Dosage of angiotensin-II receptor blockers in heart failure patients following changes in Danish drug reimbursement policies.

PURPOSE: National reimbursement policies in Denmark were changed in November 2010 favouring a shift in angiotensin-II receptor blocker (ARB) treatment to generic losartan for heart failure (HF) patients. We examined how changes in reimbursement policies affected the fraction of HF patients up-titrated to optimal or suboptimal ARB dosage. METHODS: A historical cohort study was performed including HF patients with at least one prescription of ARB in the months of May-Jul 2010 (baseline). Patients were considered up-titrated at doses 100, 16 or 160 mg for losartan, valsartan and candesartan, respectively. Individual-level linkage of nationwide registries of hospitalization and drug dispensing in Denmark was used to describe patterns of ARB prescriptions and estimate dosage before and after November 2010. Logistic regression models were used to assess the probability for being up-titrated in the period. RESULTS: Of 6036 individuals included (mean age 73.5 [standard deviation 11.2] years; 51% males), 3346 (55.4%) used losartan, 541 (9.0%) valsartan and 2149 (35.6%) candesartan at inclusion, respectively. 2887 (47.8%) were up-titrated at baseline (May-Jul 2010), followed by 2878 (48.2%) in the three months before the policy change (Aug-Oct 2010), and 2492 (43.7%) in the first months after the policy change (Feb-Apr 2011). Odds ratios for being up-titrated according to time period were 1.02 [0.95-1.09] in Aug-Oct 2010 (before policy change) and 0.84 [0.78-0.90] in Feb-Apr 2011 (after policy change), compared with May-Jul 2010 (reference). CONCLUSION: Probability of being up-titrated in ARB treatment was reduced 20% following changes in drug reimbursement policies.

Influence of multiple initiatives in Sweden to enhance ARB prescribing efficiency following generic losartan; findings and implications for other countries.

BACKGROUND: Encouraging the prescribing of ACEIs first line vs. angiotensin receptor blockers (ARBs) has been a health authority focus with generic ACEIs as ACEIs and ARBs have similar effectiveness and there is limited coughing with ACEIs. This includes Sweden with its multiple initiatives keeping expenditure on renin-angiotensin inhibitor drugs similar between 2001 and 2007 despite appreciably increased volumes. Generic losartan became available and was reimbursed in March 2010 providing further opportunities for the authorities in Sweden to save costs with all ARBs seen as similar in managing hypertension and CHF at appropriate doses. AIMS: The main aim of this study was to assess changes in the utilisation of losartan vs. other single ARBs after generic losartan alongside accompanying demand-side measures. Additional aims were to (i) assess changes in the price of generic losartan and single ARB expenditure over time; (ii) suggest additional programmes, if needed; and (iii) analyse utilisation of ARB FDCs and compare with ACEI FDCs. METHODS: Retrospective observational study using an interrupted time series design. RESULTS: Multiple demand-side measures introduced among the 21 Counties in Sweden significantly enhanced the utilisation of generic losartan, growing from 26% to 27% of total ARBs (DDD basis) before generic losartan to 40% by August 2011. Losartan was principally generics (97% by August 2011). Expenditure/DDD for generic losartan was 10% of the pre-patent loss price in August 2011. This reduced total single ARB expenditure by 26% by the study end despite a 16% increase in utilisation. Greater utilisation of ARB FDCs than seen with ACEI FDCs. This may be due to similarities in prices between single and FDC ARBs. DISCUSSION: Multiple demand-side measures appreciably enhanced ARB prescribing efficiency, mirroring other studies. No significant increase in losartan utilisation following generics was seen in European countries where no specific measures were instigated. Losartan price reduction was in line with expectations. CONCLUSION: Multiple and intensive demand-side measures are needed to change physician prescribing habits. Authorities cannot rely on physicians transferring their activities from one class to another without interventions.

Are prescribing initiatives readily transferable across classes: the case of generic losartan in Scotland?

