Use Of Angiotensin II Receptor Blockers Research Articles

Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chemoprevention of hepatocellular carcinoma: a nationwide high-risk cohort study

BackgroundResearch has revealed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may prevent cancers such as hepatocellular carcinoma (HCC). The comparative chemopreventive effects of ACEIs and ARBs in high-risk populations with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have yet to be investigated.MethodsFrom 2005 to 2014, high-risk HBV and HCV cohorts of hypertensive patients without HCC history were recruited from three linked national databases of Taiwan, and were classified into two groups based on the ACEI or ARB exposure within the initial six months after initiating antiviral agent. Intergroup differences in clinical characteristics and duration of drug exposure within study period were evaluated. HCC-free survival was compared using the log-rank test. Multivariate Cox regression including time-dependent variables for the use of ACEIs or ARBs and other medications was applied to adjust for confounders.ResultsAmong the 7724 patients with HBV and 7873 with HCV, 46.3% and 42.5%, respectively, had an initial exposure to ACEIs or ARBs. The median durations of exposure were 36.4 and 38.9 months for the HBV and HCV cohorts, respectively. The median durations of ACEI or ARB use during study period between initial exposure and nonexposure groups were 41.8 vs. 18.3 months and 46.4 vs. 22.7 months for the HBV and HCV cohorts, respectively. No significant difference was observed in HCC risk within 7 years between the initial exposure and non-exposure groups. After adjustment for comorbidities, namely liver cirrhosis, diabetes mellitus (DM), and hyperlipidemia, and medications, namely aspirin, metformin, and statins, the hazard ratios (HRs) for ACEI or ARB exposure for HCC risk were 0.97 (95% confidence interval [CI]: 0.81–1.16) and 0.96 (0.80–1.16) in the HBV and HCV cohorts, respectively. In the HCV cohort, the increased HCC risk was associated with ACEI or ARB use in patients without cirrhosis, DM, and hyperlipidemia (HR: 4.53, 95% CI: 1.46–14.1).ConclusionCompared with other significant risk and protective factors for HCC, ACEI or ARB use in the HBV and HCV cohorts was not associated with adequate protective effectiveness under standard dosages and may not be completely safe.

A Longitudinal Cohort Study of Aspirin Use and Progression of Emphysema-like Lung Characteristics on CT Imaging: The MESA Lung Study

Platelet activation reduces pulmonary microvascular blood flow and contributes to inflammation; these factors have been implicated in the pathogenesis of COPD and emphysema. We hypothesized that regular use of aspirin, a platelet inhibitor, would be associated with a slower progression of emphysema-like lung characteristics on CT imaging and a slower decline in lung function. The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants 45 to 84 years of age without clinical cardiovascular disease from 2000 to 2002. The MESA Lung Study assessed the percentage of emphysema-like lung below -950 Hounsfield units ("percent emphysema") on cardiac (2000-2007) and full-lung CT scans (2010-2012). Regular aspirin use was defined as 3 or more days per week. Mixed-effect models adjusted for demographics, anthropometric features, smoking, hypertension, angiotensin-converting enzyme inhibitor or angiotensin II-receptor blocker use, C-reactive protein levels, sphingomyelin levels, and scanner factors. At baseline, the 4,257 participants' mean (± SD) age was 61 ± 10 years, 54%were ever smokers, and 22%used aspirin regularly. On average, percent emphysema increased 0.60 percentage points over 10 years (95%CI, 0.35-0.94). Progression of percent emphysema was slower among regular aspirin users compared with patients who did not use aspirin (fully adjusted model: -0.34%/10 years, 95%CI, -0.60 to -0.08; P= .01). Results were similar in ever smokers and with doses of 81 and 300 to 325mg and were of greater magnitude among those with airflow limitation. No association was found between aspirin use and change in lung function. Regular aspirin use was associated with a more than 50%reduction in the rate of emphysema progression over 10 years. Further study of aspirin and platelets in emphysema may be warranted.

