Cost-effectiveness analysis comparing single-pill combination of perindopril/amlodipine/indapamide to the free equivalent combination in patients with hypertension from an Italian national health system perspective.

OBJECTIVE: To evaluate the cost-effectiveness of a single-pill combination (SPC) of perindopril/amlodipine/indapamide versus its free equivalent combination (FEC) in adults with hypertension in Italy. METHODS: A Markov model was developed to perform a cost-utility analysis with a lifetime horizon and an Italian healthcare payer's perspective. In the model, the additional effect of the SPC on blood pressure level compared with the FEC was translated into a decreased risk of cardiovascular events and CKD, which was modeled via Framingham risk algorithms. Difference in persistence rates of SPC and FEC were modeled via discontinuation rates. RESULTS: A perindopril/amlodipine/indapamide SPC is associated with lower cost and better health outcomes compared to its FEC. Over a lifetime horizon, it is associated with a 0.050 QALY gain and cost savings of €376, resulting from lower cardiovascular event rates. In the alternative scenario, where different approach for modeling impact of adherence was considered, incremental gain of 0.069 QALY and savings of €1,004 were observed. Results were robust to sensitivity and scenario analyses, indicating that use of this SPC is a cost-effective strategy. CONCLUSIONS: The findings indicate that a perindopril/amlodipine/indapamide SPC is a cost-saving treatment option for hypertension in Italy, compared to its FEC.

Assessment of Blood Pressure and Heart Rate Related Variables in Acute Stroke Patients Receiving Intravenous Antihypertensive Medication Infusions.

BACKGROUND: We performed an analysis of a large intensive care unit electronic database to provide preliminary estimates of various blood pressure parameters in patients with acute stroke receiving intravenous (IV) antihypertensive medication and determine the relationship with in-hospital outcomes. METHODS: We identified the relationship between pre-treatment and post-treatment systolic blood pressure (SBP) and heart rate (HR)-related variables and in-hospital mortality and acute kidney injury in patients with acute stroke receiving IV clevidipine, nicardipine, or nitroprusside using data provided in the Medical Information Mart for Intensive Care (MIMIC) IV database. RESULTS: A total of 1830 patients were treated with IV clevidipine (n = 64), nicardipine (n = 1623), or nitroprusside (n = 143). The standard deviations [SDs] of pre-treatment SBP (16.3 vs. 13.7, p ≤ 0.001) and post-treatment SBP (15.4 vs. 14.4, p = 0.004) were higher in patients who died compared with those who survived, particularly in patients with intracerebral hemorrhage (ICH). The mean SBP was significantly lower post treatment compared with pre-treatment values for clevidipine (130.7 mm Hg vs. 142.5 mm Hg, p = 0.006), nicardipine (132.8 mm Hg vs. 141.6 mm Hg, p ≤ 0.001), and nitroprusside (126.2 mm Hg vs. 139.6 mm Hg, p ≤ 0.001). There were no differences in mean SDs post treatment compared with pre-treatment values for clevidipine (14.5 vs. 13.5, p = 0.407), nicardipine (14.2 vs. 14.6, p = 0.142), and nitroprusside (14.8 vs. 14.8, p = 0.997). The SDs of pre-treatment and post-treatment SBP were not significantly different in patients with ischemic stroke treated with IV clevidipine, nicardipine, or nitroprusside or for patients with ICH treated with IV clevidipine or nitroprusside. However, patients with ICH treated with IV nicardipine had a significantly higher SD of post-treatment SBP (13.1 vs. 14.2, p = 0.0032). CONCLUSIONS: We found that SBP fluctuations were associated with in-hospital mortality in patients with acute stroke. IV antihypertensive medication reduced SBP but did not reduce SBP fluctuations in this observational study. Our results highlight the need for optimizing therapeutic interventions to reduce SBP fluctuations in patients with acute stroke.

Nicardipine or Nitroprusside for Postoperative Blood Pressure Control in Infants After Surgery for Congenital Heart Disease: Single-Center Retrospective Noninferiority and Cost Analysis, 2016-2020.

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.

