“Well, doc, it’s been a year! Now what?”
You first met your patient 12 months ago when he presented to the emergency department having a heart attack. He was rushed to the cardiac catheterization lab, where a drug-eluting stent was placed to open the blocked coronary artery responsible for his crushing chest pain.
He has done well since and has been following up with you regularly in Cardiology Clinic. He has had no further episodes of chest pain, nor any bleeding complications from the dual antiplatelet therapy of aspirin and clopidogrel that you prescribed to prevent thrombosis of his new stent. Starting the day after his heart attack – and at every follow up visit since – you stressed the importance of taking these two medications for at least one year. At the one-year mark, you told him, you would discuss whether or not to continue this regimen. He presents today ready for that conversation.
As you begin to discuss the risks and benefits of continuing these two antiplatelet drugs, you find yourself in that uncomfortable data-free zone. After placement of a drug-eluting stent, the guidelines are clear that dual antiplatelet therapy should be continued for six months to one year. Beyond one year, however, the risks and benefits have remained uncertain.
In this week’s NEJM, Mauri and colleagues report the results of the DAPT trial, which was designed to fill this void. The data from this study suggest that an additional 18 months of dual antiplatelet therapy results in improved cardiovascular outcomes but also leads to an increased risk of bleeding.
The study included 10,000 participants who – like your patient – had received an FDA-approved drug-eluting stent, had already completed 1 year of treatment with dual antiplatelet therapy without ischemic events, repeat revascularizations, or major bleeding, and who had shown a high degree of adherence to the first year of dual antiplatelet therapy. Participants were randomized to receive an additional 18 months of either continued dual antiplatelet therapy with aspirin plus a thienopyridine (either clopidogrel or prasugrel) or aspirin alone. The co-primary endpoints were the incidence of stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE) – a composite of death, MI, or stroke.
The results: continued dual antiplatelet therapy reduced the rates of both stent thrombosis (0.4% vs. 1.4%, hazard ratio 0.29, 95% CI 0.17-0.48, P<0.001) and MACCE (4.3% vs. 5.9%, hazard ratio 0.71, 95% CI 0.59-0.85, P<0.001). Moderate or severe bleeding was higher in the dual antiplatelet therapy arm (2.5% vs. 1.6%, P=0.001).
Surprisingly, at the final 33-month follow-up, all-cause mortality was higher in the dual antiplatelet therapy group: 2.3% as compared with 1.8% in the placebo arm (hazard ratio 1.36, P=0.04). This was driven by a higher rate of non-cardiovascular death, due to increased bleeding from trauma and to cancer-related deaths. Importantly, while there were some cancer deaths attributable to bleeding, this last finding seems to be due to more patients with cancer randomized by chance to the dual antiplatelet therapy arm.
NEJM Deputy Editor Dr. John Jarcho describes how this new data might inform clinical practice: “The DAPT trial highlights the pros and cons of prolonged dual anti platelet therapy. It suggests that the best approach may be to individualize patient management. Those at higher risk of atherothrombosis might benefit from prolonged treatment, while those at higher risk of bleeding might be best advised to stop at one year.”
To your patient and the decision about his medications: this study doesn’t offer a clear directive. So you talk to him about that. After a discussion of the risks and benefits, and your best attempt to share what we do – and what we don’t – know, you arrive at a decision to continue his aspirin and clopidogrel for another 18 months. At the 18-month mark, you tell him, you will discuss whether or not to continue the regimen.
As he heads out of your office, you start thinking about the data-free zone you will face a year and a half from now, when he comes back to your office again wondering, “Well, doc, it’s been 18 months! Now what?”
For more on the DAPT trial, watch the 2-minute video summary and read the accompanying editorial.