Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers After Coronary Artery Bypass Graft Surgery: A Population-Based Cohort Study.

BACKGROUND: The effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) on major adverse cardiovascular events (MACE) in patients who undergo coronary artery bypass graft surgery is equivocal. This retrospective, population-based cohort study evaluated effect of exposure to an ACEI/ARB on MACE using linked administrative databases that included all cardiac revascularization procedures, hospitalizations, and prescriptions for the population of British Columbia, Canada. METHODS AND RESULTS: All adults who underwent coronary artery bypass graft surgery between 2002 and 2020 were eligible. The primary outcome was time to MACE, defined as a composite of all-cause death, myocardial infarction, and ischemic stroke using Cox proportional hazards models with inverse probability treatment weighting. Included were 15 439 patients and 6191 (40%) were prescribed an ACEI/ARB. Mean age was 66 years, 83% were men, and 16% had heart failure (HF). Median exposure time was 40 months. Over the 5-year follow-up, 1623 MACE occurred. Impact of exposure was different for patients with and without HF (P <0.0001 for interaction). After probability-weighting and adjustment for relevant covariates, exposure to ACEI/ARBs was associated with a lower hazard of MACE in patients with HF at 1 year (hazard ratio, 0.13 [95% CI, 0.09-0.19]) and 5 years (hazard ratio, 0.36 [95% CI, 0.30-0.44]). In patients without HF, ACEI/ARBs had a lower hazard of MACE at 1 year (hazard ratio, 0.35 [95% CI, 0.27-0.46]) and 5 years (hazard ratio, 0.66 [95% CI, 0.58-0.76]). CONCLUSIONS: In this population-based study, ACEI/ARBs were associated with a lower hazard of MACE in a cohort of patients post-coronary artery bypass graft surgery irrespective of HF status.

The trends of antihypertensive drug prescription based on the Japanese national data throughout the COVID-19 pandemic period.

In 2020, concerns arose about the potential adverse effects of angiotensin II type 1 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) on patients with the Coronavirus Disease 2019 (COVID-19). However, there is no national data on antihypertensive prescriptions during the COVID-19 pandemic in Japan. This study aimed to explore the trends in antihypertensive drug prescriptions in Japan throughout COVID-19 pandemic period. This study used data from the National Database (NDB) Open Data in Japan, an annual publication by the Ministry of Health, Labour and Welfare. To capture changes before and after social activity restrictions, the present study focused on extracting the number of prescribed oral medicine tablets for outpatients from the NDB Open Data from 2018 to 2021. The fiscal year 2020 exhibited the lowest for both outpatient claims and prescribed drugs. In contrast, all categories of antihypertensive drug prescription showed annual increases, and no specific changes in the prescription patterns of ARBs and ACEIs around fiscal year 2020 were observed. This study implies that antihypertensive drug prescriptions were adequately maintained throughout the COVID-19 pandemic in Japan.

The Association between Use of Renin-Angiotensin-Aldosterone System Inhibitors and the Risk and Mortality of Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Pancreatic Cancer (PC) is one of the most malignant tumors and highly invasive neoplasms around the world. OBJECTIVE: This systematic review and meta-analysis aims to study the relationship between the use of renin-angiotensin-aldosterone system inhibitors and the incidence and mortality of PC. METHODS: The electronic search was conducted systematically until October 10, 2023. in databases, including Scopus, Web of Science (WOS), PubMed/MEDLINE, Cochrane Library, and Embase. The required data were extracted from the articles and were analyzed by Stata 15 using statistical tests (Chi-square and I2), Forest plots, and publication bias tests (Begg's and Egger's tests). RESULTS: A total of four studies (2011-2019; n=314,856) investigated the relationship between RAS antagonists and PC risk. No significant associations were found between angiotensin receptor blockers (ARBs) (OR=0.94, 95% CI: 0.77-1.14, p=0.513), angiotensin-converting enzyme inhibitors (ACEIs) (OR=0.96, 95% CI: 0.84-1.09, p=0.505), or combination therapy (ARBs + ACEIs) (OR=0.97, 95% CI: 0.87-1.09, p=0.627) and PC risk. Also, nine studies (2010-2023; n=20,483) examined the association between renin-angiotensin-aldosterone system inhibitors and PC mortality. Significant reductions in PC mortality were found for ARBs (OR=0.81, 95% CI: 0.66-0.98, p=0.032), ACEIs (OR=0.89, 95% CI: 0.80-0.99, p=0.038), and combination therapy (OR=0.83, 95% CI: 0.70-0.97, p=0.022). No evidence of publication bias was found in the study results. CONCLUSION: In summary, while renin-angiotensin-aldosterone system inhibitors did not appear to impact PC risk, their use was associated with lower PC mortality based on this meta-analysis of the current evidence. More rigorous and well-designed studies are required to validate and support these findings.

