Ticagrelor use leads to lower mortality after coronary artery bypass graft surgery

Patients with acute coronary syndrome (ACS) who undergo coronary artery bypass graft (CABG) surgery are less likely to develop fatal outcomes when given ticagrelor instead of clopidogrel as an antiplatelet medication, according to research presented at the American College of Cardiology’s 59th annual scientific session in March.

Examining a subpopulation of 1,261 patients in the Platelet Inhibition and Patient Outcomes (PLATO) Trial who underwent CABG surgery, researchers found that 10.5% of patients given ticagrelor and aspirin within 7 days of their procedure had a primary composite end point that included cardiovascular death, heart attack, and stroke, compared with 12.6% of patients given clopidogrel and aspirin. This reduction was consistent with the overall effect of ticagrelor versus clopidogrel in the main PLATO study, which was funded by AstraZeneca.

Patients taking ticagrelor had a total mortality rate of 4.6% compared with 9.2% for patients taking clopidogrel, and the cardiovascular death rates were 4.0% and 7.5%, respectively. When examined individually, there was not a statistically significant difference between the 2 groups for heart attack and stroke, and there was no significant difference in CABG-related major bleedings.

“Ticagrelor seems to be a very promising alternative to clopidogrel for patients with acute coronary syndrome who might be candidates for CABG surgery, because of the significant reduction in mortality and the similar bleeding rate,” said Claes Held, MD, PhD, associate professor of cardiology at the Uppsala Clinical Research Center and Department of Cardiology in Sweden, and the substudy’s lead researcher. “Because there is such an obvious risk of severe bleeding and fatal complications during surgery, patients with a potential need for CABG comprise an especially important group, for which platelet inhibitors with a better safety-efficacy profile are needed.” The results of the analysis are in line with data recorded from the overall PLATO trial, a double-blind study, which randomly assigned 18,624 patients in 43 countries with ACS to receive treatment with either ticagrelor or clopidogrel. The overall study found an efficacy advantage for ticagrelor compared with clopidogrel and no significant difference in major bleeding.

At the time of the original PLATO trial’s publication, ticagrelor was the first antiplatelet agent to demonstrate a reduction in cardiovascular and total deaths in patients with ACS compared with clopidogrel.

Both drugs are oral antiplatelet medications and are designed to prevent the formation of blood clots by inhibiting the clumping of platelets, but they belong to 2 different chemical classes.

“This agent [ticagrelor] is novel in several ways,” said Christopher P. Cannon, MD, senior investigator, TIMI Study Group, Cardiovascular Division at Brigham and Women’s Hospital in Boston, and associate professor of medicine, Harvard Medical School. “As a reversibly binding agent, it gives us much flexibility in acute coronary syndrome patients where we can stop it and proceed to surgery within 2 to 3 days if needed. It is more potent, but didn’t increase the overall risk of bleeding.

“Most importantly, it provides a substantial mortality benefit relative to clopidogrel, and thus is a major advance in treating high-risk ACS patients,” he added.