Analysis of Therapeutic Inertia and Race and Ethnicity in the Systolic Blood Pressure Intervention Trial: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Therapeutic inertia may contribute to racial and ethnic differences in blood pressure (BP) control. Objective: To determine the association between race and ethnicity and therapeutic inertia in the Systolic Blood Pressure Intervention Trial (SPRINT). Design, Setting, and Participants: This cross-sectional study was a secondary analysis of data from SPRINT, a randomized clinical trial comparing intensive (<120 mm Hg) vs standard (<140 mm Hg) systolic BP treatment goals. Participants were enrolled between November 8, 2010, and March 15, 2013, with a median follow-up 3.26 years. Participants included adults aged 50 years or older at high risk for cardiovascular disease but without diabetes, previous stroke, or heart failure. The present analysis was restricted to participant visits with measured BP above the target goal. Analyses for the present study were performed in from October 2020 through March 2021. Exposures: Self-reported race and ethnicity, mutually exclusively categorized into groups of Hispanic, non-Hispanic Black, or non-Hispanic White participants. Main Outcomes and Measures: Therapeutic inertia, defined as no antihypertensive medication intensification at each study visit where the BP was above target goal. The association between self-reported race and ethnicity and therapeutic inertia was estimated using generalized estimating equations and stratified by treatment group. Antihypertensive medication use was assessed with pill bottle inventories at each visit. Blood pressure was measured using an automated device. Results: A total of 8556 participants, including 4141 in the standard group (22 844 participant-visits; median age, 67.0 years [IQR, 61.0-76.0 years]; 1467 women [35.4%]) and 4415 in the intensive group (35 453 participant-visits; median age, 67.0 years [IQR, 61.0-76.0 years]; 1584 women [35.9%]) with at least 1 eligible study visit were included in the present analysis. Among non-Hispanic White, non-Hispanic Black, and Hispanic participants, the overall prevalence of therapeutic inertia in the standard vs intensive groups was 59.8% (95% CI, 58.9%-60.7%) vs 56.0% (95% CI, 55.2%-56.7%), 56.8% (95% CI, 54.4%-59.2%) vs 54.5% (95% CI, 52.4%-56.6%), and 59.7% (95% CI, 56.5%-63.0%) vs 51.0% (95% CI, 47.4%-54.5%), respectively. The adjusted odds ratios in the standard and intensive groups for therapeutic inertia associated with non-Hispanic Black vs non-Hispanic White participants were 0.85 (95% CI, 0.79-0.92) and 0.94 (95% CI, 0.88-1.01), respectively. The adjusted odds ratios for therapeutic inertia comparing Hispanic vs non-Hispanic White participants were 1.00 (95% CI, 0.90-1.13) and 0.89 (95% CI, 0.79-1.00) in the standard and intensive groups, respectively. Conclusions and Relevance: Among SPRINT participants above BP target goal, this cross-sectional study found that therapeutic inertia prevalence was similar or lower for non-Hispanic Black and Hispanic participants compared with non-Hispanic White participants. These findings suggest that a standardized approach to BP management, as used in SPRINT, may help ensure equitable care and could reduce the contribution of therapeutic inertia to disparities in hypertension. Trial Registration: ClinicalTrials.gov identifier: NCT01206062.

Relatório de recomendação final para adoção de um protocolo estadual no estado de Santa Catarina complementar ao protocolo clínico e diretrizes terapêuticas do ministério da saúde para tratamento farmacológico da hipertensão pulmonar no âmbito do SUS / Final recommendation report for the adoption of a state protocol in the state of Santa Catarina complementary to the clinical protocol and therapeutic guidelines of the Ministry of Health for pharmacological treatment of pulmonary hypertension within the scope of the SUS

