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.

Current understanding of in-stent restenosis and the potential benefit of drug eluting stents.

Percutaneous transluminal coronary angioplasty has revolutionized the management of patients with coronary artery disease. Unfortunately, the procedure's utility is limited by a frequent complication: restenosis. Coronary stenting prevents the elastic recoil and negative remodeling that can occur after angioplasty but, by inciting varying degrees of intimal expansion, it can also produce arterial renarrowing, known as in-stent restenosis (ISR). The precise mechanisms involved in the pathogenesis of ISR are incompletely understood. The recent introduction of drug-eluting stents (DESs) may help prevent ISR. However, DESs have not been universally successful, and they may introduce new complications that require further refinement. This review summarizes the current understanding of the pathogenesis of ISR and provides an objective overview of DESs.

Risperidone in the treatment of mania.

BACKGROUND: Risperidone, a 5-HT2 and D2 antagonist, has been shown to be an effective antipsychotic in the treatment of schizophrenia but has unclear efficacy in the treatment of psychotic affective disorders. The purpose of the study was to assess the efficacy of risperidone in the treatment of acute mania with psychotic features. METHOD: We conducted an open-label pilot study of risperidone and concurrent mood-stabilizing drugs in the treatment of acute mania with psychotic features. Patients were diagnosed with the Structured Clinical Interview for DSM-III-R (SCID). Efficacy was measured weekly with the use of the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). RESULTS: Ten women and 5 men (mean age = 38 years) were included in the study. Of the 13 patients who completed 2 weeks of treatment, 8 of these 13 had a 50% improvement of the BPRS, and all 13 had at least a 25% improvement (p = .002, 95% confidence interval [CI] = 46.0 to 57.8). Of the 8 patients who completed 6 weeks of treatment, 7 of the 8 had a 50% improvement, and all 8 had a 25% improvement (p = .012, 95% CI = 52.4 to 69.3). Similar results were obtained with the YMRS. By the second week of treatment, 10 of the 13 patients remaining in treatment had at least a 50% improvement, and 12 of these 13 had a 25% improvement (p = .002, 95% CI = 55.1 to 89.9). By the sixth week, all of the 8 patients remaining in treatment had a 75% improvement (p = .012, 95% CI = 90.5 to 102.8). The medication was well tolerated, and no case worsened. CONCLUSION: When used with concomitant mood-stabilizing drugs, risperidone may be effective and well tolerated in patients with acute mania with psychotic features. Considering the open design, small sample size, and limited period of observation, further studies need to be conducted.