ARB Group Research Articles

O54 THE EFFECT OF SACUBITRIL/VALSARTAN TREATMENT ON HYPERTENSIVE PATIENTS

Background and Objective: Sacubitril/Valsartan was approved in Japan in 2020 for the treatment of heart failure and subsequently for the treatment of hypertension. It is a drug with a novel mechanism of action that inhibits both angiotensin receptors and neprilysin. Besides its cardioprotective and antihypertensive effects, a subanalysis of previous clinical trials in heart failure patients has shown that it tends to slow the rate of decline in renal function, and is expected to have therapeutic effects against CKD. However, its effect on renal function in hypertensive patients is unknown. In this study, we examined renal prognosis in patients with essential hypertension. Methods: 166 consecutive patients who received an initial dose of ARNI(Sacubitril/Valsartan) (N=104) or ARB (Azilsartan) (N=42) and had blood tests performed before and within 3 months after the first dose at Osaka University Hospital from June 2020 to April 2023 were analyzed retrospectively. Results: ARNI tended to be administered to elderly patients and patients with impaired renal function in both male and female patients. eGFR did not decrease in the ARNI group at either 3 or 12 months post-dose. eGFR decreased over time in the ARB group at 3 and 12 months post-dose. 5 patients on ARNI had drug discontinuations that were thought to be due to adverse drug events (hypotension in 2, numbness in 1, dizziness in 1, syncope in 1 patient). Conclusions: In this study, ARNI tended to be administered in more elderly hypertensive patients. Although there were a few treatment interruptions due to adverse drug events, the adverse effects on renal function were rather minor compared to ARBs, and under careful management, ARNI may be a useful antihypertensive treatment modality even in elderly patients and patients with impaired renal function.

Comparison Of Transient ACE Inhibitor Vs. Angiotensin Receptor Blocker Treatment On Angiotensin II-Induced Oxidative Stress In The Heart Of Spontaneously Hypertensive Rats

Angiotensin II (Ang II) is a primary mediator of the renin angiotensin system (RAS) with strong profibrotic effects, mediated in part through increased levels of reactive oxygen species (ROS). We have previously shown that transient treatment with an Ang II converting enzyme inhibitor (ACEi) produces long-term protection against Ang II-induced fibrosis. Our goal was to compare the impact of prior transient AT1 receptor antagonist (ARB) vs. ACEi treatment on the oxidative stress response and fibrotic signaling profile in the left ventricle (LV) in response to Ang II. Male and female spontaneously hypertensive rats were initially treated with vehicle, ARB (losartan, 30mg/kg per day) or ACEi (enalapril, 30mg/kg per day) for two weeks. To assess long term protection of ARB and ACEi treatment, after two-weeks of washout, the rats then received Ang II (400ng/kg/day) for 2 additional weeks. Protein levels of pro-oxidant (NOX-2) and antioxidant (SOD1, SOD2) enzymes, fibrosis marker (LOX) in the left ventricle (LV) were measured by western blotting. Cardiac hypertrophy was evaluated by the LV mass/tibia Length (LV/TL) ratio. Data were analyzed by 2-way ANOVA. After a transient ARB treatment, Ang II promoted an increase in LV/TL in both male (+7%) and female (+9%) rats when compared to vehicle+Ang II (treatment effect, p<0.009). Ang II had no effect on LV/TL in rats previously treated with ACEi or vehicle. In response to Ang II, male and female rats that were previously treated with ACEi showed a decrease in LOX expression (treatment effect, p=0.02) in both male (-21%) and female (-22%) rats. No changes were observed in LOX in response to Ang II after ARB treatment. In rats transiently treated with ARB or ACEi, the expression of NOX2 was reduced after Ang II infusion. In the ARB group the NOX2 was reduced 25% in male and 28% in female (treatment effect, P=0.003). Similarly, in the ACEi group, NOX2 was reduced 27% in male and 26% in female rats (treatment effect, p<0.0001). Prior ACEi and ARB produced sex-selective changes in SOD1 expression following Ang II infusion. Specifically, following transient ARB treatment, Ang II increased SOD1 in females (24%), but not males (sex x ARB treatment interaction: p=0.0033). Similarly, prior treatment with ACEi produced sex-dependent effects, whereby AngII increased SOD1 in females (10%) and decreased expression in males (-8%, ACEi x sex interaction: p=0.043). Neither ARB, ACEi nor Ang II affected the expression of SOD2 Our data indicate a sex and treatment-specific response to Ang II following transient ARB or ACEi treatment. Both ARB and ACEi showed a long-term beneficial effect on oxidative stress. However, ARB appeared to sensitize males and females to a hypertrophy response to AngII. Future studies will evaluate this differential response observed in cardiac hypertrophy and the mechanisms leading to cardiac fibrosis. NHBL R01HL153112. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Beneficial Effects of Angiotensin II Receptor Blockers on Mortality in Patients with COVID-19: A Retrospective Study from 2019 to 2020 in China.