Este relatório refere-se à análise crítica do documento "Diagnóstico e Tratamento de Hipertensão Pulmonar'', elaborado pela ACAPTI e enviado como proposta para elaboração de Protocolo Estadual de Hipertensão Pulmonar, contemplando o tratamento farmacológico de HP grupo 1 (HAP) e grupo 4 (HPTEC). No documento encaminhado pelo demandante consta uma breve introdução e contextualização da patologia, diagnóstico clínico e exames complementares, critérios de inclusão e exclusão, especialidades médicas, estratificação de risco e seguimento, tratamento medicamentoso, algoritmo de tratamento medicamentoso, acessos aos medicamentos e centros de referência. Os itens relacionados ao diagnóstico foram mantidos neste relatório, conforme o documento enviado pelo demandante. Este relatório visa avaliar e emitir um parecer técnico embasado em evidências científicas sobre a disponibilização do medicamento Selexipague, a disponibilização da terapia combinada (Ambrisentana, Bosentana, Sildenafila, Ilopros a e Selexipague) para o tratamento da HP grupo 1 (HAP), a disponibilização do medicamento Riociguate para tratamento de HP grupo 4 (HPTEC), algoritmo de tratamento medicamentoso e fluxo de acesso aos medicamentos, para posterior elaboração de um Protocolo Estadual para a patologia solicitada. O Protocolo Estadual será elaborado complementarmente ao protocolo do Ministério da Saúde, assim, caso os medicamentos englobados nele sejam incorporados para a patologia em questão pela CONITEC, o fornecimento dos mesmos passa a ser por meio do CEAF.

Assessment of drug-drug interactions between moxonidine and antiepileptic drugs in the maximal electroshock seizure test in mice.

Hypertension is a common comorbid condition with epilepsy, and drug interactions between antihypertensive and antiepileptic drugs (AEDs) are likely in patients. Experimental studies showed that centrally active imidazoline compounds belonging to antihypertensive drugs can affect seizure susceptibility. The purpose of this study was to assess the effect of moxonidine, an I1 -imidazoline receptor agonist, on the anticonvulsant efficacy of numerous AEDs (carbamazepine, phenobarbital, valproate, phenytoin, oxcarbazepine, topiramate and lamotrigine) in the mouse model of maximal electroshock. Besides, the combinations of moxonidine and AEDs were investigated for adverse effects in the passive avoidance task and the chimney test. Drugs were administered intraperitoneally (ip). Moxonidine at doses of 1 and 2 mg/kg ip did not affect the convulsive threshold. Among tested AEDs, moxonidine (2 mg/kg) potentiated the protective effect of valproate against maximal electroshock. This interaction could be pharmacodynamic because the brain concentration of valproate was not significantly changed by moxonidine. The antihypertensive drug did not cause adverse effects when combined with AEDs. This study shows that moxonidine may have a neutral or positive effect on the anticonvulsant activity of AEDs in patients with epilepsy. The enhancement of the anticonvulsant action of valproate by moxonidine needs further investigations to elucidate potential mechanisms involved.

Comparative assessment of efficacy and safety of ambrisentan and bosentan in patients with pulmonary arterial hypertension: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Two endothelin receptor antagonists, ambrisentan and bosentan, have been demonstrated to be effective individually compared with placebo in the treatment of patients with pulmonary arterial hypertension (PAH). This network meta-analysis compared the efficacy and safety of ambrisentan and bosentan in patients with PAH. METHODS: Clinical trials were identified from the Cochrane Central Register of Controlled Trials (CENTRAL/CCTR), EMBASE and PubMed databases. Weighted mean differences (MD) with 95% confidence intervals (CI) were calculated for continuous outcomes (6-min walk distance [6MWD] and Borg dyspnoea index [BDI]). Hazard ratio (HR) was calculated for binary outcomes, including clinical worsening, discontinuation due to adverse events (AEs) and liver dysfunction. Surface under cumulative ranking curve (SUCRA) was used to rank the treatments in each index. RESULTS: Five clinical trials from four published studies (total patients: n = 920) were included. Ambrisentan and bosentan showed no significant difference in 6MWD (MD: -1.32; 95% CI: -27.87, 25.31, SUCRA score: ambrisentan 0.73, bosentan 0.77), BDI (MD: -0.16; 95% CI: -0.98, 0.65, SUCRA score: ambrisentan 0.83, bosentan 0.66), clinical worsening (HR: 0.99; 95% CI: 0.33, 2.94, SUCRA score: ambrisentan 0.75, bosentan 0.74) and discontinuation due to AEs (HR: 0.84; 95% CI: 0.11, 5.86, SUCRA score: ambrisentan 0.47, bosentan 0.57). However, ambrisentan was significantly better than bosentan with respect to abnormal liver function (HR: 23.18; 95% CI: 2.24, 377.20, SUCRA score: ambrisentan 0.99, bosentan 0.02). WHAT IS NEW AND CONCLUSION: The results of this network meta-analysis suggest that ambrisentan was similar to bosentan in efficacy, while it exhibited better tolerability with respect to abnormal liver function in comparison with bosentan, in patients with PAH.