BACKGROUND: There are on-going initiatives in Scotland to improve the quality and efficiency of prescribing in primary care. Activities to enhance prescribing of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin receptor blockers (ARBs) include prescribing guidance, guidelines, benchmarking, prescribing targets and financial incentives. These measures stabilised reimbursed expenditure for renin-angiotensin inhibitor drugs between 2001 and 2007 despite a 159% increase in volumes. Generic losartan was included in the Drug Tariff from July 2010. As there is no appreciable difference between ARBs, and the prices of generic losartan are falling, health boards should be actively encouraging its prescribing. AIM: To primarily assess changes in utilisation patterns of losartan versus other ARBs after July 2010. Second, to assess the utilisation of generic versus originator losartan. METHOD: We used an interrupted time series analysis of ARB utilisation, measured in defined daily doses (DDDs) before and after July 2010. Utilisation data were obtained from the NHS National Services Scotland Corporate Warehouse. RESULTS: There was no significant change in the utilisation pattern of losartan or other ARBs combined before or after the introduction of generic losartan. Losartan accounted for 32% of total ARBs 12 months after listing. Between 98 and 99% of losartan was prescribed generically. In March 2012, the price of losartan was 88% below prepatent prices with potential savings of ?8m per year. CONCLUSION: Specific measures are needed to change prescribing habits especially with complex messages. The cost of deriving savings must be weighed against other quality initiatives and other ARBs losing or shortly losing their patents.

Modifying prescribing behaviour of angiotensin receptor blockers by selectively rescinding managerial prior authorization requirements for losartan.

AIMS: To evaluate whether rescinding the prior authorization (PA) requirement (managerial pre-approval) for losartan in an health maintenance organization (HMO) could reduce prescribing of the more expensive angiotensin receptor blockers (ARBs). METHODS: HMO physicians were notified that losartan would no longer require PA, and appropriate changes were made to the electronic prescribing computer program. The monthly distribution by drug of the number of prescriptions for ARBs dispensed for new patients was calculated before and after the policy change from data captured from electronic records. The proportion of patients (percentage and 95% confidence interval) treated with losartan who met the criteria for treatment with ARBs (hypertension or cardiac insufficiency in patients who have developed adverse effects in response to angiotensin-converting enzyme inhibitors or macroproteinuria) during the first month after the PA requirement was rescinded was calculated. RESULTS: The total number of PA requests for ARBs declined by 48.6% from 961 in December 2008, the month before the policy change, to 494 the following January, rising again to 651 during January 2010. Prescription incidence changed from 121 to 255 patients treated per month (114% increase) for losartan, from 15 to 16 (6.7% increase) for candesartan, and from 89 to 71 (20.2% decrease) for valsartan. The duration of effect for decrease in ARB requests for the more expensive drugs was approximately 1 year. Only 23.3% (95% confidence interval 18.1-28.4) of patients receiving losartan met the criteria for receiving ARBs. CONCLUSIONS: Rescinding the PA requirement for this drug alone was an effective limited-duration strategy for reduction of prescription of relatively expensive drugs.

Comparative clinical- and cost-effectiveness of candesartan and losartan in the management of hypertension and heart failure: a systematic review, meta- and cost-utility analysis.

The UK National Health Service (NHS) currently spends in excess of £250 million per annum on angiotensin II receptor blockers (ARBs) for the treatment of hypertension and heart failure; with candesartan currently dominating the market. With the recent introduction of generic losartan, we set out to directly compare the branded market leader to its now cheaper alternative. The primary objectives were to compare the blood pressure (BP) lowering efficacy and cardiovascular outcomes of candesartan and losartan in the treatment of essential hypertension and chronic heart failure, respectively. The secondary objective was to model their comparative incremental cost-effectiveness in a UK NHS setting. The Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2), which contains the Hypertension and Heart Group's specialist register, Medline (1950-February 2010), and Embase (1980-February 2010) were included in the search strategy. Selection criteria were randomised studies of candesartan versus losartan in adults (> 18 years). The main outcome measures were as follows: Hypertension: mean change from baseline in trough (24 h postdose) systolic and diastolic BP. Heart failure: composite of cardiovascular death and hospital admission for management of heart failure. Two reviewers applied inclusion criteria, assessed trial quality, and extracted data. Eight (three of which met inclusion criteria) and zero trials compared candesartan directly with losartan in the treatment of hypertension and heart failure, respectively. A between-treatment difference of -1.96 mmHg [95% confidence interval (CI) -2.40 to -1.51] for trough diastolic BP and -3.00 mmHg (95% CI -3.79 to -2.22) for trough systolic BP in favour of candesartan was observed. Based on this differential, a 10-year Markov model estimates the cost per quality-adjusted life-year gained to exceed £40,000 for using candesartan in place of generic losartan. Candesartan reduces BP to a slightly greater extent when compared with losartan, however, such difference is unlikely to be cost-effective based on current acquisition costs, perceived NHS affordability thresholds and use of combination regimens. We could find no robust evidence supporting the superiority of candesartan over losartan in the treatment of heart failure. We therefore recommend using generic losartan as the ARB of choice which could save the UK NHS approximately £200 million per annum in drug costs.

