Modeling the cost effectiveness and budgetary impact of Polypills for secondary prevention of cardiovascular disease in the United States.

BACKGROUND: There is underutilization of appropriate medications for secondary prevention of cardiovascular disease (CVD). METHODS: Usual care (UC) was compared to polypill-based care with 3 versions using a validated micro-simulation model in the NHANES population with prior CVD. UC included individual prescription of up to 4 drug classes (antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone inhibitors and statins). The polypills modeled were aspirin 81 mg, atenolol 50 mg, ramipril 5 mg, and either simvastatin 40 mg (Polypill I), atorvastatin 80 mg (Polypill II), or rosuvastatin 40 mg (Polypill III). Baseline medication use and adherence came from United Healthcare claims data. RESULTS: When compared to UC, there were annual reductions of 130,000 to 178,000 myocardial infarctions and 54,000 to 74,000 strokes using Polypill I and II, respectively. From a health sector perspective, in incremental analysis the ICERs for Polypill I and II were $20,073/QALY and $21,818/QALY respectively; Polypill III was dominated but had a similar cost-effectiveness ratio to Polypill II when compared directly to usual care. From a societal perspective, Polypill II was cost-saving and dominated all strategies. Over a 5-year period, those taking Polypill I and II compared to UC saved approximately $12 and $6 per-patient-per-year alive, respectively. Polypill II was the preferred strategy in 98% of runs at a willingness to pay of $50,000 in the probability sensitivity analysis. CONCLUSIONS: Use of a polypill has a favorable cost profile for secondary CVD prevention in the United States. Reductions in CVD-related healthcare costs outweighed medication cost increases on a per-patient-per-year basis, suggesting that a polypill would be economically advantageous to both patients and payers.

A 'polypill' aimed at preventing cardiovascular disease could prove highly cost-effective for use in Latin America.

We evaluated the cost-effectiveness of administering a daily "polypill" consisting of three antihypertensive drugs, a statin, and aspirin to prevent cardiovascular disease among high-risk patients in Latin America. We found that the lifetime risk of cardiovascular disease could be reduced by 15 percent in women and by 21 percent in men if the polypill were used by people with a risk of cardiovascular disease equal to or greater than 15 percent over ten years. Attaining this goal would require treating 26 percent of the population at a cost of $34-$36 per quality-adjusted life-year. Offering the polypill to women at high risk and to men age fifty-five or older would be the best approach and would yield acceptable incremental cost-effectiveness ratios. The polypill would be very cost-effective even in the country with the lowest gross national income in our study. However, policy makers must weigh the value of intervention with the polypill against other interventions, as well as their country's willingness and ability to pay for the intervention.

An economic evaluation of antihypertensive therapies based on clinical trials.

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

An economic evaluation of antihypertensive therapies based on clinical trials

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

The lifetime cost effectiveness of amlodipine-based therapy plus atorvastatin compared with atenolol plus atorvastatin, amlodipine-based therapy alone and atenolol-based therapy alone: results from ASCOT1.

BACKGROUND: ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) showed in hypertensive patients that blood pressure-lowering treatment with an amlodipine-based regimen reduces events compared with an atenolol-based regimen and that atorvastatin was more effective than placebo. OBJECTIVE: To assess the cost effectiveness of four alternative treatment strategies in patients with hypertension and three or more cardiovascular risk factors in the UK (from the UK NHS perspective) or Sweden (from the societal perspective): amlodipine-based plus atorvastatin, atenolol-based plus atorvastatin, amlodipine-based alone and atenolol-based alone. METHODS: Based on the trial data, a Markov model was constructed where the risk of myocardial infarction, revascularization procedures and stroke and the long-term costs, quality of life and mortality associated with these events were estimated. Transition probabilities and costs (euro, 2007 values) were based on the patient-level trial data. Outcomes were reported as life-years gained and QALYs. In the latter case, utility reduction from events was based on a substudy in ASCOT patients. Treatment was applied for the duration of the lipid-lowering arm of the trial (3 years) and patients were then followed to the end of their life. RESULTS: Amlodipine-based therapy plus atorvastatin was the most expensive but also most effective treatment. Compared with amlodipine-based therapy alone, the cost to gain one QALY was euro 11,965 in the UK and euro 8,591 in Sweden. The incremental cost effectiveness of amlodipine-based therapy compared with atenolol-based therapy was euro 9,548 and euro 3,965 per QALY gained in the UK and Sweden, respectively. Atenolol-based therapy plus atorvastatin was eliminated through extended dominance. Applying the threshold values used by the National Institute for Health and Clinical Excellence (NICE) and the Swedish National Board of Health and Welfare, a combination of amlodipine-based therapy and atorvastatin appears to be cost effective in patients with hypertension and three or more additional risk factors.

