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Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction - HORIZONS-AMI Stent
Description:
Although drug-eluting stents (DES) have been shown to be superior to bare-metal stents (BMS) in a number of settings, there is still no consensus regarding the use of DES in ST-elevation myocardial infarction (STEMI). The HORIZONS-AMI trial sought to compare the safety and efficacy of paclitaxel-eluting stents (PES) over BMS in patients presenting within 12 hours of symptom onset with STEMI.
Hypothesis:
PES would be superior to BMS in patients with STEMI.
Study Design
Patients Screened: 3,602
Patients Enrolled: 3,006
Mean Follow Up: 1, 2, and 3 years
Mean Patient Age: 59.6 years (median)
Female: 23
Mean Ejection Fraction: 50%
Patient Populations:
- STEMI >20 minutes and <12 hours in duration
- ST-segment elevation of ≥1 mm in ≥2 contiguous leads; or
- Presumably new left bundle branch block; or
- True posterior MI with ST depression of ≥1 mm in ≥2 contiguous anterior leads
- Patients with cardiogenic shock, left main disease, etc., were not excluded
- Age ≥18 years
- The presence of at least one acute infarct artery target vessel in which:
- All significant lesions are eligible for stenting with study stents, and
- All such lesions have a visually estimated reference diameter ≥2.25 mm and ≤4.0 mm
- Expected ability to deliver the stent(s) to all culprit lesions (absence of excessive proximal tortuosity or severe calcification)
- Expected ability to fully expand the stent(s) at all culprit lesions (absence of marked calcification)
Exclusions:
- Contraindication to any of the study medications
- Prior administration of thrombolytic therapy, bivalirudin, GP IIb/IIIa inhibitors, low molecular weight heparin, or fondaparinux for the present admission (prior unfractionated heparin allowed)
- Current use of Coumadin
- History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions
- History of intracerebral mass, aneurysm, arteriovenous malformation, or hemorrhagic stroke; stroke or transient ischemic attack within 6 months or any permanent neurologic deficit; gastrointestinal or gastrourinary bleed within 2 months, or major surgery within 6 weeks; recent or known platelet count <100,000 cells/mm3 or hemoglobin <10 g/dl
- Planned elective surgical procedure that would necessitate interruption of thienopyridines during the first 6 months post-enrollment
- Bifurcation lesion definitely requiring implantation of stents in both the main vessel and a side branch
- Infarct-related artery is an unprotected left main
- >100 mm of study stent length anticipated
- Infarction due to stent thrombosis, or infarct lesion at the site of a previously implanted stent
- High likelihood of coronary artery bypass grafting within 30 days anticipated
Primary Endpoints:
- Incidence of MACE, defined as death, MI, stroke, or stent thrombosis at 1 year
- Ischemia-driven TLR at 1 year
Secondary Endpoints:
- Angiographic stenosis at 13 months
Drug/Procedures Used:
Randomization to PES (TAXUS Express, Boston Scientific) or BMS (Express, Boston Scientific) in a 3:1 fashion
Concomitant Medications:
Patients received either unfractionated heparin and a glycoprotein (GP) IIb/IIIa inhibitor (eptifibatide or abciximab) or bivalirudin with provisional GP IIb/IIIa inhibitors in a 2 x 2 factorial design. All patients received loading doses of aspirin and clopidogrel, with the latter continued for at least 6 months, and the former indefinitely.
Other medications: statins (96%), beta-blockers (92%)
Principal Findings:
A total of 3,006 patients were randomized, 2,257 to PES and 749 to BMS. Baseline characteristics were fairly similar between the two groups. About 16% of the patients had diabetes, and about 43% of the patients presented with an anterior myocardial infarction (MI). The median duration of symptoms prior to percutaneous coronary intervention (PCI) was 3.7 hours. An aspiration catheter was used in about 11% of the patients.