Anti-hypertensive medication access and affordability and their association with blood pressure control at a teaching hospital in Ghana.

INTRODUCTION: many hypertensive patients require two or more anti-hypertensive drugs, but in low- and middle-income countries there may be challenges with medication access or affordability. The objective of this study was to determine accessibility and affordability of anti-hypertensive medicines and their association with blood pressure (BP) control among hypertensive patients attending the Korle-Bu teaching hospital (KBTH) polyclinic. METHODS: a cross-sectional study was conducted among 310 systematically sampled hypertensive patients attending the KBTH Polyclinic in Ghana. A structured questionnaire was used to obtain data on patient demographics and clinical characteristics, prices, availability and mode of payment of generic anti-hypertensive medicines. RESULTS: fifty-nine patients (19.4%) made out-of-pocket payments. At the private pharmacy and hospital, 123 (40.5%) and 77 patients (25.3%) respectively could not afford four anti-hypertensive medicines. Medicines availability at KBTH was 60%. Continuous access to BP drugs at KBTH was 14.8%. Overall access was 74.9% (SD ± 41.3). Out-of-pocket affordability of the medicines was positively correlated with BP control (R=0.12, p=0.037). Obtaining medicines via health insurance only was more likely to result in BP control than making any out-of-pocket payments (OR= 2.185; 95% CI, 1.215 - 3.927). Access at KBTH was more likely to result in BP control (OR=1.642; 95% C.I, 0.843 - 3.201). CONCLUSION: there were access challenges although most patients obtained BP medication free. Out-of-pocket affordability is a challenge for some hypertensive patients. Access to affordable BP medication can improve BP control. These findings provide an impetus for urgently evaluating access to affordable anti-hypertensive medicines in other hospitals in Ghana.

Clinical outcomes of pharmaceutical care intervention in HIV positive patients with hypertension: A randomized controlled study.

WHAT IS KNOWN AND OBJECTIVE: Pharmaceutical care (PC) has been shown to improve clinical outcomes in hypertensive patients as well as in people living with HIV (PLWHV). The objective of this study was to evaluate the impact of PC on blood pressure (BP) control, viral load and adherence to medications in hypertensive PLWHV. METHODS: This was a prospective, randomized controlled study conducted in the University of Uyo Teaching Hospital, Uyo, Akwa Ibom State, Nigeria. Eligible ambulatory patients were randomized equally to two study arms. The control arm (CA) received the traditional care offered at the HIV clinic; the intervention arm (IA) received the traditional care in addition to PC by the research pharmacist, which included structured education/counselling. BP and self-reported medication adherence were measured at baseline, 6 months and 12 months. Viral load was obtained at baseline and after 12 months. Data were analysed with spss, version 25.0. RESULTS AND DISCUSSION: Of the 206 participants initially randomized, 182 (91 in each study arm) completed the 12-month follow-up. No significant differences existed in both arms concerning socio-demographic/clinical characteristics of participants at baseline (p > 0.05). After 12 months, BP control was significantly higher in the IA (53.4% vs. 25.2%; p < 0.001, adjusted odds ratio, aOR = 3.20 (95% CI 1.59-6.44). Systolic BP reduced by 0.9 mmHg from baseline in the CA (p = 0.668) and by 16.67 mmHg from baseline value in the IA (p < 0.001). Diastolic BP increased by 1.9 mmHg in the CA (p = 0.444), but reduced by 7.0 mmHg in the IA (p < 0.001). No significant differences were observed in the change from baseline in the proportion with undetectable plasma viral load (UPVL) in both groups (p > 0.05). PC led to an increase in mean adherence to antiretroviral drugs (Δ = 0.55; p = 0.015), and an increase in mean adherence to antihypertensive drugs (Δ = 2.32; p < 0.001) in the IA. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first prospective randomized controlled study evaluating the impacts of PC on clinical outcomes in hypertensive PLWHV with a 12-month follow-up. Our results show that PC significantly improved BP control and adherence to antiretroviral and antihypertensive medications, but had no significant effect on viral load in HIV positive patients with hypertension. Providers of care for PLWHV should leverage the established HIV treatment successes for promoting adherence to treatment for common comorbidities like hypertension in PLWHV in order to improve clinical outcomes.

Medication Adherence Among Patients With Corneal Diseases.

PURPOSE: Medication nonadherence is a ubiquitous problem. However, the adherence of patients to medications to manage corneal conditions is unknown. A prospective cohort study investigated the patterns of eye drop adherence among patients with corneal conditions. METHODS: Patients older than or equal to 18 years taking prescription eye medications were recruited from an academic center's corneal clinic. Data collected included age, sex, total doses of eye medications, and category of primary corneal diagnosis. Participants completed adapted versions of the 12-question Adherence to Refills and Medications Scale (ARMS) and the 3-question Voils' Medication Adherence Scale (VMAS). Survey data were dichotomized as "adherent" and "nonadherent," and subscales reported for reasons of nonadherence. Logistic regression analyses were used to test associations with adherence. RESULTS: A total of 199 participants were surveyed from February to March 2019 (95% response rate). Participants were aged 19 to 93 years with a mean age of 59 years (SD 17.8). The percent of participants considered nonadherent was 72% by the ARMS and 33% by the VMAS. Older age was associated with higher adherence by the ARMS (odds ratio = 1.48, 95% confidence interval, 1.14-1.93, P = 0.004) and by the VMAS (odds ratio = 1.24, confidence interval, 1.04-1.48, P = 0.012). Adherence was not significantly associated with race, sex, education, total doses of eye medications, or primary cornea diagnosis. CONCLUSIONS: Medication adherence was lower than expected, particularly on the ARMS scale that asks more detailed questions. Clinicians should engage in conversations about adherence, especially with younger patients, if they are not seeing an expected clinical response.

Effect of Intensive Versus Standard Blood Pressure Control on Stroke Subtypes.

[Figure: see text].

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial.

OBJECTIVE: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. DESIGN: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. SETTING: 76 general practices in the United Kingdom. PARTICIPANTS: 622 people with treated but poorly controlled hypertension (>140/90 mm Hg) and access to the internet. INTERVENTIONS: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. MAIN OUTCOME MEASURES: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. RESULTS: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of -3.4 mm Hg (95% confidence interval -6.1 to -0.8 mm Hg) and a mean difference in diastolic blood pressure of -0.5 mm Hg (-1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. CONCLUSIONS: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. TRIAL REGISTRATION: ISRCTN13790648.

Rationale and Design of the Genotype-Blinded Trial of Torasemide for the Treatment of Hypertension (BHF UMOD).

BACKGROUND: Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) near the uromodulin gene (UMOD) affecting uromodulin excretion and blood pressure (BP). Uromodulin is almost exclusively expressed in the thick ascending limb (TAL) of the loop of Henle and its effect on BP appears to be mediated via the TAL sodium transporter, NKCC2. Loop-diuretics block NKCC2 but are not commonly used in hypertension management. Volume overload is one of the primary drivers for uncontrolled hypertension, so targeting loop-diuretics to individuals who are more likely to respond to this drug class, using the UMOD genotype, could be an efficient precision medicine strategy. METHODS: The BHF UMOD Trial is a genotype-blinded, multicenter trial comparing BP response to torasemide between individuals possessing the AA genotype of the SNP rs13333226 and those possessing the G allele. 240 participants (≥18 years) with uncontrolled BP, on ≥1 antihypertensive agent for ≥3 months, will receive treatment with Torasemide, 5 mg daily for 16 weeks. Uncontrolled BP is average home systolic BP (SBP) >135 mmHg and/or diastolic BP >85 mmHg. The primary outcome is the change in 24-hour ambulatory SBP area under the curve between baseline and end of treatment. Sample size was calculated to detect a 4 mmHg difference between groups at 90% power. Approval by West of Scotland Research Ethics Committee 5 (16/WS/0160). RESULTS: The study should conclude August 2021. CONCLUSIONS: If our hypothesis is confirmed, a genotype-based treatment strategy for loop diuretics would help reduce the burden of uncontrolled hypertension. CLINICAL TRIALS REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03354897.

Effectiveness of Levoamlodipine Maleate for Hypertension Compared with Amlodipine Besylate: a Pragmatic Comparative Effectiveness Study.

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.

Cost-effectiveness analysis of antihypertensive triple combination therapy among patients enrolled in a Medicare advantage plan.

OBJECTIVE: To assess the cost-effectiveness of single pill fixed dose triple combination therapy vs. free triple combination therapy for the prevention of cardiovascular events among patients with hypertension. METHODS: A Markov model with a five year cycle was constructed. Two decision models incorporating strict and more relaxed adherence definitions estimated quality adjusted life years (QALYs) and health-care costs for single pill fixed triple combination therapy vs. free-drug combination therapy. RESULTS: When the strict adherence measurement criteria were applied, the total QALYs loss and cost/patient were 6.38 QALYs, $486,026.20 for the single pill triple combination therapy and 8.64 QALYs, $406,405.26 for the free combination therapy. ICER for single pill combination therapy compared to free combination therapy was 33,826.46/QALY. When the relaxed adherence measurement criteria were applied, the total QALYs loss and cost/patient were 8.09 QALYs, $493,404.26 for the single pill triple combination therapy and 8.76 QALYs, $436,415.14 for the free combination therapy. ICER for single pill combination compared with free combination therapy was 84,932.26. CONCLUSION: This study suggested that single pill triple combination therapy was cost-effective in comparison with free combination therapy under a willingness to pay threshold of 50,000 when the strict adherence measurement criteria was applied.

Informe de Evaluación de Tecnologías Sanitarias: Estudio de costo-efectividad del tratamiento farmacológico combinado en dosis fijas para la hipertensión arterial en Chile / Health Technology Evaluation Report: Cost-effectiveness study of combined pharmacological treatment in fixed doses for arterial hypertension in Chile

ANTECEDENTES: La hipertensión arterial, con su alta prevalencia nacional, constituye una preocupación creciente para la salud pública. Por otro lado, cualquier modificación a las directrices de tratamiento puede implicar un alto impacto presupuestario. El objetivo del estudio fue evaluar la costo-efectividad del tratamiento farmacológico de la hipertensión arterial en combinaciones a dosis fijas en relación al tratamiento habitual (no combinado), desde la perspectiva del sistema público de salud chileno. METODOLOGÍA: Se definió un modelo de Markov de ocho estados de salud, con ciclos anuales y probabilidades de transición dependientes del tiempo. El modelo, desarrollado en lenguaje de programación R, simula la sobrevida de una cohorte de pacientes de 45 años de edad, en tratamiento por hipertensión arterial esencial y sin antecedentes de eventos cardiovasculares previos. Se evalúa la mortalidad específica por infarto agudo al miocardio, insuficiencia cardíaca y accidente cerebrovascular. Se usan los años de vida ajustados por calidad (QALY) como medida de outcomes (efectos) final. El modelo se pobló con evidencia disponible identificada tanto a nivel nacional como internacional. Los costos (descontados al 3% al igual que los efectos), se obtuvieron del Estudio de Verificación de Costos del GES complementando con microcosteo para las patologías no cubiertas. RESULTADOS: Dado que no se encontró evidencia de mayor efectividad en favor de la terapia combinada por sobre la no combinada, se consideró que la mayor adherencia asociada a la terapia combinada en un solo comprimido se traduce en una mayor proporción de pacientes con presión arterial controlada. Se obtuvo un costo adicional por QALY ganado (ICER) positivo que cae dentro del cuadrante noreste del plano de costo-efectividad, sugiriendo que la intervención es más cara y levemente más efectiva. Los resultados obtenidos no son favorables para la terapia combinada en un solo comprimido (al compararla con un umbral de costo-efectividad de un PIB per cápita nacional). Lo anterior se explica principalmente por el mayor costo de la terapia combinada en dosis fija y la baja efectividad incremental estimada. Los resultados se mantuvieron estables tanto en el análisis de sensibilidad determinístico como probabilístico, siendo el precio de los medicamentos y el incremento de la adherencia de parámetros que más influyen en el resultado. CONCLUSIONES: La terapia combinada a dosis fija no es una alternativa costo-efectiva al compararla con el manejo farmacológico actual de pacientes con hipertensión esencial en Chile. Esta condición es susceptible de cambiar favorablemente en la medida que baje el precio de los medicamentos (por ejemplo, con la entrada de genéricos en este mercado) y mejore la adherencia de pacientes, lo que debería implementarse en el marco de un programa más integral o estandarizado del manejo de la presión arterial en Chile.

