Correspondence

Discontinuation of Antihyperlipidemic Drugs

N Engl J Med 1995; 333:1082-1083October 19, 1995

Article

To the Editor:

In their article on the discontinuation of antihyperlipidemic drugs, Andrade et al. (April 27 issue)1 discuss the generalizability of the results of randomized trials. Specifically, they state that discontinuation rates in randomized trials may not accurately reflect the tolerability or effectiveness of therapy in the general population. In reaching their conclusions, however, they appear to overlook an additional factor. There were 2369 study patients and 3223 courses of therapy. During the study period 854 participants therefore changed therapy.

The period of the study corresponds to the clinical introduction of lovastatin and simvastatin. The early results of trials showing the superiority of lovastatin over cholestyramine and probucol were available in 1988.2,3 These drugs were recognized as having fewer side effects and thus being less likely to require the cessation of therapy.4 With the introduction and marketing of these new drugs, a proportion of patients probably changed therapy because the new drugs were perceived as better. This may explain the large differences in discontinuation rates for the bile acid sequestrants, niacin, and gemfibrozil and the minor and statistically nonsignificant differences in the rates for lovastatin.

Peter Ellis, M.B., B.S.
St. George Hospital, Kogarah, NSW 2217, Australia

4 References

1. 1

   Andrade SE, Walker AM, Gottlieb LK, et al. Discontinuation of antihyperlipidemic drugs -- do rates reported in clinical trials reflect rates in primary care settings? N Engl J Med 1995;332:1125-1131
   Full Text | Web of Science | Medline

2. 2

   Lovastatin Study Group III. A multicentre comparison of lovastatin and cholestyramine for severe primary hypercholesterolemia. JAMA 1988;260:359-366
   CrossRef | Web of Science

3. 3

   Davignon J, Dujovne CA, Frohlich J, et al. A comparison of lovastatin and probucol for the treatment of primary hypercholesterolemia. Arteriosclerosis 1988;8:587a-587a abstract.
   

4. 4

   Tobert JA, Shear CL, Chremos AN, Mantell GE. Clinical experience with lovastatin. Am J Cardiol 1990;65:23F-26F
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We agree that the introduction of new drugs creates a state of flux in patterns of drug use, which has been observed with other classes of drugs.1 The study period, 1988 to 1990, corresponded to the clinical introduction of lovastatin (simvastatin was introduced later), and the perceived benefit of this agent, noted by Dr. Ellis, may have been one reason for the initiation of therapy with lovastatin. However, in only one case did the medical chart document a switch to lovastatin from another antihyperlipidemic agent specifically because of the perceived benefit of lovastatin. The primary reasons for the discontinuation of antihyperlipidemic therapy documented in our study were adverse effects and therapeutic ineffectiveness.

As a point of clarification, 790 patients (33 percent), not 854, as stated by Dr. Ellis, changed antihyperlipidemic therapies during the study period.

Susan E. Andrade, Sc.D.
Alexander M. Walker, M.D., Dr.P.H.
Harvard School of Public Health, Boston, MA 02115

1 References

1. 1

   Walker AM, Chan KW, Yood RA. Patterns of interchange in the dispensing of non-steroidal anti-inflammatory drugs. J Clin Epidemiol 1992;45:187-195
   CrossRef | Web of Science | Medline