Angiotensin Receptor Blockers Group Research Articles

Investigation of the effects of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on anemia in patients with normal or mildly low glomerular filtration rate.

The relationship between the activation of the renin-angiotensin system and the increase in erythropoiesis has been shown in many studies. In addition, the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARB) has been reported to reduce hemoglobin levels in various patient groups at risk for secondary erythrocytosis/polycythemia. The aim of our study is to investigate whether there is a change in hemoglobin levels after starting ACEIs or ARBs in patients who have not used them before. Three hundred and fifty-one patients who were started on renin angiotensin aldosterone system (RAAS) blockers were evaluated retrospectively. None of the patients had anemia before starting RAAS blockers. A median of 6 (4-12) months after the start of the drug, complete blood count and kidney function tests were evaluated. Hemoglobin values before and after the start of the drug were compared statistically. A statistically significant decrease in mean Hb value was found after starting ACEIs or ARBs (14.39 ± 1.29 g/dL vs 13.98 ± 1.36 g/dL, p < 0.001). The decrease in control Hb values was higher in the ARB group than in the ACEI group (-0.53 ± 0.06 g/dL vs -0.29 ± 0.06 g/dL, p < 0.001). A significant decrease in mean Hb level was detected in the first year following the first administration of ACEIs or ARBs.

Abstract 10482: Renin-Angiotensin-Aldosterone System Inhibition is Associated with Reduced In-Hospital Mortality in Critically Ill Covid-19 Patients with Pre-Existing Hypertension

Background: The virus responsible for COVID-19 enters human cells by binding angiotensin-converting enzyme 2. The influence of renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs), remains uncertain. Aim: To examine the role of ACEi / ARB exposure on outcomes in COVID-19 patients with pre-existing hypertension (HTN) admitted to intensive care units (ICU). Methods: The COVID-19 Critical Care Consortium is a prospective, observational cohort study of patients requiring ICU admission for active COVID-19 spanning 354 participating sites in 54 countries. Patients &gt;18 years old with pre-existing HTN requiring antihypertensive therapy were analysed. Length of stay and in-hospital mortality to 90 days post ICU admission were analysed as time-to-event outcomes by multistate survival analysis, and the influence of ACEi / ARB use on the hazards of death and discharge by multi-state Cox proportional hazard modelling and sensitivity analysis. Results: From December 1, 2019 through December 30, 2020, 663 eligible patients were registered. Of these, 480 patients had received ACEi and / or ARB therapy (median age 65 years, 67% male) in the 2 weeks before ICU admission, while 183 had not (66 years, 61% male). Average lengths of ICU and general ward stays were longer in the ACEi / ARB than non-ACEi / ARB group (20.8 days and 6.5 days vs. 15.5 and 6.0 days, respectively). ACEi / ARB use was associated with a decreased hazard of death (HR, 0.69, 95% CI, 0.54 — 0.88) that persisted after adjusting for propensity scores (0.67, 0.53 — 0.86). Cumulative probabilities (unadjusted for baseline characteristics) for death and discharge post ICU admission are depicted in the figure for ACEi/ARB (red) and non-ACEi / ARB (blue) patients. Conclusions: In 663 critically ill COVID-19 patients with pre-existing HTN, RAAS inhibition pre-ICU admission was linked to reduced in-hospital mortality.

The effects of different antihypertensive drugs on pain and joint space width of knee osteoarthritis - A comparative study with data from Osteoarthritis Initiative.

Hypertension was one common comorbidity of knee osteoarthritis (KOA), but the effect of different types of antihypertensive drugs on pain and joint space width (JSW) was unclear and not compared. Four hundred ninety KOA patients using one of the beta‐blockers, ACE inhibitors, angiotensin receptor blockers, Calcium channel blockers (CCBs), or thiazide diuretics were followed for four years. The blood pressure, cumulative knee replacement rate, Womac pain, and JSW were compared among groups. All data were from the Osteoarthritis Initiative project. The CCBs group has the highest systolic blood pressure, replacement rate, and pain score at most visit timepoints. At baseline, the CCBs group was with significantly higher pain score than the beta‐blockers group (3.3 vs 1.3, p < .05), the angiotensin receptor blockers group (3.3 vs 1.4, p < .05), and the thiazide diuretics group (3.3 vs 1.6, p < .05) in male; the CCBs group was with significantly higher pain score than the beta‐blockers group (3.8 vs 2.0, p < .01), and the angiotensin receptor blockers group (3.8 vs 2.2, p < .05) in female. The results of females at 36 months were similar to the baseline. Among the common antihypertensive drugs, CCBs were associated with high replacement rates, high pain scores, and less JSW in KOA patients.

