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When can I stop dual antiplatelet therapy in patients with drug-eluting stents?

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Stopping dual antiplatelet therapy (DAPT) (eg, clopidogrel plus aspirin) after 3 months is reasonable in patients with stable ischemic heart disease who have a second-generation drug-eluting stent and a high bleeding risk, with stable ischemic disease defined as at least 1 year free of acute coronary syndromes. However, these patients should continue lifelong aspirin monotherapy. Current guidelines suggest that in stable ischemic disease, the risk-benefit ratio may favor an even shorter duration of DAPT than the 6 months currently recommended.1

STABLE ISCHEMIC HEART DISEASE VS ACUTE CORONARY SYNDROME

Percutaneous coronary intervention for stable ischemic heart disease is indicated primarily in patients with angina that persists despite optimal antianginal therapy.

The prognostic implications of DAPT are different in stable ischemic disease than in acute coronary syndromes. The substrate treated by percutaneous intervention in stable ischemic disease is primarily fibrofatty plaque, as opposed to thrombus in acute coronary syndromes.

Percutaneous intervention significantly improves the prognosis in acute coronary syndromes, whereas its impact on overall survival in stable ischemic heart disease is not well documented. Given these differences, our discussion about DAPT in stable ischemic disease cannot be extrapolated to acute coronary syndromes.

BENEFITS OF DAPT

DAPT is mandatory early after drug-eluting stent placement, when the stent continuously releases medication, inhibiting tissue growth within the lumen of the stent.

Endothelialization of the stent normally occurs during the first 7 to 30 days after placement. During this period, the nonendothelialized stent poses a risk of thrombosis, a life-threatening, catastrophic condition with a mortality rate between 9% and 45%.1

Studies discussed in this article.
Aspirin 75 to 100 mg has been shown to be effective as secondary prevention of atherosclerotic disease and is recommended lifelong in this clinical setting. Adding a thienopyridine reduces the risk of myocardial infarction, stent thrombosis, and death from a cardiovascular event and decreases the incidence of plaque rupture in nonstented coronary vessels. Hence, prevention of these complications provides the rationale for DAPT in this clinical setting.

THERAPY BEYOND 12 MONTHS

Although guidelines have traditionally recommended 12 months of DAPT, the optimal duration is still debated.

A duration beyond 12 months in patients with a history of myocardial infarction was shown to be reasonable in 2 large trials,2,3 while a 2016 review by Bittl et al4 suggested that therapy beyond 12 months in patients with a newer-generation drug-eluting stent could increase the incidence of major bleeding. A detailed discussion of DAPT longer than 12 months is beyond the scope of this article.

EVIDENCE FOR SHORTER DURATION

The results of 5 major trials support shorter duration of DAPT in stable ischemic disease.

The OPTIMIZE5 and RESET6 trials found that 3 months of DAPT was not inferior to 12 months in terms of ischemic and safety end points.

The ISAR-SAFE,7 EXCELLENT,8 and SECURITY9 trials also reported that 6 months of DAPT was not inferior to 12 months for the primary composite end point of death, stent thrombosis, myocardial infarction, stroke, or major bleeding.

However, these trials may have been underpowered to detect a difference in rates of stent thrombosis with shorter-duration DAPT.

CURRENT GUIDELINES

For patients at high bleeding risk, the current guidelines of the American College of Cardiology and American Heart Association, updated in 2016, suggest that it may be reasonable to discontinue DAPT 3 months after drug-eluting stent placement in patients with stable ischemic heart disease, and at 6 months in patients with acute coronary syndrome (class IIb recommendation, level of evidence C).1 These recommendations are based on results of randomized controlled trials showing no difference in the rate of stent thrombosis and composite ischemic events with a shorter duration than with 12 months of therapy.5–10

The evidence for DAPT in stable ischemic disease is based on clopidogrel, with only limited data on ticagrelor.1 To our knowledge, no study to date has evaluated DAPT in this setting for less than 3 months, and further study is needed to address shorter-duration approaches with current-generation drug-eluting stents Since 2017, all coronary stents implanted in the United States have been second-generation stents.

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