The mean number of lesions treated was 1.1, with a mean number of 1.5 stents per patient. About 59% of the patients had TIMI 0 or 1 flow on presentation, whereas 88% had TIMI 3 flow post-PCI. The mean reference vessel diameter was 2.9 mm. Total stent length was longer in the PES arm compared with the BMS arm (30.8 mm vs. 27.3 mm, p < 0.0001).
There was a significant reduction in ischemia-driven target lesion revascularization (TLR) at 1 year in the PES arm compared with BMS (4.5% vs. 7.5%, hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.43-0.83, p = 0.002), as well as target vessel revascularization (5.8% vs. 8.7%, HR 0.65, 95% CI 0.48-0.89, p = 0.006). The incidence of major adverse cardiac events (MACE) at 1 year was similar between the two arms (8.1% vs. 8.0%, HR 1.02, 95% CI 0.76-1.36, p for noninferiority = 0.01, p for superiority = 0.92). There was no difference between the two arms in the incidence of mortality (3.5% vs. 3.5%, p = 0.98), stent thrombosis (3.2% vs. 3.4%, p = 0.77), or MI (3.7% vs. 4.5%, p = 0.31). Of 1,800 consecutive patients selected for angiographic follow-up, data were available for 1,204 patients at 13 months.
PES was associated with a significantly lower incidence of binary restenosis compared with BMS (9.6% vs. 23.2%, p < 0.0001). Similarly, the incidence of in-stent restenosis was significantly lower with PES (8.2% vs. 21.0%, p < 0.001).
At 2 years, there was still a significant reduction noted in the incidence of ischemia-driven TLR in the PES arm (6.8% vs. 11.6%, p < 0.001). The incidence of MACE (11.0% vs. 11.2%, p = 0.9), mortality (4.3% vs. 5.2%, p = 0.32), and stent thrombosis (4.1% in both arms, p > 0.05) was similar between the two arms.
At 3 years, about 95% of patients were on aspirin, and 25% on clopidogrel. Ischemia-driven TLR was significantly lower in the PES arm, as compared with BMS (9.4% vs. 15.1%, p < 0.001). The incidence of MACE (13.6% vs. 12.9%, p = 0.66), mortality (5.6% vs. 6.6%, p = 0.31), and stent thrombosis (4.8% vs. 4.3% in both arms, p = 0.63) was similar between the two arms.
Interpretation:
The results of the HORIZONS-AMI trial indicate that PES are superior to BMS in reducing restenosis and thereby ischemia-driven TLR at 1 year in patients presenting with STEMI. The incidence of MACE, death, MI, and stent thrombosis is similar. One limitation is that this was an open-label study, with operators aware of treatment assignment.
These results are similar to those noted in the SESAMI and TYPHOON studies, which demonstrated a benefit of DES over BMS in patients with STEMI. Two-year data seem to indicate similar results.
Two- and three-year results indicate the PES are superior to BMS in reducing ischemia-driven TLR, although other clinical outcomes were similar. An interesting finding here was that stent thrombosis rates were high (~5%), and showed a steady increase even in the BMS arm up to 3 years. This has not been noted before, and raises questions about the need to continue DAPT longer in patients with STEMI, irrespective of whether they receive a DES or BMS. This will need to be addressed in future trials.
References:
Stone GW, Lansky AJ, Pocock SJ, et al. Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction. N Engl J Med 2009;360:1946-59.
Presented by Dr. Gregg Stone at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2010), Washington, DC, September 25, 2010.
Also presented by Dr. Gregg Stone at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2008), Washington, DC, October 2008, and at TCT 2009, San Francisco, CA, September 25, 2009.
Keywords: Follow-Up Studies, Coronary Restenosis, Drug-Eluting Stents, Ticlopidine, Sirolimus, Stents, Percutaneous Coronary Intervention, Consensus, Paclitaxel, Shock, Cardiogenic, Metals, Thrombosis, Bundle-Branch Block, Confidence Intervals, Diabetes Mellitus
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