Dual Antiplatelet Therapy Tied to Better Outcomes in High Risk PAD Patients

In patients with advanced PAD, dual antiplatelet therapy (DAPT) may confer additional long-term cardiovascular and survival benefits, according to a study published online April 8, 2015, ahead of print in the Journal of Vascular SurgeryTake Home: Dual Antiplatelet Therapy Tied to Better Outcomes in High Risk PAD Patients

John R. Laird, MD, of University of California, Davis Medical Center (Sacramento, CA), and colleagues conducted an observational cohort analysis of 629 PAD patients (mean age 67 years; 44% male) who had claudication or critical limb ischemia (CLI) and were enrolled in the University of California, Davis PAD registry. In all, 348 were prescribed DAPT (98.3% of whom received clopidogrel) and 281 were prescribed aspirin alone. Antiplatelet prescriptions were verified monthly during the 3-year follow-up.

At baseline, patients in the DAPT group were more likely to have CAD (P = .007) or a history of diabetes (P = .02) and to be prescribed beta-blockers (P = .05) than those in the aspirin group.

Advantage Seen at 3 Years

After 3 years of follow-up, patients prescribed DAPT had lower rates of MACE (primary endpoint), death, and death/major amputation compared with those taking aspirin monotherapy. No differences by treatment arm were found for major amputation alone or major adverse limb events (table 1).

 Table 1. Unadjusted 3-Year Outcomes in Patients With Symptomatic PAD

After propensity weighting using monthly prescription records to adjust for DAPT duration, the likelihood of MACE (HR 0.65; 95% CI 0.44-0.96), overall mortality (HR 0.55; 95% CI 0.34-0.84), and death or amputation (HR 0.53; 95% CI 0.34-0.80) all remained lower with DAPT than with aspirin monotherapy.

In an email, Dr. Laird noted that the results are very compelling and have the potential to change clinical practice. He told TCTMD that patients with CLI have extremely high mortality, citing a recent Japanese study that found a 2-year mortality rate of 40%.

“[Our] results will need to be confirmed in a larger, prospective randomized trial,” Dr. Laid said. “It will also be interesting to see if the outcomes can be further improved by the use of DAPT with one of the newer agents (prasugrel [Effient; Eli Lilly/Daiichi Sankyo] or ticagrelor [Brilinta; AstraZeneca).” In the current study, only 5 patients received prasugrel and none ticagrelor.

Beta-blocker Use Clouds Interpretation

Ali F. Aboufares, MD, of Columbia University Medical Center (New York, NY), told TCTMD in a telephone interview that the study offers little new information about DAPT vs aspirin monotherapy yet confirmed the idea that medical therapy for PAD patients continues to show good results.

Moreover, Dr. Aboufares pointed to substantial baseline differences between the 2 groups.

“We know that PAD patients have about [a 33%] incidence of CAD. However, in this subset of patients, 56% in the DAPT arm vs 45% in the monotherapy arm had CAD, meaning this is not really an isolated PAD study,” Dr. Aboufares said. He also stressed that beta-blockers, taken by more DAPT patients at baseline, “reduce mortality, period.”

“Ultimately, what they discovered is that patients on dual-therapy did better [in terms of MACE] than [those on] monotherapy. And that is good, but is it because of the dual-therapy or because of the beta-blockers? That question remains,” Dr. Aboufares said. 

Armstrong EJ, Anderson DR, Yeo K-K, et al. Association of dual-antiplatelet therapy with reduced major adverse cardiovascular events in patients with symptomatic peripheral arterial disease. J Vasc Surg. 2015;Epub ahead of print.

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  • Drs. Laird and Aboufares report no relevant conflicts of interest.