Optimal Duration of Dual Antiplatelet Therapy After DES: 12 Months, But More Data Coming

December 23, 2009

December 23, 2009 (La Jolla, California) — A review paper published in the December 2009 issue of the Journal of the American College of Cardiology: Cardiovascular Interventions tackles the issue of the optimal duration of dual antiplatelet therapy following drug-eluting stent (DES) implantation, and while the authors are reluctant to prescribe a one-size-fits-all approach, the currently recommended 12 months of therapy is the right option, they say [1].

"While there aren't any randomized trials to specifically identify the optimal duration, consensus statements and the guidelines recommend at least 12 months of therapy," Dr Dominick Angiolillo (University of Florida College of Medicine, Jacksonville), an author of the viewpoint, told heartwire . "This is based on safety concerns that have emerged following implantation with drug-eluting stents. However, there is some evidence from registry data that suggests perhaps less than 12 months, maybe six months, might be sufficient therapy and is associated with a benefit, particularly with a reduction in stent thrombosis."

Angiolillo stressed that while the clinical trials are lacking, more data are coming, with numerous ongoing studies addressing different durations of dual antiplatelet therapy. In the meantime, "the take-home message is that we need to comply with the guidelines; whether we agree or disagree with them, they're there for a reason, and that's what I do in my practice," he added.

Treating Stent Thrombosis vs Recurrent Ischemic Events

In their review, the authors, including lead author Dr David Kandzari (Scripps Clinic, La Jolla, CA), review the evidence examining the relationship between dual antiplatelet therapy and stent thrombosis, noting that the strongest predictor of stent thrombosis is stopping thienopyridine therapy within six months of stent implantation. Observational studies have also shown that extending dual antiplatelet therapy from six to 12 months was not associated with reductions in late or very late stent thrombosis.

"One of the issues today, from my standpoint, is the question of what to do at one year," said Angiolillo. "Different physicians have different positions. I personally believe in the importance of dual antiplatelet therapy and that continuing dual antiplatelet therapy in special high-risk patients is beneficial, not necessarily for reducing stent thrombosis, but for preventing recurrent ischemic events. We know, for example, from the CHARISMA trial, although it was an overall negative study, if you take the patients with documented vascular disease, and even more so for those with a prior MI, the benefits of dual antiplatelet therapy were extended out to three years."

Angiolillo said he is in favor of prolonging dual antiplatelet therapy beyond 12 months in patients with acute coronary syndromes, patients with diabetes, and those who continue to have recurrent acute coronary syndromes on aspirin alone.

Overall, however, the authors conclude: "The rationale for a lifetime commitment to dual antiplatelet therapy uniformly in patients undergoing drug-eluting stent implantation is unsubstantiated." The bleeding and economic costs might outweigh the potential reduction in stent thrombosis, they suggest, and if treatment extends beyond 12 months, clinicians should realize they are treating systemic disease rather than issues related to the stent implantation.

Big Studies Coming Soon

In addition to these issues, Kandzari and Angiolillo, along with Drs Matthew Price and Paul Teirstein (Scripps Clinic, La Jolla, CA), highlight research that examines permanent discontinuation of dual therapy vs brief interruptions, those typically related to surgery. They also discuss the current issues related to ongoing clinical trials, noting that there are limitations as to how much information each study can provide. For example, there are variations in the durations of dual antiplatelet therapy tested, as well as different thienopyridine agents and drug-eluting stents studied. As a result, the impact of any single trial on clinical decision making will be varied.

The largest of the studies is the Dual Antiplatelet Therapy (DAPT) study, a 20 000-patient, $100-million, multisponsor randomized clinical trial testing optimal duration of dual antiplatelet therapy following stent implantation. As reported previously by heartwire , DAPT is comparing 12 vs 30 months of dual antiplatelet therapy among 15 000 patients who have been treated with a drug-eluting stent, powered to assess the primary end points of differences in stent-thrombosis rates and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety end point for DAPT is major bleeding. An additional 5000 patients treated with bare-metal stents will also be enrolled.

The ISAR-SAFE study, a 6000-patient study, is testing dual antiplatelet durations of six months vs 12 months in patients treated with a drug-eluting stent. The primary end point is death, MI, stroke, and TIMI major bleeding at 15 months.