Prescribing trends of glaucoma drugs in six major cities of China from 2013 to 2017.

OBJECTIVE: To evaluate the prescribing trends of glaucoma drugs in six major cities of China from 2013 to 2017. METHODS: A descriptive analysis using pharmacy prescription data was conducted. Outpatient prescription data was extracted from the Hospital Prescription Analysis Cooperative Project. Prescribing patterns, trends of visits, and corresponding expenditures for glaucoma medications were analyzed. RESULTS: A total of 84297 ambulatory prescriptions were included in the current study. Visits by glaucoma patients increased from 13808 in 2013 to 20060 in 2017. Over the same period, the yearly expenditure for glaucoma drugs increased from 2.33 million to 3.95 million Chinese Yuan (CNY). Among all the six classes of glaucoma drugs (prostaglandin analogues, carbonic anhydrase inhibitors, α-receptor agonists, ß-receptor antagonists, cholinergic agonists and fixed combinations), ß-receptor antagonists were the most commonly prescribed in 2013, accounting for 34.3% of patients, but gradually decreased to 27.1% in 2017. Prostaglandin analogues became the most frequently prescribed drugs in 2017, accounting for 30.2% of the visits. Prostaglandin analogues are the most expensive and yielded a total expenditure of 2.34 million CNY in 2017, followed by carbonic anhydrase inhibitors, α-receptor agonists, ß-receptor antagonists, fixed combinations, and cholinergic agonists. Combination therapy became increasingly prescribed in 2017. CONCLUSION: Glaucoma prescribing practices exhibited substantial changes over the study period. The number of glaucoma prescriptions continuously increased from 2013 to 2017, leading to increased prescription costs. These findings implied a similar trend observed in previous studies, as well as recommendations in the appropriate guidelines.

Exposure to guideline-recommended drugs after a first acute myocardial infarction in older adults: does deprivation matter?

BACKGROUND: Inequities between guideline-recommended drugs (GRD) exposure and socioeconomic status might exist. The objective was to assess the association between a material and a social deprivation index and GRD exposure following a first acute myocardial infarction (AMI) in older adults in the province of Quebec. METHODS: We conducted a retrospective cohort study using the Quebec Integrated Chronic Disease Surveillance System. Elderly ≥66 years, hospitalized for a first AMI between January 1, 2006, and December 31, 2011 and covered by the public drug plan were identified. Exposure to GRD (i.e. simultaneous use of 1) antiplatelet, 2) beta-blocker, 3) lipid-lowering and 4) angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker drugs) was assessed 30 and 365 days following hospital discharge. Associations between deprivation index and GRD exposure were estimated with log-binomial regressions adjusting for potential confounders. RESULTS: Exposure to GRD was 52.2% and 48.0%, 30 and 365 days after hospital discharge, respectively. No statistically significant association was observed in multivariate analysis for both time points. Thirty days post hospital discharge, adjusted prevalence ratio of non-exposure to GRD was 0.98 (95% confidence interval [CI]: 0.95-1.02) for most materially deprived vs. least deprived and 1.04 (95% CI: 0.99-1.08) for most socially deprived vs. least deprived. Similar results were observed for 365 days. CONCLUSION: Exposure to GRD after a first urgent AMI among older adults insured by the public drug plan in the province of Quebec is relatively low. Reasons and risk groups for this low exposure should be studied to improve secondary prevention. However, results suggest equitable access to GRD, regardless of deprivation.

Modeling the cost effectiveness and budgetary impact of Polypills for secondary prevention of cardiovascular disease in the United States.

