Authors' objectives: In the context of a Health Technology Assessment (HTA), the Federal Office of Public Health was tasked to re-evaluate public reimbursement of olmesartum medoxomilum (olmesartan for short). Olmesartan belongs to the family of angiotensin II receptor blockers (ARBs), one of the major classes of drugs recommended for essential hypertension treatment in adult patients. The efficacy, effectiveness and safety of olmesartan therapy in such patients have been questioned due to a suspected increased risk of adverse events and missing data on morbidity and mortality out-comes. The central research questions for this report addressed the efficacy, effectiveness and safety of olmesartan in adult patients with essential hypertension compared with other sartans. A second focus covered their costs, cost effectiveness and the anticipated impact on the health insurance budget if olmesartan were delisted and substituted by other available sartans. In this context, issues were also examined as to whether legal, social, ethical or organisational aspects should be consid-ered in the course of a potential delisting of olmesartan from the reimbursement list.

Authors' results and conclusions: Efficacy: Seventeen randomised controlled trials (RCTs, 4’036 participants) compared olmesartan with other sartans. Olmesartan lowered (systolic as well as diastolic) blood pressure more effectively compared with losartan and diastolic blood pressure more effectively compared with irbesartan. For olmesartan versus valsartan, azilsartan, candesartan and telmisartan as well as olmesartan/hydro-chlorothiazide versus telmisartan/hydrochlorothiazide, the results did not differ significantly. Effectiveness: Based on one study (Swindle et al.), in a limited subsample (108’567 participants), olmesartan reduced the risk of the composite outcome of cardiac events (particularly heart failure) more effectively than valsartan, losartan and irbesartan. We conducted independent statistical anal-yses of the available data and did not identify any significant differences between olmesartan, losar-tan, irbesartan and valsartan in any of the outcomes. Safety: Regarding severe adverse events, we analysed five RCTs (1’721 participants) and 12 cohort studies (>8’250’000 participants). The comparisons indicated similar risk profiles for olmesartan and other sartans in the short-term follow-up (RCTs) and the long-term follow-up (cohort studies). The results were not consistent for enteritis. Two of the cohort studies suggested that olmesartan is associated with an increased risk of enteropathies compared with other ARBs while two other cohort studies found no significant difference. Additionally, we evaluated data from 22 single-arm studies (67’922 participants) as well as the sin-gle-study arms of 11 RCTs (4’587 participants) and 8 cohort studies (125’669 participants). We identified no striking patterns regarding the occurrence of serious adverse events in olmesartan users. Cost effectiveness: The calculated incremental cost effectiveness ratio (ICER) per patient for cardiac events was between CHF -20’000 and CHF -25’000 for olmesartan compared with valsartan, losar-tan and irbesartan (perspective: health insurance; time frame: 1 year). In other words, olmesartan was associated with higher effects and lower costs for cardiac events. However, the sensitivity anal-ysis showed that the calculated cost-effectiveness results were not robust. Budget impact: The total net budget impact (pharmaceutical expenditure and additional outpatient visits) for the potential substitution of olmesartan with other sartans in the three scenarios resulted in budget savings of CHF 4.8 million (Scenario 1), further expenses of CHF 1.3 million (Scenario 2) and further expenses of CHF 2.6 million (Scenario 3) for the health insurance. In relation to phar-maceutical expenditures alone, there would be budget savings of CHF 7.4 million in Scenario 1, CHF 1.3 million in Scenario 2 and no savings in Scenario 3. The effects of a substitution of olmesar-tan depended strongly on the availability of alternative preparations within the equivalence groups (their specific prices and market shares) as well as on expenditure for additional visits to physicians in the course of changing medication. Social/ethical issues: To avoid medication adherence problems, timely information for physicians about a potential disinvestment, the reasons for the decision and available equivalent doses of al-ternative sartans would be useful. Organisational issues: It would be necessary to monitor if there were any problems with the delivery of valsartan products due to nitrosamine impurities and whether they could be provided in sufficient quantities (especially triple combinations) as this is the only alternative for olmesartan triple combi-nations. In addition, patients could expect more frequent visits to their physician during the first year in the course of switching to another sartan. Olmesartan lowered systolic as well as diastolic blood pressure more effectively com-pared with losartan and diastolic blood pressure more effectively compared with irbesartan without showing a statistically significant effect compared with candesartan, telmisartan, telmisartan plus diuretics, azilsartan and valsartan. Evidence (of low quality) from one retrospective cohort study hinted at a potential advantage of olmesartan for long-term outcomes like certain cardiac events compared with losartan, irbesartan and valsartan. The comparisons of harm indicated similar risk profiles for olmesartan and other sartans in the short-term follow-up (RCTs) and the long-term follow-up (cohort studies). Regarding enteritis, the results from four cohort studies (comparing olmesartan with other sartans) were inconsistent in terms of detecting a higher risk for olmesartan users. Despite occurring only rarely, clinicians should remain vigilant regarding this potential adverse event. The cost-effectiveness calculations were not robust enough to draw any universal conclusions when using olmesartan compared with valsartan, losartan and irbesartan. The budget impact of substituting olmesartan depended strongly on the prices and market shares of alternative preparations within the specific equivalence groups and the costs for additional medi-cal consultations associated with the change in medication. Therefore, if physicians prescribing equivalent doses of the alternative sartans to those of olmesartan, it is more likely that the substitu-tion of olmesartan would result in increased healthcare expenditures. To maintain blood pressure control after a potential disinvestment decision, physicians should re-ceive timely information as well as guidance on prescribing equivalent doses of other sartans. To avoid access problems, the current market situation should be kept under observation, especially with regard to the availability of double and triple combinations and potential future recalls of some valsartan products.

Authors' methods: For all domains of the HTA, systematic literature searches were conducted. Seventy-two primary studies were analysed for effectiveness, efficacy and safety and – whenever possible – meta-analyses were conducted. For the economic domain, six relevant studies were identified; how-ever, due to heterogenous study designs and outcomes, the results were not transferable to Swit-zerland. Therefore, the effects of the one retrospective cohort study identified with long-term out-comes were used to model the cost effectiveness of olmesartan, valsartan, losartan and irbesartan. Finally, to estimate the implications of a potential substitution of olmesartan for the health insurance budget, the allocation method was used, simulating three scenarios. In Scenario 1, the number of olmesartan preparations was allocated to the other sartans separately for mono- and combination preparations (cost and volume for 2018). The market share of the different packs of alternative sar-tan preparations was used as the redistribution key. Scenario 2 considered the doses of alternative drugs equivalent to olmesartan (cost and volume for 2018) and Scenario 3 differed from Scenario 2 in that all reimbursed packs were valued with prices as of 1 August 2019.

Project Status: Completed

URL for project: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-projekte/olmesartan.html

Year Published: 2020

URL for published report: https://www.bag.admin.ch/dam/bag/en/dokumente/kuv-leistungen/leistungen-und-tarife/hta/berichte/h0021olme-hta-report.pdf.download.pdf/h0021olme-hta-report.pdf

URL for additional information: https://www.bag.admin.ch/bag/en/home/versicherungen/krankenversicherung/krankenversicherung-leistungen-tarife/hta/hta-programm.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Switzerland

Organisation Name: Swiss Federal Office of Public Health (FOPH)

Contact Address: Federal Office of Public Health, Schwarzenburgstrasse 157, CH-3003 Berne, Switzerland

Contact Name: Stephanie Vollenweider

Contact Email: hta@bag.admin.ch

Copyright: Swiss Federal Office of Public Health