Economic evaluation of ASCOT-BPLA: antihypertensive treatment with an amlodipine-based regimen is cost effective compared with an atenolol-based regimen.

OBJECTIVE: To compare the cost effectiveness of an amlodipine-based strategy and an atenolol-based strategy in the treatment of hypertension in the UK and Sweden. DESIGN: A prospective, randomised trial complemented with a Markov model to assess long-term costs and health effects. SETTING: Primary care. PATIENTS: Patients with moderate hypertension and three or more additional risk factors. INTERVENTIONS: Amlodipine 5-10 mg with perindopril 4-8 mg added as needed or atenolol 50-100 mg with bendroflumethiazide 1.25-2.5 mg and potassium added as needed MAIN OUTCOME MEASURES: Cost per cardiovascular event and procedure avoided, and cost per quality-adjusted life-year gained. RESULTS: In the UK, the cost to avoid one cardiovascular event or procedure would be euro18 965, and the cost to gain one quality-adjusted life-year would be euro21 875. The corresponding figures for Sweden were euro13 210 and euro16 856. CONCLUSIONS: Compared with the thresholds applied by NICE and in the Swedish National Board of Health and Welfare's Guidelines for Cardiac Care, an amlodipine-based regimen is cost effective for the treatment of hypertension compared with an atenolol-based regimen in the population studied.

An economic assessment of losartan-based versus atenolol-based therapy in patients with hypertension and left-ventricular hypertrophy: results from the Losartan Intervention For Endpoint reduction (LIFE) study adapted to The Netherlands.

BACKGROUND: The Losartan Intervention For Endpoint reduction (LIFE) study was a randomized, doubleblind trial that compared the effects of losartan-based treatment with those of atenolol-based treatment on cardiovascular disease (CVD)-related morbidity and mortality in 9193 patients with hypertension and left-ventricular hypertrophy (LVH). Compared with atenolol, losartan reduced the combined risk for CVD-related morbidity and mortality by 13% (P = 0.021), and reduced the risk for stroke by 25% (P = 0.001), with comparable blood pressure control in both trial arms. OBJECTIVE: The aim of this study was to analyze the cost-effectiveness of losartan compared with atenolol in the treatment of stroke from the Dutch health care perspective. METHODS: Utilization of losartan and atenolol within the trial period (mean, 4.8 years) and an estimation of direct medical costs of stroke for The Netherlands were combined with estimates of reduction in life expectancy through stroke. Medication costs and stroke incidence during 5.5 years of patient follow-up were estimated separately, adjusted for the baseline degree of LVH and Framingham risk score. To estimate lifetime stroke costs, the cumulative incidence of stroke was multiplied by the lifetime direct medical costs attributable to stroke. All costs are in 2006 Dutch prices and discounted following the former (4% costs and effects) and new Dutch guideline (4% costs, 1.5% effects) for conducting pharmacoeconomic analyses. RESULTS: With 4% discounting, prevention of stroke was associated with a gain of 3.7 life-years. As a consequence, losartan treatment was associated with 0.059 life-year gained (LYG) per patient treated with losartan. Losartan reduced stroke-related costs by 1,076 Euros (US $1,349) per patient. After inclusion of study medication cost, net cost per patient was 51 Euros ($64) higher for losartan than atenolol. The net cost per LYG was 864 Euros ($1083), which is below the Dutch pharmacoeconomic threshold of 20,000 Euros/LYG (~$25,000/LYG) for accepting interventions. The corresponding probability of a cost-effectiveness ratio below this Dutch threshold was 0.95. Discounting money and health following the new Dutch guideline resulted in an even more favorable cost-effectiveness for losartan. CONCLUSIONS: Results from the present analysis suggest that, in The Netherlands, treatment with losartan compared with atenolol may well be a cost-effective intervention based on the reduced risk for stroke observed in the LIFE trial.

