A population-based treat-to-target pharmacoeconomic analysis of HMG-CoA reductase inhibitors in hypercholesterolemia.Clin Ther. 1999 Mar; 21(3):536-62.CT
The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have become the drugs of choice for the treatment of patients with hypercholesterolemia. However, one of the major concerns with these drugs is cost. In an attempt to develop a cost-effective treatment strategy for patients referred to our lipid clinic, we conducted a meta-analysis to estimate the lipid-lowering efficacy of the various HMG-CoA reductase inhibitors alone or in combination with niacin or cholestyramine. Based on cholesterol-lowering efficacy estimates derived from a literature-based meta-analysis, we performed a population-based treat-to-target analysis. Fifty-six trials with 101 monotherapy cohorts and 20 trials with 31 combination-therapy cohorts (573 patients) were included in the meta-analysis. Based on reduction in low-density lipoprotein cholesterol (LDL-C), the most effective monotherapy was atorvastatin and the least effective monotherapy was fluvastatin. Combination therapy was more effective in reducing LDL-C than monotherapy with the respective HMG-CoA reductase inhibitor. However, on the basis of dollars spent per percentage of LDL-C reduction, combination therapy was frequently less cost-effective than monotherapy. In addition, combination therapy was associated with a higher rate of noncompliance and a greater risk of drug-drug interactions. As a result, we based our treat-to-target analysis on the use of monotherapy as first-line treatment, with combination therapy reserved for patients failing to achieve the target LDL-C levels of the US National Cholesterol Education Program Adult Treatment Panel II (NCEP ATP-II) with monotherapy. In the population-based treat-to-target analysis, atorvastatin was the most cost-effective drug for high-risk patients (those with coronary heart disease [CHD]), whereas fluvastatin was the most cost-effective agent for low-risk patients (<2 risk factors for CHD) and moderate-risk patients (> or =2 risk factors for CHD). If 1 drug is chosen to treat all patients (i.e., in cases of formulary restriction), atorvastatin would be the most cost-effective agent. In adapting the findings on cholesterol-lowering efficacy from this analysis to our lipid clinic, we concluded that the most cost-effective treatment approach is to individualize the selection of an HMG-CoA reductase inhibitor based on both coronary risk and the LDL-C reduction required to achieve NCEP ATP-II goals. Based on our results, 2 agents--atorvastatin and fluvastatin--should be available on the formulary.