The use of angiotensin receptor blockers is associated with greater recovery of cardiac function than angiotensin-converting-enzyme inhibitors among patients with dilated cardiomyopathy

Abstract Background We previously showed that angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) were associated with heart failure with recovered ejection fraction (HFrecEF) in patients with dilated cardiomyopathy (DCM). However, the different effects of these drugs on cardiac reverse remodeling have not been fully elucidated. The aim of this study was to assess comparative effectiveness of ACEi versus ARB on recovery of left ventricular ejection fraction (LVEF) among patients with DCM. Methods We analyzed the clinical personal records of DCM, a national database of Japanese Ministry of Health, Labour and Welfare, from 2003 to 2014. Patients with LVEF &amp;lt;40% and on either ACEi or ARB were included. Eligible patients were divided into two groups according to the use of ACEi or ARB. A one-to-one propensity case-matched analysis was used. A propensity score was estimated by fitting a logistic-regression model which adjusted for age, sex, duration of HF, NYHA functional class (I-II vs. III-IV), systolic blood pressure, diastolic blood pressure, heart rate, atrial fibrillation, pacing, left bundle branch block, LVEF, hypertension, diabetes mellitus, hyperuricemia, chronic kidney disease, B-type natriuretic peptide (BNP), beta-blockers, mineralocorticoid receptor antagonists, loop diuretics, thiazides, digitalis, amiodarone, and oral inotropes. The primary outcome was defined as LVEF ≥40% at 3 years of follow-up. Results Out of 4,618 eligible patients, 2,238 patients received ACEi and 2,380 patients received ARB. Propensity score matching yielded 1,341 pairs. Mean age was 56.0 years and 2,041 (76.1%) was male. Mean LVEF was 27.6%, and median duration of HF was 1 year. The primary outcome was observed more frequently in ARB group than in ACEi group (59.8% vs. 54.1%; odds ratio [OR] 1.26; 95% confidence interval [CI] 1.08–1.47; P=0.003). The change in LVEF from baseline to 3 years of follow-up was greater in ARB group than in ACEi group (15.8±0.4 vs. 14.0±0.4%, P=0.002). In the ACEi group, 946 patients (70.6%) continued to receive ACEi at 3 years of follow-up, while 1,088 patients (81.3%) continued to receive ARB in the ARB group. Per-protocol analysis consistently showed that ARB increased the prevalence of HFrecEF (62.0% vs. 54.0%; OR 1.39; 95% CI 1.17–1.66; P&amp;lt;0.001). Subgroup analysis showed that ARB increased frequency of HFrecEF regardless systolic blood pressure, heart rate, LVEF, chronic kidney disease, and concomitant use of beta-blockers and mineralocorticoid receptor antagonists. Conclusions The use of ARB was associated with HFrecEF more frequently than ACEi among patients with DCM and reduced LVEF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Health Sciences Research Grants from the Japanese Ministry of Health, Labour and Welfare (Comprehensive Research on Cardiovascular Diseases)Japan Agency for Medical Research and Development (AMED) grant

Angiotensin converting enzyme inhibitors and incidence of lung cancer in a population based cohort of common data model in Korea

Contradictory findings exist about association of angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) with lung cancer development. This was a retrospective observational cohort study that used data from 7 hospitals in Korea, converted to the Observational Medical Outcomes Partnership Common Data Model. The primary outcome was occurrence of lung cancer. A total of 207,794 patients across the 7 databases was included in the final analysis; 33,230 (16%) were prescribed ACEi and 174,564 (84%) were prescribed ARB. Crude analysis adjusted for sex and age showed higher incidence of lung cancer in the ACEi group compared to the ARB group (hazard ratio [HR], 1.46; 95% confidence rate [CI], 1.08–1.97). After propensity-score matching, 30,445 pairs were generated, and there was no difference in incidence of lung cancer between the two groups (HR, 0.93; 95% CI, 0.64–1.35). Patients prescribed ACEi showed no difference in incidence of lung cancer development compared to those using ARB. This finding provides evidence on the association between ACEi and occurrence of lung cancer.

Association between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Lung Cancer.