[Cost-effectiveness of treatment of high blood pressure with losartan in Denmark]. / Omkostningseffektivitet ved hypertensionsbehandling med losartan i Danmark.

INTRODUCTION: The purpose of this analysis was to evaluate the cost-effectiveness of losartan compared with atenolol for the treatment of hypertension, both from the point of view of society and from that of the health care sector, based on data from the LIFE study. MATERIALS AND METHODS: The computations are based on a simple decision tree model, where the probability of stroke was obtained from the LIFE study, a double-blind, randomised clinical study of 9,193 patients with hypertensive left ventricle hypertrophy. RESULTS: The treatment of hypertension with losartan rather than atenolol entails a cost of DKK 19,668 per gained quality-adjusted life year (QALY), when only the cost of the health care sector is taken into account, and DKK 72,564 if all costs to society are included. CONCLUSION: The analysis shows that treatment with losartan is cost-effective even when the uncertainty in both data and economic evaluations is taken into account.

A cost-utility analysis of losartan versus atenolol in the treatment of hypertension with left ventricular hypertrophy.

INTRODUCTION: The LIFE (Losartan Intervention For Endpoint reduction in hypertension) study demonstrated a 13% relative risk reduction in the primary composite endpoint (myocardial infarction, stroke or death) for patients with hypertension and electrocardiographically diagnosed left ventricular hypertrophy (LVH) treated with losartan compared with atenolol. Losartan recipients also had a 25% relative risk reduction for stroke compared with atenolol recipients. Incorporating the results found in the LIFE study into an economic model, an incremental cost-effectiveness analysis was performed comparing losartan with atenolol in the treatment of 67-year old patients with hypertension and LVH. METHODS: A Markov state transition model, based on published results of the LIFE trial (mean follow-up of 4.8 years), was utilised to extrapolate the outcomes observed in this trial to the patients' lifetime. Utility estimates for the associated health states were obtained from various published sources. Lifetime treatment costs were calculated adopting a societal perspective. Both costs and benefits were discounted and incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed. RESULTS: The estimated ICER for losartan versus atenolol was 1337 Canadian dollars per QALY gained (1 Canadian dollar =0.75 US dollars, 2002 values). This ICER was robust to extensive sensitivity analysis, demonstrating a 95% probability that the ICER would be <20,000 Canadian dollars per QALY gained. CONCLUSION: From a Canadian societal perspective, losartan appears to be a cost-effective alternative to atenolol in patients with hypertension and LVH. The estimated ICERs, including the sensitivity analyses, were within the range of cost-effectiveness ratios for various currently funded interventions and drugs in developed countries.

Cost effectiveness of losartan in patients with hypertension and LVH: an economic evaluation for Sweden of the LIFE trial.

OBJECTIVE: Evaluate the cost effectiveness of losartan compared with atenolol from a Swedish national health system perspective. DESIGN: The Losartan Intervention For Endpoint reduction in hypertension study (LIFE) was a double-masked, randomized trial of losartan versus atenolol in 9193 patients with essential hypertension and left ventricular hypertrophy (LVH) ascertained by electrocardiography. Losartan reduced the primary composite end point of cardiovascular death, myocardial infarction (MI), or stroke by 13% (P = 0.021) and reduced the risk of stroke by 25% (P = 0.001), despite a comparable degree of blood pressure control. METHODS: Life years gained was estimated by combining the absolute risk reduction in stroke with the life years gained by preventing stroke. Quality-adjusted life years (QALYs) gained was estimated by combining the absolute risk reduction in stroke with the QALYs gained by preventing stroke. QALYs were estimated by weighting life years by health-related quality of life (QoL), as measured with visual analogue scale (VAS) data collected in the trial. Net costs were defined as the total of study medication cost, stroke-related costs, and costs of increased survival. Costs are in 2003 Swedish prices. All costs and effects were discounted at a 3% annual rate. RESULTS: Prevention of a stroke resulted in a gain of 5.7 life years and 4.3 QALYs. As a consequence, losartan treatment resulted in a per patient increase of 0.092 life years [95% confidence interval (CI): 0.038, 0.146] and 0.069 QALYs (95% CI: 0.028, 0.109) as compared with atenolol treatment. Losartan reduced direct stroke-related cost per patient by 1141 euros due to a lower cumulative incidence of stroke for losartan at 5.5 years (4.9%) as compared with atenolol (6.5%) (95% CI of difference: 0.7, 2.5). The reduction in stroke-related cost offset 80% of the added cost of losartan drug therapy. After inclusion of study medication cost, net cost per patient was 289 euros higher for losartan than atenolol. The net cost per QALY gained for losartan was 4188 euros (37,813 SEK), which is well within common Swedish benchmark upper values (200-500,000 SEK) for accepted cost-effective interventions. CONCLUSION: Based on the results from the LIFE trial, treatment with losartan compared with atenolol, in hypertensive patients with LVH, is a cost-effective intervention.

