SNOWMASS, COLO. – Wide local variation in the guideline-recommended use of low-dose aspirin as part of dual antiplatelet therapy after coronary stent implantation appears to be a prime target for a quality improvement effort.
American College of Cardiology/American Heart Association guidelines recommend aspirin at 81 mg/day along with an oral thienopyridine for maintenance therapy after percutaneous coronary intervention (PCI). This Class IIa/Level of Evidence B recommendation for preferential use of low- rather than high-dose aspirin is based upon the results of the OASIS 7 study (N. Engl. J. Med. 2010;354:1706-17) and other randomized trials that demonstrate that low- and high-dose aspirin (300-325 mg/day) are equally effective in reducing ischemic complications after PCI but that high-dose aspirin is associated with an increased risk of bleeding, Dr. Patrick T. O’Gara noted at the Annual Cardiovascular Conference at Snowmass.
Dr. Patrick T. O'Gara
Yet in a contemporary series of more than 23,000 U.S. patients enrolled in the major ongoing Dual Antiplatelet Therapy Study, only 28% were placed on low-dose aspirin at discharge after PCI; the rest got high-dose aspirin as part of their dual antiplatelet therapy (DAPT). In contrast, 90% of study participants from other countries got low-dose aspirin for their DAPT, commented Dr. O’Gara, who is ACC president-elect and professor of medicine at Harvard Medical School and director of clinical cardiology at Brigham and Women’s Hospital, both in Boston.
The DAPT Study investigators determined that patient characteristics explained a mere 1.6% of the total variation in aspirin dosing. Site of enrollment accounted for 46% of the unexplained variation (Am. J. Cardiol. 201;113:1146-52).
The optimal duration of DAPT after PCI with placement of a drug-eluting stent remains unclear. Current guidelines call for at least 12 months of DAPT. The massive DAPT Study is designed to learn whether longer than 12 months is better. Participants were placed on 12 months of aspirin plus a thienopyridine, then randomized to an additional 18 months of DAPT or to aspirin plus placebo. The trial includes a variety of stents and indications for implantation. Results are expected later this year.
In the meantime, Dr. O’Gara said, the use of more than 12 months of DAPT is highly variable around the world. Studies suggest that at 3 years post-PCI, 40%-50% of North American patients remain on DAPT compared to about 10% of patients in Europe and elsewhere.
The ACC/AHA guidelines state as a relatively weak Class IIb/Level of Evidence C recommendation that continuation of DAPT beyond 12 months "may be considered" in drug-eluting stent recipients. Until the results of the DAPT Study become available to provide further guidance, however, Dr. O’Gara urged his colleagues to weigh this decision carefully on a case by case basis.
"The duration of DAPT is uncertain, but if you choose to continue therapy beyond 12 months, I think you need to be aware of the increasing number of trials that show no benefit of doing that – and an excess hazard of bleeding by doing so," he cautioned.
Dr. O’Gara cited three such major randomized trials totaling more than 6,100 patients: the Italian PRODIGY trial (Circulation 2012;125:2015-26), in which patients had near-identical rates of the 2-year composite of all-cause mortality, MI, or cerebrovascular accident regardless of whether they were randomized to 6 or 24 months of DAPT; the Korean combined REAL-LATE and ZEST-LATE trials (N. Engl. J. Med. 2010;362:1374-82), in which 12 and 24 months of DAPT resulted in similar rates of MI or cardiac death at 2 years; and EXCELLENT, in which 12 months of DAPT proved no better than 6 in terms of the combined endpoint of cardiac death, MI, or target vessel revascularization (Circulation 2012;125:505-13).
Moreover, a secondary analysis of the Korean trials found a 2.96-fold increased risk of Thrombosis in Myocardial Infarction major bleeding in patients on DAPT for longer than 12 months. And PRODIGY investigators found a 2.7-fold increased major bleeding risk with 24 as compared to 6 months of DAPT.
Further uncertainty regarding the optimal duration of DAPT comes from the OPTIMIZE trial, in which 3,119 Brazilian patients with low-risk acute coronary syndrome or stable coronary artery disease received a zotarolimus-eluting stent and were randomized to 3 or 12 months of DAPT. There was no difference between the two groups in the combined endpoint of all-cause mortality, MI, stroke, or major bleeding (JAMA 2013;310:2510-22).
"Interestingly enough, in Europe the zotarolimus-eluting stent has achieved approval for a 3-month course of dual antiplatelet therapy," Dr. O’Gara said.
He reported having no financial conflicts.