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Background: For symptomatic obstructive hypertrophic cardiomyopathy (oHCM), limited evidence exists on healthcare resource utilization (HRU) and cost for patients with symptomatic oHCM by treatment categories. We evaluated whether HRU and costs vary by initial treatment in symptomatic oHCM., Methods: This is a retrospective study of medical and pharmacy claims from 2016 to 2021 to identify (per International Classification of Disease Tenth Revision diagnosis codes) adult patients in the USA with symptomatic oHCM. Patients included in the study cohort were required to be treatment naïve (≥ 12 months' activity before first treatment) and symptomatic (fatigue, chest pain, syncope, dyspnea, heart failure, or palpitations within 3 months of index date). Patients were grouped by first index treatment [beta blocker (BB), calcium channel blockers (CCB), disopyramide, combination therapy], and HRU and costs [per person per year (PPPY), in USD] by initial treatment were reported., Results: Among 7334 patients with symptomatic oHCM, initial treatment included BB (65.8%), CCB (21.1%), disopyramide (1.2%), or BB + CCB (11.9%). Overall, 87.2% were prescribed monotherapy. Outpatient visits were the main driver of all-cause HRU (mean 11.5 PPPY), and varied by initial treatment (BB: 11.0, CCB: 10.5, disopyramide: 7.2, combination therapy: 12.1). All-cause urgent care visits were more frequent than inpatient visits (means: 5.4 and 0.83 PPPY, respectively). All-cause incurred costs were $46,628 PPPY overall and varied by treatment (BB: $47,029, CCB: $42,124, disopyramide: $27,007, combination therapy: $54,024)., Conclusions: In this large, US-based cohort of patients with symptomatic oHCM, initial therapy was most commonly BB and CCB monotherapy. Costs and HRU were high for most patients, but greater for those treated initially with combination therapy., (© 2024. The Author(s).)

Objectives: In Zambia, 19.1% of the adult population had elevated blood pressure. Hence, the Ministry of Health in Zambia designated the improvement of hypertension (HTN) care services as a priority policy. However, there are limited data on cost-effective interventions to address HTN and their budget impact in sub-Saharan Africa. The objective of this paper is to investigate the cost-effectiveness of primary-level interventions for HTN (pharmaceutical treatments) compared with no treatment, and the budget impact, in the Chongwe District, rural Zambia., Methods: A cost-utility analysis was undertaken from the perspective of healthcare provider, employing a cohort Markov model with a lifetime horizon. The model was developed and populated with evidence from the literature, including novel locally collected cost data. The analysis was run for the overall population aged 40 years and above and for subpopulations stratified by three levels of risk and gender in Chongwe District by using cost data directly collected. A probabilistic analysis was performed to assess the probability of cost-effectiveness., Results: The dominant treatment for the general population was a combination therapy of diuretics and calcium blockers. The incremental cost-effectiveness ratio was US$1114 compared with no treatment. This was the most cost-effective first-line medication for HTN for all subgroup populations, except for the subgroups classified as low-risk defined by WHO. The estimated annual budget impact was US$1 015 605 in total if all HTN patients in Chongwe District received the most cost-effective treatment. Considering only material costs, the annual total budget was US$29 435., Conclusion: The most cost-effective first-line medication for HTN in rural Zambia was the combination therapy of diuretics and calcium blockers for the general population. From the perspective of budget impact, local government could need to secure approximately US$30 000 to facilitate the delivery of the most cost-effective HTN medications to the entire population over 40 years in need., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective., Methods: A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty., Results: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61-1.14), with a mean cost differential of -€12 (95% CI -9,719-8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871-€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17-7,813) and €2,027 (95% CI 19-8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574-10,640 vs. €3,710, 95% CI 263-11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status., Conclusions: The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system., (© 2024. The Author(s).)

Objectives: Postoperative hypertension frequently occurs after surgery for congenital heart disease. Given safety concerns when using calcium channel blockers in infants along with the cost and side-effect profile of nitroprusside, we retrospectively assessed our experience of using nicardipine and nitroprusside for postoperative blood pressure control in infants who underwent surgery for congenital heart disease. We also investigated the cost difference between the medications., Design: This study was a single-center retrospective, pre-post chart review of patients who had surgery for congenital heart disease between 2016 and 2020. The primary aim was a noninferiority comparison of achievement of blood pressure goal at 1-hour post-initiation of an antihypertensive agent. Secondary comparisons included achievement of blood pressure goal at 2 hours after medication initiation, Vasoactive-Inotropic Score (VIS), and blood transfusion, crystalloid volume, and calcium needs., Setting: Academic quaternary-care center., Patients: Infants under 1 year old who required treatment for hypertension with nitroprusside ( n = 71) or nicardipine ( n = 52) within 24 hours of surgery for congenital heart disease., Interventions: None., Measurements and Main Results: We failed to identify any difference in proportion of patients that achieved blood pressure control at 1-hour after medication initiation (nitroprusside 52% vs. nicardipine 54%; p = 0.86), with nicardipine noninferior to nitroprusside within a 15% margin. Of patients who did not achieve control at 1-hour post-medication initiation, receiving nicardipine was associated with blood pressure control at 2 hours post-medication initiation (79% vs. 38%; p = 0.003). We also failed to identify an association between antihypertensive types and mean VIS scores, blood transfusion volumes, crystalloid volumes, and quantities of calcium administered. Index cost of using nitroprusside was 16 times higher than using nicardipine, primarily due to difference in wholesale cost., Conclusions: In our experience of achieving blood pressure control in infants after surgery for congenital heart disease (2016-2020), antihypertensive treatment with nicardipine was noninferior to nitroprusside. Furthermore, nicardipine use was significantly less expensive than nitroprusside. Our contemporary practice is therefore to use nicardipine in preference to nitroprusside., Competing Interests: Dr. Mirea disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Purpose: Antihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting., Methods: This was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness., Results: Among the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient., Conclusion: In conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate., Trial Registration: Clinicaltrials.gov NCT01844570 registered at May 1, 2013.

Background: Uncontrolled blood pressure remains an urgent issue in clinical practice worldwide. This study aimed to compare the characteristics and effectiveness of hypertension control in family medicine pratice in the first treatment year, in relation to the geographical position, socio-economic standard, and access to medical services and public pharmacies in urban, rural and island environments (city of Split vs. Dalmatian Hinterland vs. islands in Southern Croatia)., Methods: A historical cohort study included 213 patients diagnosed from 2008 to 2014 with essential arterial hypertension (AH) and without related complications or diabetes mellitus. Each patient was followed up for 365 days from the visit when the diagnosis of hypertension was ascertained. Normotension was defined as arterial pressure < 140/90 mmHg. The annual cost of drugs prescribed for treating newly diagnosed hypertensive patient and the total price for defined daily dose per patient were also evaluated., Results: More than half patients achieved normotension within a year from the initial diagnosis in all family medicine practices (57.3%), without significant differences among the three geographic regions (P = 0.981). Higher initial systolic blood pressure was a positive predictive prognostic factor on achieveing normotension (odds ratio (OR) 0.96, 95% confidence interval 0.95-0.98). ACE inhibitors were the most commonly prescribed antihypertensive agents in monotherapy (35.1%), as well as considering overall prescriptions (25.2%). Calcium channel blockers were the most commonly prescribed initial BP-lowering single agents in urban areas (28.6%), whereas angiotensin-converting enzyme inhibitors were more common in rural (28.0%) and island areas (22.7%) (P = 0.037). The median annual antihypertensive drug cost was 169.4 (95% CI 151.5-201.8) Croatian kunas and was similar across the study sites., Conclusion: Multiple antihypertensive drugs, prescribed in accordance with the guidelines, lead to similar pharmacological effects. Primary care physicians seem to be able to overcome potential interfering socio-economic factors and successfully achieve normotension in newly diagnosed patients with uncomplicated AH after 1 year of treatment.

