LAUSR

Questions What are the relative efficacy and safety of long-term and short-term dual antiplatelet therapy (DAPT) after implantation of drug-eluting stents (DESs)? Do outcomes differ in patients with or without diabetes? Review scope Included studies compared long-term (12 mo) with short-term (3 to 6 mo) DAPT after percutaneous coronary intervention (PCI) with DESs in patients with or without diabetes. Primary outcome was major adverse cardiac events (MACE) (composite of cardiac mortality, myocardial infarction [MI], or definite/probable stent thrombosis) at 1 year. Other outcomes included major and minor bleeding, all-cause mortality, and components of MACE at 1 year. Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials databases, www.clinicaltrials.gov, www.tctmd.com, www.clinicaltrialresults.org, www.cardiosource.com, proceedings from major cardiovascular meetings, and reference lists (all to Nov 2015) were searched for randomized controlled trials (RCTs). Principal investigators were contacted for original data. 6 RCTs (n =11473, mean age 63 y, 70% men, 32% had diabetes) met the inclusion criteria and had individual patient data available for analysis. 2 RCTs compared DAPT for 12 vs 3 months, 2 for 12 vs 6 months, and 2 for 24 vs 6 months. All RCTs had adequate allocation concealment and blinded outcome adjudicators. Main results Meta-analysis individual patient data showed that patients with diabetes had a higher risk for MACE after DES implantation than did patients without diabetes (hazard ratio [HR] 2.30, 95% CI 1.01 to 5.27). Long-term and short-term DAPT did not differ for MACE, all-cause mortality, cardiac mortality, or MI in patients with or without diabetes (Table). Long-term DAPT reduced definite/probable stent thrombosis in patients with diabetes but not in those without diabetes (Table) (P for interaction =0.04). Long-term DAPT increased major or minor bleeding in patients with diabetes and without diabetes (with diabetes HR 1.89, 1.10 to 3.27; without diabetes 1.43, 0.96 to 2.11; P for interaction =0.37). Conclusion Long-term dual-antiplatelet therapy (DAPT) after drug-eluting stent implantation did not reduce major adverse cardiac events or mortality compared with short-term DAPT for patients with or without diabetes. Long-term (12 mo) vs short-term (3 to 6 mo) dual-antiplatelet therapy (DAPT) after drug-eluting stent implantation* Outcomes Diabetes status Event rates At 1 y Long-term Short-term RRR/RRI (95% CI) NNT/NNH (CI) Major adverse cardiac event Diabetes 3.3% 3.2% RRI 5% (38 to 74) Not significant No diabetes 2.1% 2.5% RRR 3% (38 to 33) Not significant All-cause mortality Diabetes 2.6% 2.1% RRI 34% (13 to 104) Not significant No diabetes 1.53% 1.48% RRI 5% (27 to 50) Not significant *Abbreviations defined in Glossary. RRR, RRI, and CI calculated from short-term DAPT rates and hazard ratios in article. Cardiac mortality (1.6% vs 1.3%, P =0.36), myocardial infarction (2.0% vs 2.1%, P =0.82), or definite/probable stent thrombosis (0.4% vs 0.9%, P =0.02). Cardiac mortality (1.0% vs 0.9%, P =0.53), myocardial infarction (1.4% vs 1.6%, P =0.60), or definite/probable stent thrombosis (0.4% vs 0.3%, P =0.35). Commentary Recent RCTs have found that long-term DAPT after implantation of newer-generation DESs reduces adverse ischemic events in higher-risk (1), but not lower-risk (2), patients and increases risk for bleeding in all patients (1, 2). The presence of diabetes increases risk for ischemic events after PCI (3), and in some trials long-term DAPT has been found to reduce death and MI (3) and target vessel failure (4) in patients with diabetes. Gargiulo and colleagues' review of 6 RCTs confirmed that diabetes was associated with a greater risk for MACE but found that long-term DAPT did not reduce MACE at 1 year, even in patients with diabetes. In those patients, long-term DAPT reduced the risk for definite/probable stent thrombosis compared with short-term DAPT (HR 0.26, 95% CI 0.09 to 0.80), but the number of events was small (7 vs 16), substantial heterogeneity existed among the trials, and no resultant change occurred in the rate of death or MI. The analyses also confirmed that long-term DAPT increased the risk for bleeding in patients with diabetes. A recent meta-regression analysis suggested that bleeding may have a greater effect on mortality than does stent thrombosis (5), and Gargiulo and colleagues have provided evidence that, in patients with diabetes, long-term DAPT increases bleeding but does not protect against ischemic events. In the absence of other high-risk characteristics, patients with diabetes can be treated with short-term DAPT, supporting the guideline recommendation (2) that decisions about DAPT duration should be based on careful analysis of individual ischemic and bleeding risks.