Assessment of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker on the split renal function in the patients with primary hypertension.

ABSTRACT: Bilateral kidney damage in hypertensive patients is not parallel. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), as a commonly used antihypertensive drug, could protect kidney function and delay its deterioration. Most studies focused on overall renal function, but the researches on split renal function (SRF) are rare. We investigated the effects of ACEI/ARB on the SRF in patients with primary hypertension.Patients with primary hypertension (n = 429; male: 213; female: 216) admitted to our department between January 2014 and December 2016 were included in this study. The glomerular filtration rate (GFR) of split and total renal function were determined using diethylenetriaminepentaacetic acid tagged with 99mTc renal dynamic imaging method. For the same patient, the side with high GFR was considered as higher GFR kidney, whereas that with a low GFR was considered as lower GFR kidney. The split function score (Q value) was utilized to evaluate the differences of bilateral renal function. The patients were divided into 3 groups based on the Q values (Group 1, Q value <5%; Group 2, Q value of 5%-10%; Group 3, Q value ≥10%). All the patients received antihypertensive therapy based on ACEI/ARB. The renal dynamic imaging was performed in the 1-year follow-up to investigate the changes of the SRF.Compared with the baseline level, significant decline was noticed in the serum creatinine (Scr) in Group 2 and Group 3 (P < .05). The cystatin C in Group 3 showed significant decline (P < .05). Compared with the baseline, there was significant decline in the Q value in Group 2, whereas the GFR of lower GFR kidney showed significant increase (P < .05). No statistical differences were noticed in the Q value and split GFR in Group 1 and Group 3 (P > .05).In primary hypertension patients, ACEI/ARB therapy could improve the SRF of lower GFR kidney in the presence of certain differences between the SRF. As a result, the SRF difference was reduced. In case of Q value in a range of 5% to 10%, ACEI/ARB could improve the renal function effectively. It may be significant for the design of antihypertensive drugs.

The role of angiotensin receptor blockers in CVD risk management.

Introduction: Angiotensin receptor blockers (ARBs) are recommended as preferential drugs in the treatment of hypertension by guidelines. In this review, we reappraise their effectiveness to preventing major cardiovascular outcomes and the recent concerns with new adverse effects.Areas covered: ARBs were not superior to placebo in the prevention of all-cause deaths and combined cardiovascular events in seven randomized controlled trials (RCT). Several meta-analyses, with large number of participants, confirmed these findings. Three RCT trials, published in top journals, were retracted due to the uncertain reliability of their findings. Beside the low effectiveness in the prevention of cardiovascular disease (CVD), ARBs were implicated in one meta-analysis with an increased risk of cancer a finding that was not confirmed in another meta-analysis. In observational studies, ARBs were associated with a higher incidence of suicides. In addition, several lots of ARBs were contaminated with carcinogens.Expert opinion: ARBs have not been proven to reduce CVD risk and therefore should not be preferential drugs to treat hypertension. The implication of ARBs with suicide and cancer needs to be further studied.

Association of combination statin and antihypertensive therapy with reduced Alzheimer's disease and related dementia risk.

BACKGROUND: Hyperlipidemia and hypertension are modifiable risk factors for Alzheimer's disease and related dementias (ADRD). Approximately 25% of adults over age 65 use both antihypertensives (AHTs) and statins for these conditions. While a growing body of evidence found statins and AHTs are independently associated with lower ADRD risk, no evidence exists on simultaneous use for different drug class combinations and ADRD risk. Our primary objective was to compare ADRD risk associated with concurrent use of different combinations of statins and antihypertensives. METHODS: In a retrospective cohort study (2007-2014), we analyzed 694,672 Medicare beneficiaries in the United States (2,017,786 person-years) who concurrently used both statins and AHTs. Using logistic regression adjusting for age, socioeconomic status and comorbidities, we quantified incident ADRD diagnosis associated with concurrent use of different statin molecules (atorvastatin, pravastatin, rosuvastatin, and simvastatin) and AHT drug classes (two renin-angiotensin system (RAS)-acting AHTs, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), vs non-RAS-acting AHTs). FINDINGS: Pravastatin or rosuvastatin combined with RAS-acting AHTs reduce risk of ADRD relative to any statin combined with non-RAS-acting AHTs: ACEI+pravastatin odds ratio (OR) = 0.942 (CI: 0.899-0.986, p = 0.011), ACEI+rosuvastatin OR = 0.841 (CI: 0.794-0.892, p<0.001), ARB+pravastatin OR = 0.794 (CI: 0.748-0.843, p<0.001), ARB+rosuvastatin OR = 0.818 (CI: 0.765-0.874, p<0.001). ARBs combined with atorvastatin and simvastatin are associated with smaller reductions in risk, and ACEI with no risk reduction, compared to when combined with pravastatin or rosuvastatin. Among Hispanics, no combination of statins and RAS-acting AHTs reduces risk relative to combinations of statins and non-RAS-acting AHTs. Among blacks using ACEI+rosuvastatin, ADRD odds were 33% lower compared to blacks using other statins combined with non-RAS-acting AHTs (OR = 0.672 (CI: 0.548-0.825, p<0.001)). CONCLUSION: Among older Americans, use of pravastatin and rosuvastatin to treat hyperlipidemia is less common than use of simvastatin and atorvastatin, however, in combination with RAS-acting AHTs, particularly ARBs, they may be more effective at reducing risk of ADRD. The number of Americans with ADRD may be reduced with drug treatments for vascular health that also confer effects on ADRD.