The effect of the four pharmacological pillars of heart failure on haemoglobin level.

Anaemia, a condition characterized by low levels of haemoglobin, is frequently observed in patients with heart failure (HF). Guideline-directed medical therapy improves HF outcomes by using medications like beta blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, along with mineralocorticoid receptor antagonists and sodium-glucose cotransporter 2 inhibitors. In this study, we aimed to review the pathophysiology of anaemia in patients with HF and present the current evidence regarding the relationship between the main recommended medications for these patients and haemoglobin levels. The authors conducted a comprehensive search in the medical literature for relevant original clinical articles in which the four pharmacological pillars of HF were given to the patients; we, then, assessed whether the association of use of these medications and haemoglobin level or development of anaemia was provided. These common medications have been shown in the literature that may exacerbate or ameliorate anaemia. Besides, it has been shown that even in the case that they result in the development of anaemia, their use is associated with positive effects that outweigh this potential harm. The literature also suggests that among patients receiving medications with negative effects on the level of haemoglobin, there was no difference in the rate of mortality between anaemic and non-anaemic patients when both were on treatment for anaemia; this point highlights the importance of the detection and treatment of anaemia in these patients. Further research is needed to explore these relationships and identify additional strategies to mitigate the risk of anaemia in this population.

Angiotensin Receptor-Neprilysin Inhibition (Sacubitril/Valsartan) Reduces Structural Arterial Stiffness in Middle-Aged Mice.

BACKGROUND: Increasing arterial stiffness is a prominent feature of the aging cardiovascular system. Arterial stiffening leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function resulting in significant morbidity and death, and specific therapies to address the underlying age-related structural arterial remodeling remain elusive. The present study investigates the potential of the recently clinically available dual angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) to counteract age-related arterial fibrotic remodeling and stiffening in 1-year-old mice. METHODS AND RESULTS: Treatment of in 1-year-old mice with ARNI (sacubitril/valsartan), in contrast to angiotensin receptor blocker monotherapy (valsartan) and vehicle treatment (controls), significantly decreases structural aortic stiffness (as measured by in vivo pulse-wave velocity and ex vivo aortic pressure myography). This phenomenon appears, at least partly, independent of (indirect) blood pressure effects and may be related to a direct antifibrotic interference with aortic smooth muscle cell collagen production. Furthermore, we find aortic remodeling and destiffening due to ARNI treatment to be associated with improved parameters of cardiac diastolic function in aged mice. CONCLUSIONS: This study provides preclinical mechanistic evidence indicating that ARNI-based interventions may counteract age-related arterial stiffening and may therefore be further investigated as a promising strategy to improve cardiovascular outcomes in the elderly.

Comparison of effects of telmisartan versus valsartan on post-induction hypotension during noncardiac surgery: a prospective observational study.

BACKGROUND: Telmisartan is considered more potent than valsartan. Hemodynamic response during anesthesia induction may be influenced by anti-hypertension (HTN) medication. The present study compared the effect of anti-HTN medications on post-induction hypotension during noncardiac surgeries. METHODS: This observational study standardized the anesthetic regimen across patients, with hypotension defined as mean blood pressure (BP) of less than 65 mmHg. The hemodynamic changes within 5 min before and after endotracheal intubation, and within 10 min before and after surgical incision were measured. Transthoracic echocardiographic evaluation of the left ventricle (LV) during anesthesia induction was performed. The primary endpoint was the decline in mean BP after anesthetic administration in telmisartan and valsartan groups. Multivariate logistic regression analysis was used to identify predictors of post-induction hypotension. RESULTS: Data from 157 patients undergoing noncardiac surgery were analyzed. No significant differences were found in mean BP decline between the two groups during anesthesia induction. Hemodynamic changes and LV ejection fraction (EF) during anesthesia induction were similar between the groups. Age and preoperative initial mean BP in operation room (OR) were associated with post-induction hypotension in both groups. CONCLUSIONS: The angiotensin receptor blocker (ARB) type did not influence post-induction hypotension during anesthesia induction. Age and preoperative initial mean BP in OR were associated with post-induction hypotension in patients taking ARBs.