Pharmaco-economic consequences of losartan therapy in patients undergoing diabetic end stage renal disease in EU and USA.

Diabetic nephropathy is the most frequent cause of end stage renal disease (ESRD). As ESRD incidence increases continuously, more resources are needed for treatment. The objective was to evaluate the economic impact of losartan added to the standard care administered to diabetic subjects with ESRD. The analysis has involved more than 500 million inhabitants. Standard methods have been used in order to conduct an economic evaluation comparing the economic outcomes deriving from the administration of losartan added to standard care versus standard care alone in patients with type 2 diabetes mellitus (DM) and nephropathy over 3.4 years. The study was hence conducted from the perspective of the third-party payer. The clinical outcome data were based on the results from the Reduction of Endpoints in Non-Insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) trial. Direct medical costs are referred to the purchase costs of losartan and to the costs of hospitalization. The costs were discounted back at an annual rate of 3%. Also sensitivity analysis was performed. The RENAAL study showed that losartan confers strong renal protection in patients with DM and nephropathy. Losartan results into cost saving in all countries considered: 3,602.98€/Italy, 4,531.35€/France, 3,019.66€/Germany, 3,949.50€/Switzer-land, and 3,855.50€/US per patient. Results are not sensitive to both clinical and economic variables. In addition to the medical benefits, this analysis demonstrates the economic relevance of the treatment with losartan in DM patients affected by nephropathy.

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 losartan in diabetic nephropathy: a Greek perspective.

BACKGROUND: Diabetic nephropathy is the primary cause of end-stage renal disease (ESRD), which involves substantial economic burden. The primary objective of this study was to estimate the potential effect of losartan on the costs associated with ESRD in patients with diabetic nephropathy in a Greek setting. A secondary aim was to approximate the direct health care cost of renal replacement therapy (RRT) in Greece. METHODS: A cost-effectiveness analysis was performed to compare losartan with placebo in patients with type 2 diabetes and nephropathy. Clinical data were derived from the RENAAL study. All costs were calculated from the perspective of the Greek social insurance system, in 2003 euros. Future costs were discounted at 3%. The time horizon was 3.5 years. Extensive sensitivity analyses were performed. RESULTS: The reduction in the number of ESRD days over 3.5 years in patients treated with losartan reduced ESRD-related costs by 3,056.54 euros, resulting in net cost savings of 1,665.43 euros per patient. Net cost savings increase thereafter, increasing to 2,686.48 euros per patient over a period of 4.0 years. The results were robust under a wide range of plausible assumptions. The weighted mean daily cost of RRT was estimated at 90.97 euros per patient. The total economic burden of RRT for the year 2003 has been estimated at 304.773 million euros. CONCLUSIONS: This study demonstrated that treatment of patients with diabetic nephropathy in Greece with losartan is cost-effective, as it leads to important savings for the social insurance system by slowing the progression to ESRD.

Farmácia Popular Program: pharmaceutical market analysis of antihypertensive acting on the renin-angiotensin system medicines.

This paper aims to analyse changes in the retail pharmaceutical market following policy changes in the Farmácia Popular Program (FP), a medicines subsidy program in Brazil. The retrospective longitudinal analyses focus on therapeutic class of agents acting on the renin-angiotensin system. Data obtained from QuintilesIMS (formerly IMS Health) included private retail pharmacy sales volume (pharmaceutical units) and sales values from 2002 to 2013. Analyses evaluated changes in market share following key FP policy changes. The therapeutic class was selected due to its relevance to hypertension treatment. Market share was analysed by therapeutic sub-classes and by individual company. Losartan as a single product accounted for the highest market share among angiotensin II antagonists. National companies had higher sales volume during the study period, while multinational companies had higher sales value. Changes in pharmaceutical market share coincided with the inclusion of specific products in the list of medicines covered by FP and with increases in or exemption from patient copayment.

Cost-effectiveness of the polypill versus risk assessment for prevention of cardiovascular disease.