BACKGROUND: There is underutilization of appropriate medications for secondary prevention of cardiovascular disease (CVD). METHODS: Usual care (UC) was compared to polypill-based care with 3 versions using a validated micro-simulation model in the NHANES population with prior CVD. UC included individual prescription of up to 4 drug classes (antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone inhibitors and statins). The polypills modeled were aspirin 81 mg, atenolol 50 mg, ramipril 5 mg, and either simvastatin 40 mg (Polypill I), atorvastatin 80 mg (Polypill II), or rosuvastatin 40 mg (Polypill III). Baseline medication use and adherence came from United Healthcare claims data. RESULTS: When compared to UC, there were annual reductions of 130,000 to 178,000 myocardial infarctions and 54,000 to 74,000 strokes using Polypill I and II, respectively. From a health sector perspective, in incremental analysis the ICERs for Polypill I and II were $20,073/QALY and $21,818/QALY respectively; Polypill III was dominated but had a similar cost-effectiveness ratio to Polypill II when compared directly to usual care. From a societal perspective, Polypill II was cost-saving and dominated all strategies. Over a 5-year period, those taking Polypill I and II compared to UC saved approximately $12 and $6 per-patient-per-year alive, respectively. Polypill II was the preferred strategy in 98% of runs at a willingness to pay of $50,000 in the probability sensitivity analysis. CONCLUSIONS: Use of a polypill has a favorable cost profile for secondary CVD prevention in the United States. Reductions in CVD-related healthcare costs outweighed medication cost increases on a per-patient-per-year basis, suggesting that a polypill would be economically advantageous to both patients and payers.

Impact of Optimal Medical Therapy at Discharge on One-year Direct Medical Costs in Patients with Acute Coronary Syndromes: A Retrospective, Observational Database Analysis in China.

PURPOSE: This study was conducted to examine the use of optimal medical therapy (OMT), consisting of an antiplatelet, a ß-blocker, an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), and a statin combined, after hospital discharge and its relationship with direct medical costs in patients with acute coronary syndromes (ACS) in Tianjin, China. METHODS: Data were obtained from the Tianjin Urban Employee Basic Medical Insurance database (2011-2015). Data from adult patients with ≥1 hospitalization for ACS between January 2012 and December 2014 were included. Medications including antiplatelets, ß-blockers, ACEIs/ARBs, and statins at discharge were recorded, with OMT defined as the use of all 4 indicated medications. Propensity-score matching was conducted to form matched OMT and non-OMT cohorts based on baseline differences. All-cause and ACS-related health care resource utilization and direct medical costs during a 12-month follow-up period were assessed and compared between cohorts. Generalized linear modeling was conducted to assess the association between OMT at discharge and direct medical costs. FINDINGS: A total of 22,041 patients were identified (mean age, 64.7 [10.7] years; 45.6% female), of whom 15.1% (3336) received OMT at discharge. The OMT cohort had fewer patients hospitalized for any cause during follow-up compared with the matched non-OMT cohort (38.1% vs 43.2%; P < 0.001), which was further associated with fewer hospitalizations (1.55 vs 1.64; P = 0.019) and shorter annualized length of stay (15.9 vs 17.2 d; P = 0.041). Despite higher costs of outpatient services (9958 vs 10,060 Chinese yuan [CNY] [P = 0.006]; adjusted difference, +456 CNY [P = 0.004]) (year-2014 1 USD = 6.20 CNY), the OMT cohort had significantly lower all-cause total costs (20,771 vs 22,877 CNY [P = 0.174]; adjusted difference, -2089 CNY [P = 0.006]), driven by lower costs of inpatient services (10,813 vs 12,817 CNY [P < 0.001]; adjusted difference, -2184 CNY [P = 0.001]). The difference in ACS-related total costs between the 2 cohorts was not statistically significant (8535 vs 9304 CNY [P = 0.128]; adjusted difference, -558 CNY [P = 0.214]). IMPLICATIONS: Receiving OMT at discharge was associated with fewer hospitalizations and lower all-cause direct medical costs in these patients with ACS in China. Strategies are needed to improve OMT prescribing rates at discharge, which would lead to better clinical prognosis and total cost-savings among patients with ACS in China.

Cycling Through Migraine Preventive Treatments: Implications for All-Cause Total Direct Costs and Disease-Specific Costs.