Cardiovascular medications used for comorbid diseases in patients with atrial fibrillation. The JoFib study.

PURPOSE: Many atrial fibrillation (AF) patients use cardiovascular medications for indications other than AF. These medications can affect morbidity and mortality. We aim to investigate the characteristics of AF patients who use different medication classes and their clinical course. METHODS: We collected data from the prospective, multicenter registry, JoFib study. We identified classes of non-AF medications (medications not used for rate control, rhythm control, or anticoagulation), described demographic and clinical characteristics, and investigated AF-related outcomes according to these medication classes. RESULTS: From a total of 2020 patients, five classes of cardiovascular non-AF medications were identified, aspirin, P2Y12 inhibitors, ACE inhibitors/ARBs, statins, and diuretics. The most commonly used non-AF medications were diuretics and ACE inhibitors/ARBs (39.2%, and 39%, respectively). 51% of AF patients took more than one non-AF medication. Multivariable Cox regression analysis demonstrated that ACE inhibitor/ARB therapy independently reduced the risks of all-cause mortality and cardiovascular mortality (aHR 0.50, 95%CI 0.37-0.68; aHR 0.51, 95%CI 0.34-0.75, respectively) and that statin therapy reduced the risk of cardiovascular mortality (aHR 0.68, 95%CI 0.48-0.98) in AF patients. Multivariable logistic regression analysis demonstrated a protective effect of statin therapy against the secondary outcome, clinically relevant non-major bleeding (CRNMB) (adjusted OR 0.62 95%CI 0.42-0.94). CONCLUSION: Our findings suggest a protective effect of ACE inhibitors/ARBs against all-cause and cardiovascular mortality, statins against cardiovascular mortality, and CRNMB in patients with AF. Accordingly, these medications should be encouraged in patients with AF when indicated. Additionally, future research should explore whether these medications should be offered to AF patients more routinely. The study was registered with Clinicaltrials.gov (unique identifier number: NCT03917992, Registration date:14/4/2019).

Long-term oral ACEI/ARB therapy is associated with disease severity in elderly COVID-19 omicron BA.2 patients with hypertension.

OBJECTIVE: To explore the effects of long-term oral ACEIs/ARBs on the incidence of exacerbation and in-hospital mortality in elderly COVID-19 Omicron BA.2 patients with hypertension, especially patients aged 80 years or older. MATERIALS AND METHODS: In this retrospective study, patients suffering mild and rcommon COVID-19 with hypertension who were hospitalized in the Shanghai Fourth People's Hospital between April 2022 and June 2022 were enrolled. Primary outcomes included the incidence of exacerbation and in-hospital mortality. Secondary outcomes included the incidence of respiratory failure of patients, use of mechanical ventilation, nucleic acid conversion time (NCT), hospitalization costs, and the temporal trend of the incidence of exacerbations and in-hospital mortality in different age groups. The data were analysed using propensity score weighting (PSW). RESULTS: In the entire cohort, there were 298 ACEI/ARB users and 465 non-ACEI/ARB users. The ACEI/ARB group showed a lower incidence of exacerbation (OR = 0.64, 95% CI for OR: 0.46-0.89, P = 0.0082) and lower in-hospital mortality (OR = 0.49, 95% CI for OR: 0.27-0.89, P = 0.0201) after PSW. Sensitivity analysis obtained the same results. The results of the subgroup of patients aged 80 years and older obtained a similar conclusion as the whole cohort. Most of the study indicators did not differ statistically significantly in the subgroup of patients aged 60 to 79 years except for rates of mechanical ventilation and respiratory failure. CONCLUSION: Antihypertensive therapy with ACEIs/ARBs might reduce the incidence of exacerbation and in-hospital mortality. The findings of this study support the use of ACEIs/ARBs in COVID-19 patients infected by Omicron BA.2, especially in patients aged 80 years or older with hypertension.

