Antiplatelet Therapy for Bare-metal (BMS) and First-generation Drug-eluting (DES 1) Stents
When bare-metal stents were first studied, initial therapy consisted of aspirin and dypiridamole.2 Subsequent to this, DAPT was recommended for 1 month in stable patients with BMS. The original comparative trials of DES 1 versus BMS employed DAPT for between 2 and 6 months only, admittedly in relatively stable and low-risk populations.7–9
However, as has been the case consistently since those early days, in patients with acute coronary syndromes (ACS) receiving stents there are competing indications for DAPT, since the evidence suggests a benefit from DAPT as a medical therapy in this setting. CURE was the first randomised trial to show that in a population of non-ST elevation ACS patients DAPT (using clopidogrel with aspirin) significantly decreased the rate of recurrent ischaemic events compared with aspirin monotherapy with placebo at a mean duration of therapy of 9 months.1,10 Importantly, 64 % of the 12,562 patients in this trial did not undergo revascularisation after randomisation. Specifically, there was a 20 % relative risk reduction in myocardial infarction, stroke or cardiovascular death with long-term DAPT use with no increase in life-threatening bleeds. In the CURE-PCI sub-study, there was a 25 % relative risk reduction in the composite of myocardial infarction or cardiovascular death with DAPT (≤12 months) compared with aspirin and placebo.10
It was largely based on this evidence that 12 months’ DAPT became the recommended default for stents post-ACS. However, given that there was a 4 % per year incidence of significant bleeding in the CURE study in the cohort on DAPT, there was clearly a balance to be struck between longer DAPT to reduce ischaemic events and shorter DAPT to minimise bleeding, which itself has been shown to be an independent risk factor for worse prognosis.1,10 That tension between ischaemic and bleeding events is indeed the driver for our current debate, just as it has been since stents were first implanted. In addition, the suspicion that patients receiving stents in elective, stable settings need DAPT for less time than patients presenting with ACS consistently remains a driver for reducing duration of DAPT therapy. Finally, the consistent iterative technologically-driven evolutions in the design of stents represent a further confounding factor in determining the optimal duration of DAPT.