SAN FRANCISCO—The incidence of non-adherence to dual-antiplatelet therapy (DAPT) was 2 percent at 30-days of follow-up, based on the “real world” international observational PARIS registry, presented Nov. 9 as a late-breaking clinical trial at the 23rd annual Transcatheter Cardiovascular Therapeutics (TCT) conference.

Premature discontinuation of DAPT (within the first six months after implantation of DES) has been associated with an increased risk of stent thrombosis, but the optimal duration of DAPT has not yet been precisely determined, especially with regard to second generation stents. 

The PARIS Registry (Patterns of Non-Adherence to Anti-Platelet Regimens In Stented patients: An observational single arm study) is a multicenter, multinational, observational study with an “all comers” design. The study will follow 5,033 subjects in 15 centers in five countries for approximately 24 months post-stent implantation (bare-metal stents and drug-eluting stents).

“We were trying to get a deeper understanding of the mode of non-adherence among these post-PCI patients,” explained the study’s lead author Roxana Mehran, MD, director of interventional cardiovascular research and clinical trials at the Zena and Michael A. Weiner Cardiovascular Institute at Mount Sinai School of Medicine in New York City.

The researchers broke the non-adherent patients into three subgroups:

• Discontinuation: Subjects discontinued use of DAPT due to a recommendation of their physician who felt the patient no longer needed therapy.
• Interruption: Subjects have interrupted DAPT use on a voluntary basis and under guidance and recommendation of their physician due to need for surgery.  DAPT will be reinstituted within 14 days.
• Disruption: Subjects have disrupted DAPT use due to bleeding or non-compliance.  Includes use of DAPT at lower dose levels than prescribed.

Importantly, Mehran pointed out that this is a contemporary registry, with 80 percent of the patient population receiving a second generation stent, 65 percent receiving an everolimus-eluting stent (Xience V, Abbott) and 15 percent receiving a zotarolimus-eluting stent (Resolute, Medtronic). Also, 92 percent of the patients received clopidogrel as their thienopyridine at discharge.

Of note, non-adherence was equally distributed for either aspirin or thienopyridines. 

For adverse events, the non-adherent group had higher event rates across the board, compared with the adherent group. Specifically, the major adverse cardiac event rate was 10.6 vs. 1.4 percent; cardiac death was 1 vs. 0.3 percent; and the BARC >3 bleeding event was 11.5 vs. 0.4 percent. There was a six-fold increase odds for stent thrombosis (definite/probable) associated with non-adherence compared to adherence to DAPT at 30 days.

Of the 5,033 patients, only 104 were non-adherent at 30 days, or 2 percent.  Overall, in the non-adherent population at 30-day:

• 69 percent had disruption of therapy (mostly due to non-compliance, 61 percent and bleeding event, 32 percent);
• 19 percent had interruption of DAPT (mostly due to surgery or medical procedures, 67 percent); and
• 12 percent had discontinuation of therapy (recommended by physician). 

“While 2 percent may seem low, I believe this population is as ‘real world’ as we will get,” Mehran told Cardiovascular Business.  “Because the first 30 days after stenting is such a precarious time for the patient, there has been a tremendous educational effort for patients and caregivers to better understand the importance of DAPT adherence.”

However, she did hint at the six month data, in which the non-adherence numbers increase “tremendously.” She also said the researchers are following up with the patients who voluntarily choose to discontinue DAPT to ascertain the reason they made this choice. The two-year data from the PARIS registry are expected to be presented at TCT.12.