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed antihypertensives, with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated this potential association in a large population using propensity matching. This was a population-based cohort study in a large healthcare system in three regions of the United States. Pairwise propensity score matching was performed using demographics and comorbidities. All of the adult patients in the healthcare system from January 1, 2000 to April 30, 2018 with at least 1 year of follow-up were included. In total, 3,253,811 patients with a median age of 59 (range 18-103) years were included. The ACEI group had a higher freedom from lung cancer versus controls at 15 years (98.47%, 95% confidence interval [CI] 98.41-98.54) versus 98.26%, (95% CI 98.20-98.33), whereas ARBs had similar rates versus controls at all time points. For patients diagnosed as having lung cancer, median all-cause survival was significantly higher in the ACEI (34.7 months, 95% CI 32.8-36.6) and ARB (30.9 months, 95% CI 28.1-33.8) groups than the control group (20.6 months, 95% CI 20.1-21.1). This study showed lower rates of lung cancer with ACEI use and no difference in risk with ARBs. In addition, use of these medications was found to be associated with increased survival in those diagnosed as having lung cancer. This study supports the continued use of these medications without concern for increasing the risk of lung cancer.

Effects of antihypertensive drugs on surgical outcomes of breast reconstruction: a nationwide population-based claim study.

Experimental studies have reported that angiotensin receptor blockers (ARBs) increase the risk of surgical complications. However, clinical data on their effect on surgical outcomes are limited. The aim of this study was to investigate the impact of perioperative use of ARBs on the outcomes of breast reconstruction using population-based claim data. Data of patients who underwent direct-to-implant or abdomen-based autologous breast reconstruction after total mastectomy from April 2015 to December 2018 were obtained from the Health Insurance Review and Assessment Service database. The patients were categorized as ARB, non-ARB, control, and non-hypertension groups. The effects of ARBs on surgical complications, length of hospital stay, and complication-related medical costs were evaluated. Of the 9,036 patients who met the inclusion criteria, 5,192 underwent direct-to-implant reconstruction, and 3,844 underwent abdomen-based autologous reconstruction. The length of hospital stay was the longest and the surgical complication rate and complication-related medical cost were the highest in the ARB group after both reconstruction methods. Compared with non-treatment with antihypertensive drugs, ARB use was found to be an independent risk factor for surgical complications in direct-to-implant reconstruction [odds ratio (OR), 1.96; 95% confidence interval (CI), 1.09-3.50; P=0.0237] and complication-related medical cost (OR, 1.93; 95% CI, 1.10-3.40; P=0.0221) in abdomen-based autologous reconstruction. Perioperative ARB use was associated with adverse postoperative breast reconstruction outcomes. These findings might have a significant impact on perioperative antihypertensive management; nevertheless, further studies are warranted to confirm the study findings.

Associated Risk of Death from Covid-19 Infection in Patients with Hypertensive Co-Morbidities

Background: The COVID-19 pandemic caused by the SARS-CoV-2 virus has left infected patients with comorbidities in severe and deadly conditions. Hypertension is a non-communicable disease (NCD) and is one of the most common comorbidities observed in COVID-19 patients. Purpose: This study aims to understand the relationship between hypertension and the risk of death through COVID-19. Method: The study employed a systematic review of journals. Journals and articles related to hypertension and COVID-19 were collected and analyzed. The inclusion criteria was COVID-19 articles pertaining to hypertensive patients, and the exclusion criteria was articles that did not use English as well as those that did not display full text. Result: Hypertension is a multifactorial disease. The presence of hypertension is often not realized by the sufferer. A COVID-19 infection can worsen the condition of the person and can cause damage to vital organs. The use of antihypertensive drugs of the angiotensin-converting enzyme inhibitor (ACEI) and the angiotensin receptor blocker (ARB) groups can be continued to be administered to hypertensive patients. There should be no cause for concern for these patients to develop COVID-19 infections by taking these drugs. Conclusion: The risk of developing hypertension is that it can cause organ damage and lead to various complications. The SARS-CoV-2 infection in people with hypertension as a comorbidity, could worsen the condition of the individual until death occurs. Thus, hypertension management is necessary to properly minimize the severity.