OBJECTIVE: There is an international trend towards recommending medication to prevent cardiovascular disease (CVD) in individuals at increasingly lower cardiovascular risk. We assessed the cost-effectiveness of a population approach with a polypill including a statin (simvastatin 20 mg) and three antihypertensive agents (amlodipine 2.5 mg, losartan 25 mg and hydrochlorothiazide 12.5 mg) and periodic risk assessment with different risk thresholds. METHODS: We developed a microsimulation model for lifetime predictions of CVD events, diabetes, and death in 259 146 asymptomatic UK Biobank participants aged 40-69 years. We assessed incremental costs and quality-adjusted life-years (QALYs) for polypill scenarios with the same combination of agents and doses but differing for starting age, and periodic risk assessment with 10-year CVD risk thresholds of 10% and 20%. RESULTS: Restrictive risk assessment, in which statins and antihypertensives were prescribed when risk exceeded 20%, was the optimal strategy gaining 123 QALYs (95% credible interval (CI) -173 to 387) per 10 000 individuals at an extra cost of £1.45 million (95% CI 0.89 to 1.94) as compared with current practice. Although less restrictive risk assessment and polypill scenarios prevented more CVD events and attained larger survival gains, these benefits were offset by the additional costs and disutility of daily medication use. Lowering the risk threshold for prescription of statins to 10% was economically unattractive, costing £40 000 per QALY gained. Starting the polypill from age 60 onwards became the most cost-effective scenario when annual drug prices were reduced below £240. All polypill scenarios would save costs at prices below £50. CONCLUSIONS: Periodic risk assessment using lower risk thresholds is unlikely to be cost-effective. The polypill would become cost-effective if drug prices were reduced.

Impact of the Commercialization of Three Generic Angiotensin II Receptor Blockers on Adverse Events in Quebec, Canada: A Population-Based Time Series Analysis.

BACKGROUND: Once the patent of a brand-name drug expires, generic drugs are commercialized, and substitution from brand-name to generics may occur. Generic drug equivalence is evaluated through comparative bioavailability studies. Few studies have assessed outcomes after generic drug commercialization at a population level. We evaluated the impact of 3 generic angiotensin II receptor blockers commercialization on adverse events: hospitalizations or emergency room consultations. METHODS AND RESULTS: This is an interrupted time series analysis using the Quebec Integrated Chronic Disease Surveillance System. Rates of adverse events for losartan, valsartan, and candesartan users (N=136 177) aged ≥66 years were calculated monthly, 24 months before and 12 months after generics commercialization. Periods before and after generics commercialization were compared by negative binomial segmented regression models. Sensitivity analyses were also conducted. For all users, there was a monthly mean rate of 100 adverse events for 1000 angiotensin II receptor blocker users before and after generic commercialization. Among generic users of losartan, valsartan, and candesartan, there was an increase in rates of adverse events of 8.0% (difference of proportions versus brand-name, 7.5% [95% confidence interval, -0.9% to 15.9%]; P=0.0643), 11.7% (difference of proportions, 17.1% [95% confidence interval, 9.9%-24.3%]; P<0.0001), and 14.0% (difference of proportions, 16.6% [95% confidence interval, 7.9%-25.3%]; P<0.0001), respectively, the month of generic commercialization. The monthly trend of adverse events was affected for generic versus brand-name losartan users only (difference of proportions, 2.0% [0.7%-3.4%]; P=0.0033) ≤1 year after generics commercialization. Similar results were found in sensitivity analyses. CONCLUSIONS: Among generic users, immediate or delayed differences in adverse events rates were observed right after generic commercialization for 3 antihypertensive drugs. Rates of adverse events remained higher for generic users. Increases were more pronounced for generic candesartan, which is the studied product with the largest difference in comparative bioavailability. Risk and survival analysis studies controlling for several potential confounding factors are required to better characterize generic substitution.

Blockade of the renin-angiotensin-aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes.