Real-world outcomes in patients with chronic stable angina treated with ranolazine and other antianginal medications as second- or third-line therapy are limited. In a historical cohort study of veterans with chronic stable angina, we compared time with coronary revascularization procedures, hospitalizations, and 1-year healthcare costs between new-users of ranolazine versus conventional antianginals (i.e., calcium channel blockers, β blockers, or long-acting nitrates) as second- or third-line. Weighted regression models calculated adjusted hazard ratios (HR) at up to 8-year follow-up, and adjusted incremental costs in the first year. Weighted groups comprised 4,699 ranolazine users and 31,815 conventional antianginal users. Percutaneous coronary intervention (PCI) occurred more often in ranolazine users compared with conventional antianginal users (HR 1.16; 95% confidence intervals [CI] 1.08 to 1.25, p <0.001), and coronary artery bypass grafting occurred less often (HR 0.82; 95% CI 0.68 to 1.00, p <0.046). All-cause and atrial fibrillation (AF) hospitalizations were less common with ranolazine users compared with conventional users (all-cause: HR 0.94; 95% CI 0.90 to 0.99, p <0.010; AF:HR 0.74; 95% CI 0.67 to 0.82, p <0.001), and acute coronary syndrome was more common (HR 1.13; 95% CI 1.00 to 1.27, p <0.042). Adjusted 1-year costs were $24,517 in ranolazine users and $24,798 in conventional users (difference, $-280; 95% CI $-1,742 to $1,181, p = 0.71). In conclusion, ranolazine users had lower rates of coronary artery bypass grafting and all-cause and AF hospitalizations, but higher rates of percutaneous coronary intervention and hospitalizations due to acute coronary syndrome compared with conventional antianginal users. Healthcare costs were similar between ranolazine and conventional antianginal users., (Copyright © 2018. Published by Elsevier Inc.)

In the past decade, the introduction of high-resolution manometry and the classification of achalasia into subtypes has made possible to accurately diagnose the disease and predict the response to treatment for its different subtypes. However, even to date, in an era of exponential medical progress and increased insight in disease mechanisms, treatment of patients with achalasia is still rather simplistic and mostly confined to mechanical disruption of the lower esophageal sphincter by different means. In addition, there is partial consensus on what is the best form of available treatments for patients with achalasia. Herein, we provide a comprehensive outlook to a general approach to the patient with suspected achalasia by: 1) defining the modern evaluation process; 2) describing the diagnostic value of high-resolution manometry and the Chicago Classification in predicting treatment outcomes and 3) discussing the available treatment options, considering the patient conditions, alternatives available to both the surgeon and the gastroenterologist, and the burden to the health care system. It is our hope that such discussion will contribute to value-based management of achalasia through promoting a leaner clinical flow of patients at all points of care., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Sodium nitroprusside (SNP) is a generically available and rapid-acting intravenous (IV) vasodilator that has been used clinically for decades. Prior to 2013, the cost of SNP was relatively low, and SNP was an affordable option for the treatment of acute hypertension. However, from 2013 to 2017, average wholesale prices for SNP rose to as high as US$900 per vial, earning the drug its status as a "hyperinflation drug." Hyperinflation drugs pose a significant challenge for pharmacy departments. A multidisciplinary effort involving stakeholders from many backgrounds, including pharmacists, physicians, and nurses, is key to developing an effective cost containment strategy. A therapeutic interchange, wherein a drug with similar efficacy is substituted for another, is often an appropriate strategy to address rising drug costs. Fortunately, alternative drugs with a solid evidence base exist for the management of acute hypertension. The dihydropyridine calcium channel blockers, clevidipine and nicardipine, are IV titratable antihypertensive agents with favorable pharmacokinetic and safety profiles. Various studies indicate that clevidipine and nicardipine are effective alternatives to SNP for indications including hypertensive crisis and postoperative hypertension. Some hospitals have reported significant cost savings without adverse outcomes by substituting clevidipine or nicardipine for SNP. This article is intended to serve as a review of the evidence for clevidipine and nicardipine as potential substitutes for SNP and to provide strategies to successfully implement this therapeutic interchange.

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, β-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 β-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 β-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., (Published by Elsevier Inc.)

Background/aim: Hypertension is one of the leading causes of cardiovascular morbidity and mortality and more than a half of all health insurance expenditures for reimbursed medicines are allocated to antihypertensive drugs in Serbia. The aim of this study was to identify the antihypertensive drug utilization patterns among hypertensive outpatients in the city of Novi Sad, Serbia, determine the adherence to clinical guidelines and address the economic aspects of current prescribing practices., Methods: This retrospective observational study was conducted in Novi Sad over a period of six months. The data on the number of packages, size their, and retail price of antihypertensives issued on prescription in outpatients with the diagnosis of essential arterial hypertension was collected from all state-owned pharmacies in Novi Sad. Drug consumption was analyzed using the Anatomical Therapeutic Chemical (ATC)/ defined daily dose (DDD) methodology., Results: Total consumption of antihypertensives issued on prescription over a 6-month period in the city of Novi sad, Serbia was 283.48 DDD per 1,000 inhabitans per day (DID). Angiotensin converting enzyme inhibitors (ACEi) were most commonly prescribed drugs, and were used 3 times more often than calcium channel blockers and 5 times more than beta-blockers. The consumption of diuretics and angiotensin receptor antagonists was low within all the groups of outpatients. Both national and international guidelines state superiority and effectiveness of diuretics in treatment of hypertension in the elderly, but their consumption was unreasonable low despite the fact that over 70% of all antihypertensive drugs in the city of Novi Sad were dispensed in people aged > 60. The use of more expensive ACEi was observed despite the guidelines deeming all the drugs of this class equally effective in treatment of hypertension., Conclusion: Large differences in utilization of different groups of antihypertensive agents were noted in this study. Underutilization of valuable, efficacious, and cost-effective thiazide diuretics and overuse of expensive ACE inhibitors is unjustifiable. There is a potential for large savings with switching to low-price ACEi, modeling the practice of Scandinavian countries.

Background: Cardiovascular disease (CVD) is a growing cause of mortality and morbidity in Tanzania, but contextualized evidence on cost-effective medical strategies to prevent it is scarce. We aim to perform a cost-effectiveness analysis of medical interventions for primary prevention of CVD using the World Health Organization's (WHO) absolute risk approach for four risk levels., Methods: The cost-effectiveness analysis was performed from a societal perspective using two Markov decision models: CVD risk without diabetes and CVD risk with diabetes. Primary provider and patient costs were estimated using the ingredients approach and step-down methodologies. Epidemiological data and efficacy inputs were derived from systematic reviews and meta-analyses. We used disability- adjusted life years (DALYs) averted as the outcome measure. Sensitivity analyses were conducted to evaluate the robustness of the model results., Results: For CVD low-risk patients without diabetes, medical management is not cost-effective unless willingness to pay (WTP) is higher than US$1327 per DALY averted. For moderate-risk patients, WTP must exceed US$164 per DALY before a combination of angiotensin converting enzyme inhibitor (ACEI) and diuretic (Diu) becomes cost-effective, while for high-risk and very high-risk patients the thresholds are US$349 (ACEI, calcium channel blocker (CCB) and Diu) and US$498 per DALY (ACEI, CCB, Diu and Aspirin (ASA)) respectively. For patients with CVD risk with diabetes, a combination of sulfonylureas (Sulf), ACEI and CCB for low and moderate risk (incremental cost-effectiveness ratio (ICER) US$608 and US$115 per DALY respectively), is the most cost-effective, while adding biguanide (Big) to this combination yielded the most favourable ICERs of US$309 and US$350 per DALY for high and very high risk respectively. For the latter, ASA is also part of the combination., Conclusions: Medical preventive cardiology is very cost-effective for all risk levels except low CVD risk. Budget impact analyses and distributional concerns should be considered further to assess governments' ability and to whom these benefits will accrue.