Impact of renin angiotensin system inhibitor on 3-year clinical outcomes in acute myocardial infarction patients with preserved left ventricular systolic function: a prospective cohort study from Korea Acute Myocardial Infarction Registry (KAMIR)

BackgroundPatients with acute myocardial infarction (AMI) are usually treated with angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) if ACEIs are not tolerated. However, there is no data regarding the impact of switching from ACEIs to ARBs on long-term clinical outcomes in AMI patients with preserved left ventricular (LV) systolic function especially beyond 1 year. To investigate the effectiveness of treatment with ACEIs or ARBs on clinical outcomes over 3 years in AMI patients with preserved LV systolic function following percutaneous coronary intervention.MethodIt is a prospective cohort study using data from a nationwide large scale registry with 53 hospitals involved in treatment of acute myocardial infarction (AMI) in Korea. Between March 2011 and September 2015, we enrolled 6236 patients with AMI who underwent primary percutaneous coronary intervention and had a left ventricular ejection fraction ≥ 50%. Main outcome measures composite of total death or recurrent AMI over 3 years after AMI. Patients were divided into an ACEI group (n = 2945), ARB group (n = 2197), or no renin-angiotensin system inhibitor (RASI) treatment (n = 1094). We analyzed patients who changed treatment. Inverse probability of treatment weighting (IPTW) analysis was also performed.ResultsAfter the adjustment with inverse probability weighting, the primary endpoints at 1 year, AMI patients receiving ACEIs showed overall better outcomes than ARBs [ARBs hazard ratio (HR) compared with ACEIs 1.384, 95% confidence interval (CI) 1.15–1.71; P = 0.003]. However, 33% of patients receiving ACEIs switched to ARBs during the first year, while only about 1.5% switched from ARBs to ACEIs. When landmark analysis was performed from 1 year to the end of the study, RASI group showed a 31% adjusted reduction in primary endpoint compared to patients with no RASI group (HR, 0.74; 95% CI 0.56–0.97; P = 0.012).ConclusionsThis result suggests that certain patients got benefit from treatment with ACEIs in the first year if tolerated, but switching to ARBs beyond the first year produced similar outcomes. RASI beyond the first year reduced death or recurrent AMI in AMI patients with preserved LV systolic function.CRIS Registration number: KCT0004990.

Evaluation of clinical parameters of patients with Covid-19 pneumonia on admission and medications used for their comorbidities

Background: Risk factors and molecular mechanisms of severe respiratory involvement of Covid-19 are investigated more intensely and some doubts about non-steroidal antiinflammatory drugs (NSAID) and renin-angiotensin-aldosterone system (RAAS) inhibitors has also emerged.&#x0D; Aims and Objective: We aimed to detect potential associations between medications taken regularly for comorbid diseases before the diagnosis of Covid-19 pneumonia and demographic or clinical features on admission.&#x0D; Materials and Methods: Patients diagnosed with pneumonia between March 11th, 2020 and April 15th, 2020 in emergency, internal medicine and cardiology outpatient clinics were recruited and their clinical and demographic features including blood tests, oxygen saturations (SO2) along with degree of lung infiltrations in computed tomography on admission were analyzed in regard to their medications used regularly.&#x0D; Results: Angiotensin converting enzyme inhibitors (ACE inh.) or angiotensin receptor blockers (ARB) users were older than no-ACE inh./ARB group and had significantly lower SO2 on admission, whereas NSAID users with Covid-19 displayed a marked female predominance and lower hemoglobin levels than no-NSAID group. Proton pump inhibitor (PPI) users had also a significant female predominance and older age with lower hemoglobin levels. Lastly, antiaggregant users with Covid-19 had a lower SO2 on admission and overall, cases with regular drug intake were markedly associated with older age.&#x0D; Conclusion: Noteworthy associations were observed between demographic and clinical features on admission for Covid-19 pneumonia and major drug groups used regularly including RAAS inhibitors, NSAIDs and proton pump inhibitors.

Different therapeutic associations of renin-angiotensin system inhibitors with coronavirus disease 2019 compared with usual pneumonia.

Background/AimsAlthough it is near concluded that renin-angiotensin system inhibitors do not have a harmful effect on coronavirus disease 2019 (COVID-19), there is no report about whether angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) offer any protective role. This study aimed to compare the association of ARBs and ACEIs with COVID-19-related mortality.MethodsAll patients with COVID-19 in Korea between January 19 and April 16, 2020 were enrolled. The association of ARBs and ACEIs with mortality within 60 days were evaluated. A comparison of hazard ratio (HR) was performed between COVID-19 patients and a retrospective cohort of pneumonia patients hospitalized in 2019 in Korea.ResultsAmong 10,448 COVID-19 patients, ARBs and ACEIs were prescribed in 1,231 (11.7%) and 57 (0.6%) patients, respectively. After adjusting for age, sex, and history of comorbidities, the ARB group showed neutral association (HR, 1.034; 95% CI, 0.765 to 1.399; p = 0.8270) and the ACEI groups showed no significant associations likely owing to the small population size (HR, 0.736; 95% CI, 0.314 to 1.726; p = 0.4810). When comparing HR between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia in 2019, the trend of ACEIs showed similar benefits, whereas the protective effect of ARBs observed in the retrospective cohort was absent in COVID-19 patients. Meta-analyses showed significant positive correlation with survival of ACEIs, whereas a neutral association between ARBs and mortality.ConclusionsAlthough ARBs or ACEIs were not associated with fatal outcomes, potential beneficial effects of ARBs observed in pneumonia were attenuated in COVID-19.