Diabetes (particularly type 2 diabetes) represents a global health problem of epidemic proportions. Individuals with diabetes are not only more likely to develop hypertension, dyslipidemia, and obesity, but are also at a significantly higher risk for coronary heart disease, peripheral vascular disease, and stroke. Angiotensin II plays a key pathophysiological role in the progression of diabetic renal disease, and blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II antagonists has therefore become an important therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. Several studies have demonstrated the effects of angiotensin II antagonists on the reduction of albuminuria and the progression of renal disease from microalbuminuria to macroalbuminuria. More importantly, several endpoint trials have shown that the antiproteinuric effects of losartan and irbesartan translate into cardiovascular and renoprotective benefits beyond blood pressure lowering, thereby delaying the need for dialysis or kidney transplantation by several years. These and other studies indicate that angiotensin II antagonists not only improve survival and quality of life of patients with diabetic nephropathy, but also have the potential to reduce the substantial healthcare burden associated with managing these patients. ACEi also appear to exert similar beneficial effects in diabetic patients, but whether clinically significant differences in renoprotection or mortality exist between angiotensin II antagonists and ACEi in patients with type 2 diabetes remains to be fully investigated in appropriate head-to-head studies.

Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study.

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study demonstrated the clinical benefit of losartan-based therapy in hypertensive patients with left ventricular hypertrophy (LVH), mainly due to a highly significant 25% reduction in the relative risk of stroke compared with an atenolol-based regimen, for a similar reduction in blood pressure. The aim of this economic evaluation was to estimate the cost-effectiveness of losartan compared with atenolol from a UK national health system perspective. Quality-adjusted survival and direct medical costs were modelled beyond the trial using the within-trial incidence of stroke. Survival with stroke, study medication use and quality of life by stroke status were taken directly from the LIFE trial. The LIFE data were supplemented with UK data on lifetime direct medical costs of stroke and life expectancy in individuals without stroke. No additional stroke events or use of study treatment were assumed beyond the trial. Costs and benefits were discounted using current UK Treasury rates. In the base-case analysis, the reduction in stroke-related costs (by 968 sterling pound) offset 86% of the increase in study medication costs (1128 sterling pound) among losartan-treated patients. The incremental cost-effectiveness ratio (ICER) for losartan versus atenolol in hypertensive patients with LVH was 2130 sterling pound per quality-adjusted life year (QALY) gained (3195 Euro/QALY), and this increased to 11,352 sterling pound per QALY gained (16,450 Euro/QALY) when the costs of stroke beyond the first 5 years were excluded. Thus, the clinical benefit of losartan was achieved at a cost well within reported thresholds for cost-effectiveness.

The impact of losartan on the lifetime incidence of end-stage renal disease and costs in patients with type 2 diabetes and nephropathy.

INTRODUCTION: The RENAAL (Reduction of Endpoints in Non-insulin dependent diabetes with the Angiotensin II Antagonist Losartan) study demonstrated that, in hypertensive patients with type 2 diabetes mellitus and nephropathy, treatment with losartan plus conventional antihypertensive therapy (CT) reduced the relative risk of end-stage renal disease (ESRD) by 29% versus placebo over the time span of the study (mean patient follow-up of 3.4 years). The objective of this study was to project the effect of losartan compared with placebo on the lifetime incidence of ESRD and associated costs (from a US healthcare system perspective). METHODS: To estimate lifetime incidence of ESRD, we used a competing risks method to account for the risk of death without ESRD. We estimated the cost (US dollars, year 2002 values) associated with ESRD by combining the cumulative incidence of ESRD with the lifetime cost associated with ESRD. Total cost was estimated as the sum of the cost associated with ESRD, the cost of losartan study therapy and other costs (non-ESRD/non-losartan) expected for patients with type 2 diabetes. Survival was estimated by weighting the life expectancies with and without ESRD by the cumulative risk of ESRD. Costs and outcomes were discounted by 3% per annum. RESULTS: We projected a lower lifetime incidence of ESRD for losartan patients (66%) compared with placebo patients (83%). This reduction in ESRD resulted in a decrease in cost associated with ESRD of US dollars 31,803 per patient and a gain of 0.99 life-years per patient (0.70 discounted). After accounting for the cost of losartan and the additional cost associated with greater survival, we projected that treatment with losartan would result in a lifetime net saving of US dollars 24,632 per patient. CONCLUSION: Treatment with losartan plus CT in patients with type 2 diabetes and nephropathy reduced the within-trial incidence of ESRD and is projected to result in lifetime reductions in ESRD and associated costs, and increased survival, versus placebo.

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.

The impact of losartan on the lifetime incidence of ESRD and costs in Mexico.

