Prolonged Dual Platelet Inhibition in Patients with Prior MI

Joel M. Gore, MD reviewing Bonaca MP et al. N Engl J Med 2015 Mar 14. Keaney JF. N Engl J Med 2015 Mar 14.

Three years of treatment offer both improved major outcomes and greater bleeding risks.

Dual antiplatelet therapy after acute coronary syndromes is recommended for 1 year, but its benefit for longer periods is unknown. Reducing further ischemic events by inhibiting platelet activation needs to be weighed against the risk for drug-associated bleeding complications. In the industry-sponsored PEGASUS-TIMI 54 trial, 21,162 patients with myocardial infarction (MI) 1 to 3 years previously (median, 1.7 years) were randomized to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo.

Patients received low-dose aspirin and were followed for a median of 33 months; 83% had undergone percutaneous coronary intervention. Treatment discontinuation occurred in 32% of the 90-mg group, 29% of the 60-mg group, and 21% of the placebo group. Both ticagrelor doses significantly reduced the rate of the combined primary endpoint (cardiovascular death, MI, or stroke); 3-year Kaplan-Meier estimates were 7.8% with either ticagrelor dose and 9.0% with placebo. Major bleeding was significantly higher with ticagrelor (3-year Kaplan-Meier estimates: 90-mg dose, 2.6%; 60-mg dose, 2.3%; placebo, 1.1%). Major subgroups showed no apparent differences in ticagrelor's efficacy or bleeding risks. Dyspnea was more frequent with ticagrelor (90-mg dose, 18.9%; 60-mg dose, 15.8%; placebo, 6.4%), as was gout.

Citation(s):

Bonaca MP et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015 Mar 14; [e-pub].

Keaney JF.Balancing the risks and benefits of dual platelet inhibition. N Engl J Med 2015 Mar 14; [e-pub].