Understanding IMPROVE-IT and LDL-C Lowering in CVD
Understanding IMPROVE-IT and LDL-C Lowering in CVD
Formalism in the statistical analysis of clinical outcome trials counts the first occurrence of a pre-specified endpoint event, e.g. a myocardial infarction or stroke but not subsequent clinical incidents. This provides a rigorous assessment of the treatment effect in terms of a relative or absolute risk reduction but does not capture the full clinical impact of the therapy. Cost-effectiveness assessments also are hampered by the lack of long-term follow-up data that stretch beyond the end of the trial. Given that vascular disease has a decades long pathogenesis and the fact that the first clinical manifestation of the underlying atherosclerotic process is but part of a disease trajectory, it makes sense to understand also the lifetime benefit of an intervention such as LDL-lowering therapy. Some of the key statin trials have published the results of prolonged follow-up that take into account events that occurred in-trial and those that happened during a period of extending surveillance either by reviewing patient records or through electronic record linkage. Fifteen years of electronic health record linkage in the case of WOSCOPS revealed that benefit from trial therapy in terms of risk reductions for heart failure (43%) and stroke (18%) occurred beyond the end of the 5-year-study period. Further, cost-effectiveness was much greater than first appreciated when a longer view was taken. By extrapolation, therefore, a full picture of the impact of ezetimibe in IMPROVE-IT, assuming that there is a small treatment effect on the primary endpoint, may only emerge when the entire disease trajectory is established for those in the two treatment arms.
Lifetime Benefit and Disease Trajectory
Formalism in the statistical analysis of clinical outcome trials counts the first occurrence of a pre-specified endpoint event, e.g. a myocardial infarction or stroke but not subsequent clinical incidents. This provides a rigorous assessment of the treatment effect in terms of a relative or absolute risk reduction but does not capture the full clinical impact of the therapy. Cost-effectiveness assessments also are hampered by the lack of long-term follow-up data that stretch beyond the end of the trial. Given that vascular disease has a decades long pathogenesis and the fact that the first clinical manifestation of the underlying atherosclerotic process is but part of a disease trajectory, it makes sense to understand also the lifetime benefit of an intervention such as LDL-lowering therapy. Some of the key statin trials have published the results of prolonged follow-up that take into account events that occurred in-trial and those that happened during a period of extending surveillance either by reviewing patient records or through electronic record linkage. Fifteen years of electronic health record linkage in the case of WOSCOPS revealed that benefit from trial therapy in terms of risk reductions for heart failure (43%) and stroke (18%) occurred beyond the end of the 5-year-study period. Further, cost-effectiveness was much greater than first appreciated when a longer view was taken. By extrapolation, therefore, a full picture of the impact of ezetimibe in IMPROVE-IT, assuming that there is a small treatment effect on the primary endpoint, may only emerge when the entire disease trajectory is established for those in the two treatment arms.
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