title: A predictive model of the health benefits and cost effectiveness of celiprolol and atenolol in primary prevention of cardiovascular disease in hypertensive patients.
abstract: This study compares the antihypertensive and lipid modifying effects of treatment of mild to moderate hypertension with celiprolol or atenolol. It also models the 5-year cardiovascular risk reduction and the cost effectiveness of monotherapy from a partial societal perspective. The effects of celiprolol and atenolol on systolic blood pressure (SBP), total serum cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were obtained from a pooled analysis of published studies. Although celiprolol and atenolol had similar effects on SBP, celiprolol reduced the ratio of TC to HDL-C by 10.2% [95% confidence intervals (95% CI) -16.4%, -4.0%) but atenolol increased the ratio by 7.7% (95% CI of 3.4%, 12.0%). The 5-year absolute risks of an initial coronary or cerebrovascular event or cardiovascular death were computed for cohorts of patients treated with either agent or remaining untreated, using an accelerated failure time (AFT) model, based on Framingham Heart Study data. Inputs to the model were age, gender, smoking status, SBP, TC and HDL-C. The change in absolute risk was estimated using the changes in SBP and TC: HDL-C obtained from the pooled analysis. Average life-months gained by therapy were computed as differences between the Kaplan-Meier survival curves estimated from the model plus differences in 5-year cardiovascular death rates multiplied by average life expectancy obtained from life tables. Direct medical costs included drug treatment, and the costs of acute care for initial coronary and cerebrovascular events deferred by therapy over the 5-year treatment period. The model shows that in the lowest-risk base case (60-year-old men who are nondiabetic and nonsmokers with SBP of 160 mm Hg and a 5-year absolute cardiovascular risk of 12%), celiprolol (271 mg/day) is 2-fold more effective than atenolol (77.4 mg/day) in reducing coronary event risk, and equally effective in reducing cerebrovascular event risk. The number of individuals that would have to be treated for 5 years to avoid 1 coronary event is about 30 for celiprolol versus 70 for atenolol. Therapy with celiprolol yields more life-months and at current prices, the cost per life-year gained by therapy is significantly lower. Both drugs are cost effective by international standards in the treatment of patients with 5-year absolute cardiovascular risk greater than 10%, and are more cost effective in those patients at higher levels of absolute cardiovascular risk. The direct medical costs of treatment for 5 years with celiprolol are the same or slightly less than treatment with atenolol at the dosages used in the clinical trials, despite a 19% higher tablet price. Both drugs are more cost effective in patients at higher levels of absolute cardiovascular risk. These findings are sensitive to the drug dosages, tablet prices and the discount rate. Based on epidemiological and clinical data, replacing atenolol with celiprolol in patients with mild to moderate hypertension, but without overt cardiovascular disease, is predicted to have similar effects on stroke risk, but to be substantially more effective in reducing the risk of coronary events at no additional direct medical cost over a 5-year treatment period.
authors.affiliation: Adis International Limited, Auckland, New Zealand. richard.milne@adis.co.nz
authors.forename: R J
authors.initials: RJ
authors.lastname: Milne
authors.forename: S
authors.initials: S
authors.lastname: Vander Hoorn
authors.forename: R T
authors.initials: RT
authors.lastname: Jackson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000191:economics* / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001262:Atenolol / Q000191:economics* / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000191:economics* / Q000517:prevention & control*; D017272:Celiprolol / Q000191:economics* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000191:economics*; D008297:Male; D008875:Middle Aged; D018803:Models, Economic