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Therapeutics

Lovastatin was more effective than pravastatin for hypercholesterolemia

ACP J Club. 1993 Nov-Dec;119:67. doi:10.7326/ACPJC-1993-119-3-067


Source Citation

The Lovastatin Pravastatin Study Group. A multicenter comparative trial of lovastatin and pravastatin in the treatment of hypercholesterolemia. Am J Cardiol. 1993 Apr 1;71:810-5.


Abstract

Objective

To compare the efficacy, tolerability, and safety of lovastatin and pravastatin in patients with primary hypercholesterolemia.

Design

Randomized, double-blind, incremental-dose trial of 18 weeks duration.

Setting

International trial.

Patients

672 patients (mean age 54 y, 49% men) with hypercholesterolemia (total cholesterol level > 250 mg/dL [6.5 mmol/L]) who had a low-density lipoprotein (LDL) cholesterol level > 160 mg/dL (4.1 mmol/L) and adequate compliance during a run-in period. Exclusion criteria were age < 25 or > 75 years, secondary hypercholesterolemia, triglyceride level > 300 mg/dL (3.42 mmol/L), ability to conceive, or diabetes mellitus. 91 % of patients completed the trial.

Intervention

After a 7-week placebo and diet run-in period, patients were randomized to receive lovastatin, 20 mg/d (n = 339), or pravastatin, 10 mg/d (n = 333), for 6 weeks. The doses were then increased, regardless of lipid response, to 40 and 80 mg/d of lovastatin, and 20 and 40 mg/d of pravastatin at 6 and 12 weeks, respectively.

Main outcome measures

Blood for lipid, lipoprotein, and safety measurements was obtained at baseline, and at weeks 6, 12, and 18. Patients were questioned at each visit about adverse events. A standard sleep questionnaire was included.

Main results

Data were analyzed at the Merck Research Laboratories. Intention-to-treat analysis was used. Lovastatin at doses of 20, 40, and 80 mg/d (at weeks 6, 12, and 18, respectively) produced LDL cholesterol reductions of 28%, 33%, and 39%, respectively. Pravastatin at doses of 10, 20, and 40 mg/d produced reductions of 19%, 25%, and 27%, respectively (P <0.001 for between-treatment differences at each week). Lovastatin was also more effective than pravastatin at each time point in reducing apolipoprotein B and very-low-density lipoprotein cholesterol and triglycerides at week 18. High-density lipoprotein levels did not differ, and neither drug affected lipoprotein (a) levels. Drug-related adverse events occurred in 25 patients (7%) taking lovastatin and in 28 (8%) taking pravastatin. Sleep scores were unchanged with lovastatin and improved at weeks 12 and 18 with pravastatin. The clinical safety profiles of the 2 drugs did not differ.

Conclusions

Lovastatin (20 to 80 mg/d) was more effective than pravastatin (10 to 40 mg/d) in reducing total and low-density lipoprotein cholesterol and apolipoprotein B in patients with primary hypercholesterolemia. The safety profiles of the 2 drugs were similar.

Source of funding: Merck Research Laboratories.

For article reprint: Dr. Y.B. Mitchel, Merck Research Laboratories, P.O. Box 2000, WBD-375, Rahway, NJ 07065-0914, USA. FAX 908-750-8484.


Commentary

Readers of medical literature are being increasingly exposed to product comparison studies. This study falls into this genre. Lovastatin was more effective than pravastatin in changing most lipid parameters. This difference may be related to the administration of pravastatin with evening meals, which reduces its bioavailability, rather than at bedtime, which is the common clinical practice. Because other studies have not shown differences in lovastatin efficacy, further studies are needed.

Both drugs significantly increased transaminase and creatine kinase levels, although we are told that the changes were clinically unimportant. This observation underscores the need to study the long-term safety of these drugs to alleviate concerns about the consequences of long-term administration.

Interestingly, the authors noted an improvement in the sleep score with pravastatin. This effect is consistent with other observations showing differences between lovastatin and pravastatin, either on nighttime sleep or daytime performance (1, 2). Whether these differences are agent specific or related to their lipid-lowering effects is unclear and needs further study. It does, however, highlight the increasingly complex relation between psychosocial behavior and cholesterol metabolism.

Finally, the protocol guidelines to initiate drug therapy do not conform with American and Canadian recommendations of an aggressive, stepped dietary intervention program before the introduction of lipid-lowering drug therapy. Is this an admission that dietary intervention has not been successful in lowering elevated cholesterol levels (3) and that as a consequence practice behavior may change?

Alexander Logan, MD
Mount Sinai Hospital Toronto, Ontario, Canada


References

1. Vgontzas AN, Kales A, Bixier EO, Manfreidl RL, Tyson KL. Effects of lovastatin and pravastatin on sleep efficiency and sleep stages. Clin Pharmacol Ther. 1991;50:730-7.

2. Roth T, Richardson GR, Sullivan JP, et al. Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance. Clin Cardiol. 1992;15:426-32.

3. Hunninghake DB, Stein EA, Dujovne CA, et al. The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia. N Engl J Med. 1993;328:1213-9.


Authors' Response

With regard to sleep, differences between lovastatin and pravastatin have not been observed in several large, well-controlled polysomnography studies. Also, a 550-patient comparative study using the same sleep questionnaire found no significant difference between simvastatin and pravastatin. All of these studies are cited in our paper.