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Therapeutic trials in coronary thrombosis should measure left ventricular function as primary end-point of treatment
1Coronary Care Unit, Green Lane Hospital, Auckland, New Zealand.
Insights
Clinical trials for coronary thrombosis should prioritize measuring left ventricular function over mortality. Assessing ejection fraction requires significantly fewer patients than tracking deaths, making it a more efficient endpoint for evaluating new treatments.
Area of Science:
- Cardiology
- Clinical Trials
- Thrombosis Research
Background:
- Clinical trials in coronary thrombosis often use mortality or left ventricular function as endpoints.
- Hospital mortality for patients under 70 with effective thrombolysis should be approximately 5%.
Purpose of the Study:
- To evaluate the efficiency of using left ventricular function as a surrogate endpoint compared to mortality in clinical trials for coronary thrombosis.
- To determine the sample size required for detecting statistically significant differences in mortality versus ejection fraction.
Main Methods:
- Statistical analysis comparing sample sizes needed for mortality reduction versus ejection fraction improvement.
- Calculation of patient numbers required for a 20% mortality reduction (to 4%) versus a 25% improvement in ejection fraction.
Main Results:
- A 20% reduction in mortality requires 15,000 patients.
- A 25% improvement in ejection fraction (from 59% to 62%) requires only 384 patients.
Conclusions:
- Left ventricular function, specifically ejection fraction, is a more statistically efficient endpoint than mortality for coronary thrombosis trials.
- Future studies investigating thrombolytic and myocardial protective agents should consider left ventricular function as the primary endpoint due to reduced sample size requirements.
Abstract:
Clinical trials in coronary thrombosis can record as end-points either death or an index of left ventricular function (ejection fraction or end-systolic volume) which can be used as a surrogate for long-term mortality. Hospital mortality for patients under 70 years of age in whom effective thrombolysis is achieved should now be no more than about 5%. To show a 20% reduction (to 4%) in mortality with an alpha error (two-sided) of 0.05 and a beta error of 0.2 requires 15,000 patients. By contrast, a 25% improvement towards normal in ejection fraction (from about 59% to about 62%) requires only 384 patients. Since it is likely that one of several thrombolytic agents will be effective in conjunction with one or more myocardial protective agents, many trials will be required, and it may be more appropriate in future studies to measure left ventricular function rather than mortality as the principal end-point.