COMBINATION-DRUG THERAPY FOR HYPERCHOLESTEROLEMIA - THE TRADE-OFF BETWEEN COST AND SIMPLICITY

Backgrounds: The National Cholesterol Education Program recommends ach ievement of a defined target level of low-density lipoprotein choleste rol (LDL-C) for the treatment of hypercholesterolemia. They endorse th e use of niacin and/or sequestrants as the first line of therapy to ac hieve such target LDL-C level. This recommendation has not been compar ed with the use of lovastatin as initial therapy if multidrug regimens are required to achieve goal LDL-C. Methods: Prospectively collected data on tolerance and effectiveness for niacin, sequestrants, and lova statin were obtained from a lipid clinic at a large midwestern Veteran s Affairs medical center. We used a decision tree to compare the compl exity and cost of three sequential drug algorithms used for the follow ing initial LDL-C levels: 4.14, 4.91, 5.69, and 6.47 mmol/L (160, 190, 220, and 250 mg/dL). Algorithm was niacin followed by a sequestrant a nd then lovastatin; algorithm 2, a sequestrant followed by niacin and then lovastatin; and algorithm 3, lovastatin followed by niacin and a sequestrant. Drug and laboratory costs were obtained from the pharmacy and pathology services at the same institution. Sensitivity analyses were performed on the tolerance and effectiveness of each drug as well as drug and laboratory cost estimates. Results: The probability of ac hieving target LDL-C level (3.36 mmol/L 1130 mg(dL!) decreased as init ial LDL-C level increased. As a rule, algorithm 3 required fewer drugs in combination to achieve the target level for all initial LDL-C leve ls modeled. In addition, the use of lovastatin was high across all alg orithms at all initial LDL-C levels modeled. Algorithm 1 was less expe nsive than algorithm 2 or 3 at a low initial LDL-C level (4.14 mmol/L 160 mg/dL!), with an average cost of $375 vs $454 vs $585, respective ly. At all other initial LDL-C levels (4.91, 5.69, and 6.47 mmol/L  1 90, 220, and 250 mg/dL!), algorithm 2 was slightly less expensive than algorithm 1. Algorithm 3 became relatively less expensive as initial LDL-C level increased: 56% more expensive than algorithm 1 at an initi al LDL-C level of 4.14 mmol/L (160 mg/dL) as compared with 7% more exp ensive than algorithm 1 at an initial LDL-C level of 6.47 mmol/L (250 mg/dL). Conclusions: Fulfillment of the target LDL-C approach recommen ded by the National Cholesterol Education Program often requires the u se of multiple drugs. When lovastatin is used initially, the regimen b ecomes simpler, albeit more expensive. At initial LDL-C levels of 4.91 mmol/L (190 mg/dL) or higher, this difference in cost becomes progres sively smaller (7% at 6.47 mmol/L 250 mg/dL!), making algorithm 3 the better alternative; at low initial LDL-C levels (4.14 mmol/L 160 mg/ dL!), a niacin-first regimen is reasonably simple and substantially le ss expensive. At moderate and severe initial LDL-C levels (4.91 and 5. 69 mmol/L 190 and 220 mg/dL!), the lovastatin-first regimen may be ad vantageous.