The COVID-19 pandemic has become a serious global public health problem. Although the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 blockers (ARBs) has been recommended in patients with COVID-19 and cardiovascular diseases (CVDs), according to the results of some small-sample retrospective analyses, there remains a lack of sufficient evidence to validate their efficacy. This multicenter retrospective study investigated whether ACEI/ARB administration was beneficial in patients with COVID-19 and CVDs. A total of 11,231 patients with confirmed COVID-19 and CVDs, from 138 hospitals in Hubei Province, were included in this multicenter retrospective study. We compared the clinical characteristics and outcomes between the ARB and non-ARB groups and analyzed the risk factors for in-hospital death using univariate and multivariate Cox regression analyses and Kaplan-Meier curves. In the multivariate Cox regression model, after adjusting for age, gender, comorbidities, and in-hospital medications, ARB use was associated with lower all-cause mortality (adjusted HR, 0.53; 95% CI, 0.38-0.73; P < 0.001). After propensity score-matched analysis, the adjusted HR for the use of ARB associated with all-cause mortality was 0.62 (95% CI, 0.40-0.88; P = 0.02). Further subgroup analyses found that the adjusted HRs for the use of ARB associated with all-cause mortality were 0.52 (95% CI, 0.30-0.89; P = 0.016), 0.37 (95% CI, 0.21-0.64; P < 0.001), 0.42 (95% CI, 0.28-0.64; P < 0.001), and 0.55 (95% CI, 0.37-0.84; P = 0.005) in patients with heart failure, diabetes, and hypercholesterolemia, and severe COVID-19, respectively. ARB administration was significantly associated with a lower risk of all-cause mortality in patients with COVID-19 and CVDs. ClinicalTrials.gov NCT05615792. https://www. gov/ct2/show/NCT05615792.

Effects of olmesartan and amlodipine on blood pressure, endothelial function, and vascular inflammation

BackgroundAnti-hypertensive drugs can improve vascular endothelial function. However, the mechanism remains to be elucidated. ObjectivesThis study sought to investigate mechanisms of anti-hypertensive drugs on improvement of vascular endothelial function in patients with essential hypertension. MethodsForty-five patients (mean age 58.5 ± 11.2 years) with uncontrolled essential hypertension were randomly assigned to receive olmesartan, an angiotensin II type 1 receptor blocker (ARB) (N = 23), or amlodipine, a calcium channel blocker (CCB) (N = 22), for 6 months. Endothelial function was evaluated by flow-mediated dilatation (FMD) of the brachial artery. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR) within the carotid arteries using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography. ResultsThere were no significant differences of baseline clinical data between the ARB and CCB groups. Both anti-hypertensive drugs comparably lowered blood pressure and increased %FMD. TBR values were reduced by olmesartan (P < .001), while blood pressure variability was decreased by amlodipine (P = .004). Changes in %FMD from baseline (Δ%FMD) were inversely associated with ΔTBR in the olmesartan group (r = − .606, P = .003) and with Δsystolic blood pressure variability in the amlodipine group (r = − .434, P = .039). ConclusionOur study indicated that olmesartan and amlodipine could improve endothelial function in patients with essential hypertension in different manners, suppression of vascular inflammation, and decrease in blood pressure variability, respectively.

1322-P: Association of Long-Term Blood Pressure Variability and Decrease in GFR on Type 2 Diabetes Mellitus Patients with Hypertension

