AHA 2017: Study finds switching between antiplatelet therapies is uncommon

November 14, 2017 – A randomized trial suggests that switching was more common for patients treated with ticagrelor than those treated with clopidogrel – even with mandatory genetic testing to predict which patients might not benefit from clopidogrel.

Each year in the United States, some 1.4 million patients are hospitalized for acute coronary syndrome (ACS), characterized by reduced blood flow to the heart, and including heart attack or unstable angina. Standard treatment includes a regimen of aspirin and antiplatelet drugs such as ticagrelor or clopidogrel.

The GEMINI ACS 1 study set out to estimate the risk of bleeding with rivaroxaban, compared with aspirin, in addition to a antiplatelet/platelet adenosine diphosphate P2Y12 receptor antagonist (P2Y12 inhibitor agent: clopidogrel or ticagrelor), in patients with a recent ACS. The results were published in The Lancet in March 2017.

Regulators required genetic testing for all patients enrolled in the GEMINI-ACS-1 trial, based on label changes including a ‘black box’ warning against the use of clopidogrel in patients who are poor metabolizers of this therapy, and therefore may not receive its full benefits, in the context of the experimental treatment strategy that replaced aspirin with low-dose rivaroxaban. Such patients are identified by pharmacogenomic testing for CYP2C19 metabolizer status.

A substudy within the GEMINI ACS 1 trial examined the effect that mandatory reporting of CYP2C19 metabolizer status had on physician decisions about initial use of clopidogrel and ticagrelor. Physicians were asked what factors influenced them to decide to switch therapies. The results were presented Tuesday at the 2017 American Heart Association (AHA) Scientific Sessions in Anaheim, California.

“Many factors influence the clinical decision to switch P2Y12 antagonist therapies for a patient with recent ACS, and we found that routine reporting of CYP2C19 metabolizer status had limited impact on that decision particularly among patients treated with clopidogrel,” said lead author Matthew T. Roe, MD, MHS, of the DCRI. “In fact, we saw the opposite of what we expected, with twice as many patients switched from ticagrelor to clopidogrel than from clopidogrel to ticagrelor, primarily for clinical reasons. Interestingly, cost had no role in these decisions, since the therapies were provided as part of the trial.”

Of 3,037 patients enrolled, 1,704 (56 percent) were initially treated with ticagrelor and 1,333 (44 percent) with clopidogrel. Out of the 3,016 patients with results for CYP2C19 metabolizer status, 3.2 percent were poor metabolizers. The initial P2Y12 inhibitor used was switched during trial follow-up in 197 of 3,037 patients (6.5 percent). Of these, 144 patients (8.5 percent) were switched from ticagrelor to clopidogrel and 53 (4 percent) were switched from clopidogrel to ticagrelor. Only one-third of clopidogrel-treated patients who were poor metabolizers were switched to ticagrelor and less than half of all patients switched from clopidogrel to ticagrelor were in response to CYP2C19 metabolizer status.

These findings, Roe said, highlight the uncertain yield and variable impact of these test results and the need for further studies to determine the utility of genetic testing for patients with ACS treated with P2Y12 inhibitors.

In addition to Roe, Duke and DCRI contributors to the study included E. Magnus Ohman, Thomas J. Povsic, Jennifer White, and Frank Rockhold.