|Cost-effectiveness of irbesartan/hydrochlorothiazide in patients with hypertension: an economic evaluation for Sweden
|Ekman M, Bienfait-Beuzon C, Jackson J
This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.
This study examined the cost-effectiveness of irbesartan in combination with hydrochlorothiazide in comparison with other selective angiotensin-II-receptor blockers. The authors concluded that irbesartan combined with hydrochlorothiazide was a cost-effective alternative to valsartan and losartan, although candesartan offered the highest value for money in patients with moderate-to-severe hypertension. The study was generally well conducted and well presented. The authors’ conclusions appear to be valid.
Type of economic evaluation
The objective was to examine the cost-effectiveness of irbesartan in combination with hydrochlorothiazide compared with other selective angiotensin-II-receptor blockers (ARBs) such as losartan, valsartan, and candesartan.
The treatments combined with hydrochlorothiazide 12.5mg, were: irbesartan 150mg; losartan 50mg; valsartan 80mg; and candesartan 16mg. The treatments combined with hydrochlorothiazide 25mg, were: irbesartan 300mg; losartan 100mg; and valsartan 160mg.
A comparison was made only among low-dose treatments or among high-dose treatments for both mild-to-moderate and moderate-to-severe patients. In addition, irbesartan low-dose and high-dose treatments were compared. Men and women were considered separately and the comparator was placebo.
This economic analysis was based on a Markov model with a lifetime horizon. The authors stated that the perspective of the health care payer was taken.
The clinical sources of data were identified through a systematic review of the literature in the MEDLINE database. Only double-blind, randomised controlled trials (RCTs) were used. The details of these RCTs were provided. A key step in the clinical analysis was to link the change in blood pressure with the risk of developing cardiovascular disease. This was based on risk equations from a published study. The duration of the treatment effect was assumed to be five years. The key clinical input was the change in blood pressure with each of the treatment strategies.
Monetary benefit and utility valuations:
The utility values were derived from published studies and reviews and the details of these were not given.
Measure of benefit:
Quality-adjusted life-years (QALYs) were the summary benefit measure and were discounted at 3% per annum. Life-years gained (LYG) were also reported, assuming a utility of one in all health states.
The economic analysis included drug costs and the hospital costs associated with various cardiovascular events (angina, heart failure, stroke, and myocardial infarction) and surgical procedures (coronary artery bypass graft, percutaneous transluminal coronary angioplasty, and heart transplant). Annual drug costs were derived from the official pharmaceutical reference book. The costs of cardiovascular events were derived from official hospital price lists and published cost-of-illness studies carried out in the Swedish setting. Total hospital costs associated with each event were reported. All costs were in Euros (EUR) and were discounted at 3% per annum. The price year was 2007.
Analysis of uncertainty:
The deterministic one-way sensitivity analyses focused on variations in the costs of events, drug prices (considering the ends of patents for losartan towards the end of 2009, in Europe, and for other ARBs around 2012), treatment duration, the age at which treatment was initiated, discount rate for both costs and benefits, and the use of life-years (LYs) rather than QALYs as the benefit measure. Various subgroup analyses based on the severity of disease were also carried out.
In a typical 55-year-old man, the expected costs were EUR 15,948 with placebo, EUR 16,329 with irbesartan, EUR 16,590 with losartan, and EUR 16,497 with valsartan. The QALYs were 13.094 with placebo, 13.204 with irbesartan, 13.195 with losartan, and 13.197 with valsartan. Both losartan and valsartan were dominated as they were less effective and more expensive than irbesartan. The incremental cost per QALY gained with irbesartan over placebo was EUR 3,451.
Similar findings were obtained for a typical 55-year-old woman, where the incremental cost per QALY gained with irbesartan over placebo was EUR 7,704.
In patients with moderate-to-severe hypertension, irbesartan remained the dominant strategy over losartan and candesartan in the low-dose comparison for both men and women. In the high-dose comparison, candesartan offered the greatest value for money, with an incremental cost per QALY gained of EUR 28,465 for men compared with irbesartan, and being the dominant strategy for women. High-dose irbesartan was more cost-effective than the low-dose regimen at commonly used thresholds for cost-effectiveness.
