PARIS: Early DAPT Nonadherence, A Small Problem with Big Consequences

SAN FRANCISCO, CALIF.—Results from the large observational PARIS study showed the consequences of early discontinuation of dual antiplatelet therapy. While only about 2% of patients stopped DAPT within the first 30 days after stent implantation, they experienced a sixfold increase in stent thrombosis and mortality compared with those who adhered to the prescribed regimen.

Late-breaking data from the international multicenter registry capturing an all-comers patient population (n=5,033) were presented at TCT 2011 by Roxana Mehran, MD, of Mount Sinai Medical Center, New York.

Overall, most patients (82%) received DES, while 16% were implanted with BMPARIS FigureS, and 2% received both types. Clopidogrel (Plavix, Sanofi-Aventis/Bristol-Myers Squibb) was by far the most commonly used thienopyridine (92%); 6% of patients received prasugrel (Effient, Daiichi Sankyo/Eli Lilly) and 2% ticlopidine (Ticlid).

The overall rate of nonadherence within 30 days was 2.1%, and was nearly equivalent for patients who discontinued aspirin (1.4%) and thienopyridines (1.3%).

Higher rates of ischemic, bleeding events with nonadherence

Analysis of 30-day major adverse events revealed that patients who failed to adhere to DAPT experienced higher rates of multiple ischemic events and major bleeding, although, according to Mehran, the study was underpowered to determine P values (see Figure). 

Specifically, the odds ratio for stent thrombosis associated with nonadherence was 6.3 (95% CI 1.9-21.4). Of note, among the 26 patients with definite or probable stent thrombosis, 14 occurred in adherent patients while only three occurred in nonadherent patients, two of whom had interrupted aspirin therapy and one had interrupted clopidogrel.

Modes of nonadherence varied. Sixty-nine percent of patients disrupted therapy, either due to episodes of bleeding or lack of compliance with the regimen. Another 19% interrupted DAPT on their own or on a physician’s advice, often due to the need for surgery or a medical procedure; in these instances DAPT was restarted within 14 days. And 12% discontinued DAPT because their physician believed it was no longer needed.

Nonadherent patients were more likely than adherent patients to have ACS (58.3% vs. 40.5%; P<.0001) or a family history of premature CAD (58.3% vs. 40.5%; P<.0001) but less likely to have dyslipidemia (63.5% vs. 76.0%; P=.003).

Additional PARIS data upcoming

According to Mehran, PARIS patients will be followed out to two years. These longer-term data “will be more definitive and should be able to link the patterns of nonadherence with important clinical events,” she said.

During a press conference, TCT Course Director Gregg W. Stone, MD, of Columbia University Medical Center, observed that as the study progresses it will be critically important to report whether nonadherence began before or after stent thrombosis.

Commenting after the presentation, Dirk Sibbing, MD, of Deutsches Herzzentrum Munchen in Munich, Germany, noted that although the expected arrival of less expensive generic clopidogrel in the United States may lessen the problem of nonadherence, his experience in Germany, where the generic version is already available, suggests that cost explains only part of the problem.

Study details

DES use in the registry included paclitaxel-eluting stents (8%) and sirolimus-eluting stents (3%), but most were second-generation, including zotarolimus-eluting stents (11%) and everolimus-eluting stents (62%). In addition, over half (56%) of patients received a single stent, while 44% were implanted with more than one.

  • The PARIS study was sponsored by Mount Sinai School of Medicine and received grant support from Sanofi-Aventis and Bristol-Myers Squibb.
  • Dr. Mehran reports receiving grant/research support from Bristol-Myers Squibb, Sanofi-Aventis and The Medicines Company, and consulting fees/honoraria from Abbott Vascular, AstraZeneca, Ortho-McNeil and Regado Biosciences.
  • Dr. Sibbing reports receiving grant support/research contracts from Daiichi-Sankyo/Eli Lilly and consulting fees from Verum Diagnostica.
  • Dr. Stone reports receiving consulting fees/honoraria from numerous manufacturers and holds equity in numerous devices.