Background: We aim to evaluate the trend of national and sub-national (provincial) utilization pattern of antihypertensive medicines in the Iranian population in the past decade and evaluate whether there is any wealth-related inequality in utilization of these medicines among different provinces., Method: Either fixed effect or random effect linear panel data model was used to check the effect of wealth index on utilization of all antihypertensive medicines and each class, adjusting for other covariates including years of schooling, urbanization, mean age, and food type of provinces. The principal component analysis was applied to make summery measures for covariates using available national datasets., Results: The effect of wealth category on the utilization of all antihypertensive medicines among Iranian provinces was positive and significant (0.84; 95% CI: 0.09, 1.59). Accordingly as subgroup analysis, in BBs and CCBs classes, the effects of wealth category on utilization of medicines were positive and significant (0.36; 95% CI: 0.12, 0.60 and 0.27; 95% CI: 0.07, 0.40, respectively). However in ACEIs and Diuretics classes, the effects of wealth category were positive but not significant. In ARBs class, the effect of wealth on utilization was negative and not significant (-0.04; 95% CI: -0.27, 0.18)., Conclusion: According to this study, an inequality could be observed in Iran related to wealth category in utilization of total antihypertensive medicines between provinces.

Purpose: The objective of this study was to explore income differences in the prevalence of moderate-to-severe hypertension, and among patients, in the use and costs of medicines., Methods: Personal income was used to classify ≥25-year-old population in quintiles (QI-QV). Patients (N = 497,560) with moderate-to-severe hypertension were identified using special refund entitlements. Medicine use and costs derived from prescription register. Direct standardisation and multivariate regression were used to adjust for demographics and comorbidities., Results: Low income was associated with higher prevalence of moderate-to-severe hypertension (overall 13%). After adjusting for age, gender, residence, diabetes and coronary heart disease, nearly all patients purchased at least one antihypertensive medicine (93 vs. 96% in QI and QV). Differences in the purchased quantities were small (mean estimates 1028 vs. 1054 defined daily doses (DDDs)/patient/year in QIV and QI). High-income patients were more likely to use angiotensin receptor blockers (37 vs. 54% in QI and QV). Low-income patients were more likely to use beta-blockers (59 vs. 49%, respectively) and ACE inhibitors (35 vs. 28%, respectively). Higher income was associated with higher annual out-of-pocket costs (mean €66 vs. €71 in QI and QV) and reimbursements (€144 vs. €163, respectively)., Conclusions: Use of more expensive medicines contributed to higher costs among patients with higher incomes.

Background: Ureteric colic, the term used to describe the pain felt when a stone passes down the ureter from the kidney to the bladder, is a frequent reason for people to seek emergency health care. Treatment with the muscle-relaxant drugs tamsulosin hydrochloride (Petyme, TEVA UK Ltd) and nifedipine (Coracten(®), UCB Pharma Ltd) as medical expulsive therapy (MET) is increasingly being used to improve the likelihood of spontaneous stone passage and lessen the need for interventional procedures. However, there remains considerable uncertainty around the effectiveness of these drugs for routine use., Objectives: To determine whether or not treatment with either tamsulosin 400 µg or nifedipine 30 mg for up to 4 weeks increases the rate of spontaneous stone passage for people with ureteric colic compared with placebo, and whether or not it is cost-effective for the UK NHS., Design: A pragmatic, randomised controlled trial comparing two active drugs, tamsulosin and nifedipine, against placebo. Participants, clinicians and trial staff were blinded to treatment allocation. A cost-utility analysis was performed using data gathered during trial participation., Setting: Urology departments in 24 UK NHS hospitals., Participants: Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures., Interventions: Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 µg, nifedipine 30 mg or placebo once daily for up to 4 weeks to make the following comparisons: tamsulosin or nifedipine (MET) versus placebo and tamsulosin versus nifedipine., Main Outcome Measures: The primary effectiveness outcome was the proportion of participants who spontaneously passed their stone. This was defined as the lack of need for active intervention for ureteric stones at up to 4 weeks after randomisation. This was determined from 4- and 12-week case-report forms completed by research staff, and from the 4-week participant self-reported questionnaire. The primary economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained over 12 weeks. We estimated costs from NHS sources and calculated QALYs from participant completion of the European Quality of Life-5 Dimensions health status questionnaire 3-level response (EQ-5D-3L™) at baseline, 4 weeks and 12 weeks., Results: Primary outcome analysis included 97% of the 1167 participants randomised (378/391 tamsulosin, 379/387 nifedipine and 379/399 placebo participants). The proportion of participants who spontaneously passed their stone did not differ between MET and placebo [odds ratio (OR) 1.04, 95% confidence interval (CI) 0.77 to 1.43; absolute difference 0.8%, 95% CI -4.1% to 5.7%] or between tamsulosin and nifedipine [OR 1.06, 95% CI 0.74 to 1.53; absolute difference 1%, 95% CI -4.6% to 6.6%]. There was no evidence of a difference in QALYs gained or in cost between the trial groups, which means that the use of MET would be very unlikely to be considered cost-effective. These findings were unchanged by extensive sensitivity analyses around predictors of stone passage, including sex, stone size and stone location., Conclusions: Tamsulosin and nifedipine did not increase the likelihood of stone passage over 4 weeks for people with ureteric colic, and use of these drugs is very unlikely to be cost-effective for the NHS. Further work is required to investigate the phenomenon of large, high-quality trials showing smaller effect size than meta-analysis of several small, lower-quality studies., Trial Registration: Current Controlled Trials ISRCTN69423238. European Clinical Trials Database (EudraCT) number 2010-019469-26., Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 63. See the NIHR Journals Library website for further project information.

Background: Combination drugs containing an angiotensin receptor blocker and a calcium channel blocker have been widely commercialized in recent years, and their advantages, such as improvements in adherence, and reductions in medication costs, have been greatly emphasized. However, the actual situations and the impact of switching to combination drugs in clinical practice of nephrology are not fully understood., Methods: This study was conducted in outpatients of nephrology who received antihypertensive medicines, and who switched to combination drugs. Changes in the potency of the antihypertensive drugs, and blood pressure were examined retrospectively before and after changing treatments. In addition, the study also involved patients' questionnaire, which examined changes in blood pressure at home, the presence or absence of missed doses, the impact on medication-related expenses, and the level of patients' satisfaction with regard to combination drugs., Results: Survey results from 90 participants revealed that changing to combination drugs resulted in a reduction of missed doses, a decrease in blood pressure measured in an outpatient setting, and a reduction in medication-related expenses in total patients, non-chronic kidney disease (CKD) patients, and CKD patients., Conclusion: Our study shows that switching to combination antihypertensive drugs resulted in an improvement in adherence and a reduction in medication-related expenses, and revealed that patient satisfaction was high. Combination drugs for hypertensive patients may be beneficial in both medical and economical viewpoints.

Background: Arterial hypertension is a common disorder that affects around 9 million adults in Poland. Single-pill combinations (SPCs) for the treatment of arterial hypertension have significant advantages over the free combinations, resulting in lower risk of cardiovascular events and lower consumption of medical resources. The current ESC/ESH 2013 guidelines for the first time recommend treatment with a combination of thiazide-like diuretic with calcium channel blocker. Currently, no such combination is reimbursed from public funds in Poland., Aim: To assess the economic value of treatment with SPC of indapamide and amlodipine (Tertens-AM®) for hypertensive patients compared with free combination therapy (FC), in the Polish setting., Methods: As there are currently no published data directly estimating the additional effect of using indapamide + amlo-dipine SPC vs. FC, two extreme approaches are presented: with difference in effectiveness due to improved adherence to the treatment estimated from published studies on other molecules used in hypertension such as SPCs and FCs - the base-case approach (1); and assuming no difference of effectiveness or adherence between SPC and FC of indapamide and amlodipine - the conservative approach (2). Modelling was carried out based on the Markov process in lifetime horizon. In the base-case approach, with the difference in effectiveness between SPC and FC, it was assumed that the differences in compliance translate into the differences in systolic blood pressure. Patients' characteristics were correlated with the risk of events associated with cardiovascular disease, based on the prediction algorithms from the Framingham Heart Study. Costs were considered from a National Health Fund (NHF) perspective and NHF and patient's perspective, and therefore direct medical costs were only included., Results: The treatment with SPC of indapamide and amlodipine in place of FC resulted in 7.6 additional days of life in full health and longer overall patient survival by 2.9 days. The replacement of FC with SPC would result in national savings from both NHF perspective and NHF and patient's perspective, irrespective of the assumption of the difference in adherence between SPC and FC. The savings would amount to 1.602-3.954 million PLN and 16.498-19.186 million PLN from NHF perspective and NHF and patient's perspective, respectively., Conclusions: The treatment with SPC of indapamide and amlodipine for hypertensive patients was found to be dominant over FC or at least less expensive than treatment with FC when the difference in effectiveness was neglected. The replacement of FC with SPC would result in savings from both NHF perspective and NHF and patient's perspective.

