagrelor is useful in clopidogrel non-responders. Clopidogrel non-responders were identified by light transmittance aggregometry after a 300 mg clopidogrel loading dose. All were patients with stable coronary artery disease on aspirin therapy. 41 non-responders and 57 responders were were evaluated in a 2-way crossover design with clopidogrel (600 mg loading and 75 mg maintenance dose) or ticagrelor (180 mg loading and 90 mg twice daily maintenance). Platelet aggregation decreased when switched from clopidogrel to ticagrelor and vice versa, with P<0.0001. Platelet reactivity was below the established threshold values for ischemic risk. This was so in nearly all treated with ticagrelor, whether they were clopidogrel responders or non-responders.

Ticagrelor is an anti-platelet agent which acts by blocking the ADP receptors of the subtype P2Y12. The drug does not need hepatic activation and action of the drug is reversible, unlike the thienopyridines. The rapid onset of action may improve outcome in patients with acute coronary syndrome. It is a purinoceptor antagonist that belongs to the class of cyclopentyltriazolopyrimidine inhibitors. The PLATO trial (N Engl J Med 2009; 361:1045-1057) showed that ticagrelor when compared with clopidogrel reduced death from vascular causes, myocardial infarction or stroke. There was no increase in the overall major bleeding, but there was an increase in non-procedure related bleeding.