The use of angiotensin receptor blockers in dementia prevention.

Alzheimer's disease (AD) and dementia are preventable and highly prevalent diseases, as is systemic arterial hypertension. Thus, it is speculated that angiotensin receptor blockers (ARBs) may be neuroprotective against AD. Objective: The aim of this study was to evaluate if the use of ARBs confers a neuroprotective effect on AD, through a systematic review. Methods: Studies published on Embase, LILACS, SciELO, and PubMed were evaluated. The selection of the studies included those that evaluated the use of antihypertensive drugs in individuals with a previous diagnosis of mild cognitive impairment. The data were extracted with the Cochrane Effective Practice and Organization of Care (EPOC) form. The risk of bias was evaluated by the EPOC "Risk of bias tool." Results: A total of 12 articles were identified, and 3 articles were selected. Two of them analyzed the use of ARB/ACEI versus other antihypertensives and the development of dementia. Conclusion: There is a tendency for ARBs to be superior to other antihypertensives in preventing dementia.

A doença de Alzheimer (DA) e a demência são doenças potencialmente preveníveis, assim como a hipertensão arterial sistêmica. Dessa forma, especula-se que os bloqueadores dos receptores de angiotensina (BRA) tenham efeito neuroprotetor contra a DA. Objetivo: Avaliar se o uso de BRA confere efeito neuroprotetor para DA, por meio de uma revisão sistemática. Métodos: Foram avaliados estudos publicados nas plataformas Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Scientific Electronic Library Online (SciELO) e United States National Library of Medicine (PubMed). Os estudos incluídos avaliaram o uso de anti-hipertensivos em indivíduos com diagnóstico prévio de comprometimento cognitivo leve. Os dados foram extraídos com base no formulário da EPOC. Risco de viés foi avaliado por meio da ferramenta da Cochrane Effective Practice and Organisation of Care (EPOC) "Risk of bias tool". Resultados: Foram encontrados 12 artigos e três foram selecionados. Dois analisaram o uso de BRA/IECA vs. o uso de outros anti-hipertensivos e o desenvolvimento de demência. Conclusão: Há uma tendência de que os BRA sejam superiores a outros anti-hipertensivos na prevenção da demência.

Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial.

BACKGROUND: Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy. METHODS: In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Patients at high risk of cardiotoxicity (cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomized to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary outcome was adjusted change in left ventricular ejection fraction at 6 months. In low-risk nonrandomized patients with cardiac troponin I concentrations in the lower 2 tertiles, we hypothesized the absence of a 6-month change in left ventricular ejection fraction and tested for equivalence of ±2%. RESULTS: Between October 2017 and June 2021, 175 patients (mean age, 53 years; 87% female; 71% with breast cancer) were recruited. Patients randomized to cardioprotection (n=29) or standard care (n=28) had left ventricular ejection fractions of 69.4±7.4% and 69.1±6.1% at baseline and 65.7±6.6% and 64.9±5.9% 6 months after completion of chemotherapy, respectively. After adjustment for age, pretreatment left ventricular ejection fraction, and planned anthracycline dose, the estimated mean difference in 6-month left ventricular ejection fraction between the cardioprotection and standard care groups was -0.37% (95% CI, -3.59% to 2.85%; P=0.82). In low-risk nonrandomized patients, baseline and 6-month left ventricular ejection fractions were 69.3±5.7% and 66.4±6.3%, respectively: estimated mean difference, 2.87% (95% CI, 1.63%-4.10%; P=0.92, not equivalent). CONCLUSIONS: Combination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment cardiac troponin I concentrations. Low-risk nonrandomized patients had similar declines in left ventricular ejection fraction, bringing into question the utility of routine cardiac troponin monitoring. Furthermore, the modest declines in left ventricular ejection fraction suggest that the value and clinical impact of early cardioprotection therapy need to be better defined in patients receiving high-dose anthracycline. REGISTRATION: URL: https://doi.org; Unique identifier: 10.1186/ISRCTN24439460. URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2017-000896-99.