BACKGROUND: Migraine is a common and disabling neurological disease associated with substantial economic burden. Among patients with migraine, it is unknown if cost differences exist when preventive migraine medication (PMM) switches occur. OBJECTIVE: To understand the cost burden and health care resource utilization of patients who discontinue or cycle through 1 (PMM1), 2 (PMM2), or ≥ 3 (PMM3) unique PMM drug classes over a 12-month period versus patients who adhere persistently to their initial PMM class. METHODS: This retrospective observational study used the Truven Health Analytics MarketScan databases to identify adult patients with migraine initiating their first PMM class (antidepressants, antiepileptics, beta blockers, or neurotoxins) from 2011-2013 (index date = first PMM claim). Patients were required to have ≥ 2 outpatient (1 if inpatient) migraine diagnosis codes (ICD-9-CM 346.xx) from 1 year pre-index to 1 year post-index with ≥ 1 code occurring pre-index. Inclusion criteria also required 12 months of pre- and post-index continuous medical and prescription enrollment. All-cause and migraine-specific total direct costs (outpatient, inpatient, emergency department, and prescriptions), based on the 2014 Consumer Price Index, were estimated for each PMM versus a persistent subgroup during the 12-month post-index period. Propensity score bin bootstrapping, controlling for patient baseline characteristics, was used to adjust separate cost comparisons between each PMM subgroup and the persistent subgroup; bootstrap simulations yielded propensity score-adjusted P values. RESULTS: The study population included 55,402 patients who received a PMM. The study population was mainly female (85%) with a mean age of 39.2 years and mean Charlson Comorbidity Index of 0.31. Antiepileptics were the most common drug class chosen at index across all subgroups; however, lower use of antiepileptics was observed in PMM2 and PMM3 subgroups, which were more likely to be prescribed either antidepressants or beta blockers at index. Mean all-cause total direct costs, including prescription costs, were significantly higher in PMM2 ($13,429) and PMM3 ($18,394) subgroups versus the persistent subgroup ($11,941; each adjusted pairwise comparison, P < 0.001). Mean migraine-specific total direct costs were significantly lower for the persistent subgroup ($2,420) versus PMM2 and PMM3 subgroups and escalated with increasing numbers of drug class discontinuations or switches, from a mean of $2,997 to $5,004 (both adjusted pairwise comparisons, P < 0.001). Subgroup differences in all-cause and migraine-specific direct costs were primarily due to variations in outpatient and emergency department services. CONCLUSIONS: All-cause total direct costs rose with increasing number of PMM switches over the 12-month post-index period, and were significantly higher than in the persistent subgroup, with the exception of PMM1. Additional analyses indicated that the lack of increase between PMM-persistent and PMM1 costs was due to higher pharmacy costs that were likely related to continuous use of medication in the PMM-persistent subgroup. These data suggest an increased cost burden among patients with migraine who cycle through ≥ 2 PMMs versus those who continue to receive their initial medication class. DISCLOSURES: Eli Lilly and Company was the sole sponsor and funder for this study and was responsible for the study design, data collection, data analysis, interpretation of data, and decision to publish the findings. All authors are employees and minor stockholders of Eli Lilly and Company. Nyhuis was employed by Eli Lilly and Company at the time of this study. The findings of this study were presented in part at the 18th Congress of the International Headache Society; September 7-10, 2017; Vancouver, Canada.

Clinical and economic impact of surgery for treating infantile hemangiomas in the era of propranolol: overview of single-center experience from La Paz Hospital, Madrid.

Propranolol has changed the management of infantile hemangiomas (IHs). We summarize the evolution of surgical treatment for IH at La Paz Children's Hospital (Madrid) in the era of propranolol, with a focus on hepatic IHs.Retrospectively, we compared surgical treatment of IHs in children referred during the periods 2004-2009 and 2009-2014. Hepatic IH mortality rates before and after the introduction of propranolol therapy were evaluated specifically.The majority of hemangiomas needing surgical excision were located on the head/face/scalp of female patients. Since the introduction of propranolol therapy, surgery for IH has decreased from about 60 to 6 procedures/year at our institution and no transplants for hepatic IH have been registered.Conclusions: Surgical procedures for IH have decreased by about 90% at our institution since the introduction of propranolol treatment and hepatic IH have not needed liver transplantation. Referrals for surgery for IH are generally the consequence of absent or delayed propranolol treatment. Given the significant reduction in the number of surgical procedures, propranolol can be considered as having a strong economic and social impact. What is Known: • The use of oral propranolol solution is currently considered as the treatment of choice in the management of infantile hemangiomas. • Propranolol treatment achieves better outcomes and less side effects than systemic corticosteroids. What is New: • Social and financial impact of the significant reduction in the number of reconstructive surgical procedures and liver transplants due to the use of propranolol in tertiary health institutions remains to be analyzed.

Clinical and Economic Outcomes of Ranolazine Versus Conventional Antianginals Users Among Veterans With Chronic Stable Angina Pectoris.

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, ß 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.

