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Evidence summaries

Dose-Response Characteristics of Cholesterol-Lowering Drug Therapies

The dose-response relationship of both statins and resins may be non-linear. The combination of low doses of statins and resins is at least as effective than a high dose of either drug. Level of evidence: "C"

A systematic review 1 including 15 trials (3,573 patients) on statins, 6 trials (196 patients) on resins, 3 trials on niacin, and 6 trials (215 patients) on combination treatments, was abstracted in DARE. The drugs evaluated included lovastatin, pravastatin, simvastatin, fluvastatin, cholestyramine, cholestipol, and niacin.

Increasing the dose of each statin to more than 20 mg produces only small incremental reductions in the LDL cholesterol level. Approximately two thirds of the expected maxium response can be expected with only one quarter of the highest dose.

Resins have no linear dose-response relationship. 3 scoops provided three quarters of the lowering effect that was achieved by 6 scoops. High doses (4 to 6 scoops a day) are associated with substantial adverse gastrointestinal effects.

3 studies evaluated combination therapy with statins and resins and found the LDL cholesterol reductions to be additive. Low dose combination therapy with statins and resins produces reductions in LDL cholesterol levels greater than or equal to higher doses of either drug used alone.

Comment: The quality of evidence is downgraded by severe limitations in review methdology. Atorvastatin and rosuvastatin were not included in this meta-analysis that was published in 1996.

    References

    • Schectman G, Hiatt J. Dose-response characteristics of cholesterol-lowering drug therapies: implications for treatment. Ann Intern Med 1996 Dec 15;125(12):990-1000. [PubMed] [DARE]

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