New Users of Angiotensin II Receptor Blocker-Versus Angiotensin-Converting Enzyme Inhibitor-Based Antihypertensive Medication Regimens and Cardiovascular Disease Events: A Secondary Analysis of ACCORD-BP and SPRINT.

BACKGROUND Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) block distinct components of the renin-angiotensin system. Whether this translates into differential effects on cardiovascular disease events remains unclear. METHODS AND RESULTS We used the ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) trial and the SPRINT (Systolic Blood Pressure Intervention Trial) to emulate target trials of new users of ARBs versus ACEIs on cardiovascular disease events (primary outcome) and death (secondary outcome). We estimated marginal cause-specific hazard ratios (HRs) and treatment-specific cumulative incidence functions with inverse probability of treatment weights. We identified 3298 new users of ARBs or ACEIs (ACCORD-BP: 374 ARB versus 884 ACEI; SPRINT: 727 ARB versus 1313 ACEI). For participants initiating ARBs versus ACEIs, the inverse probability of treatment weight rate of the primary outcome was 3.2 versus 3.5 per 100 person-years in ACCORD-BP (HR, 0.91 [95% CI, 0.63-1.31]) and 1.8 versus 2.2 per 100 person-years in SPRINT (HR, 0.81 [95% CI, 0.56-1.18]). There were no appreciable differences in pooled analyses, except that ARBs versus ACEIs were associated with a lower death rate (HR, 0.56 [95% CI, 0.37-0.85]). ARBs were associated with a lower rate of the primary outcome among subgroups of male versus female participants, non-Hispanic Black versus non-Hispanic White participants, and those randomly assigned to standard versus intensive blood pressure (Pinteraction: <0.01, 0.05, and <0.01, respectively). CONCLUSIONS In this secondary analysis of ACCORD-BP and SPRINT, new users of ARB- versus ACEI-based antihypertensive medication regimens experienced similar cardiovascular disease events rates, with important subgroup differences and lower rates of death overall. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01206062, NCT00000620.

A Rare Case of Olmesartan-Associated Enteropathy Successfully Managed With Steroid Taper.

Olmesartan is a commonly used antihypertensive medication belonging to the class of angiotensin II receptor blockers. Though generally well-tolerated, olmesartan can rarely cause olmesartan-associated enteropathy (OAE) with non-bloody diarrhea, weight loss, abdominal pain, and vomiting. Patients may develop enteropathy months to years after drug initiation. In severe cases, patients may develop complications that require hospitalization. Diagnosis is often delayed due to unfamiliarity of OAE, nonspecific presenting symptoms, and normal-appearing gross endoscopic findings. Esophagogastroduodenoscopy (EGD) with biopsy is essential to the diagnosis, showing sprue-like enteropathy with intestinal villous atrophy and mucosal inflammation. This report describes a case of a 70-year-old man who presented with three months of profuse watery diarrhea and 40-pound unintentional weight loss. After an extensive workup, including EGD with duodenal biopsies, the patient was diagnosed with OAE. The biopsies showed findings consistent with acute and chronic duodenitis, mucosal desquamation and ulceration, blunting of villi, and a sprue-like pattern with neutrophils. Celiac serologies and anti-enterocyte antibodies were negative, further supporting the diagnosis of OAE. Complete resolution of symptoms was achieved by discontinuing olmesartan and administering a steroid taper. Considering the frequent use of olmesartan, the increasing occurrence of OAE, and the wide range of associated symptoms, it is crucial for providers to recognize OAE and consider early discontinuation of olmesartan. This approach can help prevent further intestinal damage, protracted symptoms, unnecessary diagnostic tests, and financial burdens on both patients and the healthcare system.

Treatment patterns of antidiabetic and kidney protective therapies among patients with type 2 diabetes mellitus and chronic kidney disease in Colombia. The KDICO descriptive study.