This retrospective claims database analysis compared two strategies of hypertension treatment in outpatient, emergency, and inpatient departments: a fixed-dose combination (FDC) of amlodipine/valsartan vs free combinations of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) (ARB+CCB group). After a mean follow-up of 15.2 months, the FDC group had significantly lower total healthcare costs (US $1844 vs US $2158; P<.001) and hospitalization rates (14.57% vs 18.43%; P<.001), a higher proportion of days covered (80.35% vs 72.57%; P<.001), and better persistence (266 vs 225 days; P<.001) compared with the ARB+CCB group. The FDC group also had a better major adverse cardiovascular event (MACE)-free survival (hazard ratio, 0.83; 95% confidence interval, 0.73-0.94; P=.003) and decreased rates of heart failure (2.12% vs 3.26%; P<.001), malignant dysrhythmia (0.18% vs 0.42%; P=.021), and percutaneous coronary intervention (0.76% vs 1.26%; P=.015). Compared with free combinations of ARB+CCB, an FDC of amlodipine/valsartan improved MACE-free survival and medication compliance and decreased total healthcare costs and hospitalization rates in hypertensive patients., (© 2014 Wiley Periodicals, Inc.)

Background: Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications.Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation.This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones., Methods/design: The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo.Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The primary economic outcome is a reduction in the incremental cost per quality-adjusted life years, determined at 12 weeks. The analysis will be based on all participants as randomized (intention to treat). The trial has 90% power with a type I error rate of 5% to detect a 10% increase in primary outcome between the tamsulosin and nifedipine treatment groups., Trial Registration: ISRCTN69423238; EudraCT number: 2010-019469-26.

Question Under Study: Due to greater life expectancy, costs of medication have increased within the last decade. This investigation assesses health care expenditures needed to manage the current state of blood pressure (BP) control in Switzerland., Objectives: a) average day therapy costs (DTC) of substances, b) actual DTC of currently prescribed antihypertensive therapy, c) monetary differences of treatment regimens within different BP-groups and different high risk patients, d) estimated compliance-related financial loss/annum and adjusted costs/annum. Single-pill-combinations appear to be useful to increase patient's compliance, to reduce side effects and to bring more patients to their blood pressure goal., Methods: Costs were identified based on data from the Swiss department of health. We calculated DTC for each patient using prices of the largest available tablet box., Results: The average antihypertensive therapy in Switzerland currently costs CHF 1.198 ± 0.732 per day. On average beta blockers were the cheapest substances, followed by angiotensin converting enzyme inhibitors (ARBs), calcium channel blockers and diuretics. The widest price ranges were observed within the class of ARBs. Most expensive were patients with impaired renal function. Throughout all stages, single-pill-combinations appeared to be significantly cheaper than dual-free-combinations. Stage-II-hypertension yielded the highest costs for dual free combination drug use. The actual costs for all patients observed in this analysis added up to CHF 1,525,962. Based on a compliance model, only treatment amounting to CHF 921,353 is expected to be actually taken., Conclusion: A disproportionately high healthcare cost is expected due to compliance reasons. The prescription of mono-therapies appears to be a major cost factor, thus, the use of single-pill-combination therapy can be considered as a suitable approach to saving costs throughout all BP- stages.

Purpose: The use of medical expulsive therapy to hasten stone passage potentially decreases expenditures around episodes of renal colic. However, these efficiency gains may be mitigated if patients treated with medical expulsive therapy have frequent health care encounters due to pain while waiting for the stones to pass., Materials and Methods: Using claims data (2002 to 2006) we identified adult men with acute renal colic. We compared 6-week payments as well as frequency of hospitalization and emergency department revisits associated with an initial course of medical expulsive therapy with those for early endoscopic stone removal. To account for unmeasured confounding we performed an instrumental variable analysis, exploiting variation in recommended treatments based on the day of the week that a patient's first emergency department visit occurred., Results: Overall 1,835 and 4,397 men underwent medical expulsive therapy or early endoscopic stone removal, respectively. Although minimal differences existed between men with respect to the day of the week of emergency department presentation, weekend encounters were strongly associated with receiving medical expulsive therapy (p <0.001). Two-stage least squares regression revealed 6-week payments to be tenfold lower for men on medical expulsive therapy who were candidates for either treatment (p <0.001). While there was no difference in frequency of hospitalization, these men were more likely to have a repeat emergency department visit compared to those who underwent endoscopic stone removal (68.8% vs 39.6%, respectively, p = 0.025)., Conclusions: Findings on medical expulsive therapy are mixed, with lower 6-week payments but more frequent repeat emergency department visits. These data inform patients who are candidates for medical expulsive therapy or endoscopic stone removal when making decisions about their care., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the evolution of consumption of antihypertensive drugs generic among 1991-2010, to assess the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs., Methods: We used sales data from the Moroccan subsidiary of IMS Health Intercontinental Marketing Service., Results: Consumption of generic antihypertensive drugs increased from 0.08 to 10.65 DDD/1 000 inhabitants/day between 1991 and 2010. In 2010, generic of the calcium channel blockers (CCBs) represented 4.08 DDD/1 000 inhabitants/day (82.09%), followed by angiotensin converting enzyme inhibitors (ACEI) by 2.40 DDD/1 000 inhabitants/day (48.29%). The generics market of CCBs is the most dominant and represented in 2010, 79.21% in volume and 62.58% in value., Conclusion: In developing countries like Morocco, the generic drug is a key element for access to treatment especially for the poor population., (© 2013 Société Française de Pharmacologie et de Thérapeutique.)

Objective: The aim of this study is to compare the efficiency of different fixed-dose combinations of renin-angiotensin-aldosterone system (RAAS) blockers and calcium channel blockers, to use it as a guide to assist the rational prescribing in antihypertensive therapy., Methods: The efficacy of each drug was obtained from intervention studies randomized, double-blind, made with these combinations and a utility-cost modeling from the model proposed and used by NICE. The perspective of our analysis is the National Health System and the time horizon is long enough to achieve therapeutic goals., Main Outcome Measures: Cost per mmHg reduction in BP, percentage of reduction necessary to achieve the therapeutic goals for hypertension control and cost, and finally quantity and quality of life gained with these treatments in patients with hypertension, diabetes., Results: We studied three fixed-dose combinations: amlodipine/olmesartán, amlodipine/valsartan and manidipine/delapril. The cost per mmHg systolic BP ranged from 24.93 to 12.34 €/mmHg, and diastolic BP ranged from 34.24 to 18.76 €/mmHg, depending on the drug used. For an initial value of 165mmHg systolic BP the most efficient treatment to achieve the therapeutic goal of hypertension control (<140mmHg) is manidipine/delapril with a cost of 67.76 €. The use of these drugs to control diabetic and hypertensive patients resulted in all cases being cost-effective (more effective and lower cost compared to "no treatment"). Manidipine/delapril showed the best relation cost-utility (1,970 €/QALY (quality-adjusted life year)) followed by amlodipine/olmesartan and amlodipine/valsartan (2,087 and 2,237 €/QALY, respectively)., (Copyright © 2012 Elsevier España, S.L. y SEMERGEN. All rights reserved.)