Cost-effectiveness of differing perioperative beta-blockade strategies in vascular surgery patients.

OBJECTIVES: To determine the incremental value of different strategies of both oral and intravenous beta-blockade during the perioperative period in high-risk vascular patients in reducing costs and improving outcomes. DESIGN: Decision analytic model incorporating costs from provider's perspective INTERVENTIONS: Five perioperative strategies in patients undergoing abdominal aortic aneurysm surgery: (1). no routine beta-blockade, (2). preoperative oral bisoprolol for 7 days followed by perioperative intravenous metoprolol and oral bisoprolol based on preoperative titration, (3). immediate preoperative atenolol with postoperative intravenous then oral atenolol, (4). intraoperative esmolol and postoperative intravenous then oral atenolol, and (5). intraoperative and 18 hours of postoperative esmolol then atenolol. MEASUREMENTS AND MAIN RESULTS: Perioperative death was associated with a net increase of US dollars 21909 in charges to Medicare, whereas sustaining a perioperative myocardial infarction was associated with a net increase in charges of US dollars 15000. There is a net hospital saving of US dollars 500 using a strategy of titration of an oral beta-blocker medication for a minimum of 7 days, with a net increase in efficacy of 0.0304. All of the strategies involving acute perioperative blockade were associated with a net cost savings and increase in efficacy, although less than the strategy involving preoperative oral titration. CONCLUSION: Perioperative beta-blockade is both cost effective as well as efficacious from a short-term provider perspective. The optimal strategy of treatment for patients who do not present to surgery already on beta-blockers requires further study, although all strategies save money even accounting for pharmaceutical costs.

Cost-effectiveness of losartan versus atenolol in treating hypertension--an analysis of the LIFE study from a Swiss perspective.

AIMS: To determine the economic benefit of losartan versus atenolol in patients with essential hypertension from the perspective of the Swiss healthcare system. METHODS AND RESULTS: The cost-effectiveness of losartan versus atenolol in the treatment of hypertension was analyzed by applying the results of the LIFE study to the Swiss healthcare system using a decision analysis framework. The cost-effectiveness shows the losartan cohort to provide an additional life expectancy of 0.05 years per patient compared to the atenolol cohort, over a mean follow-up period of 4.8 years. Losartan therapy in hypertensive patients produced net cost savings of CHF 24 per patient and per 4.8 years compared to atenolol from the perspective of the Swiss health care system. This result was robust after varying costs of medication, stroke, myocardial infarction and life expectancy. CONCLUSION: The use of a losartan-based regimen in hypertensive patients with left ventricular hypertrophy in Switzerland is net cost-saving compared with a atenolol-based regimen.

[Medicamentous kidney protection in type 2 diabetic patients--is cheaper also more economical? A model calculation for Swiss health care]. / Medikamentöse Nephroprotektion bei Typ 2-Diabetikern--ist billiger auch ökonomischer? Eine Modellrechnung für Schweizer Verhältnisse.

