The Harmonising Outcomes with Revascularisation and Stents in Acute Myocardial Infarction (HORIZONS-AMI) was a prospective open label, multi-centre controlled trial involving patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). It incorporated two factorial randomised phases to allow a comparison of the direct thrombin inhibitor bivalirudin alone with heparin plus glycoprotein IIb-IIIa inhibitor use and a comparison of paclitaxel eluting stents (PES) with bare metal stents (BMS). Two primary clinical end-points were pre-specified: ischaemia driven TLR (analysis powered for superiority) and a composite safety end-point of major adverse cardiovascular events consisting of death, reinfarction, stroke and stent thrombosis (powered for non-inferiority with a 3.0% margin). The major secondary end-point was angiographic evidence of restenosis at 13 months
3602 patients with STEMI underwent randomisation for the pharmacological phase of the trial and of these 3006 underwent randomisation in a 3:1 ratio to the stent phase. 2257 were assigned to PES and 749 received BMS. 1 year follow up data were available for 2186 and 715 patients respectively. Patients with PES, when compared to those receiving BMS, had significantly lower ischaemia driven TLR (4.5% vs 7.5%, HR 0.59, 95%CI 0.43-0.83, p=0.002) and target vessel revascularisation (TVR) (5.8% vs 8.7%, HR 0.65, 95% CI 0.48-0.89, p=0.006), with non-inferior rates of the composite safety end-point (8.1% vs 8.0%, HR 1.02, 95%CI 0.76-1.36; absolute difference 0.1%, 95%CI -2.1 to 2.4, p=0.01 for non-inferiority, p=0.92 for superiority). Both PES and BMS had similar 12 month rates of death (3.5% and 3.5%, p=0.98) and stent thrombosis (3.2% and 3.4%, p=0.77) respectively. The 13 month rate of binary restenosis was significantly lower with PES than with BMS (10% vs 22.9%, HR 0.44, 95%CI 0.33-0.57, p<0.001).
There are some limitations of this study. Firstly, logistic complexities meant that an open label design was necessary. High rates of protocol compliance and the use of blinded clinical event adjudication and core laboratory assessments were measures taken to mitigate potential bias. There was a slightly higher rate of thienopyridine use in the PES arm than the BMS arm in the period between 6 months and 1 year. Very few patients with cardiogenic shock were included in this study and patients with unprotected left main stem disease or bifurcation disease requiring a 2 stent strategy were not included – therefore the results should not be extended to these patient populations. Longer term follow up data will be necessary to characterise the late safety and efficacy profiles of PES in patients with evolving STEMI particularly as the use of dual anti-platelet therapy declines over time after stent implantation. This is particularly important when considering the increased risk of stent thrombosis with DES when compared to BMSwhich may only become apparent at more than 1 year after stent implantation.
The HORIZONS-AMI trial provides data indicating that PES may be used in patients with evolving STEMI. The data from HORIZONS-AMI show that approximately 30 fewer/1000 patients with PES required TVR at 1 year when compared to BMS.
· Stone GW, Lansky AJ, Pocock SJ et al. Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction. The New England Journal of Medicine (2009) vol. 360 (19) pp. 1946-59