A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with Novastan and TPA (MINT) study

AbstractOBJECTIVESThis study examined the effect of a small-molecule, direct thrombin inhibitor, argatroban, on reperfusion induced by tissue plasminogen activator (TPA) in patients with acute myocardial infarction (AMI).BACKGROUNDThrombin plays a crucial role in thrombosis and thrombolysis. In vitro and in vivo studies have shown that argatroban has advantages over heparin for the inhibition of clot-bound thrombin and for the enhancement of thrombolysis with TPA.METHODSOne hundred and twenty-five patients with AMI within 6 h were randomized to heparin, low-dose argatroban or high-dose argatroban in addition to TPA. The primary end point was the rate of thrombolysis in myocardial infarction (TIMI) grade 3 flow at 90 min.RESULTSTIMI grade 3 flow was achieved in 42.1% of heparin, 56.8% of low-dose argatroban (p = 0.20 vs. heparin) and 58.7% of high-dose argatroban patients (p = 0.13 vs. heparin). In patients presenting after 3 h, TIMI grade 3 flow was significantly more frequent in high-dose argatroban versus heparin patients: 57.1% versus 20.0% (p = 0.03 vs. heparin). Major bleeding was observed in 10.0% of heparin, and in 2.6% and 4.3% of low-dose and high-dose argatroban patients, respectively. The composite of death, recurrent myocardial infarction, cardiogenic shock or congestive heart failure, revascularization and recurrent ischemia at 30 days occurred in 37.5% of heparin, 32.0% of low-dose argatroban and 25.5% of high-dose argatroban patients (p = 0.23).CONCLUSIONSArgatroban, as compared with heparin, appears to enhance reperfusion with TPA in patients with AMI, particularly in those patients with delayed presentation. The incidences of major bleeding and adverse clinical outcome were lower in the patients receiving argatroban

Prospective Validation of the Prognostic Usefulness of B-Type Natriuretic Peptide in Asymptomatic Patients With Chronic Severe Aortic Regurgitation

ObjectivesThe purpose of this study was to determine the independent and additive prognostic value of B-type natriuretic peptide (BNP) in patients with severe asymptomatic aortic regurgitation and normal left ventricular function.BackgroundEarly surgery could be advisable in selected patients with chronic severe aortic regurgitation, but there are no uniform criteria to identify candidates who could benefit from this strategy. Assessment of BNP has not been studied for this purpose.MethodsWe prospectively evaluated 294 consecutive patients with severe asymptomatic organic aortic regurgitation and left ventricular ejection fraction above 55%. The first 160 consecutive patients served as the derivation cohort and the next 134 patients served as a validation cohort. The combined endpoint was the occurrence of symptoms of congestive heart failure, left ventricular dysfunction, or death at follow-up.ResultsThe endpoint was reached in 45 patients (28%) of the derivation set and in 35 patients (26%) of the validation cohort. Receiver-operator characteristic curve analysis yielded an optimal cutoff point of 130 pg/ml for BNP that was able to discriminate between patients at higher risk in both cohorts. BNP was the strongest independent predictor by multivariate analysis in the derivation set (odds ratio: 6.9 [95% confidence interval: 2.52 to 17.57], p < 0.0001) and the validation set (odds ratio: 6.7 [95% confidence interval: 2.9 to 16.9], p = 0.0001).ConclusionsAmong patients with severe asymptomatic aortic regurgitation and normal left ventricular function, BNP ≥130 pg/ml categorizes a subgroup of patients at higher risk. Because of its incremental prognostic value, we believe BNP assessment should be used in the routine clinical evaluation of these patients

Early reperfusion and late clinical outcomes in patients presenting with acute myocardial infarction randomly assigned to primary percutaneous coronary intervention or streptokinase

Primary percutaneous coronary intervention (PCI) has become an alternative to thrombolytic therapy as a reperfusion strategy for ST-elevation acute myocardial infarction (AMI). The main goal of this study was to determine whether PCI and thrombolytic therapy achieve comparable reperfusion rates, as evidenced by ST-segment resolution. Secondary end points included infarct vessel patency rates before hospital discharge and short- and long-term outcomes. Patients with ischemic chest pain with duration ≤12 hours and no contraindication for thrombolytic therapy were included. Between October 1993 and August 1995, 58 patients were randomly assigned to streptokinase (SK) and 54 patients to primary PCI. Baseline clinical characteristics and infarct location were well balanced in both groups. Median age (interquartile range) was 68 (58, 75) years, 29% were women, and 78% of the patients met at least one criterion for “not low risk” AMI (anterior location, age >70 years old, previous MI, systolic blood pressure 100 bpm). The median time from symptom onset to random assignment was 217 (139, 335) minutes in the PCI group and 210 (145, 334) minutes in the SK group. Median random assignment to balloon time was 82 (55, 100) minutes, and median random assignment to needle time was 15 (10, 26) minutes ( P < .0001). TIMI grade 3 flow after primary PCI was obtained in 85% of patients. The proportion of patients with ST-segment resolution ≥50% at 120 minutes was 80% in the PCI group and 50% in the SK group ( P = .001). The predischarge angiogram showed the presence of TIMI 3 flow in 96% of patients who received PCI and 65% of patients who received SK ( P < .001). A composite of in-hospital death, reinfarction, severe heart failure, stroke, and major bleeding occurred in 15% of patients who received PCI and 21% of patients who received SK ( P = .4). At 3 years, freedom from the composite end point of AMI, postdischarge revascularization, and death was 61% in the PCI group and 40% in the SK group ( P = .025). Our study shows that primary PCI, as compared with SK, is associated with more effective ST-segment resolution, higher patency rates in the infarct vessel at 7 days, and more favorable clinical outcomes at 3 years of follow-up