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Cardiac rupture, mortality and the timing of thrombolytic therapy: a meta-analysis
M B Honan1, F E Harrell, K A Reimer
1Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Insights
Early thrombolytic therapy for acute myocardial infarction significantly reduces cardiac rupture risk and improves survival. Late treatment may increase rupture risk despite some survival benefits.
Area of Science:
- Cardiology
- Clinical Trials
- Medical Statistics
Background:
- Acute myocardial infarction (AMI) is a leading cause of cardiac mortality.
- Thrombolytic therapy is a cornerstone treatment for AMI.
- The relationship between treatment timing and cardiac rupture risk requires further elucidation.
Purpose of the Study:
- To investigate the association between the timing of thrombolytic therapy and the risk of cardiac rupture in patients with AMI.
- To determine if early thrombolytic administration prevents cardiac rupture while late administration promotes it.
Main Methods:
- Pooled data from randomized controlled trials of thrombolytic agents for AMI.
- Logistic regression analysis to assess the odds ratio of cardiac rupture in relation to time to treatment.
- Independent confirmation using data from the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) trial.
- Analysis of mortality data to correlate time to treatment with the odds ratio of death.
Main Results:
- A direct correlation was found between time to thrombolytic treatment and the odds ratio of cardiac rupture (p = 0.01).
- Cardiac rupture risk increased significantly with delayed treatment, with odds ratios of 0.4 at 7h, 0.93 at 11h, and 3.21 at 17h.
- A similar direct correlation was observed between time to treatment and the odds ratio of death (p = 0.006).
Conclusions:
- Administering thrombolytic therapy early after acute myocardial infarction improves survival and reduces the risk of cardiac rupture.
- Late administration of thrombolytic therapy may increase the risk of cardiac rupture, although it appears to offer some survival benefits.
Abstract:
This study examined the relation between the risk of cardiac rupture and the timing of thrombolytic therapy for acute myocardial infarction. To test the hypothesis that cardiac rupture is prevented by early thrombolytic therapy but is promoted by late treatment, randomized controlled trials of thrombolytic agents for myocardial infarction were pooled. A logistic regression model including 58 cases of cardiac rupture among 1,638 patients from four trials showed that the odds ratio (treated/control) of cardiac rupture was directly correlated with time to treatment (p = 0.01); at 7 h, the odds ratio was 0.4 (95% confidence limits 0.17 to 0.93); at 11 h, it was 0.93 (0.53 to 1.60) and at 17 h, it was 3.21 (1.10 to 10.1). Analysis of data from the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) trial independently confirmed the relation between time to thrombolytic therapy and risk of cardiac rupture (p = 0.03). Analysis of 4,692 deaths in 44,346 patients demonstrated that the odds ratio of death was also directly correlated with time to treatment (p = 0.006); at 3 h, the odds ratio for death was 0.72 (0.67 to 0.77); at 14 h, it was 0.88 (0.77 to 1.00) and at 21 h, it was 1 (0.82 to 1.37). Thrombolytic therapy early after acute myocardial infarction improves survival and decreases the risk of cardiac rupture. Late administration of thrombolytic therapy also appears to improve survival but may increase the risk of cardiac rupture.