Discontinuation of Antihyperlipidemic Drugs — Do Rates Reported in Clinical Trials Reflect Rates in Primary Care Settings?
Susan E. Andrade, Sc.D., Alexander M. Walker, M.D., Dr.P.H., Lawrence K. Gottlieb, M.D., M.P.P., Norman K. Hollenberg, M.D., Ph.D., Marcia A. Testa, M.P.H., Ph.D., Gordon M. Saperia, M.D., and Richard Platt, M.D.
Background Discontinuation rates for drugs used to treat chronicconditions may affect the success of therapy. However, the discontinuationrates reported in clinical trials may not reflect those in primarycare settings.
Methods We conducted a cohort study using computerized researchfiles and medical records on 2369 new users of antihyperlipidemictherapy at two health maintenance organizations (HMOs) from1988 through 1990. The rates of drug discontinuation in theseprimary care settings were compared with the rates reportedin clinical trials published from 1975 through 1993, locatedwith the Medline data base.
Results In the HMOs, the one-year probability of drug discontinuationwas 41 percent for bile acid sequestrants (95 percent confidenceinterval, 38 to 44 percent), 46 percent for niacin (95 percentconfidence interval, 42 to 51 percent), 15 percent for lovastatin(95 percent confidence interval, 11 to 19 percent), and 37 percentfor gemfibrozil (95 percent confidence interval, 31 to 43 percent).For the bile acid sequestrants, niacin, and gemfibrozil, therisks of discontinuation were substantially higher in the HMOsthan in randomized clinical trials, in which the summary estimatesof this risk were 31 percent, 4 percent, and 15 percent, respectively,for trials of one year or longer. The rates of discontinuationin open-label studies were similar to those in the HMOs.
Conclusions The discontinuation rates reported in randomizedclinical trials may not reflect the rates actually observedin primary care settings. The effectiveness and tolerabilityof antihyperlipidemic medications should be studied furtherin populations that typically use the agents.
Source Information
From the Departments of Epidemiology (S.E.A., A.M.W.) and Biostatistics (M.A.T.), Harvard School of Public Health, Boston; Clinical Quality Management, Harvard Community Health Plan, Brookline, Mass. (L.K.G.); the Departments of Radiology and Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (N.K.H.); the Division of Cardiology, Fallon Clinic, Worcester, Mass. (G.M.S.); the Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Community Health Plan, and Channing Laboratory and the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (R.P.). Presented in part at the 10th International Conference on Pharmacoepidemiology, Stockholm, Sweden, August 30, 1994.
Address reprint requests to Dr. Walker at the Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave., Boston, MA 02115.
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