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


Therapeutics

Lovastatin was more effective than stepped care in reducing cholesterol

ACP J Club. 1996 Sept-Oct;125:37. doi:10.7326/ACPJC-1996-125-2-037


Source Citation

Oster G, Borok GM, Menzin J, et al. Cholesterol-Reduction Intervention Study (CRIS). A randomized trial to assess effectiveness and costs in clinical practice. Arch Intern Med. 1996 Apr 8;156:731-9.


Abstract

Objective

To compare a stepped-care regimen with initial treatment with lovastatin in patients with hypercholesterolemia.

Design

1-year randomized controlled trial.

Setting

3 Kaiser Permanente centers in southern California.

Patients

612 patients who were 20 to 70 years of age (mean age 56 y, 51% men) and had a low-density lipoprotein (LDL) cholesterol level between 4.14 and 5.95 mmol/L, had a triglyceride level < 4.52 mmol/L, had never used cholesterol-lowering medication, and had been unable to attain adequate cholesterol levels through diet alone. Exclusion criteria included recent myocardial infarction, bypass surgery, angioplasty, or hemoglobin A1 level > 0.10; unstable angina; hepatic dysfunction; secondary hypercholesterolemia; history of alcohol or drug abuse; or terminal illness. Follow-up was 90%.

Intervention

Patients were allocated to stepped care (n = 306) or to initial therapy with lovastatin (n = 306). Stepped care included niacin, 50 mg/d increased over 2 weeks to 1000 mg twice/d, and concomitant treatment with aspirin. If the goal of an LDL cholesterol level of ≤ 4.14 mmol/L was not attained after 1 month, the dose of niacin could be increased. The next step included replacement with or addition of a bile acid sequestrant, gemfibrozil, probucol, or lovastatin, depending on lipid profile. Control group patients received lovastatin, 20 mg/d, which could be increased to 80 mg/d.

Main outcome measures

Attainment of goal LDL cholesterol level and change in lipid levels.

Main results

Treatment with lovastatin led to more patients achieving the goal LDL cholesterol level at 1 year than did stepped care (40% vs 24%, P < 0.001). {This absolute risk improvement of 16% means that 6 patients would need to be treated with lovastatin (instead of the stepped-care approach) for 1 year for 1 additional patient to achieve the goal LDL cholesterol level, 95% CI 4 to 12; the relative risk improvement was 40%, CI 24% to 53%.}* Patients who received lovastatin had greater decreases than did patients who received stepped care in total cholesterol (16% vs 11%, P < 0.001) and in LDL cholesterol levels (22% vs 15%, P < 0.001). The cost of care with lovastatin was $333 higher than stepped care ($786 vs $453, P < 0.001).

Conclusion

Initial treatment with lovastatin was more effective and more costly than a stepped-care regimen in lowering total and low-density-lipoprotein cholesterol in patients with hypercholesterolemia.

Source of funding: Merck and Company Incorporated.

For article reprint: Dr. G. Oster, Policy Analysis Inc, 4 Davis Court, Brookline, MA 02146, USA. FAX 617-232-1155.

*Numbers calculated from data in article.


Commentary

Recent trials have shown that cholesterol lowering with statin therapy reduces coronary heart disease risk in both primary and secondary prevention settings. The potentially high cost of this treatment, however, has caused concern (1, 2). The lower cost of other agents, including niacin, makes them attractive competitors of statins (3). Niacin lowers total and LDL cholesterol levels less effectively than statins but has the potential advantage of raising HDL cholesterol levels and lowering triglyceride and lipoprotein (a) levels (4, 5). Niacin is not as well tolerated as statins, although some clinicians have noted good compliance if patients are carefully managed (4).

In this study by Oster and colleagues, more patients who received lovastatin were taking cholesterol-lowering medication at study end than were the patients who received stepped care. Further, although the protocol seemed to encourage multi-drug therapy, at the end of the trial only 3% of stepped-care patients were receiving > 1 drug. Thus, poor compliance may well be the key to the lower success rate of stepped care.

The cost of treatment was considerably higher with lovastatin. It is possible that compliance with stepped care would be improved in a population without such widespread third-party drug coverage (90% in this study) because the cost of niacin can be less than 5% of that of statin therapy (3). For many patients it seems reasonable to start with niacin and, if unsuccessful, therapy can be transferred to a statin. Compliance with this management strategy was not addressed in the study by Oster and colleagues. A direct comparison of the efficacy of long-term niacin and statin therapy would be valuable, although expensive; also, because major pharmaceutical companies have no interest in niacin, it is unlikely to occur.

George Davey Smith, MD
University of Bristol Bristol, England, UK


References

1. Fey R, Pearson N. Lancet. 1996;347:1389-90.

2. Davey Smith G, Pekkanen J. Lancet. 1994;344:1766.

3. Schectman G, Hiatt J, Hartz A. Am J Cardiol. 1993;71:759-65.

4. Alderman JD, Pasternak RC, Sacks FM, et al.Am J Cardiol. 1989;64:725-9.

5. Carlson LA, Hamsten A, Asplund A. J Intern Med. 1989;226:271-6.