Dual renin-angiotensin-aldosterone blockade: Implementation of published research and Dear Doctor letters in ambulatory care: A retrospective observational study using prescription data.

PURPOSE: This study aims to assess the implementation of published research, contraindications, and warnings on the prescription of dual renin-angiotensin-hormone system (RAS) blockade in ambulatory care in Germany. METHODS: Cohort study based on health claims data of 6.7 million subjects from 2008 to 2015. Yearly prevalence and incidence for dual RAS blockade with (a) angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers (ACEI + ARB) and (b) aliskiren and ACEI or ARB (aliskiren + ACEI/ARB) were calculated. We assessed prescriber specialty and associations between discontinuing dual RAS blockade with specialist (internal medicine, cardiology, nephrology) visits and hospital discharge in the previous year. RESULTS: A total of 2 984 517 patients were included (age 51.4 ± SD 18.4 y, 48.5% male). Prescription rates for ACEI + ARB decreased from 0.6% (n = 17 907) to 0.4% (n = 12 237) and for aliskiren + ACEI/ARB from 0.23% (n = 6634) to 0.03% (n = 818). Incident prescriptions decreased from 0.23% (n = 6705) to 0.19% (n = 5055) (ACE + ARB) and from 0.1% (n = 2796) to 0.005% (n = 142) (aliskiren + ACE/ARB); 59% of ACEI + ARB and 48% of aliskiren + ACE/ARB combinations were prescribed only by one physician. Of those, 73% (ACEI + ARB) and 58% (aliskiren + ACE/ARB) were primary care providers (PCPs). Discontinuing dual RAS blockade was associated with specialist care and hospital discharge in the previous year (specialist care: RR 1.4, 95% CI, 1.3-1.6; hospital visit: RR 1.5, 95% CI, 1.3-1.6). CONCLUSIONS: Our results suggest a delayed uptake of treatment recommendation for ACEI + ARB and a higher impact of Dear Doctor letters addressing PCPs directly compared with published research, contraindications, and warnings. Targeted continuous medical education, practice software alerts, and stronger involvement of pharmacists might improve the implementation of medication safety recommendations in ambulatory care.

Cost-effectiveness of sacubitril/valsartan for the treatment of patients with heart failure with reduced ejection fraction in Portugal.

Objectives: This study assesses the cost-effectiveness of sacubitril/valsartan versus enalapril in patients with symptomatic heart failure with reduced ejection fraction (HFrEF).Methods: We used a previously developed Markov model calibrated with patient-level data from the PARADIGM-HF trial, adapted to the Portuguese setting. The model considers two health states (alive or dead) and uses regression analyzes to estimate hospitalizations and deaths over time. A panel of experts estimated resource consumption in the outpatient setting. To estimate resource consumption with hospitalizations, the National Health Service Diagnosis Related Groups database was used. Unit costs were based on national legislation, and on the Infomed database. The model considers a societal perspective, a time horizon of 30-years, and a 5% annual discount rate. Sensitivity analyses assessed the robustness of results.Results: Sacubitril/valsartan increases life expectancy by 0.5 life-years, corresponding to 0.4 incremental quality adjusted life-years (QALY) versus enalapril. The estimated incremental cost-effectiveness ratio (ICER) is 22,702€/QALY. Sensitivity analysis shows that results are robust, but sensitive to the parameter estimates of the cardiovascular survival curve.Conclusion: Sacubitril/valsartan is a cost-effective therapeutic option in the treatment of Portuguese patients with HFrEF and translate into significant health gains and increased life expectancy versus the current standard of care.

Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial.

AIMS: To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. METHODS AND RESULTS: Overall, 8399 patients with New York Heart Association class II-IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post-randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on-treatment analysis. CONCLUSION: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.

PARADIGM-HF Trial: Secondary Analyses Address Unanswered Questions.

Our aim was to summarize published secondary analyses of the PARADIGM-HF trial. In the original trial, published in September 2014, sacubitril/valsartan significantly reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared to enalapril. This summary provides a resource for clinicians to review subsequent analyses of the landmark trial evaluating the benefit of sacubitril/valsartan in various subgroups and providing information regarding optimal use of this new therapy in the broader heart failure population. A full list of publications of the existing PARDADIGM-HF post hoc analyses was obtained and summarized, grouped by focus (e.g., severity of illness, tolerability). Twenty-six publications and one abstract analyzing the PARADIGM-HF trial were reviewed, summarizing the most important results that compared the benefits of sacubitril/valsartan to enalapril, including pertinent subgroup information from each analysis. Key publications evaluated the treatment effect of sacubitril/valsartan based on heart failure severity (i.e., ejection fraction or heart failure risk scores), impact on alternate outcomes, influence of additional therapies, tolerability in patients with comorbidities (i.e., diabetes), long-term benefits, and cost-effectiveness. In addition, nine ongoing phase III and phase IV clinical trials with sacubitril/valsartan were briefly summarized to address potential future uses in more extensive heart failure settings. The benefit of sacubitril/valsartan over enalapril for the primary endpoint in the PARADIGM-HF trial is maintained throughout numerous secondary analyses. Though the subgroups analyzed are based on participants from a single clinical trial, clinicians can more confidently incorporate this novel therapy into practice with expanded knowledge of these existing analyses as well as ongoing prospective trials.

The Survey of the Compliance Situation to the Antihypertensive Therapy Guideline by Analyzing Japanese National Claims Data.

Kidney disease (KD) is a serious risk factor for cardiovascular event, and it is important to protect the heart and kidneys during treatment of the high blood pressure to prevent cardiovascular event. Japanese guideline (JSH2014) suggests using combination therapy to reduce the risk of comorbidities rather than high-dose monotherapy for the patients with cardiovascular disease and KD. Therefore, the present study assessed antihypertensive prescription patterns in Japanese patients with ischemic heart disease related diseases (IHDRD) and KD, and evaluated whether the prescription patterns match with the guideline-suggested therapies by analyzing the national insurance claims database (NDB). We extracted antihypertensive prescription patterns among Japanese IHDRD patients from the data of October 2011 of NDB, and examined the effect of KD on the prescription patterns. The number of prescribed antihypertensive was associated with KD among patients regardless of IHDRD. Patients with IHDRD and KD were more frequently prescribed combination therapy (calcium channel blockers/angiotensin II receptor blockers) than the calcium channel blocker monotherapy, based on the JSH2014. On the other hand, we did not observe the standard use of diuretics for patients with heart failure, which is suggested by the JSH2014. These findings suggested that patients with IHDRD and KD were frequently prescribed combination therapy to achieve its cardioprotective and renoprotective effects, according to the JSH2014, but the prescription profile to the patients with heart failure didn't match that of guideline-suggested therapies. This study provided a clinically important information and demonstrated the utility of NDB for compliance assessment for therapeutics guideline.

Assessment of Drug-Drug Interaction Potential Between Atorvastatin and LCZ696, A Novel Angiotensin Receptor Neprilysin Inhibitor, in Healthy Chinese Male Subjects.