BACKGROUND: Type 2 diabetes mellitus is one of the most common causes of chronic kidney disease (CKD) worldwide and prevalence of 1.75 per 100 inhabitants in Colombia. The aim of this study was to describe the treatment patterns of a group of patients with type 2 diabetes mellitus and CKD in an outpatient setting from Colombia. METHODS: A cross-sectional study in adult patients with type 2 diabetes mellitus and CKD identified in the Audifarma S.A. administrative healthcare database between April 2019 and March 2020 was performed. Sociodemographic, clinical and pharmacological variables were considered and analyzed. RESULTS: A total of 14,722 patients with type 2 diabetes mellitus and CKD were identified, predominantly male (51%), with a mean age of 74.7 years. The most common treatment patterns of type 2 diabetes mellitus included the use of metformin monotherapy (20.5%), followed by the combination of metformin + dipeptidyl peptidase-4 inhibitor (13.4%). Regarding the use of drugs with nephroprotective properties, the most prescribed treatments were angiotensin receptor blockers (67.2%), angiotensin converting enzyme inhibitors (15.8%), sodium glucose cotransporter 2 inhibitors (SGLT2i) (17.0%) and glucagon-like peptide-1 analogs (GLP1a) (5.2%). CONCLUSION: In Colombia, the majority of patients with type 2 diabetes mellitus and CKD identified in this study were treated with antidiabetic and protective medications to ensure adequate metabolic, cardiovascular, and renal control. The management of type 2 diabetes mellitus and CKD may be improved if the beneficial properties of new groups of antidiabetics (SGLT2i, GLP1a), as well as novel mineralocorticoid receptor antagonists, are considered.

Blood Pressure Control Following Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers: Insights from a Triple-Blind, Randomized, Clinical Trial.

Data on substituting one antihypertensive medication with the proper dose of another antihypertensive medication, in certain medical conditions, are scarce. Herein, we present the results of replacing angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) with the calcium channel blocker (CCB) amlodipine, with or without the alpha- and beta-blocker carvedilol, to control high blood pressure in patients with coronavirus disease 2019 (COVID-19). Iranian hypertensive patients with COVID-19 and a history of taking ACEI or ARB were randomized to "continue" and "change" groups. The continue group comprised patients who continued using their previous antihypertensive medication regimen as normal, whereas patients in the change group had their antihypertensive drugs changed to the CCB amlodipine, with or without the alpha- and beta-blocker carvedilol, based on their response to amlodipine. Patients' blood pressures were measured for 8 days following their recruitment. A total of 31 and 33 patients were randomly allocated to the ACEI/ARB continue and ACEI/ARB change groups, respectively. No significant deviations were seen in patients' systolic blood pressure by substituting an ACEI/ARB agent with the CCB amlodipine, with or without the alpha- and beta-blocker carvedilol. Moreover, the change group had a more balanced systolic blood pressure (ie, 110-130 mmHg) compared with the continue group (ie, 111.5-140.0 mmHg) throughout their hospitalization period. During their hospitalization, the blood pressure of the change group was well controlled with the proposed equivalent doses. Further investigations of the proposed equivalent doses in larger randomized clinical trials, populations other than Iranian COVID-19 patients, and extended duration are encouraged (clinical trial registration ID: IRCT20151113025025N3).

Post-induction hypotension with remimazolam versus propofol in patients routinely administered angiotensin axis blockades: a randomized control trial.