The sensitivity analysis showed that these findings were relatively sensitive to variations in long-term costs. Drug price changes affected the results, but irbesartan remained dominant compared with valsartan and cost-effective compared with losartan even when generic prices for the other ARBs were used, in low-dose comparisons. In high-dose comparisons irbesartan was no longer cost-effective. Changes in the discount rates had greater effects for patients who were younger at the start of therapy. The use of LYs as the summary benefit measure did not substantially alter the findings.
The authors concluded that irbesartan combined with hydrochlorothiazide was a cost-effective alternative to valsartan and losartan, although candesartan offered the highest value for money in patients with moderate-to-severe hypertension.
The selection of the comparators was appropriate as the drug under examination (irbesartan) was compared against other ARBs that were commonly prescribed in Sweden. Placebo was also considered as a background strategy. High- and low-doses in various populations of patients were appropriately compared in order to reflect the available treatment strategies. The authors stated that diuretics were not compared as no valid clinical data were found.
A systematic literature search was an appropriate approach for identifying the most relevant sources of data. The exclusive use of RCTs will have ensured the validity of the clinical inputs due to the strengths of this design. The detailed results for each source of clinical data were extensively presented along with the disease severity of the patient population. In general, the clinical analysis was well carried out, and the authors investigated the impact of variations in some key assumptions in the sensitivity analysis. The use of QALYs was appropriate given the impact of the disease on both survival and quality of life. Information on the methodology used to derive the utility values from the published sources was not given.
The economic analysis was consistent with the perspective in terms of both the cost categories and the sources of data, which reflected the Swedish setting. In general, the costs were presented as macro-categories, which may make it difficult to reproduce the study in other contexts. Details such as the price year and discount rate were provided. The costs were varied in the sensitivity analyses and the assumptions made were justified.
Analysis and results:
The costs and benefits associated with each treatment arm were clearly reported. The use of an incremental analysis to synthesise the model outcomes was appropriate and allowed the identification of dominated strategies. The sensitivity analysis explored the use of alternative assumptions deterministically. A multivariate analysis would have been more appropriate for assessing the global issue of uncertainty. The model structure and its key assumptions were explicitly presented. Some potential biases in the clinical data selected were acknowledged and discussed.
The study was generally well conducted and well presented. The authors’ conclusions appear to be valid.
Funded by Sanofi-Aventis and Bristol-Myers Squibb.
Ekman M, Bienfait-Beuzon C, Jackson J. Cost-effectiveness of irbesartan/hydrochlorothiazide in patients with hypertension: an economic evaluation for Sweden. Journal of Human Hypertension 2008; 22(12): 845-855
Other publications of related interest
Rodby RA, Chiou CF, Borenstein J, Smitten A, Sengupta N, Palmer AJ, et al. The cost-effectiveness of irbesartan in the treatment of hypertensive patients with type 2 diabetic nephropathy. Clinical Therapeutics 2003; 25: 2102-2119.
Palmer AJ, Annemans L, Roze S, Lamotte M, Rodby RA, Cordonnier DJ. An economic evaluation of irbesartan in the treatment of patients with type 2 diabetes, hypertension and nephropathy: cost-effectiveness of Irbesartan in Diabetic Nephropathy Trial (IDNT) in the Belgian and French settings. Nephrology, Dialysis and Transplantation 2003; 18: 2059-2066.
Palmer AJ, Annemans L, Roze S, Lamotte M, Rodby RA, Bilous RW. An economic evaluation of the Irbesartan in Diabetic Nephropathy Trial (IDNT) in a UK setting. Journal of Human Hypertension 2004; 18: 733-738.
Subject indexing assigned by NLM
Adult; Aged; Aged, 80 and over; Antihypertensive Agents /economics /therapeutic use; Biphenyl Compounds /economics /therapeutic use; Cost-Benefit Analysis; Drug Costs /statistics & Drug Therapy, Combination; Female; Health Services /utilization; Humans; Hydrochlorothiazide /economics /therapeutic use; Hypertension /drug therapy /economics /epidemiology; Male; Middle Aged; Patents as Topic; Quality-Adjusted Life Years; Risk Factors; Sensitivity and Specificity; Sweden /epidemiology; Tetrazoles /economics /therapeutic use; Young Adult; numerical data
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