BACKGROUND AND OBJECTIVE: LCZ696 (sacubitril/valsartan), a novel angiotensin receptor neprilysin inhibitor has been recently approved for the treatment of patients with heart failure (HF) and reduced ejection fraction. As several HF patients are likely to use statins as co-medications, the potential for a pharmacokinetic drug-drug interaction between atorvastatin and LCZ696 was evaluated. METHODS: This was an open-label, three-period, single-sequence study in 28 healthy Chinese male subjects wherein LCZ696 200 mg was administered twice daily for 5 days in period 1. Following a washout period, atorvastatin 80 mg was administered once daily for 4 days (period 2) and subsequently co-administered with LCZ696 200 mg for 5 days (period 3). Serial plasma samples were collected to determine pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan) and atorvastatin and its metabolites. RESULTS: Atorvastatin co-administration had no effect on the pharmacokinetics of LBQ657, while the AUCτ,ss and C max,ss of sacubitril increased by 30 and 19 %, respectively, and the corresponding values for valsartan decreased by 19 and 9 %, respectively. Co-administration with LCZ696 increased C max,ss of atorvastatin, o-hydroxyatorvastatin, and p-hydroxyatorvastatin by 74, 68, and 108 %, respectively, and the AUCτ,ss of corresponding analytes increased by 34, 22, and 26 %, respectively. CONCLUSIONS: While atorvastatin had no significant impact on the pharmacokinetics of LCZ696 analytes upon co-administration, the C max of atorvastatin and its metabolites increased twofold, with a marginal increase in AUC (<1.3-fold). Multiple-dose administration of LCZ696 200 mg twice daily and atorvastatin 80 mg once daily either alone or in combination was generally safe and well tolerated in healthy subjects.

Improving medication titration in heart failure by embedding a structured medication titration plan.

BACKGROUND: To improve up-titration of medications to target dose in heart failure patients by improving communication from hospital to primary care. METHODS: This quality improvement project was undertaken within three heart failure disease management (HFDM) services in Queensland, Australia. A structured medication plan was collaboratively designed and implemented in an iterative manner, using methods including awareness raising and education, audit and feedback, integration into existing work practice, and incentive payments. Evaluation was undertaken using sequential audits, and included process measures (use of the titration plan, assignment of responsibility) and outcome measures (proportion of patients achieving target dose) in HFDM service patients with reduced left ventricular ejection fraction. RESULTS: Comparison of the three patient cohorts (pre-intervention cohort A n=96, intervention cohort B n=95, intervention cohort C n=89) showed increase use of the titration plan, a shift to greater primary care responsibility for titration, and an increase in the proportion of patients achieving target doses of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) (A 37% vs B 48% vs C 55%, p=0.051) and beta-blockers (A 38% vs B 33% vs C 51%, p=0.045). Combining all three cohorts, patients not on target doses when discharged from hospital were more likely to achieve target doses of ACEI/ARB (p<0.0001) and beta blockers (p<0.0001) within six months if they received a medication titration plan. CONCLUSIONS: A medication titration plan was successfully implemented in three HFDM services and improved transitional communication and achievement of target doses of evidence-based therapies within six months of hospital discharge.

Pharmacokinetic drug-drug interaction assessment of LCZ696 (an angiotensin receptor neprilysin inhibitor) with omeprazole, metformin or levonorgestrel-ethinyl estradiol in healthy subjects.

LCZ696 is a novel angiotensin receptor neprilysin inhibitor in development for the treatment of cardiovascular diseases. Here, we assessed the potential for pharmacokinetic drug-drug interaction of LCZ696 (400 mg, single dose or once daily [q.d.]) when co-administered with omeprazole 40 mg q.d. (n = 28) or metformin 1000 mg q.d. (n = 27) or levonorgestrel-ethinyl estradiol 150/30 µg single dose (n = 24) in three separate open-label, single-sequence studies in healthy subjects. Pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan), metformin, and levonorgestrel-ethinyl estradiol were assessed. Omeprazole did not alter the AUCinf of sacubitril and pharmacokinetics of LBQ657; however, 7% decrease in the Cmax of sacubitril, and 11% and 13% decreases in AUCinf and Cmax of valsartan were observed. Co-administration of LCZ696 with metformin had no significant effect on the pharmacokinetics of LBQ657 and valsartan; however, AUCtau,ss and Cmax,ss of metformin were decreased by 23%. Co-administration of LCZ696 with levonorgestrel-ethinyl estradiol had no effect on the pharmacokinetics of ethinyl estradiol and LBQ657 or AUCinf of levonorgestrel. The Cmax of levonorgestrel decreased by 15%, and AUCtau,ss and Cmax,ss of valsartan decreased by 14% and 16%, respectively. Co-administration of LCZ696 with omeprazole, metformin, or levonorgestrel-ethinyl estradiol was not associated with any clinically relevant pharmacokinetic drug interactions.