Efficacy and Safety of Sacubitril/Valsartan Therapy for Acute Decompensated Heart Failure with Reduced Ejection Fraction during the Vulnerable Phase: A Multicenter, Assessor-Blinded, Prospective, Observational, Cohort Study

Background: The 3-month period after hospitalization for acute cardiac failure is a vulnerable phase with the highest risk of mortality and rehospitalization. Safety and efficacy of early initiation of sacubitril/valsartan during the index hospitalization for acute decompensated heart failure (ADHF) is unclear. Therefore, we tested whether sacubitril/valsartan could result in a lower rate of a composite outcome of first hospitalization for heart failure and death from cardiovascular causes compared to inhibition of the renin-angiotensin system alone. Methods: We enrolled patients hospitalized for ADHF and reduced ejection fraction at 4 sites; patients were divided into a sacubitril/valsartan group or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) group. All patients were followed up for 3 months after discharge. The primary endpoint was outcomes as a composite of death from cardiovascular causes and rehospitalization for heart failure. Results: In total, 251 patients who received sacubitril/valsartan and 251 patients who received ACEIs/ARBs had similar propensity scores and were included and compared. The primary endpoint was reached in 40 patients (15.9%) treated with sacubitril/valsartan and in 59 patients (23.5%) managed by ACEI/ARB (HR, 0.650; 95% CI: 0.435–0.971; p = 0.035). The NYHA class improved in 72.1% of patients in the sacubitril/valsartan group and in 59.8% of patients in the ACEI/ARB group (HR, 1.303; 95% CI: 1.097–1.548, p = 0.004). The key safety outcomes endpoints did not significantly differ. Conclusions: Among patients hospitalized with ADHF and reduced left ventricular ejection fraction, we observed that sacubitril/valsartan therapy led to reduction in death from cardiovascular causes and rehospitalizations for heart failure when compared to ACEI/ARB therapy alone during the vulnerable phase. Our results support that sacubitril/valsartan may be administered early in the vulnerable phase after ADHF and improves NYHA class.

Comparison of the Overtime Fasting Plasma Glucose Between Patients Receiving Angiotensin Receptor Blocker (ARB) and Non-ARB Drugs

Background: Previous studies have shown a relationship between renin angiotensin aldosterone system (RAAS) and insulin resistance. This in turn can delay the onset of diabetes mellitus (DM). The impact of angiotensin receptor blocker (ARB) on the fasting plasma glucose (FPG) level is not clear.&#x0D; Objective: To compare the overtime FPG between ARB and non-ARB using.&#x0D; Methods: A retrospective-longitudinal cohort study, data were collected from medical records of hypertensive patients who were not diagnosed DM in 2007 and 2008, each patient was followed up 10 years. The association between antihypertensive drugs and FPG by multilevel mixed-effects linear regression was evaluated. Multistate Markov chain model was used to evaluate the probability to become pre-DM or DM stage.&#x0D; Results: Of 822 patients, 571 patients were excluded and 251 patients met criteria for analysis. From multilevel mixed-effects linear regression, ARB usage was associated with a nonsignificant decreased FPG when adjusted with visit (mean FPG change, -0.98; 95% CI, -2.65 to 0.69; P = .25) and with visit plus glomerular filtration rate (mean FPG change, -1.89, 95% CI, -4.88 to 1.19; P = .24). The probability of change in 10 years from normal to pre-DM stage was 0.41 and 0.38, normal to DM stage was 0.03 and 0.01, pre-DM to DM stage was 0.08 and 0.04, in non-ARB and ARB group, respectively.&#x0D; Conclusions: ARB tended to decrease probability to become DM. Thus, physicians should prescribe ARB in hypertensive patients to prevent new-onset DM.&#x0D;

Association of Long-term Use of Antihypertensive Medications With Late Outcomes Among Patients With Aortic Dissection

