A PREDICTIVE MODEL OF THE HEALTH BENEFITS AND COST-EFFECTIVENESS OF CELIPROLOL AND ATENOLOL IN PRIMARY PREVENTION OF CARDIOVASCULAR-DISEASEIN HYPERTENSIVE PATIENTS

This study compares the antihypertensive and lipid modifying effects o f treatment of mild to moderate hypertension with celiprolol or atenol ol. It also models the 5-year cardiovascular risk reduction and the co st effectiveness of monotherapy from a partial societal perspective. T he effects of celiprolol and atenolol on systolic blood pressure (SBP) , total serum cholesterol (TC) and high density lipoprotein cholestero l (HDL-C) were obtained from a pooled analysis of published studies. A lthough 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% C I of 3.4%, 12.0%). The 5-year absolute risks of an initial coronary or cerebrovascular event or cardiovascular death were computed for cohor ts of patients treated with either agent or remaining untreated, using an accelerated failure time (AFT) model, based on Framingham Heart St udy data. Inputs to the model were age, gender, smoking: status, SEP, TC and HDL-C. The change in absolute risk was estimated using the chan ges in SEP and TC :HDL-C obtained from the pooled analysis. Average li fe-months gained by therapy were computed as differences between the K aplan-Meier survival curves estimated from the model plus differences in 5-year cardiovascular death rates multiplied by average life expect ancy obtained from life tables. Direct medical costs included drug tre atment. and the costs of acute care for initial coronary and cerebrova scular events deferred by therapy over the 5-year treatment period, Th e model shows that in the lowest-risk base case (60-year-old men who a re nondiabetic and nonsmokers with SEP of 160mm Hg and a 5-year absolu te 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 nu mber 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. T herapy 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 o f patients with 5-year absolute cardiovascular risk greater than 10%, and are more cost effective in those patients at higher levels of abso lute cardiovascular risk. The direct medical costs of treatment for 5 years with celiprolol are the same or slightly less than treatment wit h atenolol at the dosages used in the clinical trials, despite a 19% h igher tablet price. Both drugs are more cost effective in patients at higher levels of absolute cardiovascular risk. These findings are sens itive to the drug dosages, tablet prices and the discount rate. Based on epidemiological and clinical data, replacing atenolol with celiprol ol in patients with mild to moderate hypertension, but without overt c ardiovascular disease, is predicted to have similar effects on stroke risk, but to be substantially more effective in reducing the risk of c oronary events at no additional direct medical cost over a 5-year trea tment period.