Introduction: Increased long-term blood pressure variability (BPV), defined as monthly to yearly BPV, has been reported a risk factor of cardiovascular events independent of mean BP level. However, the relationship between long-term BPV and decrease in GFR remains unknown. In this study, we examined the association of Long-Term BPV and decrease in GFR. Methods: We included 214,443 type 2 diabetes mellitus patients with hypertension, registered in the Japan Diabetes Data Management Study Group, whose BP and HbA1c were simultaneously measured at least 4 times per year for 5 years from 2014-2018. BPV was defined as the 5-year coefficient of variation (CV), and the relationship between BPV and eGFR was examined. We also examined the relationship between BPV and the following background factors: (1) age (2) duration of diabetes (3) HbA1c (4) antihypertensive medications. The Ca-antagonist group was patients who took only Ca-antagonists during the 5-year period, and the ARB group was patients who took only ARBs. This study was a retrospective analysis. Data analyses were performed using the SPSS 28.0 software. Results: The group with greater 5-year BPV had lower eGFR than the group with smaller BPV, independent of mean BP (P&amp;lt;0.001). Regarding BPV and patient background, (1) BPV tended to increase with increasing age, and was significantly greater in patients over 50 years of age compared to those in their 30s (P&amp;lt;0.001). (2) The longer diabetic duration, the greater the BPV (P&amp;lt;0.001). Especially in patients more than 20 years’ diabetic duration, BPV was significantly larger than that of less than 5 years (P&amp;lt;0.001). (3) There was no association between HbA1c and BPV. (4) BPV was significantly lower in the Ca antagonist group compared with the ARB group over 5 years (0.069 vs. 0.078 P&amp;lt;0.001). Conclusion: Increased long-term BPV was observed older age and long duration of diabetes, but was not related to HbA1c. Interestingly, Patients with greater BPV had lower eGFR at 5 years. Disclosure M.Sakamoto: None. M.Yuki: None. K.Miyashita: None. T.Yamazaki: None.

Association between renin-angiotensin-aldosterone system blockade and clinical outcomes in patients with hypertension: real-world observation from a nationwide hypertension cohort.

We investigated the association between the use of ACEi, ARB, or non-renin-angiotensin-aldosterone system inhibitors (non-RASi) and incident cardiovascular events in an unselected nationwide hypertension cohort. Theinformation regarding 2,025,849 patients who underwent general health checkup between 2010 and 2011 and were on antihypertensive medication was collected. Patients were allocated into ACEi, ARB, and non-RASi groups and followed until 2019. The outcomes of interest were myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), heart failure (HF), and all-cause deaths. Patients on ACEi and ARB showed unfavorable baseline characteristics compared to those on non-RASi. After adjusting for covariates, the ACEi group showed lower risks of MI, AF, and all-cause deaths (HR (95% CI): 0.94 (0.89-0.99), 0.96 (0.92-1.00), and 0.93 (0.90-0.96), respectively), but similar risks of IS and HF (0.97 (0.92-1.01) and 1.03 (1.00-1.06), respectively), compared to the non-RASi group. Likewise, the ARB group showed decreased risks of MI, IS, AF, HF, and all-cause deaths (HR (95% CI): 0.93 (0.91-0.95), 0.88 (0.86-0.90), 0.86 (0.85-0.88), 0.94 (0.93-0.96), and 0.84 (0.83-0.85)), compared to the non-RASi group. Sensitivity analysis of patients taking a single antihypertensive medication showed similar results. In the propensity score matching (PSM) cohort, the ARB group showed similar risks of MI and decreased risks of IS, AF, HF, and all-cause deaths compared to the ACEi group. ACEi and ARB users were associated with decreased risks of MI, IS, AF, HF, and all-cause deaths, compared to non-RASi users.

The impact of angiotensin-converting-enzyme inhibitors versus angiotensin receptor blockers on 3-year clinical outcomes in elderly (≥ 65) patients with acute myocardial infarction without hypertension.

This study aimed to investigate the impact of angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) on 3-year clinical outcomes in elderly (≥ 65) acute myocardial infarction (AMI) patients without a history of hypertension who underwent successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES). A total of 13,104 AMI patients who were registered in the Korea AMI registry (KAMIR)-National Institutes of Health (NIH) were included in the study. The primary endpoint was 3-year major adverse cardiac events (MACE), which was defined as the composite of all-cause death, recurrent myocardial infarction (MI), and any repeat revascularization. To adjust baseline potential confounders, an inverse probability weighting (IPTW) analysis was performed. The patients were divided into two groups: the ACEI group, n = 872 patients and the ARB group, n = 508 patients. After IPTW matching, baseline characteristics were balanced. During the 3-year clinical follow-up, the incidence of MACE was not different between the two groups. However, incidence of stroke (hazard ratio [HR], 0.375; 95% confidence interval [CI], 0.166-0.846; p = 0.018) and re-hospitalization due to heart failure (HF) (HR, 0.528; 95% CI, 0.289-0.965; p = 0.038) in the ACEI group were significantly lower than in the ARB group. In elderly AMI patients who underwent PCI with DES without a history of hypertension, the use of ACEI was significantly associated with reduced incidences of stroke, and re-hospitalization due to HF than those with the use of ARB.

Survival outcomes of autologous breast reconstruction after mastectomy: A matched case-control study.