Repurposing existing medications as cancer therapy: design and feasibility of a randomized pilot investigating propranolol administration in patients receiving hematopoietic cell transplantation.

BACKGROUND: Repurposing existing medications for antineoplastic purposes can provide a safe, cost-effective, and efficacious means to further augment available cancer care. Clinical and preclinical studies suggest a role for the ß-adrenergic antagonist (ß-blocker) propranolol in reducing rates of tumor progression in both solid and hematologic malignancies. In patients undergoing hematopoietic cell transplantation (HCT), the peri-transplant period is a time of increased activity of the ß-adrenergically-mediated stress response. METHODS: We conducted a proof-of-concept randomized controlled pilot study assessing the feasibility of propranolol administration to patients between ages 18-75 who received an autologous HCT for multiple myeloma. Feasibility was assessed by enrollment rate, tolerability, adherence, and retention. RESULTS: One hundred fifty-four patients underwent screening; 31 (20%) enrolled in other oncology trials that precluded dual trial enrollment and 9 (6%) declined to enroll in the current trial. Eighty-nine (58%) did not meet eligibility requirements and 25 (16%) were eligible; of the remaining eligible patients, all were successfully enrolled and randomized. The most common reasons for ineligibility were current ß-blocker use, age, logistics, and medical contraindications. 92% of treatment arm patients tolerated and remained on propranolol for the study duration; 1 patient discontinued due to hypotension. Adherence rate in assessable patients (n = 10) was 94%. Study retention was 100%. CONCLUSIONS: Findings show that it is feasible to recruit and treat multiple myeloma patients with propranolol during HCT, with the greatest obstacle being other competing oncology trials. These data support further studies examining propranolol and other potentially repurposed drugs in oncology populations. TRIAL REGISTRATION: This randomized controlled trial was registered at clinicaltrials.gov with the identifier NCT02420223 on April 17, 2015.

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.

Changing Initial Glaucoma Medical Therapy Increases Healthcare Resource Utilization.

PURPOSE: To determine the frequency and economic impact of changing initial glaucoma therapy for patients with newly diagnosed open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: This retrospective longitudinal cohort study identified individuals within a large managed care network in the United States, who were newly diagnosed with OAG or OHT from 2001 to 2012 and were prescribed either a topical beta blocker (BB) or a prostaglandin analog (PGA). Claims data were analyzed over the 12-month period following their index prescription to determine physician prescribing habits, healthcare resource utilization patterns, and sociodemographic factors which may have contributed to changing the initial treatment strategy. RESULTS: A total of 15,019 beneficiaries were identified with newly diagnosed OAG or OHT and whose index therapy was either a topical BB or PGA. Among these enrollees 80.9% were started on PGAs, while 19.1% were started on BBs. Of these beneficiaries, 29.2% of those started on PGAs and 39.5% of those started on BBs underwent a change in therapy within 12 months of their index prescription. Those in the topical BB treatment group had a 38% increased odds of changing glaucoma therapy relative to those started on PGAs (odds ratio [OR] 0.61, 95% CI:0.56-0.68). Patients who changed therapy required more frequent office visits (P < 0.0001) and incurred higher median eye care related charges (P < 0.0001) compared to those who remained on the index therapy unchanged. CONCLUSIONS: Changing initial ocular hypotensive therapy is common. Individuals who undergo a change in therapy required more frequent face-to-face monitoring and incurred higher healthcare related costs. Identifying strategies capable of optimizing the process of initiating ocular hypotensive therapy are appealing and possess the potential to improve patient outcomes and reduce healthcare costs.

Effect of Electronic Reminders, Financial Incentives, and Social Support on Outcomes After Myocardial Infarction: The HeartStrong Randomized Clinical Trial.

