Shorter duration of dual antiplatelet therapy following stent implantation may be beneficial in older patients
EBM Focus - Volume 13, Issue 10
• There is some uncertainty regarding the optimal duration of dual antiplatelet therapy (DAPT) following stent implantation, particularly for older patients.
• A recent systematic review analyzed individual patient data from 6 randomized trials that compared short-term (3 or 6 months) vs. long-term (12 or 24 months) DAPT in 11,473 patients who had drug-eluting stent implantation. DAPT included clopidogrel in over 99% of patients.
• In the subgroup of patients ≥ 65 years old, short-term DAPT had a significantly lower risk of major or minor bleeding (in 1.5% vs. 2.4% with long-term DAPT), and did not have significantly altered risks of death (2.9% vs. 2.5%), myocardial infarction (1.6% vs. 2.1%), or stroke or thrombosis (each in < 1% of patients).
Dual antiplatelet therapy (DAPT) is recommended following stent implantation in patients with coronary artery disease (Eur Heart J 2018, J Am Coll Cardiol 2016). However, due in part to the balance between the risks of thromboembolic events and bleeding, there is some uncertainty regarding the optimal duration, particularly for older patients. A subgroup analysis of a trial suggests that DAPT beyond 6 months may have more harms than benefits in older patients (EuroIntervention 2017), but additional evidence is needed. To address this question, a systematic review was conducted that analyzed individual patient data from 6 randomized trials with 11,473 patients, 46% of whom were ≥ 65 years old. The included trials directly compared short-term (3 or 6 month) vs. long-term (12 or 24 month) DAPT in patients who had drug-eluting stent (DES) implantation. Stable ischemic heart disease was diagnosed in 58.5% of patients and acute coronary syndrome was diagnosed in 41.5%. Use of clopidogrel at discharge was reported in over 99% of 7,990 patients with available data, and next-generation DESs were used in 90%. A seventh trial with 4,000 patients met inclusion criteria but was not included in the analysis because individual patient data was not obtained. Patients and caregivers were not blinded in any trial. Outcomes were assessed at 12 months after DES implantation.
In the subgroup of patients ≥ 65 years old, short-term and long-term DAPT were associated with similar risks of all-cause death (in 2.9% with short-term vs. 2.5% with long-term DAPT, adjusted hazard ratio [HR] 1.15, 95% CI 0.83-1.6), myocardial infarction (MI) (1.6% vs. 2.1%, adjusted HR 0.8, 95% CI 0.52-1.2), and stroke or thrombosis (each in < 1% of patients). However, short-term DAPT was associated with a reduced risk of major or minor bleeding (1.5% vs. 2.4%, adjusted HR 0.64, 95% CI 0.43-0.95). Results in the subgroup of patients < 65 years old were mixed: short-term DAPT was associated with reduced mortality (0.7% vs. 1.3%, adjusted HR 0.51, 95% CI 0.3-0.88) but an increased risk of MI (1.9% vs. 1.2%, adjusted HR 1.56, 95% CI 1.03-2.36), while there were no significant differences between groups in risks of major or minor bleeding, stroke, or thrombosis (each in ≤ 1.2% of patients).
This study had several limitations. The exclusion of a large trial that met inclusion criteria introduces a potential bias, particularly given the low event rates in this analysis. Also, the confidence intervals for most outcomes include both clinically important and unimportant relative risks. Third, the results are based on subgroups of patients from randomized trials. Trials designed to evaluate DAPT duration specifically in older patients are needed. Finally, DAPT included clopidogrel in almost all patients. Trials that evaluate other antiplatelet drugs such as ticagrelor and prasugrel are needed. In the meantime, this systematic review is the best evidence-to-date evaluating DAPT duration in patients ≥ 65 years old and suggests that duration ≤ 6 months may reduce bleeding risks without increasing risks of death or thromboembolic events compared to longer DAPT duration.
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