Major advances in the treatment of coronary heart disease, both stable angina and acute coronary syndromes, have involved improvements in percutaneous coronary intervention; and a major component of this involves stent insertion, either of the bare metal or drug-eluting type. Preventing stent-related thrombosis involves dual anti-platelet therapy following insertion, usually aspirin and an ADP antagonist; until recently, the latter has usually been clopidogrel, although more recently the newer agents prasugrel and ticagrelor are being used in certain situations.
The evidence base regarding optimal duration of dual anti-platelet therapy post-coronary stent insertion is poor. Stent-related thrombosis is a major contributor to morbidity and mortality, and late thrombosis may be a particular issue in the case of drug-eluting as opposed to bare metal stents. Therefore it is important to define the length of time for which intensive (dual) anti-platelet therapy is indicated.
Aim of the Study
The present study examined the impact 6 (or sometimes less than 6) versus 24 months of dual antiplatelet therapy in a patient population receiving either FDA-approved drug-eluting or bare-metal stents.
The investigators randomly assigned 2013 patients to receive bare-metal, zotarolimus-eluting, paclitaxel-eluting, or everolimus-eluting stent implantation. At 30 days, patients in each group were then randomly allocated to receive up to 6 or 24 months of clopidogrel therapy in addition to aspirin. The primary endpoint was a composite of all-cause mortality, myocardial infarction or stroke.
The cumulative risks of the primary endpoint at 2 years were 10.1% and 10.0% in the 24- and 6-month-treated groups respectively, a non-significant difference. The individual risks of death, myocardial infarction, stroke or stent thrombosis did not differ between the groups. On the other hand, bleeding risk was greater in the 24 month versus 6 month-treated group, as was the need for blood transfusion.
This study showed no advantage in 24 versus 6 months of therapy with aspirin plus clopidogrel, and indeed a risk of harm with the longer regimen by virtue of increased bleeding risk. This lack of benefit from longer-term dual anti-platelet therapy was seen both in patients receiving bare metal stents and those receiving drug-eluting stents.
The results of this study are consistent with those of two previous studies from Korea, which again showed no evidence of benefit in extending the length of clopidogrel treatment post-stent implantation (to 12 versus 6 months and to 24 versus 12 months in those two studies). Indeed, the present study suggests a potential for harm with prolonged dual anti-platelet therapy. Therefore, unless there are strong clinical indications to continue aspirin plus clopidogrel for longer, it seems reasonable to recommend that dual anti-platelet therapy with these agents post-stent implantation, regardless of the type of stent inserted, should continue for 6 months only.
Corresponding author from the original article: Marco Valgimigli, MD, PhD, Chair of Cardiology, University of Ferrara, Cardiovascular Institute, Arcispedale S. Anna Hospital, C.rso Giovecca 203, 44100 Ferrara, Italy.