LOW-MOLECULAR-WEIGHT HEPARIN DURING INSTABILITY IN CORONARY-ARTERY DISEASE

Background Intravenous heparin is at least as effective as aspirin in preventing new cardiac events after an episode of unstable coronary ar tery disease (CAD), though the benefits are short-lived. Low-molecular -weight heparin has similar antithrombotic properties but can be given subcutaneously and is therefore suitable for long-term treatment. We have investigated whether subcutaneous low-molecular-weight heparin, i n addition to aspirin and antianginal drugs, is protective against new cardiac events in unstable CAD. Methods 1506 patients with unstable C AD (unstable angina or non-Q-wave myocardial infarction) took part in a double-blind trial and were randomly assigned subcutaneous daltepari n (Fragmin; 120 IU per kg bodyweight [maximum 10 000 IU] twice daily f or 6 days then 7500 IU once daily for the next 35-45 days) or placebo injections. The primary endpoint was the rate of death and new myocard ial infarction during the first 6 days. Secondary endpoints were the r ates of death and new myocardial infarction after 40 and 150 days, the frequency of revascularisation procedures and need for heparin infusi on, and a composite endpoint. Findings During the first 6 days the rat e of death and new myocardial infarction was lower in the dalteparin g roup than in the placebo group (13 [1.8%] vs 36 [4.8%]; risk ratio 0.3 7 [95% CI 0.20-0.68]), as were the frequencies of need for intravenous heparin (28 [3.8%] vs 58 [7.7%]; 0.49 [0.32-0.75]) and need for revas cularisation (3 [0.4%] vs 9 [1.2%]; 0.33 [0.10-1.10]). The composite e ndpoint(death, myocardial infarction, revascularisation, intravenous h eparin) also showed a significant difference in favour of dalteparin ( 40 [5.4%] vs 78 [10.3%]; 0.52 [0.37-0.75]). At 40 days the differences in rates of death and myocardial infarction and the composite endpoin t persisted, although subgroup analysis showed that the effect was con fined to non-smokers (80% of sample), Survival analysis showed a risk of reactivation and reinfarction when the dose was decreased, more pro nounced in smokers. 4-5 months after the end of treatment, there were no significant differences in the rates of death, new myocardial infar ction, or revascularisation. The regimen was safe and compliance was a dequate. Interpretation We recommend that treatment with a combination of dalteparin and aspirin for at least 6 days should be considered in patients with unstable CAD to reduce the risk of new cardiac events a nd to allow time for risk stratification and selection of a long-term treatment strategy. Long-term dalteparin treatment instead of or in ad dition to early invasive procedures warrants further assessment.