State and Regional Variation in Prescription- and Payment-Related Promoters of Adherence to Blood Pressure Medication.

INTRODUCTION: Medication adherence can improve hypertension management. How blood pressure medications are prescribed and purchased can promote or impede adherence. METHODS: We used comprehensive dispensing data on prescription blood pressure medication from Symphony Health's 2017 Integrated Dataverse to assess how prescription- and payment-related factors that promote medication adherence (ie, fixed-dose combinations, generic formulations, mail order, low-cost or no-copay medications) vary across US states and census regions and across the market segments (grouped by patient age, prescriber type, and payer type) responsible for the greatest number of blood pressure medication fills. RESULTS: In 2017, 706.5 million prescriptions for blood pressure medication were filled, accounting for $29.0 billion in total spending (17.0% incurred by patients). As a proportion of all fills, factors that promoted adherence varied by state: fixed-dose combinations (from 5.8% in Maine to 17.9% in Mississippi); generic formulations (from 95.2% in New Jersey to 98.4% in Minnesota); mail order (from 4.7% in Rhode Island to 14.5% in Delaware); and lower or no copayment (from 56.6% in Utah to 72.8% in California). Furthermore, mean days' supply per fill (from 43.1 in Arkansas to 63.8 in Maine) and patient spending per therapy year (from $38 in Hawaii to $76 in Georgia) varied. Concentration of adherence factors differed by market segment. Patients aged 18 to 64 with a primary care physician prescriber and Medicaid coverage had the lowest concentration of fixed-dose combination fills, mean days' supply per fill, and patient spending per therapy year. Patients aged 65 years or older with a primary care physician prescriber and commercial insurance had the highest concentration of fixed-dose combinations fills and mail order fills. CONCLUSION: Addressing regional and market segment variation in factors promoting blood pressure medication adherence may increase adherence and improve hypertension management.

The Mississippi Delta Health Collaborative Medication Therapy Management Model: Public Health and Pharmacy Working Together to Improve Population Health in the Mississippi Delta.

INTRODUCTION: The Mississippi Delta has high rates of chronic disease and is known for its poor health outcomes and health disparities. The University of Mississippi School of Pharmacy (UMSOP) and the Mississippi State Department of Health partnered in 2009 through the Mississippi Delta Health Collaborative to reduce health disparities and improve clinical outcomes by expanding the UMSOP's evidence-based medication therapy management (MTM) initiative, focused in Mississippi's 18-county Delta region, to federally qualified health centers (FQHCs) in 4 of those counties. METHODS: Between January 2009 and August 2018, the MTM initiative targeted FQHC patients aged 18 years or older with a diagnosis of diabetes, hypertension, and/or dyslipidemia. Pharmacists initially met face-to-face with patients to review all medications, provide education about chronic diseases, identify and resolve drug therapy problems, and take appropriate actions to help improve the effectiveness of medication therapies. Clinical parameters evaluated were systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and hemoglobin A1c (HbA1c). RESULTS: The analysis included 335 patients with hypertension (n = 287), dyslipidemia (n = 131), and/or diabetes (n = 331). Significant mean reductions occurred in the following metrics: SBP (7.1 mm Hg), DBP (6.3 mm Hg), LDL cholesterol (24.9 mg/dL), triglycerides (45.5 mg/dL), total cholesterol (37.7 mg/dL), and HbA1c (1.6% [baseline ≥6%] and 1.9% [baseline ≥9%]). CONCLUSION: Despite the cultural and environmental disadvantages present in the Mississippi Delta, the integrated MTM treatment program demonstrated significant health improvements across 3 chronic diseases: hypertension, dyslipidemia, and diabetes. This model demonstrates that a partnership between public health and pharmacy is a successful and innovative approach to care.