Angiotensin II receptor blockers suppress the release of stromal cell-derived factor-1α from infarcted myocardium in patients with acute myocardial infarction

BackgroundAlthough angiotensin II receptor blockers (ARBs) have been shown to have anti-inflammatory effects on infarcted myocardium in experimental models, little is known in humans. Stromal cell-derived factor-1α (SDF-1α), a pro-inflammatory chemokine, is released from infarcted tissue in patients with acute myocardial infarction (AMI). This study examined whether ARBs suppress SDF-1α production in the infarcted lesion in patients with AMI. MethodsSDF-1α levels were measured by enzyme-linked immunosorbent assays in plasma obtained from the aortic root (AO) and the anterior interventricular vein (AIV) in 50 patients with an anterior AMI. Measurement of SDF-1α levels and left ventriculography were repeated at discharge and 6 months after AMI. Patients were divided into 2 groups according to treatment with ARBs, which were administered at the discretion of the attending physician after admission. ResultsThe AIV–AO gradient of SDF-1α, reflecting SDF-1α release from the infarcted myocardial region, decreased between the time of discharge and 6 months after AMI in patients taking an ARB. In contrast, the SDF-1α transcardiac gradient did not change in patients not taking an ARB. Among the clinical parameters tested, only the use of ARBs was significantly associated with percent changes in the SDF-1α transcardiac gradient from the time of discharge to 6 months after AMI in a linear regression analysis (r=−0.31, p=0.03). The SDF-1α transcardiac gradient 6 months after AMI was inversely correlated with the percent change in left ventricular (LV) ejection fraction (r=−0.52, p<0.01) and positively correlated with the percent change in LV end-diastolic volume index (r=0.57, p<0.01) and LV end-systolic volume index (r=0.54, p<0.01) during 6 months after AMI. ConclusionsARB treatment suppressed SDF-1α release from the infarcted myocardial region, which was associated with improvement in LV dysfunction and adverse remodeling in AMI survivors.

Treatment Effectiveness in Heart Failure with Comorbidity: Lung Disease and Kidney Disease.

To assess the clinical effectiveness of beta-blocker therapy in individuals with heart failure (HF) and chronic lung disease and of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) in individuals with HF and chronic kidney disease. Retrospective cohort study. Community. Individuals with HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF). We undertook separate new-user cohort studies to assess the effectiveness of beta-blocker therapy in treating HF and chronic lung disease and ACE-Is and ARBs in treating HF and chronic kidney disease (CKD). Individuals with a chronic lung disease diagnosis were included in the group with HF and chronic lung disease (International Classification of Diseases, Ninth Revision, codes 490-496, 518). Individuals with an estimated glomerular filtration rate less than 60 mL/min per 1.73 m2 were included in the group with HF and CKD. The clinical outcomes of interest were death from any cause, hospitalization for HF, and hospitalization for any reason. We fitted pooled logistic marginal structural models using inverse probability weighting, stratified according to HF type. For individuals with HFrEF with chronic lung disease, beta-blocker therapy was protective against death (relative risk (RR) = 0.58, 95% confidence interval (CI) = 0.44-0.77) and hospitalization for HF (RR = 0.78, 95% CI = 0.60-1.00). For those with HFpEF, no statistically significant associations between beta-blocker therapy use and any of the outcomes were observed. We found ACE-I and ARB use to be protective against all three outcomes of interest in individuals with HFrEF (death from any cause: RR = 0.60, 95% 0.40-0.91; hospitalization for HF: RR = 0.43, 95% CI = 0.28-0.67; hospitalization for any reason: RR = 0.63, 95% CI = 0.45-0.89, respectively) and those with HFpEF (death from any cause: RR = 0.52, 95% CI = 0.33-0.81; hospitalization for HF: RR = 0.35, 95% CI = 0.18-0.68; hospitalization for any reason: RR = 0.67, 95% CI = 0.47-0.95). Large observational studies may allow for identification of important subgroups of individuals with HF that might benefit from existing treatment approaches. Our findings may also better inform the design of more-definitive future observational studies and randomized trials.

Renin-angiotensin system inhibitors and risk of fractures: a prospective cohort study and meta-analysis of published observational cohort studies

The renin-angiotensin system (RAS) represents an important target of antihypertensive medications. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), which are widely-used RAS inhibiting drugs, have been suggested to have beneficial effects on bone tissue. We aimed to assess the associations of use of ACEIs and/or ARBs with the risk of fractures using a population-based prospective cohort and a meta-analysis of published prospective cohort studies. Information on antihypertensive medication use (including both ACEIs and ARBs) were assessed in 1743 men and women of the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) [95% confidence intervals (CI)] of ACEIs or ARBs use with incident fractures were calculated. A total of 203 composite (hip, humeral, and wrist) fractures occurred during a median follow-up of 14.8 years. In multivariate adjusted analysis, the HR for composite fractures comparing users of ACEIs or ARBs with non-users was 1.00 (0.59–1.69). The corresponding adjusted HR for hip fractures comparing users versus non-users of ACEIs or ARBs was 0.89 (0.32–2.47). Including the current study, a total of 11 observational cohort studies involving 3526,319 participants and >323,355 fractures were included in a meta-analysis. Comparing ACEI users with non-users and ARB users with non-users, the HRs for composite fractures were 1.09 (0.89–1.33) and 0.87 (0.76–1.01) respectively. The corresponding HRs for hip fractures were 0.91 (0.86–0.95) and 0.80 (0.75–0.85) respectively. Use of RAS inhibitors was not associated with long-term risk of composite fractures in both primary and pooled analyses. Pooled evidence however suggests a beneficial effect of RAS blockers on hip fracture risk.

