Small studies have suggested that direct stenting without balloon predilatation in ST-segment elevation myocardial infarction may reduce microcirculatory dysfunction. To examine the clinical benefits of direct stenting in a large cohort of patients who underwent primary percutaneous coronary intervention treated with contemporary pharmacotherapy, the 1-year outcomes from the multicenter, randomized Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial were analyzed. A total of 3,602 patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention were enrolled. The present study cohort consisted of 2,528 patients in whom single lesions (excluding bypass grafts) were treated with stent implantation. At operator discretion, direct stenting was attempted in 698 patients (27.6%), and stenting was performed after predilatation in 1,830 patients (72.4%). Propensity-score matching was performed to reduce bias. Direct stenting was successful in 677 patients (97.0%). ST-segment resolution at 60 minutes after the procedure was improved in patients who underwent direct compared to conventional stenting (median 74.8% vs 68.9%, respectively, p = 0.01). At 1-year follow-up, direct compared to conventional stenting was associated with a significantly lower rate of all-cause death (1.6% vs 3.8%, p = 0.01) and stroke (0.3% vs 1.1%, p = 0.049), with nonsignificant differences in target lesion revascularization, myocardial infarction, stent thrombosis, and major bleeding. Death at 1 year remained significantly lower in the direct stenting group after multivariate adjustment (hazard ratio 0.42, 95% confidence interval 0.21 to 0.86, p = 0.02) and in a propensity score–based analysis (hazard ratio 0.92, 95% confidence interval 0.88 to 0.95, p = 0.02). In conclusion, compared to stent implantation after predilatation, direct stenting is safe and effective in appropriately selected lesions in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention and may result in improved survival.
By enlarging luminal dimensions and sealing dissection planes at the site of coronary artery occlusion in patients with evolving ST-segment elevation myocardial infarction (STEMI), the routine implantation of stents reduces early and late recurrent ischemia and infarct artery reocclusion compared to balloon angioplasty alone. Primary percutaneous coronary intervention (PCI) with stent implantation has thus become accepted as the preferred interventional strategy in STEMI. Compared to bare-metal stents (BMS), drug-eluting stents have been shown to further reduce the need for subsequent target lesion revascularization (TLR). Nonetheless, microcirculatory dysfunction is commonplace after primary PCI and often results in blunted myocardial recovery. Small studies have suggested that stenting without balloon predilatation in STEMI (direct stenting) is feasible in select cases and may be beneficial by reducing microvascular injury. No large study has examined the feasibility and potential clinical utility of direct stenting in patients with STEMI. We therefore evaluated the outcomes after direct stenting in patients with STEMI from the large-scale, international, prospective, randomized Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial.
Methods
HORIZONS-AMI was a prospective, open-label, multicenter, controlled trial in patients with STEMI who underwent a primary PCI management strategy, incorporating 2 factorial randomized phases to allow comparison of the direct thrombin inhibitor bivalirudin alone to heparin plus a glycoprotein IIb/IIIa inhibitor and of paclitaxel-eluting stents to BMS.
The clinical eligibility criteria for the HORIZONS-AMI trial have been previously described. In brief, consecutive patients aged ≥18 years presenting <12 hours after symptom onset and with ST-segment elevation ≥1 mm in ≥2 contiguous leads, new left bundle branch block, or true posterior myocardial infarction were considered for enrollment. Principal exclusion criteria included contraindications to study medications; current use of coumadin, conditions increasing hemorrhagic risk, or previous administration of thrombolytic therapy, bivalirudin, glycoprotein IIb/IIIa inhibitors, low–molecular weight heparin, or fondaparinux for the present admission (previous unfractionated heparin was allowed); known platelet count <100,000 cells/mm 3 or hemoglobin <10 g/dl; coronary stent implantation within 30 days; planned elective surgical procedure that would necessitate thienopyridine discontinuation during the first 6 months after enrollment; and noncardiac co-morbid conditions with life expectancy <1 year or that might interfere with protocol compliance. The study was approved by the institutional review board or ethics committee at each participating center, and all patients provided written informed consent.
Eligible patients were randomly assigned in an open-label fashion equally to unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor or bivalirudin alone, the timing and dosing of which have been previously described. After the first randomization, emergent coronary angiography with left ventriculography was performed, followed by triage to PCI, coronary artery bypass grafting, or medical management at physician discretion. Among patients who underwent immediate PCI, anatomic eligibility for randomization into the stent phase of the trial was assessed after restoration of patency in the infarct vessel (by spontaneous reperfusion, guidewire recanalization, inflation of an undersized angioplasty balloon, or thrombus aspiration). Direct stenting was allowed at operator discretion in cases in which the infarct lesion length and reference vessel diameter could be assessed at baseline or after guidewire passage.
