"In our observational study, ticagrelor use was not associated with reduced ischemic risk, but it was associated with increased hemorrhagic risk (compared with) clopidogrel use," Dr. Seng Chan You of Ajou University School of Medicine, in Suwon, South Korea, told Reuters Health by email.
"Current (American College of Cardiology/American Heart Association) guidelines recommend ticagrelor over clopidogrel or prasugrel based on the single pivotal sponsor-initiated trial, PLATO, which was published a decade ago (2009)," he explained. "Our study raised doubts about the current guideline."
For their study, Dr. You and colleagues used data from two electronic-health-record databases in the United States and one nationwide administrative claims database in South Korea.
The primary outcome, NACE, included ischemic events (recurrent acute myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding) from day 1 to 365 days after PCI. The analyses included 31,290 pairs of propensity-score-matched ticagrelor or clopidogrel users.
The one-year incidence of NACE did not differ significantly between the ticagrelor group (15.1%) and the clopidogrel group (14.6%), the team reports in JAMA.
The risk of NACE did not differ significantly between the ticagrelor and clopidogrel groups in one U.S. database (IQVIA Hospital) or in the Korean database (HIRA). But in the other U.S. database (Optum EHR), the risk of NACE was a significant 8% higher in the ticagrelor group than in the clopidogrel group.
There were no differences between the groups in the individual secondary outcomes of mortality, ischemic events, ischemic stroke, recurrent acute myocardial infarction, revascularization, all-cause mortality, cardiovascular-related mortality, or major adverse cardiovascular events.
In contrast, ticagrelor use was associated with significantly higher risks of dyspnea, hemorrhagic events, hemorrhagic stroke, and gastrointestinal bleeding, compared with clopidogrel use.
In sensitivity analyses, the risk of ischemic events did not differ between ticagrelor and clopidogrel use, but many analyses showed a higher risk of hemorrhagic events in the ticagrelor group.
"Our results suggest that clopidogrel can be an alternative for dual antiplatelet therapy (DAPT) in Korean and American patients with ACS and undergoing PCI," Dr. You said.
Coauthor Dr. Harlan M. Krumholz of Yale School of Public Health and Yale New Haven Hospital, in New Haven, Connecticut, told Reuters Health by email, "To be clear, we found no benefit (and the suggestion of a harm) from ticagrelor, even taking into account that people are more likely to stop taking ticagrelor, the more expensive drug. For now, until new information is available, we cannot assume that ticagrelor is superior in these patients. And because we know that people discontinue ticagrelor more often, the use of clopidogrel seems more appropriate."
"Some people have talked about pharmacogenomic testing, but that has also not yet been shown to be a beneficial strategy," he said. "We still have much to learn about whether there are selected patients who benefit from the more expensive regimen, but with greater bleeding and more shortness of breath associated with ticagrelor, we should not favor it."
Dr. Eric R. Bates of the University of Michigan, in Ann Arbor, who wrote a linked editorial, told Reuters Health by email, "The important message from this report and 5 prior reports that did not receive much attention is that the clinical effectiveness of ticagrelor and clopidogrel may not be much different, even though there is some evidence that ticagrelor may have better efficacy. Decreased adherence to therapy because of twice-daily dosing, side effects, and cost is one possible explanation."
"This observational report will not change guidelines," he said. "It will promote the discussion on choice of antiplatelet agents by clinicians that has previously been directed by academicians. There are three P2Y12 inhibitor drugs to choose from when prescribing DAPT. The decision has to be individualized because no one drug is best for all patients."
Dr. Bates also expressed his "chronic frustration in trying to interpret studies and treatments as a guideline author by highlighting how endpoint definitions and study protocols (and marketing) can influence drug evaluation as we attempt to determine equivalence or superiority. An aspirational goal would be to have clinical trialists, regulators, and sponsors agree on the endpoints and definitions that should consistently be used in clinical trials so that we can improve objectivity in comparative evaluations."
By Will Boggs MD
SOURCE: https://bit.ly/37HZPE9 and https://bit.ly/31PqXgz JAMA, October 27, 2020.
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