DAPT Disruption Spikes Risk, But Interruptions, Planned Stops Okay

Shelley Wood

September 01, 2013

AMSTERDAM — Major adverse cardiac events (MACE) among patients taking dual antiplatelet therapy (DAPT--typically aspirin plus clopidogrel) following stent implantation tend to happen when DAPT is "disrupted" and not when physicians make the choice to discontinue a patient's therapy or when it is interrupted temporarily, the PARISresults suggest [1].

Disruption, either a patient's noncompliance or stoppage due to bleeding, carried a 50% higher risk of MACE in the study, Dr Roxana Mehran (Mount Sinai Medical School, New York) told a morning press conference. Full results from the prospective observational registry were presented later this morning at the European Society of Cardiology (ESC) 2013 Congress and published simultaneously in the Lancet.

"The findings show that when physicians recommend discontinuation, presumably because patients are stable, there is no risk of adverse events, but when patients simply don't comply or are forced off antiplatelet therapy because they are bleeding, their risks are significantly elevated," Mehran commented in a press statement.

And Now We Have Paris

Dr Roxana Mehran

PARIS was conducted in 15 hospitals in five countries, enrolling more than 5000 patients following stent implantation. "Discontinuation" was defined as physician-recommended cessation; "interruption" was a temporary stop (up to 14 days) due to surgical necessity; and "disruption" was unplanned cessation, due to bleeding or patient noncompliance.

Strikingly, the majority (74%) of MACE events in the trial occurred when patients were actually taking DAPT. In patients who had disrupted therapy, the risk was highest in the first seven days (HF 7.04, compared with remaining on therapy, p<0.001) and continued out to 30 days.

Stent thrombosis, the most feared outcome of premature DAPT discontinuation, most commonly occurred in patients still taking their medication (80.3% of the events) but was also seen in 14.1% of patients with disrupted therapy. Numbers were negligible in patients with recommended discontinuation or interruption.

"The impact of DAPT cessation on cardiac risk after PCI is not uniform but varies substantially by underlying mode," or reason, for stopping the drugs, Mehran concluded. "The overall impact of DAPT cessation on adverse events is modest and may have been mitigated with the introduction of safer stent platforms."

Current European and AHA guidelines recommend 30 days of DAPT for bare-metal stents, six months to one year following drug-eluting-stent (DES) implantation, and 12 months for patients with ACS, Mehran noted. These new insights from PARIS, she said, highlight the need for different categories of DAPT cessation and potentially tailoring the guidance to the different categories.

Ideal DAPT Duration Questions Not Yet Answered

The ongoing 20 000 patient DAPTtrial will hopefully answer questions about dual drug duration, something the current study was not designed to answer, she stressed. What PARIS suggests, however, is that physicians trusting their judgment when it comes to planned discontinuation seem to be doing things right, and patients in this group "do quite well."

Dr Keith Fox

During the press conference, congress chair Dr Keith Fox (University of Edinburgh, Scotland) asked Mehran what she will now tell physicians dealing with a patient with a GI bleed who is taking DAPT.

"One of the things we did find is that [adverse events differed] depending on whether both drugs were stopped or just one was stopped," she said. "If both drugs were stopped, there was a much worse hazard. So I would keep patients on one of the drugs to protect them. Which one? We don't have enough power [to answer that]."

Asked what scenario would prompt her to voluntarily discontinue a patient's DAPT and at what time point, she said: "In patients who are at higher risk for bleeding complications and I don't want to expose them to the bleeding complications of the dual antiplatelet therapies, I would stop after I feel we are over the 'bump,' and that's usually three to six months [post-PCI] with the newer-generation DES."

Mehran disclosed institutional research grant support from the Medicines Company, Bristol-Myers Squibb/Sanofi, Lilly/Daiichi Sankyo, and consulting fees from Abbott Vascular, Astra Zeneca, Boston Scientific, Covidien Janssen (J&J), Regado Biosciences, Maya Medical, and Merck.

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