Review: After PCI with DESs, long- and standard-term DAPT increase some adverse outcomes vs short-term DAPT

Abstract

Question After percutaneous coronary intervention (PCI) with drug-eluting stents (DESs), what are the efficacy and safety of standard- or long-term dual-antiplatelet therapy (DAPT) vs short-term DAPT? Review scope Included studies compared durations of DAPT (long-term [>12 mo], standard [12 mo], or short-term [6 mo]) in adults who received DESs. Studies that assessed 1 month of DAPT were excluded. Outcomes included all-cause mortality, major bleeding, any bleeding, myocardial infarction (MI), definite or probable stent thrombosis, stroke, and net adverse clinical events. PROSPERO CRD42018099519. Review methods MEDLINE, EMBASE/Excerpta Medica, Cochrane Library, Web of Science, ClinicalTrials.gov, and Clinicaltrialsregister.eu (all to Apr 2018) were searched for randomized controlled trials (RCTs). 17 RCTs (n =46864, mean age 60 to 68 y, 64% to 82% men) met the selection criteria. DAPT duration ranged from 3 to 48 months. In all 17 trials, DAPT comprised aspirin plus clopidogrel; in 5 trials, some patients received prasugrel, ticlopidine, or ticagrelor rather than clopidogrel. 16 RCTs had adequate randomization sequence generation, 13 had adequate allocation concealment, 6 blinded patients and study staff, and 5 blinded outcome assessors. Main results Results of network meta-analyses are in the Table. Conclusion After percutaneous coronary intervention with drug-eluting stents, long-term DAPT reduces myocardial infarction but increases major bleeding vs short-term DAPT; standard-term DAPT increases any bleeding vs short-term DAPT. Network meta-analysis of long-term (>12 mo) or standard (12 mo) DAPT vs short-term (6 mo) DAPT after percutaneous coronary intervention with drug-eluting stents* Outcomes Odds ratio (95% CI) Long-term vs short-term DAPT Standard vs short-term DAPT All-cause mortality 1.18 (0.93 to 1.49) 1.08 (0.82 vs 1.43) Major bleeding 1.78 (1.27 to 2.49) 1.28 (0.91 to 1.80) Any bleeding 2.13 (1.46 to 3.10) 1.39 (1.01 to 1.92) Myocardial infarction 0.63 (0.46 to 0.86) 0.92 (0.70 to 1.21) Definite or probable stent thrombosis 0.57 (0.34 to 0.95) 0.98 (0.59 to 1.64) Stroke 1.08 (0.77 to 1.51) 1.04 (0.74 to 1.47) Net adverse clinical events 0.88 (0.67 to 1.15) 0.91 (0.77 to 1.08) *DAPT = dual-antiplatelet therapy; CI defined in Glossary. Commentary The results of the systematic review and network meta-analysis by Yin and colleagues provide no evidence of benefit of extending DAPT beyond 6 months in patients with coronary artery disease who have had PCI. This conclusion is based on the findings of no difference in all-cause mortality for standard-term (12 mo) or long-term (>12 mo) DAPT vs short-term (6 mo) treatment, although long-term treatment reduced MI at the cost of increased bleeding. Because of concerns about an increased risk for MI and stent thrombosis, particularly in patients with a recent acute coronary syndrome, some clinicians are reluctant to shorten the duration of DAPT after PCI (1). Because of the findings that shorter durations of DAPT increase MI and stent thrombosis compared with longer durations, the results of the network analysis by Yin and colleagues are unlikely to change this thinking. We agree with the authors conclusion that short-term DAPT should be considered for most patients after PCI with DESs. Clinicians who remain unconvinced will have to consider the tradeoff between reducing MI and stent thrombosis while increasing bleeding. Addressing this issue requires explicit consideration of patients values and preferences. Patients have been reported to place greater value on preventing strokes than on avoiding bleeding, and fear the thrombotic events being prevented here (i.e., MI) much less than they do stroke (2). We expect that many patients will interpret the lack of mortality benefit with longer-term DAPT as no overall benefit of extended treatment and will opt to receive treatment for no more than 6 months. Patients who feel that preventing MI is more important than avoiding bleeding will prefer extended-duration treatment.