Patients eligible for stent randomization were assigned in a 3:1 ratio to either the Taxus Express paclitaxel-eluting stent or otherwise the identical uncoated Express BMS (both Boston Scientific Corporation, Natick, Massachusetts). Stents were implanted at ≥14 atm of pressure using a standard technique, sized 1:1 to 1.1:1 to the distal reference vessel diameter, with a 3- to 4-mm normal reference segment margin at the proximal and distal ends when possible. Adjacent multiple stents, if required, were overlapped by 2 to 3 mm.
Aspirin 324 mg oral or 500 mg intravenous was given in the emergency room, followed by 300 to 325 mg/day oral during the hospitalization and 75 to 81 mg/day indefinitely thereafter. A clopidogrel loading dose (either 300 or 600 mg per investigator discretion) was administered before catheterization, followed by 75 mg/day oral for ≥6 months (≥1 year recommended).
Clinical follow-up was performed at 30 ± 7 days, 6 months ± 14 days, 12 months ± 14 days, and then yearly for 3 years total. The primary clinical end points of the first (pharmacology arm) randomization were prespecified at 30 days, whereas the primary end points of the second (stent arm) randomization were prespecified at 1 year. Routine angiographic follow-up at 13 months ± 14 days was prespecified in 1,800 randomized stent patients in whom stent implantation was successful and in whom neither stent thrombosis occurred nor bypass graft surgery was performed within 30 days. Because the present report is truncated at 12 months of follow-up, angiographic follow-up did not affect the clinical results.
To avoid confounding in patients with multiple treated lesions, the present analysis was restricted to patients who underwent attempted stent implantation of a single lesion in a de novo native coronary artery lesion (lesions in bypass grafts were excluded). “Direct stenting” was defined as attempted stent implantation before balloon PCI (either before or after thrombus aspiration) and was deemed successful if ≤10% residual stenosis by visual assessment with Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow was achieved and no more than a National Heart, Lung, and Blood Institute type A peristent dissection was present. Two primary 12-month clinical end points were prespecified in the main trial: ischemia-driven TLR and a composite safety measure of major adverse cardiovascular events consisting of death, reinfarction, stroke, or stent thrombosis (hereafter termed safety major adverse cardiovascular events). The component definitions of major adverse cardiovascular events have been previously described. Stent thrombosis was defined as the definite or probable occurrence of a stent-related thrombotic event according to the Academic Research Consortium classification. An independent clinical events committee blinded to treatment assignment adjudicated all primary end point events using original source documents and procedural angiograms. Independent core angiographic laboratory analysis was performed by technicians blinded to treatment assignment and clinical outcomes using validated methods, as previously described. ST-segment resolution was determined by comparing the baseline electrocardiogram to an electrocardiogram performed 60 minutes after PCI using methods previously described.
Categorical outcomes for baseline and procedural variables were compared using chi-square or Fisher’s exact tests. Continuous variables were compared using Wilcoxon’s rank-sum test. Time-to-event outcomes are displayed using Kaplan-Meier methods and were compared to the log-rank test. Cox proportional-hazards regression was performed to determine the independent correlates of mortality and major bleeding using the baseline clinical and angiographic variables listed in Tables 1 and 2 , with direct stenting forced into the final model.
| Variable | Direct Stenting (n = 698) | Conventional Stenting (n = 1,830) | p Value |
|---|---|---|---|
| Age (years) | 58.1 (50.3–66.9) | 60.0 (52.6–69.7) | 0.0002 |
| Men | 75.5% | 76.9% | 0.46 |
| Diabetes mellitus | 15.9% | 16.0% | 0.97 |
| Insulin requiring | 4.7% | 4.5% | 0.79 |
| Hypertension ⁎ | 47.9% | 51.7% | 0.08 |
| Hyperlipidemia ⁎ | 42.3% | 41.7% | 0.80 |
| Current smokers | 52.6% | 47.3% | 0.02 |
| Previous myocardial infarction | 8.2% | 10.5% | 0.08 |
| Previous PCI | 7.7% | 10.4% | 0.04 |
| Previous coronary artery bypass graft surgery | 0.7% | 1.5% | 0.13 |
| Previous heart failure | 2.0% | 2.6% | 0.41 |
| Killip class 2–4 | 7.2% | 8.9% | 0.13 |
| Creatinine clearance (ml/min) † | 92.0 (72.8–114.9) | 88.9 (68.3–115.1) | 0.11 |
| Symptom onset to balloon time (minutes) | 205 (157–303) | 225 (160–339.0) | 0.0011 |
| Antithrombin use during PCI | |||
| Unfractionated heparin | 53.3% | 49.7% | 0.11 |
| Bivalirudin | 46.8% | 51.3% | 0.05 |
| Medications at discharge | |||
| Aspirin | 98.8% | 99.0% | 0.73 |
| Thienopyridines | 99.9% | 99.2% | 0.08 |
| β blockers | 92.6% | 90.2% | 0.07 |
| Angiotensin-converting enzyme inhibitors or receptor blockers | 86.8% | 82.2% | 0.01 |
| Statins | 95.5% | 96.2% | 0.43 |
⁎ Hypertension and hyperlipidemia were defined as requiring medical treatment.