The associations between long-term treatment of aortic dissection with various medications and late patient outcomes are poorly understood. To compare late outcomes after long-term use of β-blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or other antihypertensive medications (controls) among patients treated for aortic dissection. This population-based retrospective cohort study using the National Health Insurance Research Database in Taiwan included 6978 adult patients with a first-ever aortic dissection who survived to hospital discharge during the period between January 1, 2001, and December 31, 2013, and who received during the first 90 days after discharge a prescription for an ACEI, ARB, β-blocker, or at least 1 other antihypertensive medication. Data analysis was conducted from July 2019 to June 2020. Long-term use of β-blockers, ACEIs, or ARBs, with use of other antihypertensive medications as a control. The primary outcomes of interest were all-cause mortality, death due to aortic aneurism or dissection, later aortic operation, major adverse cardiac and cerebrovascular events, hospital readmission, and new-onset dialysis. Of 6978 total participants, 3492 received a β-blocker, 1729 received an ACEI or ARB, and 1757 received another antihypertension drug. Compared with patients in the other 2 groups, those in the β-blocker group were younger (mean [SD] age, 62.1 [13.9] years vs 68.7 [13.5] years for ACEIs or ARBs and 69.9 [13.8] years for controls) and comprised more male patients (2520 [72.2%] vs 1161 [67.1%] for ACEIs or ARBs and 1224 [69.7%] for controls). The prevalence of medicated hypertension was highest in the ACEI or ARB group (1039 patients [60.1%]), followed by the control group (896 patients [51.0%]), and was lowest in the β-blocker group (1577 patients [45.2%]). Patients who underwent surgery for type A aortic dissection were more likely to be prescribed β-blockers (1134 patients [32.5%]) than an ACEI or ARB (309 patients [17.9%]) or another antihypertension medication (376 patients [21.4%]). After adjusting for multiple propensity scores, there were no significant differences in any of the clinical characteristics among the 3 groups. No differences in the risks for all outcomes were observed between the ACEI or ARB and β-blocker groups. The risk of all-cause hospital readmission was significantly lower in the ACEI or ARB group (subdistribution hazard ratio [HR], 0.92; 95% CI, 0.84-0.997) and β-blocker group (subdistribution HR, 0.87; 95% CI, 0.81-0.94) than in the control group. Moreover, the risk of all-cause mortality was lower in the ACEI or ARB group (HR, 0.79; 95% CI, 0.71-0.89) and the β-blocker group (HR, 0.82; 95% CI, 0.73-0.91) than in the control group. In addition, the risk of all-cause mortality was lower in the ARB group than in the ACEI group (HR, 0.85; 95% CI, 0.76-0.95). The use of β-blockers, ACEIs, or ARBs was associated with benefits in the long-term treatment of aortic dissection.

Effect of medications after cardiac surgery on long-term outcomes in patients with cirrhosis.

The aim of this study was to evaluate the effect of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) after cardiac surgery in the liver cirrhosis (LC) patients. We conducted a population-based cohort study using data from the Taiwanese National Health Insurance Research Database (NHIRD) from 2001 to 2013. The outcomes of interest included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE) and liver and renal outcomes. Among 1470 LC patients, 35.6% (n = 524) received beta-blockers and 33.4% (n = 491) were prescribed ACEIs and/or ARBs after cardiac surgery. The risk of negative liver outcomes was significantly lower in the ARB group compared with the ACEI group (9.6% vs 22.7%, hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.31–0.83). Furthermore, the risk of MACCE (44.2% vs 54.7%, HR 0.79, 95% CI 0.65–0.96), all-cause mortality (35.3% vs 46.4%, HR 0.74, 95% CI 0.60–0.92), composite liver outcomes (9.6% vs 16.5%, HR 0.56, 95% CI 0.38–0.85) and hepatic encephalopathy (2.7% vs 5.7%, HR 0.45, 95% CI 0.21–0.94) were lower in the ARB group than the control group. Our study demonstrated that ARBs provide a greater protective effect than ACEIs in regard to long-term outcomes following cardiac surgery in patients with LC.

Evaluation of TReatment With Angiotensin Converting Enzyme Inhibitors and the Risk of Lung Cancer: ERACER-An Observational Cohort Study.

