Duration of Dual Antiplatelet Therapy After Coronary Stenting

Posted On 2012-04-24 11:05:28
Posted by Qianqian Liu and Paul Schoenhagen

The optimal duration of dual-antiplatelet therapy and the risk-benefit ratio for long-term dual-antiplatelet therapy after coronary stenting remain incompletely defined. Valgimigli et al. evaluated the impact of up to 6 versus 24 month duration of dual-antiplatelet therapy in randomized multicentre trial (Clinical trial registration: clinicaltrials.gov; Identifier: NCT00611286). (1)

2,013 patients were randomly assigned to receive bare-metal, zotarolimus-eluting, paclitaxel-eluting, or everolimus-eluting stent implantation. At 30 days, patients in each stent group were randomly allocated to receive up to 6 or 24 months clopidogrel therapy on top of aspirin. The primary endpoint was a composite of death from any cause, myocardial infarction or cerebrovascular accident. The cumulative risk of the primary outcome at 2 years was 10.1% with the 24-month dual antiplatelet therapy, as compared to 10.0% with the 6-month dual antiplatelet therapy (hazard ratio, 0.98; 95% CI, 0.74 to 1.29; P = 0.91). The individual risks of death, myocardial infarction, cerebrovascular accident or stent thrombosis did not differ between the study groups. However, there was a consistent greater risk of haemorrhage in the 24-month clopidogrel group according to all pre-specifed bleeding definitions including the recently proposed Bleeding Academic Research Consortium classification.

The authors conclude that a 24-month clopidogrel therapy in patients who had received a balanced mixture of drug-eluting or bare-metal stents was not significantly more effective than a 6-month clopidogrel regimen in reducing the composite of death for any cause, myocardial infarction or cerebrovascular accident. 
An accompanying editorial places these important data in the context of prior trial results and current clinical recommendations. (2) 

It is interesting that two trials, the PRODIGY and the LATE trials, with nearly 5,000 patients, indicate that courses of clopidogrel exceeding 12 months may be detrimental.  Based on The CREDO trial and TRITON-TIMI 38, the logical approach remains to continue dual antiplatelet therapy for a minimum of twelve months for patients who have received DES.  Patients who had complex presentations or difficult stent procedures may benefit from longer durations, and patients with poor drug tolerance from earlier termination. The results of the Dual Antiplatelet Therapy Study (DAPT) are expected to be more definitive (Clinical trial registration: clinicaltrials.gov; Identifier: NCT00977938). (3)

1. Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C, Castriota F, Colombo F, Tebaldi M, Fucà G, Kubbajeh M, Cangiano E, Minarelli M, Scalone A, Cavazza C, Frangione A, Borghesi M, Marchesini J, Parrinello G, Ferrari R. Short- Versus Long-term Duration of Dual Antiplatelet Therapy After Coronary Stenting: A Randomized Multicentre Trial. Circulation. 2012 Mar 21. [Epub ahead of print]
2. Kleiman NS. Grabbing the Horns of a Dilemma: The Duration of Dual Antiplatelet Therapy After Stent. Circulation. 2012 Mar 21. [Epub ahead of print]
3. Mauri L, Kereiakes DJ, Normand SL, Wiviott SD, Cohen DJ, Holmes DR, Bangalore S, Cutlip DE, Pencina M, Massaro JM. Rationale and design of the dual antiplatelet therapy study, a prospective, multicenter, randomized, double-blind trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronary intervention with either drug-eluting stent or bare metal stent placement for the treatment of coronary artery lesions. Am Heart J. 2010 Dec;160(6):1035-41, 1041.e1.