Cost-effectiveness Analyses of Antihypertensive Medicines: A Systematic Review.

CONTEXT: Hypertension affects one third of the U.S. adult population. Although cost-effectiveness analyses of antihypertensive medicines have been published, a comprehensive systematic review across medicine classes is not available. EVIDENCE ACQUISITION: PubMed, Embase, Cochrane Library, and Health Technology Assessment were searched to identify original cost-effectiveness analyses published from 1990 through August 2016. Results were summarized by medicine class: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), thiazide-type diuretics, ß-blockers, and others. Incremental cost-effectiveness ratios (ICERs) were adjusted to 2015 U.S. dollars. EVIDENCE SYNTHESIS: Among 76 studies reviewed, 14 compared medicines with no treatment, 16 compared medicines with conventional therapy, 29 compared between medicine classes, 13 compared within medicine class, and 11 compared combination therapies. All antihypertensives were cost effective compared with no treatment (ICER/quality-adjusted life year [QALY]=dominant-$19,945). ARBs were more cost effective than CCBs (ICER/QALY=dominant-$13,016) in nine comparisons, whereas CCBs were more cost effective than ARBs (ICER/QALY=dominant) in two comparisons. ARBs were more cost effective than ACEIs (ICER/QALY=dominant-$34,244) and ß-blockers (ICER/QALY=$1,498-$18,137) in all eight comparisons. CONCLUSIONS: All antihypertensives were cost effective compared with no treatment. ARBs appeared to be more cost effective than CCBs, ACEIs, and ß-blockers. However, these latter findings should be interpreted with caution because these findings are not robust due to the substantial variability across the studies, including study settings and analytic models, changes in the cost of generic medicines, and publication bias.

Comparative effectiveness of antihypertensive drugs in nondiabetic patients with hypertension: A population-based study.

The authors compared the effectiveness of thiazide diuretic (TD), angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and calcium channel blocker (CCB) monotherapies for the treatment of nondiabetic hypertension using MarketScan Databases 2010-2014. Multivariable Cox regression models assessed whether the addition of a new antihypertensive drug, treatment discontinuation, or switch and major cardiovascular or cerebrovascular events varied across groups. A total of 565 009 patients started monotherapy with ACEIs (43.6%), CCBs (23.6%), TDs (18.8%), or ARBs (14.0%). Patients who took TDs had a higher risk for either drug addition or discontinuation than patients who took ACEIs (hazard ratio [HR], 0.69 [95% CI, 0.68-0.70] vs HR, 0.81 [95% CI, 0.80-0.81]), ARBs (HR, 0.67 [95% CI, 0.66-0.68] vs HR, 0.66 [95% CI, 0.65-0.67]), and CCBs (HR, 0.85 [95% CI, 0.84-0.87] vs HR, 0.94 [95% CI, 0.93-0.95]). Conversely, patients who took TDs experienced a lower risk of clinical events compared with patients who took ACEIs (HR, 1.24 [95% CI, 1.15-1.33]), ARBs (HR, 1.28 [95% CI, 1.18-1.39]), and CCBs (HR, 1.35 [95% CI, 1.25-1.46]). Our results provide a strong rationale for choosing TDs as first-line monotherapy for the control of hypertension.

Cost-utility of angiotensin-converting enzyme inhibitor-based treatment compared with thiazide diuretic-based treatment for hypertension in elderly Australians considering diabetes as comorbidity.

The objective of this study was to examine the cost-effectiveness of angiotensin-converting enzyme inhibitor (ACEI)-based treatment compared with thiazide diuretic-based treatment for hypertension in elderly Australians considering diabetes as an outcome along with cardiovascular outcomes from the Australian government's perspective.We used a cost-utility analysis to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Data on cardiovascular events and new onset of diabetes were used from the Second Australian National Blood Pressure Study, a randomized clinical trial comparing diuretic-based (hydrochlorothiazide) versus ACEI-based (enalapril) treatment in 6083 elderly (age ≥65 years) hypertensive patients over a median 4.1-year period. For this economic analysis, the total study population was stratified into 2 groups. Group A was restricted to participants diabetes free at baseline (n = 5642); group B was restricted to participants with preexisting diabetes mellitus (type 1 or type 2) at baseline (n = 441). Data on utility scores for different events were used from available published literatures; whereas, treatment and adverse event management costs were calculated from direct health care costs available from Australian government reimbursement data. Costs and QALYs were discounted at 5% per annum. One-way and probabilistic sensitivity analyses were performed to assess the uncertainty around utilities and cost data.After a treatment period of 5 years, for group A, the ICER was Australian dollars (AUD) 27,698 (&OV0556; 18,004; AUD 1-&OV0556; 0.65) per QALY gained comparing ACEI-based treatment with diuretic-based treatment (sensitive to the utility value for new-onset diabetes). In group B, ACEI-based treatment was a dominant strategy (both more effective and cost-saving). On probabilistic sensitivity analysis, the ICERs per QALY gained were always below AUD 50,000 for group B; whereas for group A, the probability of being below AUD 50,000 was 85%.Although the dispensed price of diuretic-based treatment of hypertension in the elderly is lower, upon considering the potential enhanced likelihood of the development of diabetes in addition to the costs of treating cardiovascular disease, ACEI-based treatment may be a more cost-effective strategy in this population.