Impact of Angiotensin Receptor Blocker Use on Overall Survival Among Patients Undergoing Resection for Pancreatic Cancer.

Pancreatic cancer has higher concentrations of angiotensin II compared with other cancers. This study sought to assess the effect of angiotensin II receptor blockers (ARBs) on survival of patients undergoing resection using a large, nationally representative dataset. Patients undergoing pancreatic cancer resection were identified in the Truven Health MarketScan database. Multivariable Cox proportional hazards regression was used to assess the effect of ARB use on overall survival. A total of 4299 patients were identified, among whom 479 (11.1%) filled a prescription for an ARB. Mean patient age was 54.5years (SD=8.6years); 2187 (51.1%) were female. Exactly 49.4% (n=2125) of patients had a Charlson comorbidity index >2 at the time of surgery (n=2125, 49.4%) and 59.6% (n=2563) underwent a pancreaticoduodenectomy. Kaplan-Meier estimates of survival at 1, 2, and 4years were 62.8% (95% CI: 61.3-64.2%), 38.2% (95% CI: 36.6-39.8%), and 19.0% (95% CI: 17.1-21.0%), respectively. On multivariable analysis, ARB use was associated with a 24% decreased risk of death over the 5-year period in which patients were under observation (HR=0.76, 95% CI: 0.67-0.87, p<0.001). ARB use was associated with improved survival in patients undergoing resection of pancreatic cancer. Further research is required into the differential effect of ARBs in the treatment of pancreatic cancer.

The Significance of Angiotensin Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Use in Sudden Cardiac Death

Objectives: To investigate the relationship between the use of angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) and hyperkalemia in patients diagnosed with sudden cardiac death. Methods: We examined oral ACE inhibitor or ARB use among cardiopulmonary arrest patients brought by ambulance to our emergency room during a 5-year period from January 2012 to December 2016. The cause of death was determined to be sudden cardiac death, despite temporary return of spontaneous circulation after starting cardiopulmonary resuscitation. Subjects were dichotomized into 2 groups, those taking and those not taking an ACE inhibitor or ARB. Variables determined retrospectively included serum potassium, estimated glomerular filtration rate as an index of kidney function and time from cardiopulmonary arrest to return of spontaneous circulation. The Mann-Whitney U-test was used to compare continuous data, and the chi-square test to compare categorical data between groups. The results are expressed as the median plus range. Statistical significance was assumed at p < 0.05. Results: Thirty-five patients met the inclusion criteria. The mean age was 77.1 years (range, 35 - 93 years), and there were 26 males and 9 females. Eleven subjects were ACE inhibitor or ARB users, and 24 were non-users. The serum potassium level was significantly higher in users than non-users (median, 6.2 mEq/L (range, 4.5 - 10.0) vs. 5.2 mEq/L (range, 3.6 - 8.3); p = 0.001). The estimated glomerular filtration rate was significantly lower in users than non-users (median, 25.1 mL/min/1.73 m2 (range, 4.6 - 60.3) vs. 46.9 mL/min/1.73 m2 (range, 19.8 - 97.1); p = 0.009). There was no significant difference in time from cardiopulmonary arrest to return of spontaneous circulation between the 2 groups (median, 24 minutes (range, 3 - 111) vs. 29 minutes (range, 10 - 54); p = 0.355). Conclusion: It is possible that hyperkalemia induced by ACE inhibitor or ARB use is a cause of sudden cardiac death, especially in patients with chronic kidney disease.

Does contrast media volume affect long-term survival in patients with chronic kidney disease?