Impaired renal function occurs in about 50% of patients suffering from type 2 diabetes, and diabetic nephropathy has become the leading cause of endstage renal disease. Reduction of blood pressure to levels around 120/80 mmHg is one of the most effective way to slow progression of diabetic nephropathy. Recent meta-analyses, however, have emphasized on the fact that ACE inhibitors (ACEI) and non-dihydropyridine calcium channel blockers (NDHP-CCB) exert nephro-protective effects which go beyond the effect of blood pressure reduction. This has lately been confirmed by a prospective trial in comparison to the betablocker atenolol. Based on these data, demographics of the Swiss population, literature data on mortality rates of type 2 diabetics with impaired renal function and studies on true costs of antihypertensives, we calculated the costs of a longterm intervention (20 years) with antihypertensives in 3536 middle-aged Swiss patients with type 2 diabetes and macro-albuminuria whose antihypertensive regimen was based either on the ACEI lisinopril, or the ND-HP-CCB verapamil, or the betablocker atenolol. Under atenolol, acquisition costs were lowest, whereas faster loss of renal function over time increased mortality rate and thus reduced the number of patients to be treated. Nevertheless, due to the fact that patients reached uremia and had to be dialyzed, 20 years of atenolol-based regimen with costs of 316 millions of Swiss francs turned out to be much more expensive than the lisinopril- or the verapamil-based regimen with 121 and 38 millions of Swiss francs, respectively. Thus, low acquisition cost is not necessarily the only important determinant of overall costs of drug therapy.

An economic evaluation of atenolol vs. captopril in patients with Type 2 diabetes (UKPDS 54).

AIMS: To compare the net cost of a tight blood pressure control policy with an angiotensin converting enzyme inhibitor (captopril) or beta blocker (atenolol) in patients with Type 2 diabetes. DESIGN: A cost-effectiveness analysis based on outcomes and resources used in a randomized controlled trial and assumptions regarding the use of these therapies in a general practice setting. SETTING: Twenty United Kingdom Prospective Diabetes Study Hospital-based clinics in England, Scotland and Northern Ireland. SUBJECTS: Hypertensive patients (n = 758) with Type 2 diabetes (mean age 56 years, mean blood pressure 159/94 mmHg), 400 of whom were allocated to the angiotensin converting enzyme inhibitor captopril and 358 to the beta blocker atenolol. MAIN OUTCOME MEASURES: Life expectancy and mean cost per patient. RESULTS: There was no statistically significant difference in life expectancy between groups. The cost per patient over the trial period was 6485 UK pounds in the captopril group, compared with 5550 UK pounds in the atenolol group, an average cost difference of 935 UK pounds (95% confidence interval 188 UK pounds, 1682 UK pounds). This 14% reduction arose partly because of lower drug prices, and also because of significantly fewer and shorter hospitalizations in the atenolol group, and despite higher antidiabetic drug costs in the atenolol group. CONCLUSIONS: Treatment of hypertensive patients with Type 2 diabetes using atenolol or captopril was equally effective. However, total costs were significantly lower in the atenolol group. Diabet. Med. 18, 438-444 (2001)

Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40. UK Prospective Diabetes Study Group.

OBJECTIVES: To estimate the economic efficiency of tight blood pressure control, with angiotensin converting enzyme inhibitors or beta blockers, compared with less tight control in hypertensive patients with type 2 diabetes. DESIGN: Cost effectiveness analysis incorporating within trial analysis and estimation of impact on life expectancy through use of the within trial hazards of reaching a defined clinical end point. Use of resources driven by trial protocol and use of resources in standard clinical practice were both considered. SETTING: 20 hospital based clinics in England, Scotland, and Northern Ireland. SUBJECTS: 1148 hypertensive patients with type 2 diabetes from UK prospective diabetes study randomised to tight control of blood pressure (n=758) or less tight control (n=390). MAIN OUTCOME MEASURE: Cost effectiveness ratios based on (a) use of healthcare resources associated with tight control and less tight control and treatment of complications and (b) within trial time free from diabetes related end points, and life years gained. RESULTS: Based on use of resources driven by trial protocol, the incremental cost effectiveness of tight control compared with less tight control was cost saving. Based on use of resources in standard clinical practice, incremental cost per extra year free from end points amounted to pound1049 (costs and effects discounted at 6% per year) and pound434 (costs discounted at 6% per year and effects not discounted). The incremental cost per life year gained was pound720 (costs and effects discounted at 6% per year) and pound291 (costs discounted at 6% per year and effects not discounted). CONCLUSIONS: Tight control of blood pressure in hypertensive patients with type 2 diabetes substantially reduced the cost of complications, increased the interval without complications and survival, and had a cost effectiveness ratio that compares favourably with many accepted healthcare programmes.

A predictive model of the health benefits and cost effectiveness of celiprolol and atenolol in primary prevention of cardiovascular disease in hypertensive patients.

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.