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.

Reducing costs and improving hypertension management.

OBJECTIVE: To quantify the cost-savings that could be realized by switching patients from two separate agents, ACE inhibitor/ARB and thiazide diuretic, to a fixed dose combination product. METHODS: CompuScript and Longitudinal Rx (LRx) Insights data from IMS Health Canada for Oct 2006-Sept 2007 was used. From the LRx data, the proportion of patients taking both ACE inhibitors/ARBs and thiazide diuretics as two separate products was calculated to determine how many would qualify for a combination product. From the CompuScript data, the total number of prescriptions for ACE inhibitors and ARBs and the actual average dollar value per prescription for thiazide diuretics, ACE inhibitors, ARBs, and ACE inhibitor/ARB with thiazide diuretic combination products was used to determine the potential cost savings of switching from two separate drugs to a combination product. As a sensitivity analysis, the proportion of patients receiving two separate products who could be switched to a combination product was varied from 60-100%. This analysis was done for Alberta and Canada. RESULTS: The conversion of ACE inhibitor/ARB and thiazide diuretic as two separate agents to a combination product could potentially result in a yearly cost-savings of $27 to $45 million for Canada ($1.1 to $1.9 million for Alberta), based on 60-100% conversion to a combination product. CONCLUSIONS: The present analysis has shown that a simple intervention of converting patients receiving separate ACE inhibitor/ARB and thiazide diuretic prescriptions to a single combination product prescription will produce substantial cost-savings for the health care system and simplify the medication regimen for patients.

Rational prescribing in primary care (RaPP): economic evaluation of an intervention to improve professional practice.

BACKGROUND: Interventions designed to narrow the gap between research findings and clinical practice may be effective, but also costly. Economic evaluations are necessary to judge whether such interventions are worth the effort. We have evaluated the economic effects of a tailored intervention to support the implementation of guidelines for the use of antihypertensive and cholesterol-lowering drugs. The tailored intervention was evaluated in a randomized trial, and was shown to significantly increase the use of thiazides for patients started on antihypertensive medication, but had little or no impact on other outcomes. The increased use of thiazides was not expected to have an impact on health outcomes. METHODS AND FINDINGS: We performed cost-minimization and cost-effectiveness analyses on data from a randomized trial involving 146 general practices from two geographical areas in Norway. Each practice was randomized to either the tailored intervention (70 practices; 257 physicians) or control group (69 practices; 244 physicians). Only patients that were being started on antihypertensive medication were included in the analyses. A multifaceted intervention was tailored to address identified barriers to change. Key components were an educational outreach visit with audit and feedback, and computerized reminders. Pharmacists conducted the visits. A cost-minimization framework was adopted, where the costs of intervention were set against the reduced treatment costs (principally due to increased use of thiazides rather than more expensive medication). The cost-effectiveness of the intervention was estimated as the cost per additional patient being started on thiazides. The net annual cost (cost minimization) in our study population was 53,395 US dollars, corresponding to 763 US dollars per practice. The cost per additional patient started on thiazides (cost-effectiveness) was 454 US dollars. The net annual savings in a national program was modeled to be 761,998 US dollars, or 540 US dollars per practice after 2 y. In this scenario the savings exceeded the costs in all but two of the sensitivity analyses we conducted, and the cost-effectiveness was estimated to be 183 US dollars. CONCLUSIONS: We found a significant shift in prescribing of antihypertensive drugs towards the use of thiazides in our trial. A major reason to promote the use of thiazides is their lower price compared to other drugs. The cost of the intervention was more than twice the savings within the time frame of our study. However, we predict modest savings over a 2-y period.

[When is it worth reducing overuse of health care services? The example of prescribing expensive antihypertensives]. / Wann lohnt es, eine medizinische Uberversorgung abzubauen? Das Beispiel der Verschreibung teurer Antihypertonika.