Angiotensin converting enzyme inhibitors (ACEIs) are widely prescribed medications. A recent British study reported a 14% increased risk of lung cancer with ACEI versus angiotensin receptor blocker (ARB) prescriptions, and risk increased with longer use. We sought to validate this observation. We searched the Intermountain Enterprise Data Warehouse from 1996 to 2018 for patients newly treated with an ACEI or an ARB and with ≥1 year's follow-up or to incident lung cancer or death. Unadjusted and adjusted hazard ratios (HRs) for lung cancer and for lung cancer or all-cause mortality were calculated for ACEIs compared to ARBs. A total of 187,060 patients met entry criteria (age 60.2 ± 15.1 y; 51% women). During a mean of 7.1 years follow-up (max: 20.0 years), 3,039 lung cancers and 43,505 deaths occurred. Absolute lung cancer rates were 2.16 and 2.31 per 1000 patient-years in the ARB and ACEI groups, respectively. The HR of lung cancer was modestly increased with ACEIs (unadjusted HR = 1.11, CI: 1.02, 1.22, P = .014; adjusted HR = 1.18, CI: 1.06, 1.31, P = .002; number needed to harm [NNH] 6,667). Rates of the composite of lung cancer or death over time also favored ARBs. Lung cancer event curves separated gradually over longitudinal follow-up beginning at 10-12 years. We noted a small long-term increase in lung cancer risk with ACEIs compared with ARBs. Separation of survival curves was delayed until 10-12 years after treatment initiation. Although the observed increases in lung cancer risk are small, implications are potentially important because of the broad use of ACEIs. Thus, additional work to validate these findings is needed.

Clinical outcomes between calcium channel blockers and angiotensin receptor blockers in hypertensive patients without established cardiovascular diseases during a 3-year follow-up

Although both angiotensin receptor blockers (ARBs) and dihydropyridine calcium channel blockers (CCBs) are all suitable for the initiation of antihypertensive treatment, studies investigating efficacy and safety between ARBs and CCBs are limited, and there is no previous study comparing their clinical outcomes during long-term follow-up periods in real world setting. We compared cardiovascular (CV) events between ARBs and CCBs in 464,948 hypertensive adults using the Korean National Health Insurance Service database during a 3-year follow-up. The patients with hypertension without heart failure, ischemic heart disease, cerebrovascular disease, or peripheral artery disease were enrolled. The CV events between only single prescription of CCBs and ARBs were finally compared. The primary endpoint for this study was the first occurrence of a major adverse CV events, defined as the composite of all-cause death, cardiac death, nonfatal myocardial infarction, or nonfatal stroke. ARB was significantly more administered in male and patients with higher income, diabetes mellitus, chronic kidney diseases, and higher Charlson comorbidity index. The primary endpoints occurred in 10,526 patients (5.2%) in the ARB group and in 19,363 patients (7.3%) in the CCB group (p < 0.001) during a 3-year follow-up (HR 0.96, 95% CI 0.93–0.98). All the components of CV events including all-cause death, cardiac death, nonfatal myocardial infarction, and nonfatal stroke occurred more frequently in the CCB group. With multivariable models adjusting age, sex, income, diabetes, chronic kidney disease, and Charlson comorbidity index, the primary endpoints less frequently developed in the ARB group than in the CCB group (HR 0.957, 95% CI 0.933–0.983, p < 0.001). After the propensity-score matching, baseline characteristics were similar and still showed significantly better primary endpoints in ARB group than CCB group (5.3% vs. 5.8%, p < 0.001). In this nationwide population-based simple hypertension study, administration of ARBs showed superior protection against CV events than CCBs during a 3-year follow-up. Our results suggest that ARBs could be preferred over CCBs as the initial choice of antihypertensive treatment regardless of age in real-world practice.

Effect of Shenkang on renal fibrosis and activation of renal interstitial fibroblasts through the JAK2/STAT3 pathway

BackgroundActivation of renal fibroblasts is a critical mechanism in the process of renal fibrosis. As a commonly used herbal formula, Shenkang (SK) has been found to attenuate renal fibrosis and renal parenchyma destruction. However, the effect of SK on renal fibroblast activation in unilateral ureteral obstruction (UUO) mice and its molecular mechanism remain undetermined. The present study was performed to elucidate the effect of SK on renal fibroblast activation and renal fibrosis, as well as the potential underlying mechanism, in both NRK-49F cells and UUO mice.MethodsNRK-49F cells were stimulated with 10 ng/ml TGF-β1 for 48 h. After SK treatment, the CCK-8 method was used to evaluate cell viability. Thirty-six C57BL/6 mice were randomly divided into the sham group, UUO group, angiotensin receptor blocker (ARB) group, and SK high-, moderate- and low-dose groups. UUO was induced in mice except those in the sham group. Drugs were administered 1 day later. On the 13th day, the fractional anisotropy (FA) value was determined by MRI to evaluate the degree of renal fibrosis. After 14 days, serum indexes were assessed. Hematoxylin and eosin (HE) and Sirius red staining were used to observe pathological morphology and the degree of fibrosis of the affected kidney. Western blotting and PCR were used to assess the expression of related molecules in both cells and animals at the protein and gene levels.ResultsOur results showed that SK reduced extracellular matrix (ECM) and α-smooth muscle actin (α-SMA) expression both in vitro and in vivo and attenuated renal fibrosis and the pathological lesion degree after UUO, suppressing JAK2/STAT3 activation. Furthermore, we found that SK regulated the JAK2/STAT3 pathway regulators peroxiredoxin 5 (Prdx5) in vitro and suppressor of cytokine signaling protein 1 (SOCS1) and SOCS3 in vivo.ConclusionsThese results indicated that SK inhibited fibroblast activation by regulating the JAK2/STAT3 pathway, which may be a mechanism underlying its protective action in renal fibrosis.

