Extended dual antiplatelet therapy demonstrated to improve post-DES implantation outcome

The duration of dual antiplatelet therapy (aspirin plus clopidogrel) following drug-eluting stent (DES) implantation has been a source of much recent debate. FDA currently recommends either 3 or 6 months of clopidogrel therapy following DES implantation, depending on the type of stent used.

In a large observational cohort study published in the New England Journal of Medicine (NEJM), extended use of combination antiplatelet therapy demonstrated a reduction in the incidence of death or myocardial infarction (MI) among patients with a DES.

This study included 4,666 patients who received either a bare-metal stent (BMS) or a DES at the Duke Heart Center between January 1, 2000, and July 31, 2005, for BMS (n=3,165) and between April 1, 2003, and July 31, 2005, for DES (n=1,501). Two separate landmark analyses were performed, 1 at 6 months and 1 at 12 months after stent implantation. In both of these analyses, patients were event free (no death, MI, or revascularization) during the defined period. The patients were separated into 4 groups based on stent type and clopidogrel use (DES plus clopidogrel, DES alone, BMS plus clopidogrel, or BMS alone). Outcomes (death or MI) were evaluated for ≤24 months after the initial stent implantation.

Based upon their research, the authors said that "the long-term risk for death and major cardiac events was significantly increased among patients in the DES group who had discontinued clopidogrel therapy at 6 or 12 months." The authors also acknowledged the need for additional research, namely randomized clinical trials, to further investigate their findings.

A recent meta-analysis of clinical trials comparing the risk of late thrombosis in patients who received DES versus patients who received BMS demonstrated that the risk of very late thrombosis (>1 year after the initial procedure) was significantly greater in patients who received a DES versus those who received a BMS (RR=5.02; 95% CI, 1.29–19.52; P=.02).

In response to the recent research, a multidisciplinary group of medical societies issued an advisory statement regarding duration of dual antiplatelet therapy following coronary artery stent implantation. The experts recommended careful patient selection when determining the type of stent to implant, taking into account social, economic, and bleeding risks; they also stressed the importance of 12-month dual anti-platelet therapy following DES implantation in addition to diligent healthcare provider and patient education regarding the consequences of early discontinuation of antiplatelet therapy in patients receiving coronary artery stents.

SOURCES Eisenstein EL, Anstrom KJ, Kong DF, et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA. 2007;297:159–168.

Bavry AA, Kumbhani DJ, Helton TJ, et al. Late thrombosis of drug-eluting stents: A meta-analysis of randomized clinical trials. Am J Med. 2006;119:1056-1061.

Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. A science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation. 2007[Epub ahead of print]. Available at: http:// http://circ.ahajournals.org/cgi/reprint/circulationaha.106.180944v1. Accessed January 23, 2007.