Importance: Adherence to medications prescribed after acute myocardial infarction (AMI) is low. Wireless technology and behavioral economic approaches have shown promise in improving health behaviors. Objective: To determine whether a system of medication reminders using financial incentives and social support delays subsequent vascular events in patients following AMI compared with usual care. Design, Setting, and Participants: Two-arm, randomized clinical trial with a 12-month intervention conducted from 2013 through 2016. Investigators were blinded to study group, but participants were not. Design was a health plan-intermediated intervention for members of several health plans. We recruited 1509 participants from 7179 contacted AMI survivors (insured with 5 large US insurers nationally or with Medicare fee-for-service at the University of Pennsylvania Health System). Patients aged 18 to 80 years were eligible if currently prescribed at least 2 of 4 study medications (statin, aspirin, ß-blocker, antiplatelet agent), and were hospital inpatients for 1 to 180 days and discharged home with a principal diagnosis of AMI. Interventions: Patients were randomized 2:1 to an intervention using electronic pill bottles combined with lottery incentives and social support for medication adherence (1003 patients), or to usual care (506 patients). Main Outcomes and Measures: Primary outcome was time to first vascular rehospitalization or death. Secondary outcomes were time to first all-cause rehospitalization, total number of repeated hospitalizations, medication adherence, and total medical costs. Results: A total of 35.5% of participants were female (n = 536); mean (SD) age was 61.0 (10.3) years. There were no statistically significant differences between study arms in time to first rehospitalization for a vascular event or death (hazard ratio, 1.04; 95% CI, 0.71 to 1.52; P = .84), time to first all-cause rehospitalization (hazard ratio, 0.89; 95% CI, 0.73 to 1.09; P = .27), or total number of repeated hospitalizations (hazard ratio, 0.94; 95% CI, 0.60 to 1.48; P = .79). Mean (SD) medication adherence did not differ between control (0.42 [0.39]) and intervention (0.46 [0.39]) (difference, 0.04; 95% CI, -0.01 to 0.09; P = .10). Mean (SD) medical costs in 12 months following enrollment did not differ between control ($29 811 [$74 850]) and intervention ($24 038 [$66 915]) (difference, -$5773; 95% CI, -$13 682 to $2137; P = .15). Conclusions and Relevance: A compound intervention integrating wireless pill bottles, lottery-based incentives, and social support did not significantly improve medication adherence or vascular readmission outcomes for AMI survivors. Trial Registration: clinicaltrials.gov Identifier: NCT01800201.

Prescription Patterns and the Cost of Migraine Treatments in German General and Neurological Practices.

OBJECTIVES: The aim of this study was to analyze prescription patterns and the cost of migraine treatments in general practices (GPs) and neurological practices (NPs) in Germany. METHODS: This study included 43,149 patients treated in GPs and 13,674 patients treated in NPs who were diagnosed with migraine in 2015. Ten different families of migraine therapy were included in the analysis: triptans, analgesics, anti-emetics, beta-blockers, antivertigo products, gastroprokinetics, anti-epileptics, calcium channel blockers, tricyclic antidepressants, and other medications (all other classes used in the treatment of migraine including homeopathic medications). The share of migraine therapies and their costs were estimated for GPs and NPs. RESULTS: The mean age was 44.4 years in GPs and 44.1 years in NPs. Triptans and analgesics were the 2 most commonly prescribed families of drugs in all patients and in the 9 specific subgroups. Interestingly, triptans were more commonly prescribed in NPs than in GPs (30.9% to 55.0% vs. 30.0% to 44.7%), whereas analgesics were less frequently given in NPs than in GPs (11.5% to 17.2% vs. 35.3% to 42.4%). Finally, the share of patients who received no therapy was higher in NPs than in GPs (33.9% to 58.4% vs. 27.5% to 37.9%). The annual cost per patient was €66.04 in GPs and €94.71 in NPs. Finally, the annual cost per patient increased with age and was higher in women and in individuals with private health insurance coverage than in men and individuals with public health insurance coverage. CONCLUSION: Triptans and analgesics were the 2 most commonly prescribed drugs for the treatment of migraine. Furthermore, approximately 30% to 40% of patients did not receive any therapy. Finally, the annual cost per patient was higher in NPs than in GPs.

Patterns of prescription antihypertensive drug utilization and adherence to treatment guidelines in the city of Novi Sad.

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.

Pharmacotherapy Treatment Patterns, Outcomes, and Health Resource Utilization Among Patients with Heart Failure with Reduced Ejection Fraction at a U.S. Academic Medical Center.

