Clinical Geriatrics

American College of Cardiology 59th Annual Scientific Session
March 14-16, 2010; Atlanta, GA

Ticagrelor Reduces Mortality as Compared with Clopidogrel After CABG Surgery

Atlanta, GA—Patients with acute coronary syndrome (ACS) who had coronary artery bypass graft (CABG) surgery had lower death rates from any cause or from cardiovascular causes when treated with the novel antiplatelet agent ticagrelor versus standard clopidogrel. The improvement in mortality with ticagrelor was achieved despite major bleeding that was similar in the two treatment arms. These findings from an exploratory subgroup analysis of the PLATO (PLATelet Inhibition and Patient Outcomes) trial, presented at a late-breaking clinical trials session during the ACC meeting, surprised some investigators.

Lead investigator Claes Held, MD, said that the PLATO investigators are puzzled by the substantial reduction in death with ticagrelor despite similar bleeding rates. “We are trying to understand the mechanism, so we are reanalyzing the causes of death according to vascular and nonvascular categories to try to answer this question,” he told reporters at a press conference. Dr. Held is Associate Professor of Cardiology at the Uppsala Clinical Research Center, Uppsala, Sweden. Despite this puzzle, he said, “Ticagrelor appears to be a promising alternative to clopidogrel for ACS patents who are potential candidates for CABG surgery, because of the significant reduction in mortality with similar bleeding rates.”

The main results of PLATO, presented at the European Society of Cardiology meeting in 2009, showed lower mortality with ticagrelor versus clopidogrel in 18,624 patients with ACS (with or without ST-segment elevation). In the trial, patients also received aspirin 75-100 mg/day. Treatment was for 1 year. At 12 months, ticagrelor was superior to clopidogrel for the primary end point, a composite of death from vascular causes, myocardial infarction, or stroke (9.8% vs 11.7%, respectively; P < 0.001).

The subgroup analysis presented at this year’s ACC meeting included 1261 patients who underwent CABG surgery and were supposed to have the study drug withdrawn within 7 days prior to surgery. Not all patients had the study drug withdrawn within 7 days to achieve recovery of platelet function prior to surgery. However, some patients required surgery sooner, which increased the risk of bleeding and other complications. Of the 1261 patients included in the subgroup analysis, 632 were in the ticagrelor group and 629 were in the clopidogrel group. Patient characteristics, including cardiovascular risk factors and cardiovascular history, were well balanced between the two arms. Median age was 64 years, approximately 80% were male, and approximately 90% underwent coronary angiography.

CABG surgery patients treated with ticagrelor had a 50% reduction in total mortality and a 48% reduction in cardiovascular mortality at 12 months. All-cause mortality at 12 months after CABG surgery was 4.7% in the ticagrelor arm versus 9.7% in the clopidogrel arm (P < 0.01). Cardiovascular death occurred in 4.1% and 7.9%, respectively (P = 0.009). Looking at the composite end point of cardiovascular death, myocardial infarction, and stroke, as well as myocardial infarction and stroke, respectively, no significant difference was seen between the two treatment arms at 12 months. No difference was observed in the two arms for bleeding or transfusion requirement, as well as the number of units of blood, platelets, or fresh frozen plasma.

Dr. Held cautioned that this was a retrospective review of a nonrandomized subgroup of CABG surgery patients with ACS, and said that prospective randomized trials of ticagrelor versus clopidogrel are needed in this patient population.