The American journal of cardiology
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Randomized Controlled Trial Clinical Trial
Effects of sildenafil citrate on human hemodynamics.
Nitric oxide (NO) induces the formation of intracellular cyclic guanosine monophosphate (cGMP) by guanylate cyclase. Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in men with erectile dysfunction. The NO-cGMP pathway also plays an important role in mediating blood pressure. ⋯ Sildenafil was well tolerated by subjects and patients in all studies, with headache and other symptoms of vasodilation the most commonly reported adverse effects of treatment. Modest, transient hemodynamic changes were observed in healthy men after single intravenous or oral doses of sildenafil even at supratherapeutic doses. In men with stable ischemic heart disease, sildenafil produced modest effects on hemodynamic parameters at rest and during exercise.
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Randomized Controlled Trial Clinical Trial
Economics, health-related quality of life, and cost-effectiveness methods for the TACTICS (Treat Angina With Aggrastat [tirofiban]] and Determine Cost of Therapy with Invasive or Conservative Strategy)-TIMI 18 trial.
Concern over escalating health care costs has led to increasing focus on economics and assessment of outcome measures for expensive forms of therapy. This is being investigated in the Treat Angina With Aggrastat [tirofiban] and Determine Cost of Therapy with Invasive or Conservative Strategy (TACTICS)-TIMI 18 trial, a randomized trial comparing outcome of patients with unstable angina or non-Q-wave myocardial infarction treated with tirofiban and then randomized to an invasive versus a conservative strategy. Hospital and professional costs initially and over 6 months, including outpatient costs, will be assessed. ⋯ By knowing utility and survival, quality-adjusted life years will be determined. These measures will permit the performance of a cost-effectiveness analysis, with the cost-effectiveness of the invasive strategy defined and the difference in cost between the invasive and conservative strategies divided by the difference in quality-adjusted life years. The economic and health-related quality of life aspects of TACTICS-TIMI 18 are an integral part of the study design and will provide a comprehensive understanding of the impact of invasive versus conservative management strategies on a broad range of outcomes after hospitalization for unstable angina or non-Q-wave myocardial infarction.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Direct thrombin inhibition and thrombolytic therapy: rationale for the Hirulog and Early Reperfusion/Occlusion (HERO-2) trial.
Worldwide, streptokinase continues to be used widely in the treatment of myocardial infarction because it is inexpensive and causes fewer intracranial hemorrhages than other thrombolytic regimens. However, in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-I) trial, the 90-minute angiographic Thrombolysis in Myocardial Infarction (TIMI) trial grade 3 flow rate with streptokinase was 43% lower than that with accelerated tissue plasminogen activator, and there was a higher incidence of death or disabling stroke with streptokinase (7.8% vs 6.9%, p <0.01). In the first Hirulog and Early Reperfusion/Occlusion (HERO-1) trial, 48% of patients given the direct thrombin inhibitor bivalirudin (formerly Hirulog, The Medicines Company) after streptokinase had TIMI 3 patency at 90 minutes, compared with 35% of patients given intravenous heparin (p <0.05). ⋯ In the HERO-2 trial, 17,000 patients presenting within 6 hours after the onset of acute myocardial infarction will be given aspirin and randomized to receive either intravenous heparin or bivalirudin before streptokinase is administered. The primary endpoint will be 30-day mortality, and secondary endpoints will include death or myocardial infarction within 30 days, and death or nonfatal disabling stroke. If the thrombin hypothesis is supported by improved clinical outcomes with bivalirudin in the HERO-2 trial, large-scale clinical trials will be needed to evaluate the administration of direct thrombin inhibitors before other thrombolytic regimens.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Invasive versus conservative strategies in unstable angina and non-Q-wave myocardial infarction following treatment with tirofiban: rationale and study design of the international TACTICS-TIMI 18 Trial. Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy. Thrombolysis In Myocardial Infarction.
In the management of unstable angina and non-Q-wave acute myocardial infarction (AMI), there is considerable debate regarding the use of invasive strategy versus conservative strategy. The Thrombolysis In Myocardial Infarction (TIMI) III B trial found similar clinical outcomes for the 2 strategies, but the Veterans Administration Non-Q-Wave Infarction Strategies in-Hospital trial found a higher mortality with the invasive strategy. Both these trials were conducted before platelet glycoprotein IIb/IIIa inhibition and coronary stenting, both of which improve clinical outcome. ⋯ Patients are randomized to an invasive strategy, involving cardiac catheterization within 4 to 48 hours and revascularization with angioplasty or bypass surgery if feasible, versus a conservative strategy, where patients are referred for catheterization only for recurrent pain at rest or provokable ischemia. The primary end point is death, MI, or rehospitalization for acute coronary syndromes through a 6-month follow-up. The trial is also testing the "troponin hypothesis," that baseline troponins T and I will be useful in selecting an optimal management strategy.
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Low-molecular-weight heparins in non-ST-segment elevation ischemia: the ESSENCE trial. Efficacy and Safety of Subcutaneous Enoxaparin versus intravenous unfractionated heparin, in non-Q-wave Coronary Events.
Combination antithrombotic therapy with heparin plus aspirin decreases the risk of recurrent ischemic events in patients with acute coronary syndromes without persistent ST-segment elevation. Compared with standard unfractionated heparin, low-molecular-weight heparin (LMWH) has a more predictable antithrombotic effect, is easier to administer, and does not require coagulation monitoring. At 176 hospitals in 3 continents, 3,171 patients with rest unstable angina or non-wave myocardial infarction were randomly assigned to either enoxaparin (a LMWH), 1 mg/kg twice daily subcutaneously, or to continuous intravenous unfractionated heparin, for a minimum of 48 hours to a maximum of 8 days. ⋯ The 30-day incidence of major bleeding complication was 6.5% versus 7.0% (p = not significant), but the incidence of minor bleeding was significantly higher in the enoxaparin group (13.8% vs 8.8%, p <0.001) due primarily to injection-site ecchymosis. Thus, combination antithrombotic therapy with enoxaparin plus aspirin is more effective than unfractionated heparin plus aspirin in decreasing ischemic outcomes in patients with unstable angina or non-Q-wave myocardial infarction in the early (30 days) phase. The lower recurrent ischemic event rate seen with the LMWH, enoxaparin, is achieved without an increase in major bleeding, but with an increase in minor bleeding complications due mainly to injection-site ecchymosis.