BACKGROUND AND PURPOSE: Reducing overuse of health care services saves costs only if implementation costs are lower than savings from avoided health care services. Predicting the expected net benefit helps policymakers to make a choice among the various overuse problems and components of implementation programs in health care. The goal of this paper is to demonstrate how to calculate the net benefit of reducing overuse. In an application example feedback or outreach visits to primary care physicians in Germany reduce the prescription of expensive antihypertensives with questionable benefit. METHODS: In a mathematical model secondary data were used to portray the relationship between the net benefit from reducing overuse and the degree of overuse. RESULTS: Assuming that currently 30% of treated hypertensive patients could switch to thiazides and combinations with other drugs, an overuse reduction through feedback or outreach visits to primary care physicians is efficient. CONCLUSION: If the degree of overuse is large, an overuse reduction can be efficient. The explicit consideration of the size of an overuse problem may contribute to a more efficient use of health care resources.

First-line first? Trends in thiazide prescribing for hypertensive seniors.

BACKGROUND: Evidence of reduced cardiovascular morbidity and mortality as well as cost support thiazide diuretics as the first-line choice for treatment of hypertension. The purpose of this study was to determine the proportion of senior hypertensives that received thiazide diuretics as first-line treatment, and to determine if cardiovascular and other potentially relevant comorbidities predict the choice of first-line therapy. METHODS AND FINDINGS: British Columbia PharmaCare data were used to determine the cohort of seniors (residents aged 65 or older) who received their first reimbursed hypertension drug during the period 1993 to 2000. These individual records were linked to medical and hospital claims data using the British Columbia Linked Health Database to find the subset that had diagnoses indicating the presence of hypertension as well as cardiovascular and other relevant comorbidities. Rates of first-line thiazide prescribing as proportion of all first-line treatment were analysed, accounting for patient age, sex, overall clinical complexity, and potentially relevant comorbidities. For the period 1993 to 2000, 82,824 seniors who had diagnoses of hypertension were identified as new users of hypertension drugs. The overall rate at which thiazides were used as first-line treatment varied from 38% among senior hypertensives without any potentially relevant comorbidity to 9% among hypertensives with previous acute myocardial infarction. The rate of first-line thiazide diuretic prescribing for patients with and without potentially relevant comorbidities increased over the study period. Women were more likely than men, and older patients were more likely than younger, to receive first-line thiazide therapy. CONCLUSIONS: Findings indicate that first-line prescribing practices for hypertension are not consistent with the evidence from randomized control trials measuring morbidity and mortality. The health and financial cost of not selecting the most effective and least costly therapeutic options are significant.

Thiazide diuretics in the management of hypertension.

Hypertension is highly prevalent in Canada, affecting more than 20% of all adults. Thiazide diuretics have been shown in numerous studies to be effective agents for controlling blood pressure and reducing cardiovascular disease and death in hypertensive patients. Thiazide diuretics are recommended as initial first line therapy for uncomplicated hypertension in the 2003 Canadian Hypertension recommendations. However, these agents are underutilized and in Canada, the proportion of persons with hypertension treated with diuretics is declining. To improve understanding of thiazide diuretic use, this document outlines the clinical pharmacology of thiazide diuretics, evidence for effectiveness in treating hypertension, as well as the side effects and controversies surrounding their use.

The potential savings of using thiazides as the first choice antihypertensive drug: cost-minimisation analysis.

BACKGROUND: All clinical practice guidelines recommend thiazides as a first-choice drug for the management of uncomplicated hypertension. Thiazides are also the lowest priced antihypertensive drugs. Despite this, the use of thiazides is much lower than that of other drug-classes. We wanted to estimate the potential for savings if thiazides were used as the first choice drug for the management of uncomplicated hypertension. METHODS: For six countries (Canada, France, Germany, Norway, the UK and the US) we estimated the number of people that are being treated for hypertension, and the proportion of them that are suitable candidates for thiazide-therapy. By comparing this estimate with thiazide prescribing, we calculated the number of people that could switch from more expensive medication to thiazides. This enabled us to estimate the potential drug-cost savings. The analysis was based on findings from epidemiological studies and drug trials, and data on sales and prescribing provided by IMS for the year 2000. RESULTS: For Canada, France, Germany, Norway, the UK and the US the estimated potential annual savings were US13.8 million dollars, US37.4 million dollars, US72.2 million dollars, US10.7 million dollars, US119.7 million dollars and US433.6 million dollars, respectively.