IntroductionThe aim of this study was to investigate the relationships between survival and related features in patients with chronic kidney disease undergoing cardiac catheterization and coronary angiography.Material and methodsThree hundred and seven consecutive patients with an estimated glomerular filtration rate (e-GFR) less than 60 ml/min/1.73 m2 undergoing coronary angiography were enrolled in the study. The study population was pursued with a median follow-up duration of 41.5 months.ResultsIn the Cox proportional hazards regression model, age (HR = 1.047, 95% CI: 1.011–1.084, p = 0.01), contrast media volume (HR = 1.004, 95% CI: 1.001–1.007, p = 0.008), angiotensin II receptor blocker (ARB) use (HR = 0.485, 95% CI: 0.261–0.901, p = 0.02), and e-GFR (HR = 0.978, 95% CI: 0.940–1.016, p = 0.04) were found to be independent predictors of long-term all-cause mortality. The survival analysis showed that the long-term all-cause mortality rate was higher in patients using contrast media volume greater than 140 ml compared to patients given less than or equal to 140 ml during the coronary angiography (3.6% vs. 11.6% log-rank, p = 0.001).ConclusionsIn patients with chronic kidney disease undergoing cardiac catheterization, age, contrast media volume, e-GFR and low ARB use were found to be independent predictors of long-term all-cause mortality. Contrast media volume used > 140 ml was independently associated with long-term all-cause mortality compared to less than or equal to 140 ml during cardiac catheterization.

PP.13.18] LONG-TERM OUTCOMES IN THE TREATMENT IN HIPERTENSIVE PATIENTS WITH ANGIOTENSIN-CONVERTING ENZYME INHIBITORS OR RENIN-ANGIOTENSIN RECEPTOR BLOCKERS

Objective: The ACEIs (Angiotensin-Converting-Enzyme Inhibitors) and ARBs (Angiotensin II Receptor Blocker AT-1) effectiveness’ in reducing the systemic hypertension (SH) is widely known. However their comparative outcomes resulting from prolonged use remain unknown. The objective of this study is to compare by a Meta-Analysis of prospective randomized double-blind clinical trials all the events results from prolonged use of ACEIs or ARBs in hypertensive patients. Design and method: Three reviewers, independently, made the selection in the following databases: PUBMED, LILACS and SCIELO. We used the combination of inclusion and exclusion criteria to select randomized double-blind clinical trials. After the final selection of trials the statistical analysis was made by the program Comprehensive Meta-Analysis®. Results: We retrieved 1,621 studies in the databases for analysis of titles, being selected 855 abstracts for analysis. Were allocated to analyze the content 75 of these, in the end, 17 studies and 73,761 patients were reviewed. The use of ACEIs when compared to the control group, proved to be significant in reducing total mortality (TM) (OR = 0.851, 95% CI [0.776 to 0.935], P = 0.001) and reduction in cardiovascular mortality (CVD) (OR = 0.775, 95% CI [0.669 to 0.872], P = 0.000). The ARBs’ therapy did not show reduction of TM (OR = 1.024, 95% CI [0.960 the 1,091], P = 0.471) and CVD (OR = 0.947, 95% CI [0.849 the 1,056], P = 0.324). For Acute Myocardial Infarction (AMI), cerebrovascular accident (stroke) and heart failure (HF)/Internment, the reductions were significant for both classes. Conclusions: To lowering blood pressure in addition, the use of ACE inhibitors or ARBs reduces, in long-term use, the risk of AMI, Stroke and IC/Internment. However, the use of ACEI's is effective in reducing TM and CVD, an outcome that was not observed with the use of ARBs. This fact is assumed to be related to the higher plasma concentration of bradykinin in the use of ACEIs, a well-known cardio-vascular-protective factor.

Utilization of Evidence-Based Secondary Prevention Medications at the Time of Discharge in Patients with Acute Coronary Syndrome (ACS) in Qatar.

In Qatar, ACS (Acute Coronary Syndrome) has become the leading cause of morbidity and mortality. Guidelines recommend that ACS patients should receive indefinite treatment with antiplatelets, β-blockers, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and statins. The study objectives were to assess the use of evidence-based secondary prevention medication at discharge among ACS patients in Qatar and to determine the clinical and demographic characteristics associated with the use of these medications. A retrospective medical record review was conducted at the Heart Hospital in Qatar. A random sample of 1068 ACS patients was selected. Patient characteristics were summarized. Prevalence of medications at discharge were computed for each medication as well as for medication combinations. Multiple logistic regression was used to detect patient variables that were associated with the outcomes. A p≤0.05 was considered significant. -Percentage of ACS patients discharged on each of the following medications: antiplatelets (aspirin, clopidogrel), β-blockers, ACEI or ARBs and statins and on the combination of these medications-Association between the use of these medications and patient characteristics. In total, 1064 records were reviewed. The majority were males (85.3%) and about 1 in 5 (18.7%) were Qatari. At discharge, patients were prescribed the following: aspirin (96.0%), clopidogrel (92.0%), β-blockers (90.6%) and statins (97.7%). ACEI and ARBs were prescribed to 63.5 and 11.3%, respectively. The concurrent 4 medications (aspirin or clopidogrel, statins or other lowering cholesterol medication, β-blockers and ACEI or ARB) were prescribed to 773 patients (77.8%; 95% confidence interval: 75.2-80.4%). Being overweight or obese, and having PCI (percutaneous coronary intervention) or hypertension were associated with higher prescription of the concurrent medications. Those with diabetes had a 52% increase in the odds of prescribing the 4 medications. Those with kidney disease had a 67% reduction in the odds of prescribing. Most ACS patients were prescribed antiplatelets, β-blockers and statins, but the use of ACEIs or ARBs was suboptimal. Strategies are needed to enhance ACEI or ARB prescribing, especially for high risk patients who would have the greatest therapeutic benefit from these drugs.