STUDY OBJECTIVE: To assess clinical characteristics, pharmacotherapy treatment patterns, resource utilization and associated charges, and morbidity and mortality outcomes among a real-world cohort of patients with heart failure with reduced ejection fraction (HFrEF) in an academic medical center setting. DESIGN: Retrospective analysis. DATA SOURCE: Electronic health record database that includes clinical, laboratory, and administrative data for all facilities of the University of Utah Health Care System. PATIENTS: A total of 989 adults with prevalent (preexisting) HFrEF, identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code 428.x (heart failure) between January 1, 2007, and June 30, 2013, and who had a left ventricular ejection fraction of 40% or lower. MEASUREMENTS AND MAIN RESULTS: The cohort had a mean age of 64 ± 15 years and was predominantly white (71%) and male (74%). Patients received ß-blockers, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), and aldosterone receptor antagonists (ARAs) at rates of 79%, 69%, and 29%, respectively. Patients achieved target doses of ß-blockers, ACEIs, and ARBs at rates of only 24%, 31%, and 13%, respectively. Overall, 58% of patients were prescribed dual therapy with a ß-blocker and an ACEI or ARB, and 19% were prescribed triple therapy (ß-blocker, an ACEI or ARB, and an ARA). Univariate and multivariate logistic regression models were used to assess the association between baseline characteristics with the presence of triple therapy. Two variables were statistically significant in both models: increasing age was associated with a lower odds of triple therapy (univariate: odds ratio [OR] 0.760, 95% confidence interval [CI] 0.673-0.857; multivariate: OR 0.768, 95% CI 0.625-0.942), whereas receipt of an implantable cardiac device was associated with a 2-fold increase in the odds of triple therapy (univariate: OR 2.1, 95% CI 1.4-3.1; multivariate: OR 2.1, 95% CI 1.3-3.5). During a mean ± SD follow-up of 36 ± 27 months, all-cause mortality was 0.12 per person-year. There were 1311 all-cause hospitalizations of which 611 (47%) were for worsening heart failure. The rate of all-cause and heart failure-specific hospitalizations was 0.44 and 0.21 per person-year of follow-up, respectively. The median length of stay was 6.4 ± 8.8 days, and the median charge was $22,310. The 30-day all-cause readmission rate was 20%, and the primary reason for readmission was heart failure in 65% of cases. CONCLUSION: This study demonstrates the continuing significant disease and economic burden for patients with HFrEF. Challenges remain in utilization of established disease-modifying therapy and in the treatment of patients with HFrEF and multiple comorbidities.

Wealth-related Inequality in Utilization of Antihypertensive Medicines in Iran: an Ecological Study on Population Level Data.

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.

Relation of Elevated Heart Rate in Patients With Heart Failure With Reduced Ejection Fraction to One-Year Outcomes and Costs.

There are limited data describing outcomes associated with an elevated heart rate in patients with heart failure with reduced ejection fraction (HFrEF) in routine clinical practice. We identified patients with HFrEF at Duke University Hospital undergoing echocardiograms and heart rate assessments without paced rhythms or atrial fibrillation. Outcomes (all-cause mortality or hospitalization and medical costs per day alive) were assessed using electronic medical records, hospital cost accounting data, and national death records. Patients were stratified by heart rate (<70 and ≥70 beats/min) and compared using generalized linear models specified with gamma error distributions and log links for costs and proportional hazard models for mortality/hospitalization. Of 722 eligible patients, 582 patients (81%) were treated with ß blockers. The median heart rate was 81 beats/min (25th and 75th percentiles 69 to 96) and 527 patients (73%) had a heart rate ≥70 beats/min. After multivariate adjustment, a heart rate ≥70 beats/min was associated with increased 1-year all-cause mortality or hospitalization, hazard ratio 1.37 (95% CI 1.07 to 1.75) and increased medical costs per day alive, cost ratio 2.03 (95% CI 1.53 to 2.69). In conclusion, at a large tertiary care center, despite broad use of ß blockers, a heart rate ≥70 beats/min was observed in 73% of patients with HFrEF and associated with worse 1-year outcomes and increased direct medical costs per day alive.

Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data.

BACKGROUND: WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability. METHODS: We analysed information about availability and costs of cardiovascular disease medicines (aspirin, ß blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry. FINDINGS: Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0·14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24,776), 33% of lower middle-income countries (13,253 of 40,023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16,874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio [OR] 0·16, 95% CI 0·04-0·57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0·16, 0·04-0·55). INTERPRETATION: Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHO's targets of 50% use of key medicines by 2025. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

Income differences in the type of antihypertensive medicines used in ambulatory settings in Finland: a register-based study.

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.