Lancet: Ticagrelor could redefine care of ACS patients due to mortality reduction
Antiplatelet agent ticagrelor (Brilinta, AstraZeneca) reduces death rates without increasing bleeding compared with the current standard treatment of clopidogrel for heart attack patients, based on the PLATO-Invasive trial published online Jan. 13 in the Lancet. An accompanying commentary describes the introduction of ticagrelor as “a landmark event that should redefine the care of patients with acute coronary syndromes (ACS).”

“We see today that using a stronger anticlotting drug lowered the chance of having a second heart attack—and reduced the risk of dying from one. This is a key advance for heart attack patients,” said principal investigator Christopher P. Cannon, MD, from the cardiovascular division at Brigham and Women's Hospital in Boston.

Ticagrelor is an antiplatelet drug that has a more consistent antiplatelet effect than does clopidogrel (Plavix, Bristol-Myers Squibb), with a faster onset and offset of action, according to the authors. In this PLATO (PLATelet inhibition and patient Outcomes) study, the authors compared the two drugs in patients with ACS who were planned to undergo invasive procedures (such as angioplasty and PCI).

At the beginning of the study, an invasive strategy was planned for 13,408 (72 percent) of 18,624 patients hospitalized for ACS. Patients were randomly assigned in a one-to-one ratio to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for six months. All patients were given aspirin. The primary endpoint was any of cardiovascular death, MI or stroke.

According to the authors, patients in the ticagrelor group were 16 percent less likely to experience the primary endpoint than those in the clopidogrel group. The endpoint of cardiovascular death, MI or stroke occurred in fewer patients in the ticagrelor group than in the clopidogrel group (event rate at 360 days, 9 vs. 10.7 percent).

The risk of death also was significantly reduced from 5 percent (clopidogrel) to 3.9 percent (ticagrelor), a reduction in the risk of dying over one year of around one-fifth, Cannon and colleagues reported. Blood clots developing inside heart stents were also significantly reduced.

Also, there was no statistically significant difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (12 percent each group) or severe bleeding (3 percent both groups), the researchers reported.

“The benefits with respect to clinical events and stent thrombosis were consistent whether or not patients were given standard or higher loading doses of clopidogrel, as advocated for patients undergoing invasive strategies, the authors wrote. “Thereby, ticagrelor has important advantages, and improves the early invasive and long-term management of patients with ACS."

"We estimate that use of ticagrelor instead of clopidogrel for one year in 1,000 patients with ACS and who are planned to undergo an invasive strategy at the start of drug treatment would lead to 11 fewer deaths, 13 fewer MIs and six fewer cases of stent thrombosis without an increase in the rates of major bleeding or transfusion," Cannon and colleagues concluded.

In an accompanying commentary, Gregg W. Stone, MD, from Columbia University Medical Center in New York City, wrote: "These compelling results support ticagrelor as a new standard of care in ACS. However, a personalized approach to drug selection should be used wherein each patient's individualized risk of ischemia versus bleeding is considered. Clopidogrel might still be appropriate for selected patients who are at relatively low risk of MI or stent thrombosis and/or high risk of major bleeding, and/or for whom non-compliance with ticagrelor because of cost or other considerations (eg, twice daily dosing) is a concern.

“Nonetheless, the introduction of ticagrelor, a more potent and effective agent which is as safe as its predecessor, is a landmark event that should redefine the care of patients with ACS," he concluded.