Angiotensin II receptor blockers versus angiotensin-converting enzyme inhibitors in patients with stable coronary artery disease: Prevalence, correlates, and prognostic impact (from the CORONOR study)

BackgroundIn international guidelines for patients with stable coronary artery disease (CAD), angiotensin-converting enzyme inhibitors (ACE-I) are recommended while angiotensin II receptor blockers (ARB) are proposed as an alternative in case of intolerance. There are no real-life data on the frequency and correlates of ARB use in this setting. MethodsWe studied 3363 outpatients included in a prospective registry on stable CAD (the CORONOR study) and receiving an ARB or an ACE-I at inclusion. ResultsAltogether, 944 patients received an ARB (28.1%). Factors positively and independently associated with ARB use versus ACE-I use were a history of hypertension, the absence of prior myocardial infarction, age, female gender, estimated glomerular filtration rate <60ml/min/m2, and left ventricular ejection fraction ≥40%. In the whole study population, the hazard ratio (HR) for the combined endpoint (cardiovascular death, myocardial infarction, stroke) of patients with ARB use was 0.95 (0.69–1.31) (p=0.765) (patients with ACE-I use as reference). Similar results were observed when the analysis was restricted to a propensity-matched cohort: HR=0.91 (0.62–1.34) (p=0.632). ConclusionsOur study shows that a significant proportion of stable CAD patients are treated with ARB rather than with ACE-I in modern practice. Several correlates of ARB prescription were identified. Our results suggest that patients receiving ARB have similar outcome than patients receiving ACE-I.

Angiotensin II Receptor Blockers and Cancer Risk: A Meta-Analysis of Randomized Controlled Trials.

Angiotensin II receptor blockers (ARB) are widely used drugs that are proven to reduce cardiovascular disease events; however, several recent meta-analyses yielded conflicting conclusions regarding the relationship between ARB and cancer incidence, especially when ARB are combined with angiotensin-converting enzyme inhibitors (ACEI).We investigated the risk of cancer associated with ARB at different background ACEI levels.Search of PubMed and EMBASE (1966 to December 17, 2015) without language restriction.Randomized, controlled trials (RCTs) had at least 12 months of follow-up data and reported cancer incidence was included.Study characteristics, quality, and risk of bias were assessed by 2 reviewers independently.Nineteen RCTs including 148,334 patients were included in this study. Random-effects model meta-analyses were used to estimate the risk ratio (RR) of cancer risk. No excessive cancer risk was observed in our analyses of ARB alone versus placebo alone without background ACEI use (risk ratio [RR] 1.08, 95% confidence interval [CI] 1.00–1.18, P = 0.05); ARB alone versus ACEI alone (RR 1.03, 95%CI 0.94–1.14, P = 0.50); ARB plus partial use of ACEI versus placebo plus partial use of ACEI (RR 0.97, 95%CI 0.90–1.04, P = 0.33); and ARB plus ACEI versus ACEI (RR 0.99, 95%CI 0.79–1.24, P = 0.95).Lack of long-term data, inadequate reporting of safety data, significant heterogeneity in underlying study populations, and treatment regimens.ARB have a neutral effect on cancer incidence in randomized trials. We observed no significant differences in cancer incidence when we compared ARB alone with placebo alone, ARB alone with ACEI alone, ARB plus partial use of ACEI with placebo plus partial use of ACEI, or ARB plus ACEI combination with ACEI.

Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and the risk of major adverse cardiac events in patients with diabetes and prior stroke: a nationwide study.