BACKGROUND: Certain routine medication could result in post-induction hypotension (PIH), such as angiotensin axis blockades, which are frequently administered as a first-line therapy against hypertension. Remimazolam is reportedly associated with lesser intraoperative hypotension than propofol. This study compared the overall incidence of PIH following remimazolam or propofol administration in patients managed by angiotensin axis blockades. METHODS: This single-blind, parallel-group, randomized control trial was conducted in a tertiary university hospital in South Korea. Patients undergoing surgery with general anesthesia were considered for enrollment if the inclusion criteria were met: administration of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, 19 to 65 years old, American Society of Anesthesiologists physical status classification ≤ III, and no involvement in other clinical trials. The primary outcome was the overall incidence of PIH, defined as a mean blood pressure (MBP) < 65 mmHg or decrease by ≥ 30% of the baseline MBP. The time points of measurement were baseline, just before the initial intubation attempt, and 1, 5, 10, and 15 min following intubation. The heart rate, systolic and diastolic blood pressures, and bispectral index were also recorded. Groups P and R included patients administered propofol and remimazolam, respectively, as an induction agent. RESULTS: A total of 81 patients were analyzed, of the 82 randomized patients. PIH was less frequent in group R than group P (62.5% versus 82.9%; t value 4.27, P = 0.04, adjusted odds ratio = 0.32 [95% confidence interval 0.10-0.99]). The decrease in the MBP from baseline was 9.6 mmHg lesser in group R than in group P before the initial intubation attempt (95% confidence interval 3.3-15.9). A similar trend was observed for systolic and diastolic blood pressures. No severe adverse events were observed in either group. CONCLUSION: Remimazolam results in less frequent PIH than propofol in patients undergoing routine administration of angiotensin axis blockades. TRIAL REGISTRATION: This trial was retrospectively registered on Clinical Research Information Service (CRIS), Republic of Korea (KCT0007488). Registration date: 30/06/2022.

Comparison of Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in the Management of Arterial Stiffness and Target Organ Damage in Patients with Hypertension

Abstract Background Arterial stiffness and hypertension are strong predictors of cardiovascular disease and mortality. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are first-line antihypertensive agents in reducing blood pressure and arterial stiffness. Objective The objective of this study was to compare the effects of ACEI and ARB in reducing arterial stiffness and preventing target organ damage in patients with hypertension. Methods This observational study included 654 participants who attend routine consultations at an outpatient hypertension clinic in 2 university hospitals. Patients were interviewed, and they underwent central and peripheral blood pressure measurements. Doppler echocardiography, carotid ultrasound, biochemical tests, and anthropometric parameters were carried out. Shapiro-Wilk, chi-square, and Fisher's exact test were used. A significance level of 5% was adopted. Results A total of 659 participants were evaluated in the study (398 from the ARB group and 256 from the ACEI group). Age, body mass index (BMI), central and peripheral blood pressure measurements, pulse wave velocity (PWV), left ventricular mass index, and carotid intima-media thickness did not show differences between the groups (p > 0.05). After linear regression analysis, the ACEI group had lower values of total vascular resistance (TVR) (p = 0.003) and augmentation pressure (p = 0.008), when compared to the ARB group. Conclusion This study showed that the ACEI group had a greater reduction in augmentation pressure and PWV. There were no differences between the groups regarding the improvement of outcomes related to central arterial pressure, PWV, and cardiac and vascular target organ damage.

Discontinuation of Antihypertensive Drug Use Compared to Continuation in COVID-19 Patients: A Systematic Review with Meta-analysis and Trial Sequential Analysis.

INTRODUCTION: COVID-19 related mortality is about 2%, and it increases with comorbidities, like hypertension. Regarding management, there is debatable evidence about the benefits of continuation vs. discontinuation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB). AIM: We performed a systematic review to assess the effects and safety of in-hospital discontinuation compared to continuation of ACEI/ARB in COVID-19 patients. METHODS: We systematically searched on PubMed, Scopus, and EMBASE from inception to June 19, 2021. We included observational studies and trials that compared the effects and safety of continuing ACEI/ARB compared to discontinuing it in COVID-19 patients. Effects sizes for dichotomous variables were expressed as risk ratios (RR) and 95% confidence intervals. For continuous variables, effects were expressed as mean difference (MD). We used random effect models with the inverse variance method. We assessed certainty of evidence using the GRADE approach. RESULTS: We included three open-label randomized controlled trials and five cohort studies. We found that the continuation group had lower risk of death compared with the discontinuation group only in the cohort group (RR: 0.46, 95% CI: 0.24-0.90), but not in the RCT group (RR: 1.22, 95% CI: 0.75-2.00). The ICU admission rate was significantly lower in the continuation group (RR: 0.46, 95% CI: 0.31-0.68) in the cohort group, but not in RCT group (RR: 1.03, 95% CI: 0.67-1.59). We did not find significant differences between groups regarding hospitalization length, hypotension, AKI needing renal replacement therapy, mechanical ventilation, new or worsening heart failure, myocarditis, renal replacement therapy, arrhythmias, thromboembolic events and SOFA AUC. The GRADE approach revealed that the certainty ranged from moderate to high level. CONCLUSIONS: There is no significant difference in mortality and other outcomes between continuation and discontinuation groups.