Due to the lack of strong evidence-based medical evidence, the relationship between autologous breast reconstruction (ABR) after mastectomy and long-term prognosis is unclear. This study aims to explore if ABR after mastectomy is associated with the prognosis of breast cancer (BC) patients based on the data from the Surveillance, Epidemiology, and End Results (SEER) database. We collected data for all cases diagnosed with BC who underwent or did not undergo ABR after mastectomy from 2010-2015 in the SEER database. The primary outcome of our study was overall survival (OS) and cancer specific survival (CSS). The Propensity Score-Matched (PSM) analysis was used to eliminate the effects of non-random statistics, setting the caliper as 0.0001 to balance the baseline variables within the groups. Chi-square test, Kaplan-Meier method, univariate and multivariate cox regression analysis were used to analyze the data and subgroup analysis was performed to find the subgroups of people who might benefit from ABR. Of 27893 eligible patients, 11038 patients were matched. The cohort consisted of 5519 (50%) ABR patients and 5519 (50%) non-ABR patients after PSM. After PSM, on multivariate cox regression analysis, ABR still exerted a significant influence on the OS (hazard ratio (HR), 0.83, P< 0.05). However, no statistical difference was shown on CSS (HR, 0.93, P = 0.31). Kaplan-Meier survival analysis showed ABR group had better OS (P = 0.001), but similar CSS (P= 0.174) between ARB and mastectomy groups. Subgroup analysis showed that after matching, those with 50-59 years old, earlier stages of disease, without a marital partner and living in urban areas had better OS after ABR. ABR after mastectomy was associated with better OS, but not affect CSS.

Effect of angiotensin receptor-neprilysin inhibitor on atrial electrical instability in atrial fibrillation.

Around 33.5 million patients suffered from atrial fibrillation (AF), causing complications and increasing mortality and disability rate. Upstream treatment for AF is getting more popular in clinical practice in recent years. The angiotensin receptor-neprilysin inhibitor (ARNI) is one of the potential treatment options. Our study aimed to investigate the effect of ARNI on atrial electrical instability and structural remodeling in AF. Our research consisted of two parts - a retrospective real-world clinical study and an animal experiment on calmness to verify the retrospective founding. In the retrospective study, we reviewed all patients (n = 110) who had undergone the first AF ablation from 1 August 2018 to 1 March 2022. Patients with ARNI (n = 36) or angiotensin II receptor antagonist (ARB) (n = 35) treatment were enrolled. Their clinical data, ultrasound cardiogram (UCG) and Holter parameters were collected before radiofrequency catheter ablation (RFCA) as baseline and at 24-week follow-up. Univariate and multivariate logistic regression analysis were performed. In the animal experiment, we established an AF model (n = 18) on canines by rapid atrial pacing. After the successful procedure of pacing, all the 15 alive beagles were equally and randomly assigned to three groups (n = 5 each): Control group, ARB group, and ARNI group. UCG was performed before the pacing as baseline. Physiological biopsy, UCG, and electrophysiological study (EPS) were performed at 8-week. Clinical data showed that the atrial arrhythmia rate at 24-week was significantly lower in ARNI group compared to ARB group (P < 0.01), and ARNI was independently associated with a lower atrial arrhythmia rate (P < 0.05) at 24-week in multivariate regression logistic analysis. In the animal experiment, ARNI group had a higher atrial electrical stability score and a shorter AF duration in the EPS compared to Control and ARB group (P < 0.05). In the left atrium voltage mapping, ARNI group showed less low voltage and disordered zone compared to Control and ARB group. Compared to Control group, right atrium diameter (RAD), left ventricle end-diastolic volume index (LVEDVI), E/A, and E/E' were lower in ARNI group (P < 0.05) at the 8-weeks follow-up, while left atrium ejection fraction (LAEF) and left ventricle ejection fraction (LVEF) were higher (P < 0.01). Compared to ARB group, LVEF was higher in ARNI group at the 8-week follow-up (P < 0.05). ARB and ARNI group had a lower ratio of fibrotic lesions in the left atrium tissues compared to Control group (P < 0.01), but no difference was found between the ARB and the ARNI group. ARNI could reduce atrial electrical instability in AF in comparison with ARB in both retrospective study and animal experiment.