Renin-angiotensin-aldosterone system blockers are the preferred antihypertensive medications in patients with diabetes and prior stroke. This study aimed to compare the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in terms of major adverse cardiac events (MACEs) in patients with diabetes who survived ischemic stroke. We conducted an observational, nationwide, propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. Patients aged at least 20 years with type 2 diabetes who initiated ACEI (n = 15,959) or ARB (n = 23,929) use within 90 days after discharge for first ischemic stroke between January 2000 and December 2011 were allocated to ACEI and ARB groups, respectively. The primary outcomes were MACEs (myocardial infarction, ischemic stroke, and cardiovascular mortality). The secondary outcomes were hospitalization for acute kidney injury and hyperkalemia. Intention-to-treat and as-treated models were used. Intention-to-treat analysis showed no significant difference between the ACEI and ARB groups in the outcomes of MACEs [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.95-1.04], including ischemic stroke (HR, 1.01; 95% CI, 0.97-1.06), myocardial infarction (HR, 1.06; 95% CI, 0.95-1.18), and cardiovascular mortality (HR, 0.98; 95% CI, 0.91-1.06). As-treated analysis produced similar results. Additionally, the groups showed no difference in the risk of hospitalization for acute kidney injury or hyperkalemia. Our study supports the hypothesis that the risks of MACEs and two additional secondary outcomes in patients with diabetes who survived ischemic stroke did not differ according to ACEI versus ARB use.

Abstract TP152: Angiotensin II Receptor Blockers for the Prevention of Post-stroke Epilepsy

Introduction: Previous animal studies suggest that post-stroke epileptogenesis is facilitated by activation of albumin-mediated TGF- β signaling and that blockade of this pathway with the angiotensin II receptor blocker (ARB) losartan prevents the development of recurrent spontaneous seizures in rat models. We used a large national retrospective cohort to examine the association between post-stroke seizures and ARB exposure among Veterans with ischemic stroke. Hypothesis: ARB exposure is negatively associated with post-stroke seizures. Methods: We reviewed data from the Veteran’s Affairs Office of Quality and Performance retrospective cohort stroke study, which included Veterans discharged from a VA hospital in 2007 with a primary diagnosis of ischemic stroke. Clinical and demographic data were abstracted by chart review, including NIHSS score. Abstracted data were linked to ICD9 codes for seizure and epilepsy 2 years before and 3 years after stroke admission and to pharmacy data. Patients with seizures prior to stroke admission were excluded. Patients were considered to have ARB exposure if they had a prescription for an ARB at any time during the data collection period. The association between clinical, demographic, and ARB exposure and post-stroke seizures was examined using univariate and multivariate logistic regression analysis. Results: Of 3299 eligible patients, 453 (13.7%) were prescribed ARB therapy and 307 (9.3%) had a diagnosis of seizure or epilepsy. In univariate analysis, age, NIHSS, history of ischemic stroke, seizure at onset of stroke, and history of head trauma within 3 months were independently associated (p≤0.10) with post-stroke seizures. In multivariate analysis, only age (OR 1.026; 95% CI 1.014-1.038), NIHSS (0.973; 0.953-0.993), history of ischemic stroke (0.603; 0.460-0.789), and seizure at onset (0.033; 0.014-0.079) were independently associated (p≤0.05) with post-stroke seizures. Conclusion: In this retrospective post-stroke cohort, ARB exposure was not associated with a reduction in post-stroke seizures. Further, prospective studies assessing the development of post-stroke seizures and the use of ARBs over time are required.

Renin–angiotensin–aldosterone system blockers for heart failure with reduced ejection fraction or left ventricular dysfunction: Network meta-analysis

BackgroundRenin–angiotensin–aldosterone system (RAAS) blockers are effective therapies for heart failure and reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVD). We aimed to assess the efficacy and safety of RAAS blockers in these patients. MethodsWe searched MEDLINE, EMBASE, and Cochrane Library in May 2015. Twenty-one double-blind randomized controlled trials (RCTs) with 69,229 patients were included this network meta-analysis. ResultsCompared with placebo, an angiotensin receptor–neprilysin inhibitor (ARNI) had the highest probability of reducing all-cause mortality (odds ratio [OR]=0.67, 95% credible interval [CrI]: 0.48–0.86), followed by an aldosterone receptor antagonist (ARA, OR=0.74, 95% CrI: 0.62–0.88) and an angiotensin-converting enzyme inhibitor (ACEI, OR=0.80, 95% CrI: 0.71–0.89). The most efficacious therapy for preventing heart failure hospitalization was ARNI (OR=0.55, 95% CrI: 0.40–0.71), followed by combination therapy with an angiotensin II receptor blocker (ARB) plus an ACEI (OR=0.61, 95% CrI: 0.49–0.75), then an ACEI alone (OR=0.69, 95% CrI: 0.61–0.77). Sensitivity analysis restricted to nine RCTs with a high background use of ACEI and/or ARB (>80%) indicated that adding an ARA to current standard therapy significantly reduced mortality (OR=0.73, 95% CrI: 0.51–0.95) and hospitalization risk (OR=0.67, 95% CrI: 0.47–0.87), but did not significantly increase the discontinuation risk (OR=1.29, 95% CrI: 0.83–2.31). ConclusionsARNI has the highest probability of being the most efficacious therapy for HFrEF in reducing death and hospitalization for heart failure. ARA has the most favorable benefit–risk profile as an adjunct to background ACEI and/or ARB therapy.

