Principal Findings:

The primary outcome of cardiovascular death, MI, or stroke occurred in 7.8% of the ticagrelor 90 mg bid group (hazard ratio [HR] vs. placebo = 0.85, p = 0.008), 7.8% of the ticagrelor 60 mg bid group (HR vs. placebo = 0.84, p = 0.004), and 9.0% of the placebo group. This translates into 83 individuals who need to be treated to prevent one adverse event. The association of ticagrelor on the primary outcome was the same in all tested subgroups.

Secondary outcomes:

• TIMI major bleeding: 2.6% with ticagrelor 90 mg (HR vs. placebo = 2.7, p < 0.001), 2.3% with ticagrelor 60 mg (HR vs. placebo = 2.3, p < 0.001), and 1.1% with placebo
• Intracranial hemorrhage: 0.6% with ticagrelor 90 mg, 0.6% with ticagrelor 60 mg, and 0.5% with placebo (p = NS for either group vs. placebo)
• All-cause mortality: 5.2% with ticagrelor 90 mg, 4.7% with ticagrelor 60 mg, and 5.2% with placebo (p = 0.99 for ticagrelor 90 mg vs. placebo and p = 0.14 for ticagrelor 60 mg vs. placebo)
• MI: 4.4% with ticagrelor 90 mg (HR vs. placebo = 0.81, p = 0.01), 4.5% with ticagrelor 60 mg (HR vs. placebo = 0.84, p = 0.03), and 5.3% with placebo
• All stroke: 1.5% with ticagrelor 60 mg versus 1.9% with placebo (p = 0.034)
• Ischemic stroke: 1.3% with ticagrelor 60 mg versus 1.7% with placebo (p = 0.063)
• Dyspnea adverse event: 18.9% with ticagrelor 90 mg, 15.8% with ticagrelor 60 mg, and 6.4% with placebo (p < 0.01 for either group vs. placebo)
• Total costs: $10,016 with ticagrelor 60 mg versus $2,333 with placebo (p < 0.001). Cost-effectiveness for ticagrelor was enhanced when there was >1 prior MI, multivessel disease, diabetes, renal dysfunction, age <75 years, and peripheral artery disease.

Multivessel coronary disease: A total of 59.4% of patients had multivessel coronary artery disease. Among these, ticagrelor was associated with a reduction in major adverse cardiac events (HR 0.82, p = 0.004) and coronary events (HR 0.76, p < 0.0001). Ticagrelor was associated with an increase in major bleeding (HR 2.67, p < 0.0001), but not intracranial hemorrhage.

Coronary stent (n = 16,891) vs. no coronary stent (n = 4,199):

• Cardiovascular death, MI, or stroke among those with no prior coronary stent: 11.1% with ticagrelor vs. 13.2% with placebo (HR 0.82, p = 0.04)
• Cardiovascular death, MI, or stroke among those with prior coronary stent: 7.0% with ticagrelor vs. 8.0% with placebo (HR 0.85, p = 0.009; p for interaction = 0.76)
• MI among those with no prior coronary stent: 4.8% with ticagrelor vs. 5.6% with placebo (HR 0.86, p = 0.33)
• MI among those with prior coronary stent: 4.4% with ticagrelor vs. 5.2% with placebo (HR 0.81, p = 0.008; p for interaction = 0.74)