HORIZONS and Drug-eluting Stent Usage in Acute Myocardial Infarction

HORIZONS and Drug-eluting Stent Usage in Acute Myocardial Infarction

Kolodgie Frank, Nakano Masataka , Nakazawa Gaku, Virmani Renu, Vorpahl Marc

Interventional Cardiology, 2009;4:53-6

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Myocardial infarction (MI) is one of the few clinical presentations whereby percutaneous coronary intervention reduces the risk of death compared with medical therapy alone. However, treatment with drug-eluting stents (DES) – so-called ‘off-label’ use for patients with STsegment- elevation MI (STEMI) – raises safety concerns with respect to the morbidity and mortality attributed to late stent thrombosis (LST). Pathology data clearly indicate delayed healing as the primary substrate in all cases of DES-related LST, where differences in lesion morphology invariably show a greater prevalence of uncovered struts, accumulated fibrin and inflammation in ruptures relative to stable plaques. The prolonged risk of LST appears to persist up to at least four years after DES implantation. Results from the recently published Harmonising Outcomes with Revascularisation and Stents – Acute Myocardial Infarction (HORIZONS-AMI) trial of 3,006 prospective patients presenting with STEMI, randomised to paclitaxel-eluting (PES) or identical bare-metal stents (BMS), show similar 12-month death and stent thrombosis rates. Despite a significant reduction in ischaemia-driven target lesion revascularisation, a sub-study analysis showed a greater incidence of malapposition in patients receiving PES. Along these same lines, other registry studies point towards inconsistencies inadvocating the use of DES for AMI. Considering that arterial healing in response to DES is delayed for periods longer than one year, longterm follow-up beyond this point is required to confirm the results of the HORIZONS trial. However, despite the final outcome, the results may remain disputable since the trial may not have been sufficiently powered to address the relative risks of LST or mortality. Clearly, there remains a need for larger randomised controlled studies before the broader use of this technology in AMI patients is settled.

The limited information regarding the long-term safety of drug-eluting stents (DES) for the treatment of ST-segment-elevation myocardial infarction (STEMI) has raised concern regarding its clinical safety, in particular with respect to the associated morbidity and mortality attributed to late stent thrombosis (LST). Observational studies in daily practice have shown that the risk of LST continues at a constant rate up to at least four years after DES implantation.1 Given that MI is one of the few clinical presentations in which percutaneous coronary intervention (PCI) has been shown to reduce the risk of death, compared to medical therapy alone, the long-term outcomes after DES for the treatment of acute MI (AMI) is of immense clinical importance.2,3

Previous Studies of Drug-eluting Stents for Acute Myocardial Infarction
Several randomised clinical trials have compared clinical outcomes for patients with AMI treated with either bare-metal stents (BMS) or DES.4–7 A meta-analysis of these trials, with limited follow-up of one to two years,demonstrated a significant reduction in re-intervention with no differences in stent thrombosis, myocardial infarction or deaths between patients treated with BMS versus DES.8 Despite favourable clinical outcomes of generally low death and re-infarction rates of 4.6 and 3.5%, respectively, it remains questionable how applicable these results are to the broader use of this technology in the STEMI population.

Keywords:
HORIZON, drug-eluting stent, acute myocardial infarction, pathology, late-stent thrombosis

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