Objectives: Since treatment regimen type can influence adherence and other outcomes, this study examined adherence, cardiovascular events, and economic outcomes in patients with hypertension treated with fixed-dose combination (FDC) amlodipine/olmesartan (AML/OM), FDC AML/benazepril (AML/BEN), and loose-dose combination AML plus angiotensin II receptor blockers (LDC AML/ARBs)., Methods: Commercial health plan enrollees aged at least 18 years with index claim(s) for AML/OM, AML/BEN, or LDC AML/ARB were identified. Absence of study drug 6 months pre index, and continuous enrollment for at least 12 months post index were required. Descriptive analyses were executed to make comparisons between treatments, as well as multivariate models adjusting for baseline demographic and clinical characteristics, including propensity for assignment to study drug., Results: Descriptive results suggested mean follow-up adherence was higher in the AML/OM cohort [proportion of days covered (PDC) = 0.63] compared with the AML/BEN (PDC = 0.55; p < 0.001) and LDC AML/ARB cohorts (PDC = 0.34; p < 0.001). The proportion of individuals with an incident follow-up cardiovascular event composite was lower in the AML/OM cohort versus the AML/BEN and LDC AML/ARB cohorts (5.94% versus 7.85% and 16.89% respectively). Adjusted Cox models suggested that patients initiated on LDC AML/ARB (hazard ratio 1.35; p < 0.001), but not on AML/BEN, were at greater risk of a follow-up cardiovascular event (composite) compared with AML/OM. Adjusted generalized linear models suggested that mean follow-up per-member-per-month overall costs were higher in the AML/BEN (cost ratio = 1.169; p < 0.001; unadjusted mean cost US$780) and LDC AML/ARB cohorts (cost ratio = 1.286; p < 0.001; unadjusted mean cost US $1394) compared with the AML/OM cohort (unadjusted mean cost US $740)., Conclusion: The results suggested that treatment with FDC AML/OM was associated with greater likelihood of adherence and lower overall costs than with FDC AML/BEN and LDC AML/ARB, and lower risk of cardiovascular event composite versus LDC AML/ARB.

Poor antihypertensive treatment adherence adversely affects blood pressure control. We analyzed US health plan data to assess the impact of fixed- versus loose-dose triple-combination therapy on adherence, clinical, and economic outcomes. Patients initiating triple therapy with an angiotensin receptor blocker, angiotensin-converting enzyme inhibitor, or beta blocker plus amlodipine and hydrochlorothiazide comprised three cohorts. Within-cohort comparisons were made between fixed-dose combinations of two antihypertensives plus a second pill (two pills) or three separate pills. Outcomes included adherence, cardiovascular events, health care resource use, and costs for patients with ≥ 12 months follow-up. A total of 16,290 patients were matched. Patients receiving two pills were more likely to be adherent (P < .001) and less likely to discontinue treatment (P < .001) across all cohorts. Therapy with two versus three pills resulted in significantly lower adjusted risk of cardiovascular events (hazard ratio = 0.76, P = .005) in the beta blocker cohort only. Total adjusted health care costs were significantly lower for two- versus three-pill therapy in the beta blocker cohort only (cost ratio = 0.74 overall, P < .01; 0.71 hypertension-attributable, P < .01). In patients with hypertension requiring triple therapy, fixed-dose combinations that lower pill burden may improve adherence (seen across all cohorts) and clinical outcomes (seen in the beta blocker cohort) without increasing health care costs., (Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

We enrolled 196 patients with hypertension who were already being treated with free-drug combinations of angiotensin-II receptor blocker (ARB) and amlodipine. The free-drug combinations of ARB and amlodipine were replaced with the same dose of the fixed-dose combinations. The average home blood pressure (BP) in all patients receiving fixed-dose combinations was significantly lower than those receiving free-drug combinations (131 ± 10/75 ± 8 vs. 136 ± 11/77 ± 9 mm Hg, P < .01) accompanied with increasing drug adherence. After lowering BP by fixed-dose combinations, the costs for medications decreased by 31% over the 3 months.

Background: Cardiovascular disease is the leading cause of death worldwide. Like many countries, Australia is currently changing its guidelines for cardiovascular disease prevention from drug treatment for everyone with 'high blood pressure' or 'high cholesterol', to prevention based on a patient's absolute risk. In this research, we model cost-effectiveness of cardiovascular disease prevention with blood pressure and lipid drugs in Australia under three different scenarios: (1) the true current practice in Australia; (2) prevention as intended under the current guidelines; and (3) prevention according to proposed absolute risk levels. We consider the implications of changing to absolute risk-based cardiovascular disease prevention, for the health of the Australian people and for Government health sector expenditure over the long term., Methods: We evaluate cost-effectiveness of statins, diuretics, ACE inhibitors, calcium channel blockers and beta-blockers, for Australian men and women, aged 35 to 84 years, who have never experienced a heart disease or stroke event. Epidemiological changes and health care costs are simulated by age and sex in a discrete time Markov model, to determine total impacts on population health and health sector costs over the lifetime, from which we derive cost-effectiveness ratios in 2008 Australian dollars per quality-adjusted life year., Results: Cardiovascular disease prevention based on absolute risk is more cost-effective than prevention under the current guidelines based on single risk factor thresholds, and is more cost-effective than the current practice, which does not follow current clinical guidelines. Recommending blood pressure-lowering drugs to everyone with at least 5% absolute risk and statin drugs to everyone with at least 10% absolute risk, can achieve current levels of population health, while saving $5.4 billion for the Australian Government over the lifetime of the population. But savings could be as high as $7.1 billion if Australia could match the cheaper price of statin drugs in New Zealand., Conclusions: Changing to absolute risk-based cardiovascular disease prevention is highly recommended for reducing health sector spending, but the Australian Government must also consider measures to reduce the cost of statin drugs, over and above the legislated price cuts of November 2010.

Background: Cardiovascular disease (CVD) is a major source of mortality and morbidity in dialysis patients. Population-level descriptions of CVD medication use are lacking in this population., Study Design: Retrospective cohort study., Setting & Participants: Adult dialysis patients in the United States, alive on December 31, 2006, with Medicare Parts A and B and enrollment in Medicare Part D continuously in 2007., Predictor: CVDs and demographic characteristics., Outcome: ≥1 prescription fill during follow-up (2007)., Measurements: Average out-of-pocket costs per user per month and average total drug costs per member per month were calculated., Results: Of 225,635 dialysis patients who met inclusion criteria during the entry period, 70% (n = 158,702) had continuous Part D coverage during follow-up. Of these, 76% received the low-income subsidy. β-Blockers were the most commonly used CVD medication (64%), followed by renin-angiotensin system inhibitors (52%), calcium channel blockers (51%), lipid-lowering agents (44%), and α-agonists (23%). Use varied by demographics, geographic region, and low-income subsidy status. For CVD medications, mean out-of-pocket costs per user per month were $3.44 and $49.59 and mean total costs per member per month were $124.02 and $110.32 for patients with and without the low-income subsidy, respectively., Limitations: Information was available for only filled prescriptions under the Part D benefit; information for clinical contraindications was lacking, information for over-the-counter medications was unavailable, and medication adherence and persistence were not examined., Conclusions: Most Medicare dialysis patients in 2007 were enrolled in Part D, and most enrollees received the low-income subsidy. β-Blockers were the most used CVD medication. Total costs of CVD medications were modestly higher for low-income subsidy patients, but out-of-pocket costs were much higher for patients not receiving the subsidy. Further study is warranted to delineate sources of variation in the use and costs of CVD medications across subgroups., (Published by Elsevier Inc.)

Objective: To compare adherence, healthcare costs and utilization of valsartan/amlodipine single-pill combination (SPC) and angiotensin-receptor blocker/calcium-channel blocker multiple-pill free-combination (ARB + CCB FC) therapy using real-world data., Methods: A retrospective study (January 1, 2007 to April 30, 2009) was conducted using US commercial healthcare insurance claims. Patients were assigned to two cohorts: 'valsartan/amlodipine SPC cohort' and 'ARB + CCB FC therapy cohort'. The primary endpoints were adherence and persistence. The secondary endpoints were 1-year healthcare costs and utilization., Results: Out of 12,628 eligible patients 3259 (26%) were included in the valsartan/amlodipine SPC cohort and 9369 (%74) in the ARB + CCB FC cohort. Risk-adjusted adherence rates were higher for valsartan/amlodipine SPC patients [OR: 1.38, 95% CI: (1.24, 1.53)]. The Cox proportional hazard model showed that valsartan/amlodipine SPC cohort patients were less likely to discontinue medication (HR: 0.87, p < 0.001). Comparison between the groups also yielded that total healthcare costs of valsartan/amlodipine SPC patients were 16-20% lower than ARB + CCB FC therapy patients (p < 0.0001)., Limitations: Since claims data are collected for payment purposes rather than research purposes, the study is bound by limitations for the retrospective analysis. For example, the presence of a claim for a filled prescription does not indicate that the medication was consumed or taken as prescribed. Data on health behaviors and patient lifestyle were not available. Over-the-counter medications and clinical disease severity were not available in the dataset. Incorrect coding is also a possibility. However, we have used previously validated datasets where these effects are minimal. Heterogeneity of the sample may create bias in our estimates, however, we have used advanced statistical methods to control for observed and unobserved bias., Conclusion: The real-world use of valsartan/amlodipine SPC was associated with better adherence and persistence relative to ARB + CCB FC therapy among patients with hypertension. Moreover, patients taking single-pill combination therapy had lower healthcare costs and utilization.