Appropriate baseline laboratory testing following ACEI or ARB initiation by Medicare FFS beneficiaries.

BACKGROUND: Laboratory testing to identify contraindications and adverse drug reactions is important for safety of patients initiating angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Rates and predictors of appropriate testing among Medicare fee-for-service beneficiaries are unknown. PURPOSE: The study's purpose was to examine baseline laboratory testing rates, identify predictors of suboptimal testing, and assess the prevalence of abnormal creatinine and potassium among beneficiaries initiating ACE inhibitors or ARBs. DESIGN AND SUBJECTS: Retrospective cohort of 101 376 fee-for-service beneficiaries from 10 eastern US states in 1 July to 30 November 2011. MAIN MEASURES: Appropriate monitoring for serum creatinine or serum potassium was defined as evidence of an outpatient claim within 180 days before or 14 days after the index prescription fill date. KEY RESULTS: Thirty-eight percent of beneficiaries were men, 78% were White race, 26% had prevalent heart failure, and 89% had prevalent hypertension. Rates of appropriate baseline laboratory testing were 82.7% for potassium, 83.2% for creatinine, and 82.6% for both potassium and creatinine 180 days prior to initiation. In logistic regression, men (odds ratio [OR] = 1.15, 95% confidence interval [CI]: 1.11, 1.19), African-Americans (OR = 1.26, 95%CI: 1.20, 1.32), and beneficiaries with Alzheimer's disease and related disorders (OR = 1.22, 95%CI: 1.15, 1.28) or stroke (OR = 1.34, 95%CI: 1.26, 1.43) were more likely to experience suboptimal testing. At baseline, hyperkalemia was relatively uncommon (5.8%), and elevated creatinine values were rare (1.4%). CONCLUSIONS: Appropriate monitoring could be improved for African-American beneficiaries and beneficiaries with a history of stroke or Alzheimer's disease and related disorders initiating ACE inhibitors or ARBs. Copyright © 2016 John Wiley & Sons, Ltd.

Comparison of diagnostic evaluations for cough among initiators of angiotensin converting enzyme inhibitors and angiotensin receptor blockers.

PURPOSE: Differential diagnostic evaluation associated with a drug may bias effect estimates because of an increased detection of preclinical outcomes. Persistent cough is a common side effect with angiotensin-converting enzyme inhibitors (ACEI), and we hypothesized that ACEI initiators would undergo more diagnostic evaluations, potentially leading to diagnosis of preclinical lung cancer. We compared the incidence of cough-related diagnostic evaluations and lung cancer among ACEI versus angiotensin receptor blockers (ARB) initiators. METHODS: Using a 20% sample of Medicare claims 2007-2012, we identified initiators of ACEI or ARB, age 66-99 years. Incidence of diagnostic evaluation and lung cancer were compared using adjusted Cox models. Monthly probabilities of workup were compared using proportion differences. RESULTS: There were 342 611 and 108 116 ACEI and ARB initiators, respectively. Monthly probability of chest X-rays ranged from minimum 4.7% to maximum 21.2% in the 6 months pre and post-initiation. Differences in incidence of diagnostic procedures in the 6 months after initiation were only minimal (chest X-rays hazard ratio (HR) = 1.12; 95% CI: 1.10-1.14), chest-MRI (0.86, 95% CI: 0.74-0.99), CT-scans (1.09, 95% CI: 0.99-1.18) or bronchoscopies (1.03, 95% CI: 0.83-1.29). Proportion differences for chest X-rays peaked in the month pre-initiation (8.4%, 95% CI: 8.1-8.6) but negligible thereafter. There was no difference in the incidence of lung cancer among ACEI versus ARB initiators (HR = 0.99, 95% CI: 0.84-1.16). CONCLUSION: Results indicate minimal differential chest workup after ACEI versus ARB initiation and no difference in lung cancer incidence, but suggest differential workup in the month before the first recorded prescription. The latter may reflect drug use before the first observed pharmacy claim or increased workup before initiation of ACEI therapy. Copyright © 2016 John Wiley & Sons, Ltd.

Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study.