Antihypertensive treatments in adult autosomal dominant polycystic kidney disease: network meta-analysis of the randomized controlled trials.

Blood pressure (BP) control is one of the most important treatments of Autosomal dominant polycystic kidney disease (ADPKD). The comparative efficacy of antihypertensive treatments in ADPKD patients is inconclusive. Network meta-analysis was used to evaluate randomized controlled trials (RCT) which investigated antihypertensive treatments in ADPKD. PubMed, Embase, Ovid, and Cochrane Collaboration were searched. The primary outcome was estimated glomerular filtration rate (eGFR). Secondary outcomes were serum creatinine (Scr), urinary albumin excretion (UAE), systolic BP (SBP), diastolic BP (DBP), mean artery pressure (MAP) and left ventricular mass index (LVMI). We included 10 RCTs with 1386 patients and six interventions: angiotensin-converting enzyme inhibitors (ACEI), Angiotensin II receptor blocker (ARB), combination of ACEI and ARB, calcium channel blockers (CCB), β-blockers and dilazep. There was no difference of eGFR in all the treatments in both network and direct comparisons. No significant differences of Scr, SBP, DBP, MAP, and LVMI were found in network comparisons. However, ACEI significantly reduced SBP, DBP, MAP and LVMI when compared to CCB. Significantly increased UAE was observed in CCB compared with ACEI or ARB. Bayesian probability analysis found ARB ranked first in the surrogate measures of eGFR, UAE and SBP. There is little evidence to detect differences of antihypertensive treatments on kidney disease progression in ADPKD patients. More RCTs will be needed in the future. Use of ARB may be an optimal choice in clinical practice.

Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients With CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials

There is much uncertainty regarding the relative effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in populations with chronic kidney disease (CKD). Systematic review and Bayesian network meta-analysis. Patients with CKD treated with renin-angiotensin system (RAS) inhibitors. Randomized trials in patients with CKD treated with RAS inhibitors. ACE inhibitors and ARBs compared to each other and to placebo and active controls. Primary outcome was kidney failure; secondary outcomes were major cardiovascular events, all-cause death. 119 randomized controlled trials (n = 64,768) were included. ACE inhibitors and ARBs reduced the odds of kidney failure by 39% and 30% (ORs of 0.61 [95% credible interval, 0.47-0.79] and 0.70 [95% credible interval, 0.52-0.89]), respectively, compared to placebo, and by 35% and 25% (ORs of 0.65 [95% credible interval, 0.51-0.80] and 0.75 [95% credible interval, 0.54-0.97]), respectively, compared with other active controls, whereas other active controls did not show evidence of a significant effect on kidney failure. Both ACE inhibitors and ARBs produced odds reductions for major cardiovascular events (ORs of 0.82 [95% credible interval, 0.71-0.92] and 0.76 [95% credible interval, 0.62-0.89], respectively) versus placebo. Comparisons did not show significant effects on risk for cardiovascular death. ACE inhibitors but not ARBs significantly reduced the odds of all-cause death versus active controls (OR, 0.72; 95% credible interval, 0.53-0.92). Compared with ARBs, ACE inhibitors were consistently associated with higher probabilities of reducing kidney failure, cardiovascular death, or all-cause death. Trials with RAS inhibitor therapy were included; trials with direct comparisons of other active controls with placebo were not included. Use of ACE inhibitors or ARBs in people with CKD reduces the risk for kidney failure and cardiovascular events. ACE inhibitors also reduced the risk for all-cause mortality and were possibly superior to ARBs for kidney failure, cardiovascular death, and all-cause mortality in patients with CKD, suggesting that they could be the first choice for treatment in this population.