Objective: To evaluate the impact of angiotensin receptor blocker (ARBs)/dihydropyridine calcium channel blockers (CCBs) single-pill combination (SPC) on adherence to antihypertensive treatment in comparison to free combination of ARBs and CCBs., Research Design and Methods: A retrospective data analysis was performed using pharmacy claims data from a national pharmacy benefit management company. The study included patients who were newly initiated on ARB/CCB treatment between 01/01/2007 and 08/31/2008, aged ≥ 18 years, and continuously enrolled in the same health plan for 12 months prior to and 13 months after starting ARB/CCB treatment. Outcome variables were persistence, defined as time to discontinuation of therapy, and adherence, defined as proportion of days covered (PDC)  ≥ 0.80. Propensity score weighting was used to balance the characteristics of the two groups., Results: The final sample contained 2312 patients in the free-combination group and 2213 patients in the SPC group. Patients in the SPC group and the free-combination group were different in age, gender, type of insurance, history of antihypertensive therapy and co-morbidities. These differences were largely normalized after propensity score adjustment. Multivariate logistic model regression showed that patients in the SPC group had a 90% greater odds of being adherent to index therapy compared to patients in the free-combination group (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.75-2.08, p< 0.001). A Cox proportional hazards model showed that patients in the SPC group were less likely to discontinue ARB/CCB SPC therapy compared to patients in the free-combination group (hazard ratio [HR] 0.66, 95% CI 0.63-0.70, p < 0.001). In both models, higher copayment (copayment $50 and above) was associated with worse persistence and adherence in comparison to patients who had a lower copayment ($0-$5): HR = 1.23, p < 0.001 and OR = 0.67, p < 0.001., Conclusion: Patients using SPC ARB/CCB therapy were more likely to be persistent and adherent to treatment compared to patients taking free-combination therapy.

Introduction: Little evidence exists to guide investigators on the effectiveness and cost-effectiveness of various recruitment strategies in primary care research. The purpose of this study is to describe the effectiveness and cost-effectiveness of eight clinical trial recruitment methods for postmenopausal women in a community-based setting., Methods: A retrospective analysis of the yield and cost of eight different recruitment methods: 1) family physician (FP) recruiters, 2) FP referrals, 3) community presentations, 4) community events, 5) newsletters, 6) direct mailings, 7) posters, and 8) newspaper advertisements that were used to recruit postmenopausal women to a randomized clinical trial (RCT) evaluating the effectiveness of gabapentin in treating hot flashes., Results: We recruited 197 postmenopausal women from a total of 904 screened, with 291 of the remainder being ineligible and 416 declining to participate. Of the 904 women screened, 34 (3.8%) were from FP recruiters and 35 (3.9%) were from other FP referrals while 612 (67.7%) resulted from newspaper advertisements. Of the 197 women enrolled, 141 (72%) were from newspaper advertisements, with 26 (13%) following next from posters. Word of mouth was identified as an additional unanticipated study recruitment strategy. Metropolitan newspaper advertising at $112.73 (Canadian) per enrolled participant and posters at $119.98 were found to be cost-effective recruitment methods., Conclusion: Newspaper advertisements were the most successful method to recruit postmenopausal women into a community-based, primary care RCT., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background and Purpose: In Germany, hypertension has a prevalence of about 20%. Cardiovascular morbidity and mortality are closely associated with hypertension. Therefore, antihypertensive medical treatment is of crucial importance. Currently, five groups of drugs for the medical treatment of hypertension are available: diuretics, beta-receptor blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers. Besides medical considerations for the treatment of hypertension costs of treatment and other economic aspects become more and more important. Within this article, the antihypertensive treatment of insurants of the statutory health insurance and the private health insurance is compared with regard to the medical treatment and associated costs., Methods: The analyzed data derive from the general practice morbidity research network CONTENT (CONTinuous morbidity registration Epidemiologic NeTwork). The implementation of this network is funded by the German Federal Ministry of Research and Education (BMBF) for a continuous registration of health-care utilization, morbidity, course of disease, and outcome parameters within primary care., Results: Altogether 4,842 patients from the participating general practitioners were regularly treated with antihypertensive drugs in 2007 and corresponding episodes were documented within electronic medical records. The proportion of insurants of the private health insurance was 7.6%. The costs of the antihypertensive medical treatment within the total sample in 2007 constituted 1.03 million Euros overall and per patient on average 212.82 Euros. Although the regarded sample of private health insurants was less morbid and the sum of defined daily doses (DDDs) within the observation period was notably lower (582.6 vs. 703.1; p < 0.0001), the annual therapy costs of the private health insurants compared to the statutory health insurants were 35.2% higher (280.29 Euros vs. 207.29 Euros; p < 0.0001). Hence, costs per DDD for antihypertensive medical treatment for private health insurants were 63.2% higher than for statutory health insurants. This refers to the great proportion of angiotensin II receptor blockers as well as the low proportion of generic drugs prescribed for private health insurants., Conclusion: Antihypertensive treatment with original drugs and/or angiotensin II receptor blockers is an expensive option. Based on the actual state of knowledge it must be questioned critically whether this constitutes a superior treatment option concerning the potential for lowering high blood pressure levels and organ protection.

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.

Hypertension and dyslipidemia are two of the most commonly co-occurring cardiovascular risk factors which together cause an increase in coronary heart disease-related events that is more than simply additive for anticipated event rates with each condition. Data have shown that even relatively small reductions in both blood pressure and cholesterol levels can lead to large reductions in the risk for cardiovascular events. However, though there are robust data on the beneficial effect of concomitant reduction in these risk factors, the reality is that this is achieved in <10% of patients. There is nonadherence with prescribed therapies with up to 50% of patients stopping their medications of their own volition for a variety of reasons. There is a reasonable evidence base to suggest that simplifying drug regimens and reducing pill burden will enhance patient adherence. The fixed-dose combination containing the antihypertensive agent amlodipine besylate and the statin atorvastatin is the first combination of its kind, which is both efficacious and safe and could potentially improve medication compliance, thereby improving the outcomes in these patients.

Objective: To estimate potential savings associated with the Consumer Reports Best Buy Drugs program, a national educational program that provides consumers with price and effectiveness information on prescription drugs., Data Sources: National data on 2006 prescription sales and retail prices paid for angiotensin-converting enzyme inhibitors (ACEIs), β-blockers, calcium channel blockers, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-coA) reductase inhibitors (statins)., Study Design: We converted national data on aggregate unit sales of drugs in the four classes to defined daily doses (DDD) and estimated a range of potential savings from generic and therapeutic substitution., Principal Findings: We estimated that $2.76 billion, or 7.83 percent of sales, could be saved if use of the drugs recommended by the educational program was increased. The recommended drugs' prices were 15-65 percent lower per DDD than their therapeutic alternatives. The majority (57.4 percent) of potential savings would be achieved through therapeutic substitution., Conclusions: Substantial savings can be achieved through greater use of comparatively effective and lower cost drugs recommended by a national consumer education program. However, barriers to dissemination of consumer-oriented drug information must be addressed before savings can be realized., (© Health Research and Educational Trust.)

