Coronary stent patients need individualized DAPT duration

DAPT treatment extending longer than 12 months switches the focus from preventing stent thrombosis to secondary prevention of all ischemic events, including those that occur elsewhere in a patient’s coronary arteries, noted Dr. Montalescot, who served as the meeting’s designated discussant for the DAPT trial and the other reported DAPT studies. This option, which can now be offered to appropriate patients, also raised the possibility of continuing DAPT indefinitely beyond 30 months in patients who continue to show no bleeding risk and can pay for ongoing treatment with a thienopyridine. But he advised waiting on the use of very prolonged DAPT until results arrive next year from the PEGASUS study.

ITALIC and ISAR-SAFE

Results from two other studies reported at the meeting looked at the other end of the spectrum, the safety of stopping DAPT after just 6 months. One of these, the ITALIC study, randomized 1,850 patients to 6 months or 24 months of treatment with aspirin and clopidogrel, and exclusively enrolled patients who received the Xience V everolimus-eluting, third-generation coronary stent. The results showed low and nearly identical 1.5% and 1.6% rates of the combined endpoint of major adverse events, including bleeds, in the two comparator arms after 24 months of follow-up. The results also appeared in an article published simultaneously online (J. Am. Coll. Card. 2014 [doi:10.1016/j.jacc.2014.11.008]).

A similarly designed study, ISAR-SAFE, randomized 4,005 PCI patients who received a DES to DAPT with aspirin and clopidogrel for either 6 or 12 months, and also showed a similar and low, roughly 1.5% rate of combined major adverse cardiovascular events and bleeds in both treatment arms, reported Dr. Stefanie Schulz-Schüpke, an interventional cardiologist at the German Heart Center in Munich.

These two studies, along with five prior reports that collectively randomized nearly 16,000 patients to 6 months of DAPT or a longer duration show a statistically significant reduction in major bleeds with good protection against ischemic events when DAPT stopped after 6 months, said Dr. Montalescot. “We can accept that 6 months is safer than 12 months of DAPT,” and it makes sense to stop after 6 months in a patient with a bleeding risk, but not in a patient with a high ischemia risk such as those with left main coronary disease, a history of stent thrombosis or myocardial infarction, a patient who received a first-generation DES, patients with extensive coronary disease or coronary stenting.*

While Dr. Montalescot, Dr. Antman, and others who heard these results agreed that they all pointed to the need for individualized decisions on DAPT duration, they also said the new findings were unlikely to change current guidelines. Existing PCI guidelines from the American Heart Association and American College of Cardiology call for a standard 12 months of DAPT in DES recipients, but offer clinicians to reduce or extend the duration when judged appropriate (J. Am. Coll. Cardiol. 2011;58:e44-e122). Guidelines from the European College of Cardiology call for 6 months of DAPT as standard, but also suggest that clinicians can reduce or lengthen the duration when appropriate (Eur. Heart J. 2014 [doi.org/10.1093/eurheartj/ehu278]).

According to three staffers from the FDA who also spoke at the session, the agency is also unlikely to change its guidance on DAPT in the immediate future, even though it triggered launch of the DAPT trial.

The DAPT trial “is large enough to allow us to answer some really critical public-health questions, and to potentially expand the indications for drug-eluting coronary stents,” said Dr. Bram D. Zuckerman, director of the division of cardiovascular devices of the FDA. But he and his colleagues who spoke during the session said that the agency will not update its recommendations or labels until the FDA staff has had a chance to study in detail the full data set collected in the DAPT trial. Concurrent with Dr. Mauri’s report, the agency issued a statement calling on physicians to continue to prescribe DAPT as they have in the past and for patients to continue to take all their prescribed medications.

Many physicians have already concluded that 6 months of DAPT is a practical way to enhance patient compliance with their regimen and minimize the money they spend on these medications, commented Dr. Richard C. Becker, professor of medicine and director of the Cardiovascular Institute at the University of Cincinnati. The three trials reported at the meeting “do not answer the question [of whether 6 months is adequate] because in each trial patients had already tolerated a period of DAPT before entering the study” Dr. Becker said in an interview.