Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Pravastatin reduced total and LDL cholesterol more than gemfibrozil in primary hypercholesterolemia

ACP J Club. 1991 May-June;114:77. doi:10.7326/ACPJC-1991-114-3-077


Source Citation

Crepaldi G, Baggio G, Arca M, et al. Pravastatin vs gemfibrozil in the treatment of primary hypercholesterolemia. The Italian Multicenter Pravastatin Study I. Arch Intern Med. 1990;151:146-52.


Abstract

Objective

To compare the efficacy and safety of pravastatin with gemfibrozil for primary (familial and polygenic) hypercholesterolemia.

Design

Randomized, double-blind, controlled trial of 24 weeks' duration.

Setting

13 lipid clinics in Italy.

Patients

The study enrolled 385 patients (mean age 53 y, 51% men) after an inadequate lipid and weight response to an 8-week isocaloric standardized dietary period. Patients were included if they had a diagnosis of primary hypercholesterolemia (polygenic or heterozygous familial). Exclusions included other hypercholesterolemias, obesity, abnormal liver or renal function, recent myocardial infarction or coronary artery bypass, organ transplants, significant gastrointestinal diseases, symptomatic cholelithiasis, potential for pregnancy, or use of hormones or hypolipidemic drugs. 94% completed the study.

Intervention

Patients received an intensive, low-cholesterol diet and either pravastatin (40 mg at bedtime) (n = 193) or gemfibrozil (600-mg tablet 1 hour before morning and evening meals) (n = 192). Placebos were given to match the alternative treatment.

Main outcome measures

Serum total cholesterol and low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)- cholesterol levels and side effects were measured every 4 weeks.

Main results

With pravastatin, mean total cholesterol levels fell from 9.2 mmol/L at baseline to 7.0 mmol/L at 24 weeks 23% decrease, P < 0.001). With gemfibrozil, mean total cholesterol levels fell from 9.1 mmol/L at baseline to 7.8 mmol/L 14% decrease, P < 0.001). The difference between the 2 groups was significant (P < 0.001). The decrease in the serum cholesterol level was almost all because of decreased LDL-cholesterol levels. Both pravastatin and gemfibrozil were more effective in reducing the LDL-cholesterol level in patients with polygenic rather than familial hypercholesterolemia, but pravastatin was more effective than gemfibrozil for both groups. Both drugs raised HDL-cholesteral levels over baseline: pravastatin by 5% (P < 0.05) and gemfibrozil by 13% (P < 0.05). 1 patient in the pravastatin group and 6 in the gemfibrozil group were withdrawn because their LDL-cholesterol reduction was less than 5%: 4 were withdrawn from the gemfibrozil group because of side effects (biliary colic, libido reduction, plasma creatinine increase, and upper gastrointestinal tract bleeding).

Conclusions

Pravastatin compared with gemfibrozil produced greater reductions in total and LDL-cholesterol levels in patients with both polygenic and familial hypercholesterolemia. Adverse events occurred infrequently and at the same levels in both treatment groups.

Source of funding: Squibb, Italy.

Address for article reprint: Dr. G. Baggio, Institute of Internal Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.


Commentary

The Italian multicenter trial is the largest study assessing the efficacy (measured in a setting designed to maximize compliance) and safety of pravastatin, a new HMG-CoA reductase inhibitor. Pravastatin is a hydrophilic compound approved for use in Canada, Japan, and several European countries, which, in animal studies, results in less extrahepatic impairment of cholesterol synthesis than do other members of this class.

Reduction of total and LDL-cholesterol levels were greater with pravastatin than with gemfibrozil and were comparable to estimates obtained in recent small trials of pravastatin in patients with heterozygous familial hypercholesterolemia and in trials of lovastatin in patients with both severe and moderate hypercholesterolemia (1). Pravastatin appeared to be well tolerated, resulting in no drug-related withdrawals from treatment. Transaminase elevations were slightly less common with pravastatin than gemfibrozil, and creatine kinase elevations were equally common.

Lovastatin remains the preferred member of this class of drugs because of more extensive clinical experience and a better characterized side-effect profile. The role of HMG-CoA reductase inhibitors in the pharmacologic treatment of hyperlipidemia, however, remains controversial. Their efficacy and relative scarcity of short-term side effects (transaminase elevation, myopathy, and possible lenticular abnormalities) have resulted in wide use. Long-term experience with these drugs, however, remains limited. Moreover, only bile acid-binding resins and fibric acid derivatives have shown reductions in myocardial infarction and coronary heart disease mortality associated with cholesterol lowering. HMG-CoA reductase inhibitors are most clearly indicated for severe or refractory hypercholesterolemia.

Murray Krahn, MD
Toronto Western DivisionThe Toronto HospitalToronto, Ontario, Canada


Reference

1. Grundy SM. HMG-CoA reductase inhibitors for treatment of hypercholesterolemia. N Engl J Med. 1988;319:24-33.