Improved reperfusion and clinical outcome with enoxaparin as an adjunct to streptokinase thrombolysis in acute myocardial infarction. The AMI-SK study.

AIMS: To establish whether the addition of enoxaparin (a low-molecular-weight heparin) to streptokinase therapy improves early and sustained coronary patency and clinical outcome in patients with evolving myocardial infarction. METHODS AND RESULTS: A total of 496 patients with acute myocardial infarction treated with streptokinase were randomized to an intravenous bolus (30 mg) and subcutaneous injections (1mg x kg(-1), twice daily) of enoxaparin (n=253), or placebo (n=243) for 3-8 days. The median duration of treatment in both groups was 5 days. ST-segment resolution at 90 min and 180 min measured by electrocardiogram was improved in patients receiving enoxaparin. Complete, partial and no ST-segment resolution at 180 min was observed in 36%, 44% and 19% in the enoxaparin group vs 25%, 44% and 31% in the placebo group, respectively (P=0.004). Assessment of the primary end-point revealed improved TIMI-3 flow with enoxaparin vs placebo (70% vs 58%, P=0.01). Combined TIMI-2 and -3 flow was also improved (88% vs 72%, P=0.001), as was TIMI frame count (P=0.003). The triple clinical end-point of death, reinfarction and recurrent angina at 30 days was reduced with enoxaparin (13% vs 21%, P=0.03). CONCLUSION: Streptokinase in combination with enoxaparin is associated with better ST-segment resolution and better angiographic patency at days 5-10, suggesting more effective reperfusion. This was associated with a significant reduction in clinical events, indicating less reocclusion.

Randomized comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin and Aspirin Reperfusion Therapy (HART II).

BACKGROUND: Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecular-weight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI. METHODS AND RESULTS: Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI grade 3 to TIMI 0 or 1 flow, respectively, occurred in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1% in the UFH group. Adverse events occurred with similar frequency in both treatment groups. CONCLUSIONS: Enoxaparin was at least as effective as UFH as an adjunct to thrombolysis, with a trend toward higher recanalization rates and less reocclusion at 5 to 7 days.

The TETAMI trial: the safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and of tirofiban versus placebo in the treatment of acute myocardial infarction for patients not thrombolyzed: methods and design.

Patients with acute myocardial infarction (AMI) who do not receive early reperfusion therapy are at high risk of reinfarction or death, and the efficacy and safety of antithrombotic therapy in this group of patients has not been evaluated. Enoxaparin is a low-molecular-weight heparin (LMWH) that has previously been shown to reduce the incidence of ischemic events in patients with unstable angina or non-Q-wave MI. The principal aims of the TETAMI study are to investigate the efficacy and safety of treatment with enoxaparin or tirofiban (a glycoprotein IIb/IIIa receptor antagonist) alone or in combination for 2 to 8 days in patients with AMI who are not eligible for early reperfusion therapy. In this 2 by 2 factorial design study approximately 900 patients will be randomly assigned, in a blinded manner, to one of four treatments: enoxaparin alone, enoxaparin plus tirofiban, unfractionated heparin (UFH), or UFH plus tirofiban, with appropriate matched placebos. The primary end point is the composite of death, recurrent AMI, and recurrent angina, analyzed at 30 days after AMI. The design and methods of the TETAMI study are described in this article.

Inter-regional differences and outcome in unstable angina; analysis of the international ESSENCE trial. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events.

AIMS: Worldwide there is a large variation in outcome (death, myocardial infarction and recurrent myocardial infarction) in patients with unstable angina or non-Q wave myocardial infarction. These variations may be explained by differences in characteristics of the presenting patients. Here we describe differences in patient presentation, treatment protocols and outcome and we investigate their relationship using data from the ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events) trial. METHODS: A total of 2981 patients from six countries which enrolled more than 100 patients were included in the present analysis: United States, Canada, Argentina, France, the Netherlands and United Kingdom. Logistic regression analysis was performed to determine the effect of baseline characteristics on regional outcome. RESULTS: At day 30, the lowest triple end-point rate, irrespective of study drug treatment, was noted in the Netherlands (18.9%) and the highest in Argentina (30.5%). A model including the variables age > or = 65 years, prior angina, diabetes, prior aspirin use, ECG changes at baseline and diagnosis of non-Q wave myocardial infarction and dummy variables for Argentina and France resulted in concordance of about 60%. CONCLUSIONS: Inter-regional differences in outcome in unstable angina and non-Q wave myocardial infarction patients can reasonably well be explained by differences in patient characteristics. However, other so far unidentified variables present in Argentina and France also contributed to differences in outcome and their effect warrants further investigation.

[Male osteoporosis]. / L'ostéoporose masculine.

AN UPCOMING PUBLIC HEALTH PROBLEM: There has been a considerable focus on osteoporosis in men recently. Bone mass is high in men who have larger bones than women. The frequency of fractures is also higher due to post-trauma lesions. Femoral neck fractures have also increased over the last few years although the F/M ratio remains about 2.8. Overall, there is a trend towards an increased incidence of masculine osteoporosis (and vertebral fractures) due to population aging. FAVORING FACTORS IN MEN: The most important factors are hypoandrogenism, hypoestrogenism (pre or post-puberty), the alcohol-smoking association, malnutrition, lack of sun exposure and chronic liver disease. Other causes of osteoporosis (hyperthyroidism, Cushing's disease, hemochromatosis, gastrectomy, inflammatory rheumatic disease, tubulopathy, hypercalciuria and iatrogenic causes) should also be taken into consideration. PRETHERAPY WORK-UP: All the different possible etiologies should be investigated. Therapeutic protocols should provide hormone replacement when required, withdrawal of causal drugs, better nutrition and reduced alcohol and tobacco use.