BACKGROUND: The RENAAL (Reduction of Endpoints in Type 2 Diabetes with the Angiotensin II Antagonist Losartan) study demonstrated that treatment with losartan reduced the risk of ESRD by 29% among hypertensive patients with type 2 diabetes and diabetic nephropathy. The objective of this study was to project the effect of losartan compared to placebo on the lifetime incidence of ESRD and associated costs from a third-party payer perspective in Mexico. METHODS: A competing risks method was used to estimate lifetime incidence of ESRD, while accounting for the risk of death without ESRD. The cost associated with ESRD was estimated by combining the cumulative incidence of ESRD with the lifetime cost associated with ESRD. Total cost was estimated as the sum of the cost associated with ESRD from the three main public institutions in Mexico, the lifetime cost of losartan therapy, and other costs (non-ESRD/non-losartan) expected for patients with type 2 diabetes. Survival was estimated by weighting the life expectancies with and without ESRD by the cumulative risk of ESRD. RESULTS: The projected lifetime incidence of ESRD for losartan patients was lower (66%) compared with placebo patients (83%). This reduction in ESRD resulted in a decrease in ESRD-related cost of M dollar 49,737 per patient and a discounted gain of 0.697 life years per patient. After accounting for the cost of losartan and the additional cost associated with greater survival, we projected that treatment with losartan would result in a net savings of M dollar 24,073 per patient. CONCLUSION: Treatment with losartan in patients with type 2 diabetes and nephropathy not only reduced the within-trial incidence of ESRD but is projected to result in lifetime reductions in ESRD, increased survival, and overall cost savings to public institutions in Mexico.

Losartan reduces the costs associated with diabetic end-stage renal disease: the RENAAL study economic evaluation.

OBJECTIVE: To evaluate the within-trial effect of losartan and conventional antihypertensive therapy (CT) compared with placebo and CT on the economic cost associated with end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: The Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) study was a multinational double-blind randomized placebo-controlled clinical trial designed to evaluate the renal protective effects of losartan on a background of CT (excluding ACE inhibitors and angiotensin II receptor agonists [AIIAs]) in patients with type 2 diabetes and nephropathy. The primary composite end point was doubling of serum creatinine, ESRD, or death. Data on the duration of ESRD were used to estimate the economic benefits of slowing the progression of nephropathy. The cost associated with ESRD was estimated by combining the days each patient experienced ESRD with the cost of ESRD over time. The cost of ESRD for individuals with diabetes was estimated using data from the U.S. Renal Data System. Total cost was estimated as the sum of the cost associated with ESRD and the cost of study therapy. RESULTS-We estimated that losartan and CT compared with placebo and CT reduced the number of days with ESRD by 33.6 per patient over 3.5 years (P = 0.004, 95% CI 10.9-56.3). This reduction in ESRD days resulted in a decrease in cost associated with ESRD of 5144 US dollars per patient (P = 0.003, 95% CI 1701 to 8587 US dollars). After accounting for the cost of losartan, the reduction in ESRD days resulted in a net savings of 3522 US dollars per patient over 3.5 years (P = 0.041, 143 to 6900 US dollars). CONCLUSIONS: Treatment with losartan in patients with type 2 diabetes and nephropathy not only reduced the incidence of ESRD, but also resulted in substantial cost savings.

Losartan and the United States costs of end-stage renal disease by baseline albuminuria in patients with type 2 diabetes and nephropathy.

BACKGROUND: Type 2 diabetes is the leading cause of end-stage renal disease (ESRD). The Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study provided the opportunity to estimate costs associated with ESRD by baseline albuminuria from a United States perspective. METHODS: Costs for ESRD in patients with diabetes were estimated by baseline albuminuria using the U.S. Renal Data System by using the number of days each patient experienced ESRD and the daily estimated U.S. cost of ESRD. RESULTS: The losartan-based antihypertensive therapy group experienced a 28.6% (P=0.002) reduction in the risk of the development of ESRD compared with placebo-based conventional antihypertensive therapy. The previously estimated annual ESRD-related cost saving in the losartan group was 5,144 dollars (95% CI 1,701-8,586 dollars, P=0.003) at 3.5 years. With the cost of losartan, the net savings in the losartan group was estimated at 3,522 dollars (143-6,900 dollars, P=0.041) by 3.5 years. More ESRD-free days were observed and reduced ESRD costs estimated with losartan-based treatment over all levels of baseline albuminuria. CONCLUSION: Treatment with losartan in patients with type 2 diabetes and nephropathy in the RENAAL study not only reduces the incidence of ESRD, but is also estimated from a U.S. perspective to result in substantial cost savings over the 3.5-year duration of the trial across all levels of baseline albuminuria.