A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI study.

Treatment of carriers of the CYP2C19*2 allele and ABCB1 TT genotype with clopidogrel is associated with increased ischemic complications after percutaneous coronary intervention (PCI). We sought to evaluate a pharmacogenomic strategy among patients undergoing PCI for ST-elevation myocardial infarction (STEMI), by performing a randomized trial, enrolling 102 patients. Point-of-care genetic testing for CYP2C19*2, ABCB1 TT and CYP2C19*17 was performed with carriers of either the CYP2C19*2 allele or ABCB1 TT genotype randomly assigned to a strategy of prasugrel 10 mg daily or an augmented dosing strategy of clopidogrel (150 mg daily for 6 days then 75 mg daily). The primary end point was the proportion of at-risk carriers exhibiting high on-treatment platelet reactivity (HPR), a marker associated with increased adverse cardiovascular events, after 1 month. Fifty-nine subjects (57.8%) were identified as carriers of at least one at-risk variant. Treatment with prasugrel significantly reduced HPR compared with clopidogrel by P2Y12 reaction unit (PRU) thresholds of >234 (0 vs 24.1%, P=0.0046) and PRU>208 (3.3 vs 34.5%, P=0.0025). The sensitivity of point-of-care testing was 100% (95% CI 88.0-100), 100% (86.3-100) and 96.9% (82.0-99.8) and specificity was 97.0% (88.5-99.5), 97.1% (89.0-99.5) and 98.5% (90.9-99.9) for identifying CYP2C19*2, ABCB1 TT and CYP2C19*17, respectively. Logistic regression confirmed carriers as a strong predictor of HPR (OR=6.58, 95% CI 1.24-34.92; P=0.03). We confirmed that concurrent identification of three separate genetic variants in patients with STEMI receiving PCI is feasible at the bedside. Among carriers of at-risk genotypes, treatment with prasugrel was superior to an augmented dosing strategy of clopidogrel in reducing HPR.

ST segment resolution in patients with tenecteplase-facilitated percutaneous coronary intervention versus tenecteplase alone: Insights from the Combined Angioplasty and Pharmacological Intervention versus Thrombolysis ALone in Acute Myocardial Infarction (CAPITAL AMI) trial.

BACKGROUND: Compared with fibrinolysis alone, fibrinolysis followed by immediate percutaneous coronary intervention (PCI) reduced clinical events in the Combined Angioplasty and Pharmacological Intervention versus Thrombolysis ALone in Acute Myocardial Infarction (CAPITAL AMI) study. It is unclear whether the benefits go beyond achieving epicardial reperfusion. OBJECTIVES: To determine the differences in ST segment resolution (STR) among patients treated with tenecteplase (TNK)-facilitated PCI compared with patients treated with TNK alone. METHODS AND RESULTS: A formal ST segment analysis was conducted on the 170 patients with ST elevation myocardial infarction in the CAPITAL AMI trial: 86 patients treated with TNK-facilitated PCI were compared with 84 patients who were treated with TNK alone. Epicardial flow measured by percentage with Thrombolysis In Myocardial Infarction (TIMI) 3 flow improved from 52% (pre-PCI) to 89% (post-PCI) in those assigned to facilitated PCI. ST segment resolution was stratified by complete (70% or greater), partial (less than 70% to 30%) or no (less than 30% to 0%) resolution. The baseline mean ST segment elevation was 11.3+/-7.5 mm in the facilitated PCI patients and 11.8+/-7.1 mm in patients with TNK alone (P=0.66). Complete STR in the facilitated PCI patients versus the TNK-alone patients was present in 55.6% versus 54.6%, respectively (P=0.58) at 180 min and 62.0% versus 55.3% (P=0.64), respectively at day 1. The mean STR at 180 min and day 1 were similar in patients who experienced death, reinfarction, recurrent unstable ischemia or stroke at six months compared with patients who remained event free: 56.3% versus 64.6% at 180 min (P=0.40); and 67.7% versus 67.6% at day 1 (P=0.99), respectively. CONCLUSIONS: TNK-facilitated PCI did not demonstrate differences in ST segment resolution compared with TNK alone, despite improvement in epicardial flow after PCI. Further studies are required to clarify these findings.

Stenting versus thrombolysis in acute myocardial infarction trial (STAT).

OBJECTIVES: We sought to directly compare primary stenting with accelerated tissue plasminogen activator (t-PA) in patients presenting with acute ST-elevation myocardial infarction (AMI). BACKGROUND: Thrombolysis remains the standard therapy for AMI. However, at some institutions primary angioplasty is favored. Randomized trials have shown that primary angioplasty is equal or superior to thrombolysis, while recent studies demonstrate that stent implantation improves the results of primary angioplasty. METHODS: Patients presenting with AMI were randomly assigned to primary stenting (n = 62) or accelerated t-PA (n = 61). The primary end point was the composite of death, reinfarction, stroke or repeat target vessel revascularization (TVR) for ischemia at six months. RESULTS: The primary end point was significantly reduced in the stent group compared with the accelerated t-PA group, 24.2% versus 55.7% (p < 0.001). The event rates for other outcomes in the stent group versus the t-PA group were as follows: mortality: 4.8% versus 3.3% (p = 1.00); reinfarction: 6.5% versus 16.4% (p = 0.096); stroke: 1.6% versus 4.9% (p = 0.36); recurrent unstable ischemia: 9.7% versus 26.2% (p = 0.03) and repeat TVR for ischemia: 14.5% versus 49.2% (p < 0.001). The median length of the initial hospitalization was four days in the stent group and seven days in the t-PA group (p < 0.001). CONCLUSIONS: Compared with accelerated t-PA, primary stenting reduces death, reinfarction, stroke or repeat TVR for ischemia. In centers where facilities and experienced interventionists are available, primary stenting offers an attractive alternative to thrombolysis.

