Meta-analysis: Long-term DAPT decreases ischemic events in patients with prior MI

LONDON — Dual antiplatelet therapy for more than 1 year was associated with a lower rate of ischemic events compared with aspirin alone in stable but high-risk patients with prior MI, according to a meta-analysis presented at the European Society of Cardiology Congress.

In that patient population, long-term DAPT was associated with a higher rate of major bleeding, but not fatal bleeding or non-CV death, according to the researchers, who simultaneously published their findings in the European Heart Journal.

Jacob A. Udell, MD, MPH, and colleagues analyzed 33,435 patients (mean follow-up, 31 months) from one trial of patients with previous MI (PEGASUS–TIMI 54) and subgroups of five trials consisting of patients who presented with MI or had experienced one previously (ARCTIC-Interruption, CHARISMA MI, DAPT, DES-LATE and PRODIGY). Patients received DAPT for 1 year, followed by either aspirin alone or DAPT beyond 1 year.

“Who were those high-risk patients at low risk of bleeding that derive benefit from extended [DAPT]?,” Udell asked during a presentation. “Typically across the trials, these were patients within 1 to 3 years of a troponin-positive history of [MI], often with additional [CV] risk factors … Very few patients studied across the trials in this analysis had a history of prior stroke or TIA.”

The primary endpoint was major cardiac adverse events, defined as CV death, nonfatal MI or nonfatal stroke. Secondary endpoints included the individual parts of the primary endpoint, major bleeding and all-cause or non-CV mortality. The researchers also analyzed stent thrombosis among those who had a stent.

Compared with aspirin alone, DAPT beyond 1 year was associated with a lower risk for MACE (6.4% vs. 7.5%; risk ratio = 0.78; 95% CI, 0.67-0.9) and CV death (2.3% vs. 2.6%; RR = 0.85; 95% CI, 0.74-0.98), and a similar risk for non-CV death (RR = 1.03; 95% CI, 0.86-1.23) and all-cause mortality (RR = 0.92; 95% CI, 0.83-1.03), they found.

Udell, from Peter Munk Cardiac Centre and Cardiovascular Division, University Health Network, Heart and Stroke Richard Lewar Centre of Excellence, University of Toronto, and colleagues determined that extended DAPT was associated with lower risk for MI (RR = 0.7; 95% CI, 0.55-0.88), stroke (RR = 0.81; 95% CI, 0.68-0.97) and stent thrombosis (RR = 0.5; 95% CI, 0.28-0.89).

According to the researchers, extended DAPT was also linked with elevated risk for major bleeding (1.85% vs. 1.09%; RR = 1.73; 95% CI, 1.19-2.5). However, this association did not extend to fatal bleeding (0.14% vs. 0.17%; RR = 0.91; 95% CI, 0.53-1.58).

The results did not vary by age, sex, DAPT regimen, index coronary event, timing from index coronary event to randomization or history of PCI, Udell said. He noted that the trials excluded patients with a history of major bleeding, so extended DAPT remains inappropriate in those patients.

“Compared with aspirin alone, extended [DAPT] beyond 1 year in stabilized high-risk patients with previous [MI] decreased the risk of MACE, recurrent MI, stroke alone and [CV] death alone,” he said. “It increased the risk of major bleeding, but not fatal bleeding or intracranial hemorrhage, with no excess of non-[CV] causes of death observed.” – by Erik Swain

References:

Udell JA, et al. Clinical Trial Update II – Antiplatelet Therapy. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 2, 2015; London.

Udell JA, et al. Eur Heart J. 2015;doi:10.1093/eurheartj/ehv443.

Disclosure: Udell reports serving on advisory boards for Merck, Novartis and Sanofi Pasteur and receiving honoraria from Elsevier.