Enalaprilat and losartan decrease erythroid precursors frequency in cells from patients with polycythemia vera.

OBJECTIVE: Polycythemia Vera (PV) is a myeloproliferative neoplasm characterized by the overproduction of red blood cells. First-line therapies are directed at lowering hematocrit levels. After the discovery of a mutation in the Janus kinase 2 (JAK2V617F), JAK2 inhibitors have been tested as second-line therapies. Despite these approaches, there is still the need for a major comprehension of the mechanisms involved in PV erythrocytosis and of more effective therapies. Angiotensin-converting enzyme (ACE) stimulates hematopoietic precursors proliferation and erythroid differentiation. We thus hypothesized that ACE inhibition could help in controlling erythrocytosis in PV. METHODS: We assessed the clonogenic potential by colony-forming unit (CFU) assay of mononuclear cells isolated from PV JAK2 positive or JAK2 negative patients with erythrocytosis treated with enalaprilat or losartan. RESULTS: Treatment with drugs led to a decrease of erythroid precursor frequency both in the presence and absence of JAK2 mutation, with a high extent in JAK2 positive cells and without affecting other types of precursors. No dose-dependent effect was observed. CONCLUSIONS: Our results demonstrate that ACE inhibition reduces erythroid precursor frequency, confirming the involvement of ACE in erythrocytosis despite the presence of JAK2 mutation and encouraging the hypothesis that ACE inhibitors and AT1R antagonists could help in directly managing erythrocytosis in PV.

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

OBJECTIVE: 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. METHODS: The information 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. RESULTS: 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. CONCLUSIONS: ACEi and ARB users were associated with decreased risks of MI, IS, AF, HF, and all-cause deaths, compared to non-RASi users.

Self-Management Support Using Advertising Principles for Older Adults With Low Income at High Cardiovascular Risk: A Randomized Controlled Trial.

BACKGROUND: Self-management education and support (SMES) interventions have modest effects on intermediate outcomes for those at risk of cardiovascular disease, but few studies have measured or demonstrated an effect on clinical end points. Advertising for commercial products is known to influence behavior, but advertising principles are not typically incorporated into SMES design. METHODS: This randomized trial studied the effect of a novel tailored SMES program designed by an advertising firm among a population of older adults with low income at high cardiovascular risk in Alberta, Canada. The intervention included health promotion messaging from a fictitious "peer" and facilitated relay of clinical information to patients' primary care provider and pharmacist. The primary outcome was the composite of death, myocardial infarction, stroke, coronary revascularization, and hospitalizations for cardiovascular-related ambulatory care-sensitive conditions. Rates of the primary outcome and its components were compared using negative binomial regression. Secondary outcomes included quality of life (EQ-5D [EuroQoL 5-dimension] index score), medication adherence, and overall health care costs. RESULTS: We randomized 4761 individuals, with a mean age of 74.4 years, of whom 46.8% were female. There was no evidence of statistical interaction (P=0.99) or of a synergistic effect between the 2 interventions in the factorial trial with respect to the primary outcome, which allowed us to evaluate the effect of each intervention separately. Over a median follow-up time of 36 months, the rate of the primary outcome was lower in the group that received SMES compared with the control group (incidence rate ratio, 0.78 [95% CI, 0.61 to 1.00]; P=0.047). No significant between-group changes in quality of life over time were observed (mean difference, 0.0001 [95% CI, -0.018 to 0.018]; P=0.99). The proportion of participants who were adherent to medications was not different between the 2 groups (P=0.199 for statins and P=0.754 for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers). Overall adjusted health care costs did not differ between those receiving SMES and the control group ($2015 [95% CI, -$1953 to $5985]; P=0.320). CONCLUSIONS: For older adults with low income, a tailored SMES program using advertising principles reduced the rate of clinical outcomes compared with usual care. The mechanisms of improvement are unclear and further studies are required. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02579655.