Continuation of mortality reduction after the end of randomized therapy in clinical trials of lipid-lowering therapy

Abstract

Background: Long-term follow-up of clinical trials with lipid-lowering medications has suggested a continuation of event reduction after study completion.

Objective: To evaluate the persistence of the benefit of lipid-lowering therapy in decreasing mortality after the end of clinical trials, when all patients were advised to take the same open-label lipid-lowering therapy.

Methods: Through searches of MEDLINE, the Cochrane Library, the Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov until June 2010 we identified randomized clinical trials of lipid-lowering agents with a second report describing results after the end of the trial.

Results: Among the 459 trials reviewed, only 8 including 44,255 patients and 8144 deaths qualified for the meta-analysis. All-cause and cardiovascular mortality were lower in the active intervention group during the first phase (0.84, 95% confidence interval [CI] 0.76-0.93; P = .0006 and 0.72, 95% CI 0.63-0.82, P < .0001, respectively) when 71 ± 23% of the patients randomized to receive active therapy actually received it compared with 13 ± 5% of patients who received active therapy although they were randomized to placebo (P = .0001). The lower mortality among those initially randomized to active therapy persisted during the second phase (odds ratio 0.90, 95% CI 0.84-0.97, P = .0035, and 0.82 95% CI 0.73-0.93, P = .0014), when patients in both randomized groups received active therapy in the same proportions (5 ± 2% for both groups). Numerous sensitivity analyses support the conclusions of the paper.

Conclusion: The decrease in mortality with lipid-lowering therapy in clinical trials persists after discontinuation of randomized therapy when patients in the treatment and placebo groups receive active therapy.