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Low-molecular-weight heparin during instability in coronary artery disease, Fragmin during Instability in Coronary
Insights
Subcutaneous low-molecular-weight heparin (dalteparin) combined with aspirin significantly reduces cardiac events in unstable coronary artery disease (CAD) patients. Early treatment is recommended for risk stratification, with long-term benefits requiring further study.
Area of Science:
- Cardiology
- Pharmacology
- Thrombosis
Background:
- Unstable coronary artery disease (CAD) poses a significant risk for new cardiac events.
- Intravenous heparin offers short-term benefits, while low-molecular-weight heparin (LMWH) presents a subcutaneous option for sustained treatment.
- The efficacy of subcutaneous LMWH in conjunction with aspirin for unstable CAD requires investigation.
Purpose of the Study:
- To evaluate the protective effect of subcutaneous dalteparin, in addition to aspirin and antianginal drugs, against new cardiac events in patients with unstable CAD.
Main Methods:
- A double-blind trial involving 1506 patients with unstable CAD (unstable angina or non-Q-wave myocardial infarction).
- Random assignment to subcutaneous dalteparin or placebo for an initial 6 days, followed by a 35-45 day maintenance phase.
- Primary endpoint: rate of death and new myocardial infarction within the first 6 days; secondary endpoints included longer-term outcomes and revascularization procedures.
Main Results:
- Significantly lower rates of death and new myocardial infarction in the dalteparin group during the first 6 days (1.8% vs. 4.8%).
- Reduced need for intravenous heparin and revascularization procedures in the dalteparin group.
- Benefits were primarily observed in non-smokers, with a noted risk of reinfarction upon dose reduction in smokers. Long-term differences were not significant.
Conclusions:
- Combination therapy with dalteparin and aspirin for at least 6 days is recommended for unstable CAD patients to mitigate early cardiac events.
- This regimen allows for risk stratification and selection of appropriate long-term treatment strategies.
- Further research is warranted to assess the role of long-term dalteparin therapy versus early invasive procedures.
Background:
Intravenous heparin is at least as effective as aspirin in preventing new cardiac events after an episode of unstable coronary artery 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, in addition to aspirin and antianginal drugs, is protective against new cardiac events in unstable CAD.
Methods:
1506 patients with unstable CAD (unstable angina or non-Q-wave myocardial infarction) took part in a double-blind trial and were randomly assigned subcutaneous dalteparin (Fragmin; 120 IU per kg bodyweight [maximum 10 000 IU] twice daily for 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 myocardial infarction during the first 6 days. Secondary endpoints were the rates of death and new myocardial infarction after 40 and 150 days, the frequency of revascularisation procedures and need for heparin infusion, and a composite endpoint.
Findings:
During the first 6 days the rate of death and new myocardial infarction was lower in the dalteparin group than in the placebo group (13 [1.8%] vs 36 [4.8%]; risk ratio 0.37 [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 revascularisation (3 [0.4%] vs 9 [1.2%]; 0.33 [0.10-1.10]). The composite endpoint (death, myocardial infarction, revascularisation, intravenous heparin) 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 endpoint persisted, although subgroup analysis showed that the effect was confined to non-smokers (80% of sample). Survival analysis showed a risk of reactivation and reinfarction when the dose was decreased, more pronounced in smokers. 4-5 months after the end of treatment, there were no significant differences in the rates of death, new myocardial infarction, or revascularisation. The regimen was safe and compliance was adequate.
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 and to allow time for risk stratification and selection of a long-term treatment strategy. Long-term dalteparin treatment instead of or in addition to early invasive procedures warrants further assessment.