† Baseline calculated creatinine clearance using the Cockcroft-Gault equation <60 ml/min.
| Variable | Direct Stenting | Conventional Stenting | p Value |
|---|---|---|---|
| Infarct artery | |||
| Left anterior descending | 41.9% | 41.9% | 0.98 |
| Left circumflex | 15.1% | 14.1% | 0.53 |
| Right | 42.9% | 43.6% | 0.74 |
| Left main | 0.1% | 0.3% | 1.00 |
| Any side branch lesion treated | 2.7% | 4.1% | 0.10 |
| Paclitaxel-eluting stents used | 72.1% | 75.3% | 0.11 |
| Number of stents implanted | 1.30 ± 0.6 | 1.40 ± 0.70 | 0.01 |
| Total stent length (mm) | 20 (16–28) | 24 (20–32) | <0.0001 |
| Maximum balloon diameter (mm) | 3.4 ± 0.55 | 3.2 ± 0.61 | <0.0001 |
| Maximum pressure (atm) | 15.2 ± 3.4 | 14.9 ± 3.6 | 0.09 |
| Poststent dilation balloon used | 30.6% | 39.8% | <0.0001 |
| Aspiration catheter used | 14.9% | 9.5% | 0.0001 |
| Total fluoroscopy time (minutes) | 9.0 (6.0–13.0) | 11.0 (8.0–16.0) | <0.0001 |
| Total amount of contrast dye (ml) | 200 (150–250) | 230 (180–290) | <0.0001 |
| Angiographic core laboratory measurements | |||
| Left ventricular ejection fraction (%) | 61.2 (52.6–68.9) | 59.7 (49.7–67.3) | 0.005 |
| Baseline TIMI flow grade | |||
| 0/1 | 39.1% | 71.5% | <0.0001 |
| 2 | 19.6% | 11.3% | <0.0001 |
| 3 | 41.3% | 17.3% | <0.0001 |
| Final TIMI flow grade | |||
| 0/1 | 0.4% | 1.6% | 0.02 |
| 2 | 6.3% | 12.3% | <0.0001 |
| 3 | 93.3% | 86.1% | <0.0001 |
| Baseline QCA | |||
| Reference vessel diameter (mm) | 2.9 (2.6–3.3) | 2.9 (2.6–3.2) | 0.14 |
| Minimal luminal diameter (mm) | 0.4 (0.0–0.7) | 0.0 (0.0–0.3) | <0.0001 |
| Diameter stenosis (%) | 86.3 (75.1–100.0) | 100.0 (87.8–100.0) | <0.0001 |
| Lesion length (mm) | 14.7 (10.8–20.9) | 15.0 (11–22) | 0.06 |
| Final QCA | |||
| Reference vessel diameter (mm) | 3.0 (2.7–3.3) | 3.0 (2.6–3.3) | 0.11 |
| Minimal luminal diameter (mm) | 2.5 (2.2–2.8) | 2.4 (2.0–2.7) | 0.0003 |
| Lesion diameter stenosis (%) | 17.2 (11.7–24.1) | 18.8 (13.1–25.3) | 0.0003 |
| Final slow reflow | 0.9% | 2.0% | 0.0432 |
| Final no reflow | 0.1% | 0.3% | 1.000 |
| Distal embolization | 2.6% | 3.3% | 0.33 |
| Side branch closure (lesion level, TIMI grade 0) | 4.8% | 5.3% | 0.56 |
| Relative ST-segment resolution at 60 minutes | 74.8% (46.2%–100.0%) | 68.9% (37.5%–94.8%) | 0.01 |
| Complete (>70%) | 54.8% | 49.3% | 0.03 |
| Partial (30%–70%) | 26.0% | 28.6% | 0.23 |
| Absent (<30%) | 19.2% | 22.1% | 0.16 |
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