Abstract 13037: RAS Inhibition is Associated With Higher Risk of 60-Day COVID-19-Induced Myocarditis

Background: COVID-19 related myocarditis (MC) can manifest with no symptoms, chest pain, life-threatening arrhythmia with hemodynamic instability, or new heart failure. Evidence suggests that RAS inhibition may be beneficial for some patients during COVID-19 infection; however, the effect of these drugs on risk of developing COVID-19-induced MC is not well characterized. Methods: Using ICD-10 codes, a cohort of patients admitted between March-October 2020 with the primary diagnosis of COVID-19 was identified from the PearlDiver database (PearlDiver Technologies, Fort Wayne, IN). Use of RAS inhibitors over the past 6 months was used to split the cohort into two case-control matched groups based on age, gender, and Elixhauser Comorbidity Index. Using the same matching criteria, the RAS group was divided into ACEi and ARB groups. Records of all groups were reviewed to determine the incidence of MC, 60 days after admission. We used Pearson's chi-squared test to compare the MC frequencies. Kaplan-Meier plot and log-rank test were used to compare time-to-event between groups. The strength of association was reported as Risk Ratios (RR) and 95% CI. A p-value &lt;0.05 was deemed significant. Results: Patients using RAS inhibitors had a higher risk of 60-day MC than those who did not (RR = 3.71, 95% CI = 1.61-8.58, p = 0.0017). The p-value of the log-rank test for the 60-day Kaplan-Meier analysis was 0.0006. There was no significant risk difference between ACEi and ARB groups (RR = 0.4, 95% CI = 0.12-1.27, p = 0.18). (Figure 1) Discussion: Our study showed a significant increased risk of 60-day MC in COVID-19 patients taking RAS inhibitors, with no difference between ACEi and ARBs. A plausible explanation is that the RAS inhibition leads to cardiomyocyte's ACE2 overexpression, thereby permitting SARS-CoV-2's cellular entry. This interpretation is limited due to the inherent bias associated with retrospective research and the paucity of additional evidence.

The impact of Sacubitril/Valsartan on cardiac fibrosis early after myocardial infarction in hypertensive rats.

Sacubitril/Valsartan, a dual inhibitor of the neprilysin and angiotensin receptor, exerts cardioprotective effects in heart failure. Little is known on the impact of Sacubitril/Valsartan in hypertensive patients early post myocardial infarction. Spontaneously hypertensive rats (SHR) were pretreated by daily angiotensin receptor blocker (ARB; 30 mg/kg intraperitoneally), Sacubitril/Valsartan (ARNI; 60 mg/kg intraperitoneally) or the same dosage of physiological saline for 1 week. Then each group underwent myocardial infarction induction and received the same treatment for another week. The blood pressure and cardiac function were evaluated prior to sacrifice. We performed histological and molecular evaluation of fibrosis in vivo and in vitro. The blood pressure was comparable between three groups both 1 week prior to and post myocardial infarction. ARNI and ARB restore the decreased ejection fraction (57.3 ± 7.6 vs. 42.9 ± 5.2%, P < 0.05; 54.3 ± 6.9 vs. 42.9 ± 5.2%, P < 0.01, respectively) and fractional shortening (31.6 ± 5.4 vs. 22.1 ± 3.1%, P < 0.05; 29.4 ± 4.5 vs. 22.1 ± 3.1%, P < 0.05, respectively) post myocardial infarction. The infarct size and collagen deposition were also significantly mitigated in ARNI and ARB groups. In addition, ARNI and ARB treatment reduced the expression of cardiac remodeling-related factors, such as Bnp, α-SMA, Vimentin, and Col1a1 (all P < 0.05 vs. MI group). Finally, ARNI and ARB decreased the expression of α-SMA in cardiac fibroblasts treated with Ang II. In conclusion, pretreatment with ARNI maintained cardiac function and reduced myocardial fibrosis in myocardial infarction, probably prior to any anti-hypertensive effect.

Different cardiovascular responses to exercise training in hypertensive women receiving β-blockers or angiotensin receptor blockers: A pilot study

ABSTRACT Aim To verify the influence of β-blockers or angiotensin receptor blockers on cardiovascular responses to exercise training in hypertensive post-menopausal women. Methods Postmenopausal women were allocated into: healthy control group (CON; n = 9); angiotensin receptor blockers users (ARB; n = 19); and β-adrenergic blockers users (BB; n = 19). Before and after 12 weeks of combined (aerobic and resistance) exercise training they were evaluated by: heart rate (HR) and its variability (HRV), blood pressure (BP) under stress (Cold pressor and Stroop color tests), and ambulatorial BP and its variability. Results In ambulatorial BP analysis only in ARB group awake systolic BP decreased (p = .011; ARB: From 122 ± 11 to 117 ± 9; BB: From 118 ± 7 to 114 ± 5; CON: From 121 ± 7 to 127 ± 11 mmHg). There were time effects in BP reactivity to stress, where BP reactivity after Stroop color and Cold pressor test decreased in all groups. In BP variability analysis, only BB group has significative decreased values in systolic SD24 (p = .007; ΔARB = −0.3 ± 2.0; ΔBB = −1.3 ± 2.0; ΔCON = 0.8 ± 1.7 mmHg) and SDdn (p = .006; ΔARB = −0.2 ± 1.6; ΔBB = −1.3 ± 2.0; ΔCON = 0.4 ± 2.1 mmHg). HRV analysis demonstrated that post-training, only in BB group LF/HF decreased (p = .001; ΔARB = 0.1 ± 0.8; ΔBB = −0.4 ± 1.5; ΔCON = 1.0 ± 1.7). Conclusion ARB present pronounced responses in awake ambulatorial systolic BP, while β-blockers users present greater responses in BP variability. Besides that, exercise can mitigate BP reactivity to stress with no differences between groups. Lastly, there were no major differences in HRV. Trial registry at “Clinicaltrials.gov” NCT03529838

