We have 3-6-12-30 … No, we’re not talking about random lottery picks here, but rather the well-deliberated number of months of dual antiplatelet therapy (DAPT) for patients treated with drug-eluting stents. A growing evidence base is helping cardiologists make decisions with reasonable confidence about the optimal duration of DAPT for certain patient populations.
When to end
Drug-eluting stents address the problem of restenosis that was associated with bare-metal stents in patients who underwent PCI, but they bring their own baggage in the form of stent thrombosis. The combination of a P2Y12-receptor inhibitor and aspirin reduces the risk of stent thrombosis and recurrent ischemic events, at the cost of potential increased bleeding. Guidelines in the U.S. recommend at least 12 months of DAPT after placement of drug-eluting stents and European recommendations call for six months of DAPT after stent implantation.
Many physicians wonder if widening or narrowing those windows might benefit some patients. Not every patient tolerates DAPT, while others may not be compliant and yet others will require a respite for planned surgeries or other reasons. Interventional cardiologists must weigh the risk of thrombosis against the risk of bleeding, both infrequent but potentially devastating. And the relatively low number of adverse events on either side of the equation make it difficult to conduct sufficiently powered clinical trials to answer questions about duration and outcomes.
“Event rates were so low,” says Anil Pandit, MD, a cardiologist at HaysMed’s DeBakey Heart Institute in Hays, Kan. As a fellow at the Mayo Clinic in Scottsdale, Ariz., he and colleagues reviewed the efficacy and safety of six months or less or 12 months or more of DAPT in a meta-analysis of four randomized trials that included 8,163 patients with acute coronary syndrome (Catheter Cardiovasc Interv online April 18, 2014). There was no difference in the rates of all-cause mortality, cardiac death, MI and cerebrovascular accidents between the groups. Stent thrombosis rates were similar, at 0.75 percent with the shorter duration and 0.58 percent for the longer duration. Major bleeding was higher with longer duration DAPT but it was still less than 1 percent.
“Even in our group at Mayo, some would say when rates are so low, what is the harm in prolonging dual antiplatelet therapy for 12 months or even after 12 months? When rates are so low anyway it might not make any clinical sense to us,” he observes.
Adding clarity on DAPT
The individual trials assessed by Pandit and colleagues had several limitations. They under-represented women; they had different endpoints and studied different durations; they included stable and unstable patients; they used only clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) as the P2Y12-receptor inhibitor; and they were all open-label and stent-specific. Despite those drawbacks, they were among the more robust DAPT trials. Other studies have been plagued by slow enrollment, with some terminating early.
Also, some DAPT studies are too small to draw definitive conclusions, says Robert W. Yeh, MD, an interventional cardiologist at Massachusetts General Hospital in Boston and an investigator in the Dual Antiplatelet Therapy (DAPT) study. DAPT, conducted at the request of the FDA, used an unusual design to avoid the pitfalls in previous trials. The international, randomized, placebo-controlled study compared 12 and 30 months of DAPT after placement of one of four different drug-eluting stents.
Stent thrombosis (ST) outcomes at one year in first- (A) and second-generation drug-eluting stents (DES) (B). ATD = Antiplatelet therapy discontinuation. Source: The American Journal of Cardiology
“As a practicing interventional cardiologist, I know that the primary reason we continue DAPT for many of these patients is to avoid stent thrombosis and also myocardial infarctions in the nonstented region,” he says. “The DAPT study is the only study that was sufficiently powered to answer the question we were interested in.”
The DAPT trial allowed a combination of either clopidogrel or prasugrel (Effient, Daiichi Sankyo), plus aspirin in patients enrolled through either the Harvard Clinical Research Institute or postmarketing surveillance studies (N Engl J Med online Nov. 16, 2014). Before randomization, patients had to be adherent to their therapy and have had no major adverse cardiovascular or cerebrovascular events, repeat revascularization,