Shifting trends in the pharmacologic treatment of hypertension in a Nigerian tertiary hospital: a real-world evaluation of the efficacy, safety, rationality and pharmaco-economics of old and newer antihypertensive drugs.

The current prescription patterns for essential hypertension and the efficacy, safety, tolerability and cost-effectiveness of the newer antihypertensive drugs were evaluated in Nigerian patients. The findings were compared with that of a previous study conducted in the same tertiary hospital 10 years earlier. A cross-sectional evaluation of blood pressure (BP) control in a hypertension clinic was undertaken among 150 Nigerian patients aged 61 +/- 12 years (55% females), with a duration of treatment on a particular drug class or combination of 9 +/- 3 months. The initial blood pressure was 176 +/- 20/108 +/- 11 mmHg and 22% of the patient had concurrent diabetes mellitus. Thiazide diuretics (D) alone or in combination remained the most commonly prescribed drugs in 56% of all patients. There were significant increases in the prescriptions of calcium channel blockers (CCBs) (51%), P < 0.0001, and ACE-inhibitors (ACEIs) (24%), P < 0.0001, but a slight reduction in the use of methyldopa, and fixed drug combinations (P < 0.01) compared to the previous study. The fall in systolic blood pressure on D (r = 0.65, P < 0.001) or CCB (r = 0.48, P < 0.02) was significantly correlated with the initial systolic blood pressure, but not age. More patients achieved normotension BP < 140/90 mmHg on CCB monotherapy (71%), than D monotherapy (56%). Combination therapy with ACEIs + D or methyldopa+thiazides normalized BP in 63 and 68%, respectively. Pulse pressure, a surrogate marker for cardiovascular complications and mortality in essential hypertension, was significantly reduced (P < 0.01) equally by all treatments, with 95% confidence intervals ranging from -28 to -1 mmHg. However, hypertensive-diabetic (HT-DM) patients (n = 33) exhibited no significant change in pulse pressure in response to treatment. Adverse drug reactions that occurred in 11% were impotence or postural dizziness with D, headache and pitting oedema with CCB, and dry cough with ACEI. Pharmaco-economic comparison of the drug classes revealed that for every US dollar (dollar) spent per month, the percentage of treated patients attaining normotension was 18.6 for D, 4.73 for CCB, 3.5 for ACEI + D and 13.6 for methyldopa + thiazides. A combination of ACEI + CCB or D was the preferred treatment for hypertensive-diabetic Nigerians, but only 24% attained a BP < 130/85 mmHg. These results demonstrate a shift in trend to a more rational and efficacious treatment of hypertension over a 10 year period. This may be associated, at least in part, with the intensive and continuous education of the prescribers in rational drug use and the introduction of a hospital formulary. Methyldopa is still a highly efficacious and cost-effective drug in this population. Black HT-DM Africans still constitute a subgroup who not only require more and costlier antihypertensive drugs, but whose BP control is suboptimal, and exhibit a poor therapeutic response to other risk factors (pulse pressure) that constitute a continuing risk for cardiovascular mortality.

Changes in the phamacologic treatment of hypertension in the Department of Veterans Affairs 1997-1999: decreased use of calcium antagonists and increased use of beta-blockers and thiazide diuretics.

Older studies of antihypertensive treatment have shown that prescribing patterns are not consistent with recommendations from expert national panels. We determined whether prescribing patterns for antihypertensive drugs changed recently in the largest integrated health care system in the United States. Specifically, we determine 1) patterns of antihypertensive medication use at all Department of Veterans Affairs (VA) medical facilities for fiscal years 1997 to 1999, 2) the cost of this care, and 3) savings associated with changes in treatment patterns. Data were aggregated by individual medication as well as by antihypertensive drug class. Estimates of VA national antihypertensive drug costs are based on the median cost and the number of units for each dosage form of each medication dispensed at all facilities. At VA medical facilities, calcium antagonist use went from 33% to 29.3% of antihypertensive treatment days between 1997 and 1999, angiotensin converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) use from 36.4% to 36.8%, beta-blockers from 19.1% to 21.1%, and thiazide diuretic use from at 11.5% to 12.8%. If treatment patterns had remained the same between 1997 and 1999 in terms of the proportion of medications from each drug class, an additional six million dollars would have been spent on antihypertensive medications in 1999. Although calcium antagonists and ACE inhibitors/ARB remained the most commonly dispensed antihypertensives at VA facilities from 1997 to 1999, there was a proportional decrease in calcium antagonist use and an increase in the use of thiazide diuretics and beta-blockers. These changes were consistent with improved compliance with VA national guidelines. The cost implications of these changes in practice patterns were considerable.