Stenting of an unprotected left main coronary artery stenosis in a cardiac transplant patient.

Cardiac allograft vasculopathy is the leading cause of death in cardiac transplant patients who survive the first year. Retransplantation is limited by shortage of donors and reduced survival rates compared with the initial transplant. Recent reports of successful stenting in these patients may offer some hope, although randomized trials are lacking. Successful stenting of an 'unprotected' left main coronary artery stenosis under cardiopulmonary support is presented in a cardiac transplant patient. A 16-month follow-up angiogram demonstrated a patent stent without restenosis and no interim clinical events.

Predictors of long-term outcome after stent implantation in a saphenous vein graft.

Stenting of saphenous vein graft (SVG) lesions is associated with significant clinical events at late follow-up. We sought to determine predictors of clinical outcome after this procedure. One hundred twenty-eight balloon-expandable stents were implanted in the SVGs of 106 patients. Baseline clinical and angiographic characteristics were analyzed. All grafts, including those not stented, were scored for extent of disease involving the luminal surface of the graft, and for the presence of low profile lesions (< 50% graft stenosis) and/or high profile lesions (> or = 50% graft stenosis). The in-hospital success rate was 98.1%. Before discharge, no patient died, required bypass surgery, or had repeat angioplasty of the same graft. Follow-up was obtained on all the patients. At a median of 18 months, 15% had died, 17% had experienced myocardial infarction, 20% had required repeat bypass surgery, and 37% needed repeat angioplasty to either the same site or a different lesion. Event-free survival was recorded in only 44% of the patients. The cumulative Kaplan-Meier survival at 2.4 years was 78.7%. Using the Cox proportional hazards model, predictors of survival were the absence of a high profile lesion in any nonstented patent graft (p = 0.004), and the use of lipid-lowering agents at follow-up (p = 0.01). Stenting SVG lesions can be performed with a high degree of procedural success, but at long-term follow-up there is a high rate of cardiac events. The absence of a high profile lesion in any nonstented patent graft is the strongest predictor of survival.

Late clinical and angiographic follow-up after stenting in evolving and recent myocardial infarction.

OBJECTIVES: This study sought to assess the late clinical and angiographic outcomes of patients who received stents within the first week of acute myocardial infarction (AMI). BACKGROUND: Recent studies have demonstrated that stenting of the infarct-related artery is a useful adjunct to balloon angioplasty in patients with AMI. However, there are limited data on the late clinical and angiographic outcomes of these patients. METHODS: Between January 1994 and September 1995, 32 patients at our institution underwent stenting of the infarct-related artery within 1 week of AMI: 13 within 14 hours (evolving group) and 19 between days 2 and 7 (recent AMI group). Late clinical follow-up was obtained on all survivors. Quantitative angiographic measurements were recorded on the stented segments before stenting, immediately after stenting, and on the follow-up angiograms. RESULTS: At 13.1+/-6.4 months from the time of stenting, three patients died and three required repeat angioplasty, but no patient had reinfarction or required bypass surgery. At follow-up 26 (81%) of 32 patients remained free of major cardiac events; of these, 24 (92%) were free of angina. Repeat angiography performed at 10.8+/-7.5 months in 26 (87%) of 30 discharged patients showed that all infarct-related arteries were patent and the restenosis rate was low: 22% in the 13 patients with evolving AMI (<14 hours) and 12% in the 19 patients with recent AMI (days 2 through 7). CONCLUSION: In this study stenting of the infarct-related artery in patients with evolving and recent AMI was associated with a favorable late clinical outcome. Patency of the infarct-related artery was well maintained, and the restenosis rate was low.

Coronary stenting in acute myocardial infarction--patency demonstrated postmortem.

This report describes a patient with an acute anterior myocardial infarction treated by primary angioplasty and stenting of the infarct-related artery. The patient died 48 h later and at postmortem examination, patency of the stented artery was demonstrated, despite the adverse conditions which preceded death.

Usefulness of intracoronary stenting in acute myocardial infarction.

Data on the feasibility, safety, and clinical outcome of intracoronary stenting in acute myocardial infarction (AMI) are limited. This study examined the immediate angiographic results and the early and late outcomes in 32 patients who had stenting during AMI. Coronary angiograms recorded at the time of stenting were reviewed with quantitative measurements obtained on the "target" coronary lesion before and after stenting. Immediate angiographic success was achieved in 30 patients (94%). The minimal luminal diameter increased from 0.36 +/- 0.37 to 2.58 +/- 0.41 mm (p<0.0001). Two patients died in the hospital. Of the remainder, none had reinfarction or required bypass surgery, whereas 2 required repeat coronary angioplasty for recurrent ischemia. Although thrombus at the infarct-related coronary lesion was initially detected in 41% of the patients, its presence was not associated with adverse procedural outcome. Only 1 patient had persistent thrombus after stenting, which resolved with intracoronary urokinase. At a mean follow-up of 6.1 +/- 4.1 months, there was 1 additional cardiac death, and no patient had AMI or required repeat coronary angioplasty or bypass; among the 29 survivors, 86% were free of angina. Thus, intracoronary stenting of the infarct-related artery in the setting of AMI is associated with excellent immediate angiographic success and a favorable clinical outcome, and remains an option even in the presence of thrombus.

Refractory ventricular fibrillation complicating acute myocardial infarction terminated by intracoronary stenting.

We report on a case of intractable recurrent ventricular fibrillation that responded poorly to antiarrhythmic medication and balloon angioplasty, but resolved instantaneously following intracoronary stenting.