Elsevier

Journal of Clinical Lipidology

Volume 5, Issue 2, March–April 2011, Pages 97-104
Journal of Clinical Lipidology

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

https://doi.org/10.1016/j.jacl.2011.01.006Get rights and content

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-anlaysis. 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.

Section snippets

Methods

The methods used in the meta-analysis have been published elsewhere.9 Of the 488 relevant titles identified from the MEDLINE, Cochrane Library, Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov (Fig. 1), 27 appropriate studies were reviewed, and only 8 fulfilled the inclusion criteria (randomized, pertaining to lipid-lowering medications, and with data on all-cause mortality, Table 1, Table 2).6, 8, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 In the

Description of the studies

The eight studies included in this analysis are described in Table 1, Table 2. Five studies pertain to the use of statins: atorvastatin,8, 14 fluvastatin,12, 13 pravastatin (two studies),20, 21, 22, 23 and simvastatin10, 11; one study to cholestyramine6, 17; one to gemfibrozil18, 19, 24; and one to niacin.15, 16 The total number of patients included in the first phase (average follow-up 66 months) of the 8 studies was 44,255. Of the enrolled patients, 3788 died during the first phase, 40,043

Discussion

This analysis shows that in randomized clinical trials, the benefit of lipid-lowering therapy with bile acid sequestrants, gemfibrozil, niacin, and statins persisted after discontinuation of blinded therapy when all study patients received active therapy. The probability of receiving active therapy during the first phase of the studies was, on average, six times greater for patients randomized to active therapy compared with for those randomized to placebo. A similar lowering of all-cause and

References (33)

  • M. Briel et al.

    Effects of early treatment with statins on short-term clinical outcomes in acute coronary syndromes: a meta-analysis of randomized controlled trials

    JAMA

    (2006)
  • P.M. Ridker et al.

    Jupiter Study Group. Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein

    N Engl J Med

    (2008)

  • The Lipid Research Clinics Coronary Primary Prevention Trial Results. I Reduction in incidence of coronary heart disease

    JAMA

    (1984)
  • Brown MS, Goldstein JL. Lowering LDL—not only how low, but how long? Science....
  • P.S. Sever et al.

    ASCOT Investigators: the anglo-Scandinavian Cardiac Outcomes Trial Lipid Lowering Arm: extended observations 2 years after trial closure

    Eur Heart J

    (2008)
  • W.J. Kostis et al.

    Persistence of mortality reduction after the end of randomized therapy in clinical trials of blood pressure lowering medications

    Hypertension

    (2010)

    • Cited by (0)

    View full text
    Copyright © 2011 National Lipid Association. Published by Elsevier Inc. All rights reserved.