Objective: To evaluate the cost-effectiveness of first-line treatments for hypertension., Background: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) found that first-line treatment with lisinopril or amlodipine was not significantly superior to chlorthalidone in terms of the primary endpoint, so differences in costs may be critical for optimizing decision-making., Methods: Cost-effectiveness analysis was performed using bootstrap resampling to evaluate uncertainty., Results: Over a patient's lifetime, chlorthalidone was always least expensive (mean $4,802 less than amlodipine, $3,700 less than lisinopril). Amlodipine provided more life-years (LYs) than chlorthalidone in 84% of bootstrap samples (mean 37 days) at an incremental cost-effectiveness ratio of $48,400 per LY gained. Lisinopril provided fewer LYs than chlorthalidone in 55% of bootstrap samples (mean 7-day loss) despite a higher cost. At a threshold of $50,000 per LY gained, amlodipine was preferred in 50%, chlorthalidone in 40%, and lisinopril in 10% of bootstrap samples, but these findings were highly sensitive to the cost of amlodipine and the cost-effectiveness threshold chosen. Incorporating quality of life did not appreciably alter the results. Overall, no reasonable combination of assumptions led to 1 treatment being preferred in over 90% of bootstrap samples., Conclusions: Initial treatment with chlorthalidone is less expensive than lisinopril or amlodipine, but amlodipine provided a nonsignificantly greater survival benefit and may be a cost-effective alternative. A randomized trial with power to exclude "clinically important" differences in survival will often have inadequate power to determine the most cost-effective treatment.

Background: Controlling the growth of pharmaceutical expenditures is a major global challenge. Promotion of generic drug prescriptions or use is gaining increased support. There are substantial contextual differences in international experiences of implementing pharmaceutical policies related to generic drugs. Reporting these experiences from varied perspectives can inform future policy making. This study describes an experience of Taiwan, where patients with chronic (long-term) conditions are usually managed in hospitals and drugs are provided in this setting with costs reimbursed through the National Health Insurance (NHI). It investigates the effects of Taiwan's reimbursement rate adjustment based on chemical generic grouping in 2001. This research also demonstrates the use of micro-level longitudinal data to generate policy-relevant information. The research can be used to improve efficiency of health care resource use., Methods: We chose the three most-used classes of cardiovascular drugs for this investigation: beta blocking agents, calcium channel blockers mainly with vascular effects, and plain ACE inhibitors. For each drug class, we investigated changes in daily expense, consumption volume, and total expenditures from a pre-action period to a corresponding post-action period. We compared an exposure or "intervention" group of patients targeted by the action with a comparisonor "control" group of patients not targeted by the action. The data sources are a longitudinal database for 200,000 NHI enrolees, corresponding NHI registration data of health care facilities, and an archive recording all historical data on the reimbursement rates of drugs covered by the NHI. We adopted a fixed effects linear regression model to control for unobserved heterogeneity among patient-hospital groups. Additional descriptive statistics were applied to examine whether any inappropriate consumption of drugs in the three classes existed., Results: The daily drug expense significantly decreased from the pre-action period to the post-action period for the exposure group. The average magnitudes of the decreases for the three classes of drugs mentioned above were 14.8%, 5.8% and 5.8%, respectively. In contrast, there was no reduction for the comparison group. The number of days of the prescription increased significantly from the pre- to the post-action period for both exposure and comparison groups. The total expense also significantly increased for both patient groups. For the exposure group, the average magnitudes of the growth in the total expenditure for the three classes of drugs were 47.7%, 60.0% and 55.3%, respectively. For the comparison group, they were 91.6%, 91.6% and 63.2%, respectively. After the action, approximately 50% of patients obtained more than 180 days of prescription drugs for a six-month period., Conclusion: The 2001 price adjustment action, based on generic grouping, significantly reduced the daily expense of each of the three classes of cardiovascular drugs. However, in response to this policy change, hospitals in Taiwan tended to greatly expand the volume of drugs prescribed for their regular patients. Consequently, the total expenditures for the three classes of drugs grew substantially after the action. These knock-on effects weakened the capability of the price adjustment action to control total pharmaceutical expenditures. This means that no saved resources were available for other health care uses. Such expansion of pharmaceutical consumption might also lead to inefficient use of the three drug classes: a large proportion of patients obtained more than one day of drugs per day in the post-action period, suggesting manipulation to increase reimbursement and offset price controls. We recommend that Taiwan's government use the NHI data to establish a monitoring system to detect inappropriate prescription patterns before implementing future policy changes. Such a monitoring system could then be used to deter hospitals from abusing their prescription volumes, making it possible to more effectively save health care resources by reducing drug reimbursement rates.

Amlodipine/atorvastatin (Caduet) is a once-daily fixed-dose combination of the dihydropyridine calcium channel antagonist amlodipine and the HMG-CoA reductase inhibitor atorvastatin. In Europe, the combination is indicated for the prevention of cardiovascular events in hypertensive patients with three concomitant cardiovascular risk factors and, in the US, it is indicated for the management of hypertension and dyslipidemia in patients for whom treatment with both agents is appropriate. In clinical trials, the fixed-dose combination of amlodipine/atorvastatin effectively managed two important risk factors simultaneously in hypertensive patients at risk of cardiovascular disease or in those with concomitant hypertension and dyslipidemia. The combination is bioequivalent to amlodipine and atorvastatin given alone and does not modify the efficacy of either single agent. Amlodipine/atorvastatin is generally well tolerated, with a tolerability profile consistent with that of each single agent. Compared with the coadministration of each single agent, the convenience of single-pill amlodipine/atorvastatin has the potential to improve patient adherence and the management of cardiovascular risk in selected patients, thereby improving clinical outcomes.

Background: Treatment regimens that require fewer dosage units and less frequent dosing to decrease the complexity and cost of care are among the strategies recommended to improve compliance with antihypertensive therapy. Simplifying therapy may be particularly important for elderly patients, who are more likely to have co-morbid conditions and to be taking multiple medications., Objective: To determine rates of compliance with antihypertensive therapy and total costs of care among elderly Medicaid recipients treated with fixed-dose combination amlodipine besylate/benazepril versus a dihydropyridine calcium channel antagonist and ACE inhibitor prescribed as separate agents (free combination)., Study Design: A longitudinal, retrospective, cohort analysis of South Carolina Medicaid claims for ambulatory services, hospital services, Medicare crossover, and prescription drug for the years 1997-2002. Follow-up was 12 months from the index date, defined as the first prescription dispensing date for a study drug., Patients: South Carolina Medicaid beneficiaries aged >or=65 years., Main Outcome Measure: Outcomes variables included compliance defined as the medication possession ratio (MPR), which was the total days' supply of drug (excluding last prescription fill) divided by the length of follow-up (with number of hospital days subtracted from the numerator and denominator). We hypothesized that elderly individuals receiving fixed-dose combination amlodipine besylate/benazepril HCl would be more compliant with therapy than those receiving a dihydropyridine calcium channel antagonist and ACE inhibitor as free combination., Results: There were 2336 individuals in the fixed-combination group and 3368 in the free-combination group. The mean age was 76.0 +/- 7.2 years, and 82.6% were female. Compliance rates were significantly higher with fixed-dose versus free-combination therapy (63.4% vs 49.0%; p < 0.0001). The average total cost of care for patients receiving the fixed-dose combination was $US3179 compared with $US5236 (2002 values) for the free-combination regimen. In multivariate regression analyses on the log of total cost of care, average total costs increased by 0.5% for each 1-unit increase in MPR, and for each additional co-morbidity (measured by the chronic disease score) there was an increase of 10.4%. However, average total costs were reduced by 12.5% for patients using fixed-dose versus free-combination therapy (p < 0.003)., Conclusion: Use of fixed-dose amlodipine besylate/benazepril HCl by elderly Medicaid recipients was associated with improved compliance and lower healthcare costs compared with a dihydropyridine calcium channel antagonist and ACE inhibitor prescribed as separate agents.

Objectives: To analyse 2-year hospitalization and cost data collected during a prospective, double-blind, randomized, controlled trial comparing amlodipine, enalapril and placebo in normotensive patients with coronary artery disease (CAD)., Methods: All patients who were enrolled in the CAMELOT study were included in this economic substudy. Patients with CAD and normal blood pressure were randomized to amlodipine, enalapril or placebo, and followed up for 24 months (between 1999 and 2004). Data on hospitalizations and medication use were obtained from the clinical trial. Costs were assigned from secondary sources. Total costs ($US, year 2004 values) were estimated as the sum of costs associated with cardiovascular hospitalizations, study medications and concomitant cardiovascular medications. Costs and resource use were analysed by treatment arm overall and for selected patient subgroups. Cost differences were evaluated using nonparametric bootstrap techniques., Results: Of 1991 patients enrolled, 663 were treated with amlodipine, 673 were treated with enalapril and 655 were treated with placebo. Significantly fewer patients were hospitalized for cardiovascular reasons in the amlodipine group (16.4%) than in the placebo group (22.7%; p < 0.01), but not compared with the enalapril group (20.1%; p = 0.09). The amlodipine group also had numerically fewer days in hospital per patient (1.1) than the enalapril (1.3) and placebo (1.5) groups. Mean 2-year per-patient costs in the amlodipine group were estimated to be $US 609 and $US 717 lower than for the placebo and enalapril groups, respectively., Conclusions: These results suggest that use of amlodipine may reduce costs of care among CAD patients with normal blood pressure.

Calcium channel blockers are most commonly used in hypertensive patients in Japan. However, information on the efficacy and safety of generic calcium channel blockers is insufficient. The objective of the present study was to retrospectively evaluate the efficacy and safety of manidipine hydrochloride in 21 essential hypertensive patients (mean age; 70.6+/-10.6 years, male/female; 14/7) in Sendai Postal Services Agency Hospital who were switched (substituted) from a brand product (Calslot) to a generic product (Manidip). For this retrospective study, we used data from patient medical records and drug prescription information. Data from patients who were taking both types of manidipine hydrochloride, whose regimen were not changed for > 6 months before and after switching, and who provided informed consent were included in the analysis. Control values of blood pressure were not significantly different between before and after substitution (systolic/diastolic; from 137.9+/-9.1/78.7+/-5.4 mmHg to 137.3+/-9.1/77.8+/-6.3 mmHg, p=0.73/p=0.36). The level of patient compliance for the antihypertensive drugs was also not different between before and after substitution (from 94.0+/-8.8% to 93.1+/-9.6%, p=0.72). There were 8 cases of adverse effects before substitution and 4 after substitution. No patient stopped taking the generic drug due to an adverse effect. In conclusion, significant differences in the efficacy, safety, and patient compliance were not observed between the brand product and generic product among patients who were switched from the brand product to the generic product.

Antihypertensive treatment regimen persistence and compliance were measured using a retrospective cohort study of pharmacy claims data. Newly treated patients receiving monotherapy with angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), beta-blockers (BBs), or diuretics were followed for 1 year (N=242,882). A higher proportion of ARB patients (51.9%) were persistent in taking prescribed medication compared with those in the ACEI (48.0%), BB (40.3%), CCB (38.3%), and diuretic groups (29.9%). Compared with patients receiving diuretics, those receiving ARBs (hazard ratio [HR], 0.593; P<.0001), ACEIs (HR, 0.640; P<.0001), CCBs (HR, 0.859; P<.0001), and BBs (HR, 0.819; P<.0001) were all less likely to discontinue therapy. Compliance was similar in ACEI and ARB patients, but patients receiving ARBs and ACEIs had better compliance than those receiving BBs, CCBs, or diuretics. The lesser degree of compliance and persistence observed in patients receiving diuretics compared with other antihypertensive medications may have public health as well as cost implications.

Background and Objective: Published clinical trial data rarely allow assessment of the health care resource utilization implications of treatment. We give an example of how these can be assessed given appropriate tabulation of data., Methods: Data from a trial comparing long-acting nifedipine gastrointestinal therapeutic system to placebo in 7,665 patients with stable angina pectoris was analyzed., Results: Relative to placebo, nifedipine significantly increased mean cardiovascular (CV) event-free survival by 41 days but had no effect on mean survival. Per 100 years of follow-up, 78.1 patient-years of double-blind nifedipine administration reduced use of another calcium antagonist, an angiotensin converting enzyme inhibitor, an angiotensin receptor blocker, a diuretic and a cardiac glycoside by 1.54, 3.73, 2.63, 2.23, and 0.64 years, respectively, whereas 0.21 less hospitalization for overt heart failure, 0.47 less hospitalization for any stroke or transient ischemic attack, 0.8 less coronary angiogram, 0.38 less coronary bypass procedure, and 0.13 additional orthopedic procedure was required. Combining resource utilization with cost data for one particular hospital showed that one additional year of CV event-free survival costs an average additional euro 3,036 in the setting considered., Conclusion: Appropriately tabulated clinical trial data allows clinicians to judge the resource utilization implications and economic effect of treatment decisions.

Since the 1960s, calcium antagonists have been available for the treatment of angina pectoris and hypertension. The first of this class, nifedipine, was introduced and readily accepted as the third treatment option for angina, alongside beta-blockers and nitrates. However, the short-acting formulations of nifedipine had pharmacokinetic properties that were far from ideal and in 1995, several studies involving various dosing regimens reported possible dangerous effects in secondary prevention. Since then, large-scale, randomized controlled trials with new controlled-released formulations of nifedipine have demonstrated the effectiveness and safety of this drug. As a consequence of these results, guidelines for both hypertension and angina pectoris have been recently reconsidered, and have put the modern formulations of calcium channel blockers in a pole position. Within this group of therapeutics, nifedipine gastrointestinal therapeutic system has a unique position and it cannot be replaced by other controlled-release formulations of nifedipine, the pharmaceutical properties of which have yet to be tested in large-scale outcome trials.

In hypertensive patients with chronic renal disease, angiotensin receptor blockers (ARBs) are among the first-line drugs, and calcium channel blockers (CCBs) are recommended as a second line. We examined the effects of two therapeutic strategies using ARBs and benidipine, a CCB, on blood pressure (BP), urinary albumin excretion (UAE), and cost-effectiveness in hypertensive patients with albuminuria. Patients whose BP was 140/90 mmHg or higher despite treatment with low- or medium-dose ARBs were assigned randomly to two groups. In Group A (n=14), the ARB dose was maximized and then benidipine was added until BP targets were reached (<130/85 mmHg). In Group B (n=18), benidipine was administered first and then the ARB dose was increased until BP targets were reached. The BP targets were achieved by ARB alone in 36% of Group A patients and by the addition of benidipine in 83% of Group B patients. Finally, BP decreased in each group, reaching the targets in 93% of Group A patients and 94% of Group B patients after a 4-month therapeutic period. UAE was decreased in both groups after a 4-month therapeutic period compared to the allocation period (-33+/-6% in Group A, -31+/-6% in Group B; p<0.001, respectively). The monthly drug cost was higher (11,426+/-880 vs. 8,955+/-410 yen, p=0.012) and the cost-effectiveness of antihypertensive treatment was lower (p=0.003) in Group A than in Group B. We conclude that the addition of benidipine to low- or medium-dose ARB is, in light of the renal protection and the cost-effectiveness of this approach, a useful therapeutic strategy for controlling BP in hypertensive patients with albuminuria.

This study was designed to compare the clinical efficacy of two calcium channel blocker-based combination therapies with an angiotensin receptor blocker in Japanese patients with essential hypertension. A 16-week, double-blind, parallel-arm, randomized clinical trial was performed to compare the efficacy and safety of the combination therapy of controlled release nifedipine (nifedipine CR) plus valsartan vs. that of amlodipine plus valsartan. The primary endpoint was the target blood pressure achievement rate. Eligible patients were randomly allocated to nifedipine CR-based or amlodipine-based treatment groups. Patients were examined every 4 weeks to determine whether the blood pressure had reached the target level. When the target level was not achieved, the drug regimen was changed; when the target blood pressure was achieved, the same study medication was continued. A total of 505 patients were enrolled in the study (nifedipine CR group: 245 cases; amlodipine group: 260 cases). After 16 weeks of treatment, blood pressure was significantly reduced in both groups, but to a larger extent in the nifedipine CR group than in the amlodipine group (p < 0.01). The target blood pressure achievement rate was also significantly higher in the nifedipine CR group (p < 0.001). There was no significant difference in the incidence of drug-related adverse events between the groups. These results indicate that the nifedipine CR-based combination therapy was superior to the amlodipine-based therapy for decreasing blood pressure and achieving the target blood pressure in patients with essential hypertension.