Retrospective analysis of Tripterygium wilfordii polyglycoside combined with angiotensin receptor blockers for the treatment of primary membranous nephropathy with sub-nephrotic proteinuria

Introduction Primary membranous nephropathy (PMN) is one common cause of end-stage kidney disease. There is no optimal treatment for PMN patients with sub-nephrotic proteinuria currently. Tripterygium wilfordii polyglycoside (TWG) is a widely used traditional medicine in China and has been used to treat nephropathy for decades. Objective To investigate the effect of TWG combined with angiotensin receptor blocker (ARB) on the treatment of PMN with sub-nephrotic proteinuria. Methods Biopsy-proven sub-nephrotic PMN patients with normal kidney function and treated with TWG combined with ARB or ARB alone were retrospectively analyzed. The primary outcome was remission rate (complete or partial remission), and the secondary outcomes included proteinuria, serum albumin levels, estimated glomerular filtration rate (eGFR), relapse rate, and adverse events. Results The clinical trial included 55 patients. The overall remission rates for the TWG + ARB and ARB groups after 9 months of treatment were 74.3% and 35%, respectively (p = 0.004). Moreover, the complete remission (CR) rate for the TWG + ARB and ARB groups in the 9th month were 45.7% and 15%, respectively (p = 0.044). Treatment with TWG + ARB was the independent predictor of complete remission of proteinuria (p = 0.048). Besides, the remission rate was higher in the TWG + ARB group than in the ARB group among patients who were positive for anti-phospholipase A2 receptor (PLA2R) antibodies (65.4% vs. 21.4%, p = 0.02). Conclusions These data demonstrate that TWG may be a promising treatment for PMN patients with sub-nephrotic proteinuria, whether anti-PLA2R antibody is positive or negative.

Alpha Blocker – A Better Antihypertensive Option for Postendarterectomy Hypertension

Introduction: The immediate postoperative hemodynamic alterations occurring after carotid endarterectomy (CEA) is called postendarterectomy hypertension (PEH). PEH results in prolonged hospital admission, increased peri-operative morbidity, and mortality. The exact causes of the PEH whether it is due to carotid sinus denervation or due to the increased norepinephrine production in cerebral and peripheral circulation remain unclear. Materials and Methods: A prospective analysis of 62 patients who underwent CEA from 2018 to 2019 were carried out by dividing into two groups based on the technique of surgery (conventional CEA [c-CEA], n = 31; eversion CEA [e-CEA], n = 31), and the effect of four class of drugs mainly beta blockers (βBs), calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs), and alpha blockers (αBs) were studied for the prevention of PEH. Results: 72.6% of patients developed PEH irrespective of the technique of surgery (e-CEA n = 25 c-CEA n = 20;P= 0.15). The mean postoperative dose of antihypertensive drugs (Mpostoperative) were found significantly increased compared to mean preoperative dose (Mpreoperative) in all PEH patients among βB? group (Mpreoperative 18.95 mg vs. Mpostoperative 45.76 mg;P= 0.00); CCB group (preoperative Mpreoperative 6.21 mg vs. Mpostoperative 9.79 mg;P= 0.01); ARB group (Mpreoperative 14.03 mg vs. Mpostoperative 38.23 mg;P= 0.01); but those patients with preoperative αBs have well controlled BP in the postoperative period without significant change in mean dosage; αB (Mpreoperative 0.16 mg vs. Mpostoperative 3.74 mg:P= 0.27). Conclusions: This study indirectly showed that fluctuations of sympathetic system are happening in both e- and c-CEA irrespective of the technique of surgery. These fluctuations were better controlled in patients who had adequate sympathetic blockade preoperatively. In other words, αB can be considered a drug of choice for PEH.