Development and validation of a model to project the long-term benefit and cost of alternative lipid-lowering strategies in patients with hypercholesterolaemia.
BACKGROUND
Patients not currently reaching their lipid goals, even with the use of statins, are at elevated coronary heart disease (CHD) risk. Ezetimibe, when coadministered with a patient's current statin, has been shown to effectively reduce cholesterol in patients with hypercholesterolaemia. In order to help healthcare decision makers assess the cost effectiveness of this treatment strategy, a model is needed to compare ezetimibe coadministration versus alternative statin titration strategies among patients who have failed to reach their lipid goal with their current statin dose.


METHODS
A flexible decision-analytic model that projects the long-term benefit and cost of alternative lipid-lowering strategies is described. Using a Markov process, the model allows movement from one health state to another based on the predicted risk of CHD events (fatal and nonfatal) and the risk of death from non-CHD causes. Each health state can be assigned a quality-of-life weight and an expected cost in order to determine the total survival time, quality-adjusted survival time and cost associated with the alternative treatment strategies. The accuracy of the model in projecting the percentage of patients who experience fatal and nonfatal CHD events was assessed by using individual baseline patient characteristics from two long-term outcomes trials: the Air Force Coronary Atherosclerosis Prevention Study, a primary prevention trial, and the Scandinavian Simvastatin Survival Study, a secondary prevention trial.


RESULTS
Compared with event rates in the two outcome trials, the model appears to underestimate both the absolute risk of nonfatal CHD events and its reduction due to lipid lowering. But the model appears to provide reasonable estimates of the absolute reduction in fatal CHD events following lipid treatment.


CONCLUSIONS
The model will allow one to assess the cost effectiveness of alternative treatment strategies for hypercholesterolaemia including statin titration and the coadministration of ezetimibe in patients who have failed to reach their lipid goal with a statin. Because the benefit of reducing nonfatal CHD events may be underestimated, the model may overestimate the cost-effectiveness ratio of ezetimibe coadministration.
Cook
John R
JR
Merck & Co., Inc., Whitehouse Station, New Jersey, USA. john_cook@merck.com
Yin
Don
D
Alemao
Evo
E
Drummond
Michael
M
D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D003363:Cost Control; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D016527:Drug Costs; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000191:economics*; D018803:Models, Economic; D015203:Reproducibility of Results; D013997:Time Factors
D000924:Anticholesteremic Agents; D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe