A double-blind randomized multicenter dose-ranging trial of intravenous streptokinase in acute myocardial infarction.

Intravenous streptokinase administration is now a widely applied therapy for patients in the early hours of acute myocardial infarction (AMI). The dosages used do not appear to be based on comparative clinical investigations. Therefore a double-blind randomized trial was carried out to establish the optimal dose of streptokinase. A total of 189 patients who had symptoms of AMI for less than 4 hours were treated with 200,000, 750,000, 1,500,000 or 3,000,000 IU streptokinase intravenously. At coronary angiography 2.8 +/- 2.7 hours (mean +/- standard deviation) after the start of streptokinase infusion, patency of the infarct-related coronary artery was observed in 38, 75, 60 and 82% of the patients, respectively, in the 4 groups. The result of the dosage of 200,000 IU was significantly poorer than that of the other dosages (p less than 0.01). The result of a dosage of 3,000,000 IU was significantly better than that of 1,500,000 IU (p less than 0.05), but the differences with 750,000 IU were not significant. Blood transfusion was required in 4 patients (2%), distributed over the 4 groups in 0, 2, 1 and 1 of the patients. One patient had major bleeding; this patient had been treated with 750,000 IU. The 3-month mortality-rate in the whole study population was 5%. Thus, of the 4 doses of streptokinase tested, 750,000 IU is the minimal therapeutic dosage, and the arguments for 1,500,000 IU as standard therapy for comparison with other fibrinolytic drugs are poor. The best results in this study were achieved with 3,000,000 IU, but further research will be needed to establish the efficacy and safety of this new regimen.

Magnesium therapy in acute myocardial infarction.

The trials reviewed in this study investigated the effect of intravenous magnesium on arrhythmias and mortality in acute myocardial infarction. Nine trials were carried out in the pre-thrombolytic era. They varied in set-up, number of patients, dose of magnesium, follow-up and the type of arrhythmias analyzed. Magnesium reduced mortality in most studies, but the reduction was significant in only three of them. Two meta-analyses of the smaller studies revealed a 55% reduction in mortality. In the LIMIT-2, in which 2300 patients were enrolled, magnesium reduced mortality significantly by 24%. The effect of magnesium on arrhythmias was less clear. Preliminary results of ISIS-4, in which magnesium among others was administered together with thrombolytic agents, did not provide evidence of benefit in patients with suspected myocardial infarction. At present there are no arguments for the use of magnesium in acute myocardial infarction.

Diagnostic value of a heart-type fatty acid-binding protein (H-FABP) bedside test in suspected acute coronary syndrome in primary care.

BACKGROUND: To determine the diagnostic accuracy of a rapid heart-type fatty acid-binding protein (H-FABP) test in patients suspected of acute coronary syndrome (ACS) in primary care. METHODS: General practitioners included 298 patients suspected of ACS. In all patients, whether referred to hospital or not, ECG and cardiac biomarker testing was performed. ACS was determined in accordance with international guidelines. Multivariate analysis was used to determine the value of H-FABP in addition to clinical findings. RESULTS: Mean patient age was 66 years (SD 14), 52% was female and 66 patients (22%) were diagnosed with ACS. The H-FABP bedside test was performed within 24h (median 3.1, IQR 1.5 to 7.1) after symptom onset. The positive predictive value (PPV) of H-FABP was 65% (95% confidence interval (CI) 50-78). The negative predictive value (NPV) was 85% (95% CI 80-88). Sensitivity was 39% (29-51%) and specificity 94% (90-96%). Within 6h after symptom onset, the PPV was 72% (55-84) and the NPV was 83% (77-88), sensitivity 43% (31-57%) and specificity 94% (89-97%). Adding the H-FABP test to a diagnostic model for ACS led to an increase in the area under the receiver operating curve from 0.66 (95% CI 0.58-0.73) to 0.75 (95% CI 0.68-0.82). CONCLUSION: The H-FABP rapid test provides modest additional diagnostic certainty in primary care. It cannot be used to safely exclude rule out ACS. The test can only be used safely in patients otherwise NOT referred to hospital by the GP, as an extra precaution not to miss ACS ('rule in').