OBJECTIVES: Severe sprue-like enteropathy associated with olmesartan has been reported, but there has been no demonstration of an increased risk by epidemiological studies. AIM: To assess, in a nationwide patient cohort, the risk of hospitalisation for intestinal malabsorption associated with olmesartan compared with other angiotensin receptor blockers (ARB) and ACE inhibitors (ACEIs). DESIGN: From the French National Health Insurance claim database, all adult patients initiating ARB or ACEI between 1 January 2007 and 31 December 2012 with no prior hospitalisation for intestinal malabsorption, no serology testing for coeliac disease and no prescription for a gluten-free diet product were included. Incidence of hospitalisation with a discharge diagnosis of intestinal malabsorption was the primary endpoint. RESULTS: 4 546 680 patients (9 010 303 person-years) were included, and 218 events observed. Compared with ACEI, the adjusted rate ratio of hospitalisation with a discharge diagnosis of intestinal malabsorption was 2.49 (95% CI 1.73 to 3.57, p<0.0001) in olmesartan users. This adjusted rate ratio was 0.76 (95% CI 0.39 to 1.49, p=0.43) for treatment duration shorter than 1 year, 3.66 (95% CI 1.84 to 7.29, p<0.001) between 1 and 2 years and 10.65 (95% CI 5.05 to 22.46, p<0.0001) beyond 2 years of exposure. Median length of hospital stay for intestinal malabsorption was longer in the olmesartan group than in the other groups (p=0.02). Compared with ACEI, the adjusted rate ratio of hospitalisation for coeliac disease was 4.39 (95% CI 2.77 to 6.96, p<0.0001) in olmesartan users and increased with treatment duration. CONCLUSIONS: Olmesartan is associated with an increased risk of hospitalisation for intestinal malabsorption and coeliac disease.

Fixed-Dose Combinations of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in the Treatment of Hypertension: A Comparison of Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors.

Fixed-dose combinations (FDCs) of different regimens are recommended in guidelines for the treatment of hypertension. However, clinical studies comparing FDCs of angiotensin receptor blocker (ARB)/calcium channel blocker (CCB) and angiotensin-converting enzyme inhibitor (ACE inhibitor)/CCB in hypertensive patients are lacking.Using a propensity score matching of 4:1 ratio, this retrospective claims database study compared 2 FDC regimens, ARB/CCB and ACE inhibitor/CCB, in treating hypertensive patients with no known atherosclerotic cardiovascular disease. All patients were followed for at least 3 years or until the development of major adverse cardiovascular events (MACEs) during the study period. In addition, the effect of medication adherence on clinical outcomes was evaluated in subgroup analysis based on different portions of days covered.There was no significant difference in MACE-free survival (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 0.98-1.50; P = 0.08) and survival free from hospitalization for heart failure (HR: 1.15; 95% CI: 082-1.61; P = 0.431), new diagnosis of chronic kidney disease (HR: 0.98; 95% CI: 071-1.36; P = 0.906), and initiation of dialysis (HR: 0.99; 95% CI: 050-1.92; P = 0.965) between the 2 study groups. The results remained the same within each subgroup of patients with different adherence statuses.ARBs in FDC regimens with CCBs in the present study were shown to be as effective as ACE inhibitors at reducing the risks of MACEs, hospitalization for heart failure, new diagnosis of chronic kidney disease, and new initiation of dialysis in hypertensive patients, regardless of the medication adherence status.

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.

Review of ongoing initiatives to improve prescribing efficiency in China; angiotensin receptor blockers as a case history.

INTRODUCTION: Pharmaceutical expenditure is rising by 16% per annum in China and is now 46% of total expenditure. Initiatives to moderate growth include drug pricing regulations and encouraging international non-proprietary name prescribing. However, there is no monitoring of physician prescribing quality and perverse incentives. OBJECTIVES: Assess changes in angiotensin receptor blocker (ARB) utilization and expenditure as more generics become available; compare findings to Europe. METHODOLOGY: Observational retrospective study of ARB utilization and expenditure between 2006 and 2012 in the largest hospital in Chongqing district. RESULTS: Variable and low use of generics versus originators with a maximum of 31% among single ARBs. Similar for fixed dose combinations. Prices typically reduced over time, greatest for generic telmisartan (-54%), mirroring price reductions in some European countries. However, no preferential increase in prescribing of lower cost generics. Accumulated savings of 33 million CNY for this large provider if they adopted European practices. CONCLUSION: Considerable opportunities to improve prescribing efficiency in China.