Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin

https://doi.org/10.1016/0002-9343(91)90053-ZGet rights and content

Abstract

This randomized, double-blind, multicenter, diet-and-placebo-controlled study was designed to clarify the dose-response relationship of lovastatin therapy to lipid-modifying efficacy and drug-related adverse events. Exclusion criteria were minimized so that study patients were representative of the majority of patients with moderate hypercholesterolemia seen in medical practice. After 6 weeks on the American Heart Association Step 1 Diet, a total of 8,245 patients were randomly assigned to 48 weeks of treatment with diet and placebo or lovastatin at dosages of 20 or 40 mg once a day or 20 or 40 mg twice a day. All adverse events were monitored, with particular attention to evaluation of liver and muscle. Liver transaminase elevations suggestive of possible hepatotoxicity, defined as successive elevations in either aspartate transaminase or alanine aminotransferase >3 times the upper limit of normal, occurred in equal numbers of placebo and lovastatin 20 mg/day treated patients (0.1%). The frequencies were higher in lovastatin 40 mg/day and 80 mg/day patient groups (0.9 and 1.5%, respectively). No patient was diagnosed as having clinically symptomatic hepatic dysfunction. Creatine kinase (CK) elevations above the upper limit of normal occurred frequently in placebo- (29%), as well as lova- statin-treated patients (29–35%), and muscle symptoms were reported with similar frequency in all groups (7–9%). The combination of muscle symptoms with marked CK elevations (>10 times the upper limit of normal) was seen in only five patients: one in a 40 mg/ day dose group and four in the 80 mg/day dose group. No patient developed rhabdomyolysis. The incidence of clinical and laboratory adverse events requiring discontinuation was 6% for the placebo group and from 7% (20 mg/day) to 9% (80 mg/day) for lovastatin treatment groups. No new types of adverse experiences related to lovastatin treatment were reported. Lovastatin, as an adjunct to diet for the reduction of elevated LDL cholesterol, was generally very well tolerated.

References (16)

  • AM Laties et al.

    The Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. II. Assessment of the human lens after 48 weeks of treatment with lovastatin

    Am J Cardiol

    (1991)
  • AW Alberts et al.

    Lovastatin

    Cardiovasc Drug Rev

    (1989)
  • DW Bilheimer et al.

    Mevinolin stimulates receptor-medicated clearance of low-density lipoprotein from plasma in familial hypercholesterolemia heterozygotes

    Trans Assoc Am Phys

    (1983)
  • SM Grundy

    HMG-CoA reductase inhibitors for treatment of hypercholesterolemia

    N Engl J Med

    (1988)
  • JM Hoeg et al.

    3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in the treatment of hypercholesterolemia

    JAMA

    (1987)
  • RJ Havel et al.

    Lovastatin (Mevinolin) in the treatment of heterozygous familial hypercholesterolemia

  • Therapeutic response to lovastatin (Mevinolin) in nonfamilial hypercholesterolemia

  • A multicenter comparison of lovastatin and cholestyramine therapy for severe primary hypercholesterolemia

    JAMA

    (1988)
There are more references available in the full text version of this article.

Cited by (120)

  • Safety of Statins and Nonstatins for Treatment of Dyslipidemia

    2022, Endocrinology and Metabolism Clinics of North America
    Citation Excerpt :

    Clinical trials have documented transaminase elevation greater than 3 times ULN, with a similar repeat measurement, in 1% of patients taking the highest statin doses.11 Elevations in alanine aminotransferase (ALT) usually exceed elevations in aspartate aminotransferase (AST).44,45 If AST exceeds ALT, another etiology, such as muscle injury or alcohol, could be the cause.

  • Dyslipidemia in the Elderly

    2020, Endocrinology of Aging: Clinical Aspects in Diagrams and Images
  • Dyslipidemia and Type II Diabetes

    2019, Pediatric Type II Diabetes
  • Statins: Rationale, mode of action, and side effects

    2019, The Impact of Nutrition and Statins on Cardiovascular Diseases
View all citing articles on Scopus
View full text