Giuseppe Gargiulo, cardiologist1 2, Stephan Windecker, professor1, Bruno R da Costa, head of statistics and methodology1 3, Fausto Feres, interventional cardiologist4, Myeong-Ki Hong, professor5, Martine Gilard, professor6, Hyo-Soo Kim, professor7, Antonio Colombo, interventional cardiologist8, Deepak L Bhatt, professor9, Byeong-Keuk Kim, interventional cardiologist5, Marie-Claude Morice, interventional cardiologist6, Kyung Woo Park, professor7, Alaide Chieffo, interventional cardiologist8, Tullio Palmerini, interventional cardiologist10, Gregg W Stone, professor11, Marco Valgimigli, professor1
Abstract
Objective To compare clinical outcomes between short term (up to 6 months) and long term (12 months) dual antiplatelet therapy (DAPT) after placement of a drug eluting stent in patients with and without diabetes.
Design Individual participant data meta-analysis. Cox proportional regression models stratified by trial were used to assess the impact of diabetes on outcomes.
Data source Medline, Embase, and Cochrane databases and proceedings of international meetings searched for randomised controlled trials comparing durations of DAPT after placement of a drug eluting stent. Individual patient data pooled from six DAPT trials.
Primary outcome Primary study outcome was one year risk of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, or definite/probable stent thrombosis. All analyses were conducted by intention to treat.
Results Six trials including 11 473 randomised patients were pooled. Of these patients, 3681 (32.1%) had diabetes and 7708 (67.2%) did not (mean age 63.7 (SD 9.9) and 62.8 (SD 10.1), respectively), and in 84 (0.7%) the information was missing. Diabetes was an independent predictor of MACE (hazard ratio 2.30, 95% confidence interval 1.01 to 5.27; P=0.048 At one year follow-up, long term DAPT was not associated with a decreased risk of MACE compared with short term DAPT in patients with (1.05, 0.62 to 1.76; P=0.86) or without (0.97, 0.67 to 1.39; P=0.85) diabetes (P=0.33 for interaction). The risk of myocardial infarction did not differ between the two DAPT regimens (0.95, 0.58 to 1.54; P=0.82; for those with diabetes and 1.15, 0.68 to 1.94; P=0.60; for those without diabetes (P=0.84 for interaction). There was a lower risk of definite/probable stent thrombosis with long term DAPT among patients with (0.26, 0.09 to 0.80; P=0.02) than without (1.42, 0.68 to 2.98; P=0.35) diabetes, with positive interaction testing (P=0.04 for interaction), although the landmark analysis showed a trend towards benefit in both groups. Long term DAPT was associated with higher rates of major or minor bleeding, irrespective of diabetes (P=0.37 for interaction).
Conclusions Although the presence of diabetes emerged as an independent predictor of MACE after implantation of a drug eluting stent, compared with short term DAPT, long term DAPT did not reduce the risk of MACE but increased the risk of bleeding among patients with stents with and without diabetes.
BMJ