A Case of Diffuse Lymphocytic Gastritis Associated With Valsartan

Valsartan is an angiotensin II receptor blocker (ARB) used for the treatment of hypertension. Rare gastrointestinal adverse events associated with ARB use have been reported. The ARB olmesartan has been linked to celiac-like enteropathy with variable degrees of gastric and colonic inflammation. In one prior report, lymphocytic gastritis (LG) was seen in 5 of 22 patients with celiac-like enteropathy related to olmesartan. One case of valsartan associated celiac-like enteropathy has also been published. To our knowledge, no case linking valsartan to LG has been reported. Here we describe a case of diffuse LG associated with valsartan use. A 57-year-old Taiwanese man with hypertension presented with epigastric pain, nausea and post-prandial fullness for 6 months. He denied weight loss or diarrhea. A prior endoscopy 3 months earlier demonstrated mild erythematous gastropathy. Gastric antral biopsies showed LG. Duodenal biopsies were normal. His current medications included valsartan 80 mg, which he began 3 months before symptom onset. Physical examination was unremarkable. A complete blood count and comprehensive metabolic panel were normal. Repeat upper endoscopy demonstrated patchy, gastric nodularity, erythema and erosions. Multiple gastric biopsies from the cardia, fundus, body and antrum showed pan-lymphocytic gastritis with multiple erosions. Given the recent association of ARBs with celiac-like intestinal disease including LG, valsartan was discontinued. The patient's symptoms began to improve within 2 weeks. Repeat gastric biopsies 8 months later showed normal mucosa with complete resolution of LG. Based on the rapid symptom improvement and resolution of LG after stopping the drug, a valsartan-associated adverse effect was suspected. The patient declined valsartan rechallenge. He remained asymptomatic at 1-year clinical follow-up. We describe a patient with unexplained diffuse LG associated with valsartan. LG is an uncommon form of chronic gastritis characterized by marked intraepithelial lymphocytosis of the gastric surface and pit epithelium comprising > 25 intraepithelial lymphocytes per 100 epithelial cells. Approximately 38% of patients with LG have celiac disease. LG has also been associated with Helicobacter pylori infection, gastric lymphoma, and common variable immunodeficiency (CVID). The etiology of LG remains unknown in many cases. Recent reports have linked the ARB olmesartan to celiac-like duodenal lymphocytosis and LG. We propose that valsartan may similarly be associated with LG.

Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on major adverse cardiac events in patients with newly diagnosed type 2 diabetes: A nationwide study

BackgroundGuidelines for hypertension management recommend either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) as first-line therapies for diabetes population. No head-to-head trial has been conducted to determine the priority of ACEI/ARB use for major adverse cardiac events (MACEs) in diabetes mellitus. MethodsData on patients with newly diagnosed diabetes treated with ACEIs or ARBs were collected from Taiwan's National Health Insurance Research Database for the period 2000–2010. A total of 30,777 ARB users and 21,436 ACEI users were identified. One ARB user was matched to one ACEI user by propensity score. Intention-to-treat (ITT) and as-treated (AT) models were used. The primary outcomes were myocardial infarction, ischemic stroke, and all-cause mortality. The secondary outcomes were hospitalization for acute kidney injury and hyperkalemia. FindingsCompared with ACEI users (n=21,436), ARB users (n=30,777) showed no significant difference in the outcomes of myocardial infarction (hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.80 to 1.07), ischemic stroke (HR: 0.95; 95% CI: 0.87 to 1.04), or all-cause mortality (HR: 0.95; 95% CI: 0.89 to 1.01) in the ITT analysis. The risks of hospitalization for acute kidney injury and hyperkalemia also did not differ between groups. ACEI and ARB use also had similar effects on MACEs and adverse effects in the AT analysis. ConclusionsThis large cohort study supports the comparative effectiveness of ACEIs and ARBs in terms of MACE outcomes in patients with incident diabetes.

Possible prevention of dialysis-requiring congestive heart failure by angiotensin-II receptor blockers in non-dialysis Japanese patients with Stage 5 chronic kidney disease.

Preventive medications for dialysis-requiring congestive heart failure (CHF) in non-dialysis Japanese patients with Stage 5 chronic kidney disease (CKD) are unknown. Our aim was to explore which CKD medication was associated with a reduced prevalence of dialysis-requiring CHF in non-dialysis Japanese patients with Stage 5 CKD. The present multicenter, retrospective, cross-sectional study examined the association between CKD medications and the prevalence of dialysis-requiring CHF in non-dialysis Japanese patients with Stage 5 CKD. There were 1536 Japanese Stage 5 CKD patients who satisfied our inclusion criteria. We had 309 (20.1%) patients whom had developed dialysis-requiring CHF and 940 patients (60.8%) whom had been using angiotensin-II receptor blockers (ARBs) before initiating dialysis. In our multivariate analysis, only ARB use was significantly associated with a lower risk of CHF (Odds ratio (OR): 0.680, 95% confidence interval (CI): 0.516-0.897; p = 0.0064), of the CKD treatments examined in this study. We found that ARB use during the pre-dialysis period is associated with a lower prevalence of CHF in the non-dialysis Japanese patients with Stage 5 CKD, suggesting a possible prevention of dialysis-requiring CHF by ARBs, in non-dialysis Japanese patients with Stage 5 CKD.