Assessment of optimal renin-angiotensin-system inhibition strategy in Asian patients with STEMI after primary myocardial revascularization.

For the Asian patients with STEMI undergoing PCI, ACEIs are known to have a better outcome than ARBs. However, there is limited evidence to suggest so. Among the STEMI registry consist of 1142 Korean patients, we compared the MACE, the composite of myocardial infarction, stoke, death, admission for heart failure, and target vessel revascularization, between the ACEI and ARB groups (Set 1). Further, we defined adequate medication as the administration of a dose equal to or higher than the initiation dose of ACEI according to the heart failure guideline recommendation with a mandatory addition of beta-blockers, and compared the outcomes between the inadequate and adequate medication groups (Set 2). Propensity score matching was used to eliminate difference. In the Set 1 comparison, patients in the ACEI group had a better outcome than those in the ARB group for both whole and matched populations (whole and matched population: Cox regression hazard ratio [HR], 0.645 and 0.535; 95% confidence interval [CI], 0.440-0.944 and 0.296-0.967; p = 0.024 and p = 0.039, respectively). In the Set 2 comparison for the whole population, patients in the inadequate medication group had more MACE than those in the adequate medication group (HR, 0.673; 95% CI, 0.459-0.985; p = 0.042). However, no difference was observed after propensity score matching (HR, 1.023; 95% CI, 0.654-1.602; p = 0.919). ACEIs might be a better choice than ARBs after primary revascularization. However, this study's findings suggest that early ACEI dose escalation combined with beta-blocker use may not improve prognosis.

Differential Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on COVID-19

ABSTRACTBackground:The effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) on the coronavirus disease 2019 (COVID-19) remains controversial from clinic evidence.Objectives:The objectives of this study were to report the major characteristics and clinical outcomes of COVID-19 patients treated with ACEIs and ARBs and compare the different effects of the two drugs for outcomes of COVID-19 patients.Methods:This is a retrospective, two-center case series of 198 consecutive COVID-19 patients with a history of hypertension.Results:Among 198 patients, 58 (29.3%) and 16 (8.1%) were on ARB and ACEI, respectively. Patients who were on ARB or ACEI/ARB had a significantly lower rate of severe illness and acute respiratory distress syndrome (ARDS) when compared with patients treated with ACEI alone or not receiving RAAS blocker (P < 0.05). The Kaplan–Meier survival curve showed that patients with ARB in their antihypertensive regimen had a trend toward a higher survival rate when compared with individuals without ARB (adjusted hazard ratio, 0.27; 95% confidence interval [CI], 0.07–1.02; P = 0.054). The occurrence rates of severe illness, ARDS, and death were similar in the two groups regardless of receiving ACEI. The Cox regression analyses showed a better survival in the ARB group than the ACEI group (adjusted hazard ratio, 0.03; 95% CI, 0.00–0.58; P = 0.02).Conclusions:Our data may provide that some evidence of using ARB, but not ACEI, was associated with a reduced rate of severe illness and ARDS, indicating their potential protective impact in COVID-19. Further large sample sizes and multiethnic populations are warranted to confirm our findings.

ARNI versus ACEI/ARB in Reducing Cardiovascular Outcomes after Myocardial Infarction.

