Can Antiplatelet Drugs Reduce Cardiac Events After Major Noncardiac Surgery?

A new study undertaken by Cleveland Clinic researchers will determine whether platelet inhibitors can reduce cardiovascular events following major noncardiac surgery in patients with elevated troponin levels.

“We know that elevated troponin levels are associated with increased risk of death at 30 days and one year. The question is, Can this risk be modified?” says Cleveland Clinic cardiologist Venu Menon, MD. “The clinical benefit of using antiplatelet agents to treat patients with postoperative troponin elevation has been unexplored.”

Dr. Menon is the national principal investigator of the Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery (INTREPID), a trial initiated by the Cleveland Clinic Coordinating Center for Clinical Research (C5Research).

The study will enroll 1,000 patients ages 55 and older who experience troponin levels greater than twice the upper limit of normal within the first seven days following noncardiac surgery. Patients will be randomized in open-label fashion to 12 months of treatment with ticagrelor 90 mg twice daily or aspirin 81 mg once daily and followed for 13 months following randomization.

First study of its kind in postoperative setting

Ticagrelor has been shown to be superior to clopidogrel in acute coronary syndrome. Although neither drug has been studied in the setting of post-operative myocardial injury, the recent PEGASUS-TIMI 54 study of more than 21,000 patients showed ticagrelor to be effective in reducing the risk of cardiovascular death, myocardial infarction (MI) and stroke one year after MI. Ticagrelor’s short half-life and potent antiplatelet effect makes it favorable to use in this setting.

The primary outcome of INTREPID is the composite of major adverse cardiovascular events (cardiovascular death, nonfatal MI, nonfatal stroke or coronary revascularization) at one year. Secondary outcomes include each individual component of the composite, plus all-cause death and bleeding events.

The troponin mystery

Data from current studies suggest that myocardial injury detected by minor elevations in troponin levels within three days after noncardiac surgery occurs in 10 to 24 percent of patients and is associated with increased mortality at 30 days and one year.

“The mechanism of asymptomatic cardiac muscle injury in this setting is likely multifactorial, but it may be a marker for underlying vulnerability to cardiovascular instability,” says Dr. Menon.

There are no guidelines for the care of patients with elevated troponin in the absence of acute coronary syndrome. Whether the disease process can be modified to reduce risk is unknown. Cleveland Clinic researchers hope to have an answer shortly after the study terminates in January 2018.

“This is an unmet need in a population that requires some proven intervention,” says Patricia Hodge, project manager for the trial.