AimsThis study aimed to compare the efficacy of angiotensin receptor‐neprilysin inhibitor (ARNI) therapy with angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) therapy for cardiovascular outcomes in patients with acute myocardial infarction (AMI).Methods and resultsData were collected from the Biobank of the First Affiliated Hospital of Xi'an Jiaotong University between January 2016 and December 2020. A total of 7556 AMI patients were screened for eligibility. Propensity score matching based on age, sex, blood pressure, kidney function, baseline left ventricular ejection fraction (LVEF), and cardiovascular medication were conducted, resulting in 291 patients with AMI being assigned to ARNI, ACEI, and ARB group, respectively. Patients receiving ARNI had significantly lower rates of the composite cardiovascular outcome than ACEI {hazard ratio [HR] 0.51, [95% confidence interval (CI), 0.27–0.95], P = 0.02}, and ARB users [HR 0.47, (95%CI, 0.24–0.90), P = 0.02]. Patients receiving ARNI showed lower rates of cardiovascular death than ACEI [HR 0.37, (95%CI, 0.18–0.79), P = 0.01] and ARB users [HR 0.41, (95%CI, 0.18–0.95), P = 0.04]. Subgroup analysis indicated that patients with LVEF no more than 40% tend to benefit more from ARNI as compared with ACEI [HR 0.30, (95%CI, 0.11–0.86), P = 0.01] or ARB [HR 0.21, (95%CI, 0.04–1.1), P = 0.05]. Patients aged no more than 60 years exhibited reduced composite endpoints [HR for ARNI vs. ARB: 0.11, (95%CI, 0.03–0.46), P = 0.002].ConclusionsIn patients with AMI, ARNI was superior to ACEI/ARB in reducing the long‐term adverse cardiovascular outcomes. Subgroup analysis further indicates that ARNI is more likely to benefit patients with LVEF less than 40% and aged less than 60 years.

Comparative effect of angiotensin converting enzyme inhibitor versus angiotensin ii type i receptor blocker in acute myocardial infarction with non-obstructive coronary arteries; from the Korea Acute Myocardial Infarction Registry - National Institute of Health.

Selecting angiotensin converting enzyme inhibitor (ACEI) or angiotensin II type I receptor blocker (ARB) in patients diagnosed as acute myocardial infarction (AMI) with non-obstructive coronary arteries (MINOCA) is not established. The purpose of this study is to compare the clinical effect of ACEI vs. ARB in MINOCA patients. A total of 273 patients between November 2011 to June 2015, diagnosed with MINOCA who were registered in the Korea Acute Myocardial Infarction Registry - National Institute of Health were enrolled. Patients were divided into ACEI (n = 112) and ARB groups (n = 161). The primary endpoint was cumulative incidence of major adverse cardiac events (MACE) defined as cardiac death, recurrent MI, any new revascularization during 2 years clinical follow-up. Secondary endpoint was heart failure requiring re-hospitalization. Propensity score matching analysis was done. The incidence of primary endpoint was similar (10.4% vs. 15.6%, HR: 0.65; 95% CI: 0.29-1.47; p = 0.301) among both groups. However, the incidence of recurrent MI was significantly lower in ACEI group compared to ARB group (2.1% vs. 10.4%, HR: 0.18, 95% CI: 0.04-0.86; p = 0.031). In the present study, the risk and incidence of MACE was similar between ACEI and ARB therapy in MINOCA patients. However, ACEI significantly reduced the risk of recurrent MI. Further larger scale multi-center randomized clinical trials are needed to clarify the proper use of renin-angiotensin-aldosterone system blocker in these patients.

Telmisartan use and risk of dementia in type 2 diabetes patients with hypertension: A population-based cohort study.

BackgroundAngiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)–modulating effects, has additional benefits compared to other ARBs remains unclear.Methods and findingsBetween 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set at p < 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19% versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97; p = 0.030). They also had lower risk of dementia diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95; p = 0.022) and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97; p = 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%; HR, 0.79; 95% CI, 0.67 to 0.94; p = 0.008) during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data.ConclusionsThe current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population.

Coeliac disease enteropathy and symptoms may be aggravated by angiotensin receptor blockers in patients on a gluten-free diet.

BackgroundAngiotensin receptor blocker‐associated enteropathy (ARB‐e) is an increasingly recognised clinical entity with symptoms and histological findings identical to coeliac disease (CD). There is evidence to suggest immune‐mediated mucosal injury in ARB‐e with a high prevalence of DQ2/DQ8; however, as IgA anti‐tissue transglutaminase (anti‐TTG) is usually negative, an insult other than TTG‐mediated injury is suspected. The impact of ARBs on disease activity in patients with CD is not known.ObjectiveTo assess the effect of ARB exposure on patients with established CD.MethodsA patient record search of 1142 individual patients attending a dedicated coeliac clinic from 2010 to the present identified 59 patients treated with ARB. Those with CD confirmed by serology (TTG + ve/EMA + ve) and histopathology (Marsh criteria) were included (n = 40, 0.52%). Data collected included disease duration, compliance with gluten‐free diet (GFD), reported symptoms (diarrhoea, weight loss and abdominal pain), surrogate markers of absorption (Vitamin D, Iron, Calcium and Haemoglobin), in addition to anti‐TTG titre and histological grade at last follow up. Patients were age and sex‐matched in a 1:2 ratio with CD patients not taking ARBs (controls), with comparable rates of disease duration and compliance with GFD.ResultsThe ARB and control groups were matched in terms of age (mean 66.2 years) and gender (female 63%). Strict compliance with GFD was reported in 55% and 56%, respectively. Persistent symptoms were reported in 10/40 (25%) of the ARB group compared with 7/82 (9%) of controls (p = 0.0181). There were lower rates of mucosal healing (Marsh grade 0) in the ARB group (36% n = 11) compared to controls (55%, n = 33). There was no significant difference in anti‐TTG titres. Surrogate markers of absorption were comparable across the groups, except for Vitamin D which was lower in those taking olmesartan (p = 0.0015).ConclusionsARBs may aggravate the enteropathy and lead to increased symptoms in patients with bone fide diagnosed CD following a GFD.

Retrospective study of the efficacy of vascularized tissue transfer for treating antibiotic-resistant bacteria-infected wound: Comparison with clean and antibiotic-sensitive bacteria-infected wound.

If wounds are infected with bacteria resistant to an empirical antibiotic regimen, effective wound treatment will be delayed. This can delay wound healing and lengthen hospital stays, increasing the costs to patients. Long-term antibiotic use can also result in minor and major complications, such as diarrhea, antibiotic resistance, or life-threatening leukopenia. Multidrug-resistant (MDR) bacteria make wound treatment even more difficult. Traditionally, surgeons thought that adequate infection control should be established before soft tissue coverage. However, wounds infected by MDR do not heal well with this traditional method and there are no optimal treatment guidelines for MDR bacteria-contaminated wounds.We reviewed 203 patients who underwent vascularized flap surgery from 2012 to 2019 to cover wounds. Class IV and I wounds were compared according to the Centers for Disease Control and Prevention classification. Class IV was further classified as antibiotic-resistant (ARB) and antibiotic-sensitive (ASB) bacteria. Wound size, mode, location, pathogens, healing time, and basic demographics were evaluated. Data were compared using Cramer's V and one-way ANOVA or independent t tests.The average healing time was longer in the ARB (19.7 [range 7–44] days) and ASB (17.9 [range 2–36] days) groups than in the Clean group (16.5 [range 7–28] days). Healing time differed in the 3 groups (P = .036). It was longer in the class IV group than in the class I group (P = .01). However, it was not statistically different between the ARB and ASB groups (P = .164).In our study the difference in healing time was small when vascularized tissue transfer was done in ARB-infected wound compared with ASB-infected and clean wound. It is necessary to perform surgery using vascularized tissue for the infected wound of antibiotic-resistant bacteria.

Mechanism of angiotensin receptor-neprilysin inhibitor in suppression of ventricular arrhythmia

BackgroundThe mechanisms underlying angiotensin receptor-neprilysin inhibitor (ARNi) suppression of ventricular arrhythmia (VA) are unclear. This study aimed to investigate the mechanism of ARNi-related suppression of VA in a heart failure (HF) model. MethodsNew Zealand white rabbits (n = 6 per group) were assigned to normal, HF [4 weeks of left ascending artery (LAD) ligation], angiotensin receptor blocker (ARB, valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation), and ARNi (sacubitril at 34 mg/kg/day and valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation) groups. Experiments involving echocardiogram, optical mapping, histological of trichrome stain and immunostain, and flow cytometry were performed. ResultsHF group had larger left ventricular (LV) internal dimensions in diastole and systole, and lower LV ejection fraction and fractional shortening than normal, ARB, and ARNi groups. HF group had a prolonged action potential duration (APD) and decreased conduction velocity (CV), which was mitigated in ARB and ARNi groups. HF group had a prolonged QRS duration, QT and QTc intervals, which was reversed in ARB and ARNi groups. HF group had a steeper maximum slope of APD restitutions, which was attenuated in normal, ARB, and ARNi groups. HF group had increased number of phase singularities (PSs) and VA inducibility than normal, ARB, and ARNi groups. A higher content of fibrosis was found in HF group than that in normal, ARB, and ARNi groups. Compared to ARB group, ARNi had a lower context of fibrosis. HF group had more peripheral blood CD4+ and CD8+ cells count than normal, ARB, and ARNi group. ConclusionsIn a rabbit model of ischemic HF, ventricular arrhythmogenesis could be suppressed by ARNi treatment. This appears to be mediated by reversing changes in the APD, CV, maximum slope of the APDR, PSs, fibrosis, and inflammation.