Angiotensin-converting Enzyme Inhibitor Group Research Articles

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.

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.

Effect of Angiotensin Receptor Blocker and Angiotensin Converting Enzyme Inhibitor on Kidney Function and Blood Potassium Level in Indonesian Type 2 Diabetes Mellitus with Hypertension: A Three-Month Cohort Study.

PurposeNational formulary restrictions in Indonesia (2019) require estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 to be able to prescribe telmisartan and valsartan and ACE-I intolerance to be able to prescribe irbesartan and candesartan. These restrictions are based on economic considerations and differ from American Diabetes Association (ADA) (2020) guidelines which allow equal use of angiotensin II receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACE-I) without restriction. Since there is a need to evaluate the different effects of ACE-I and ARB in the Indonesian hypertensive type 2 diabetes mellitus (T2DM) population, we compare their effects on urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and blood potassium level.Patients and MethodsA prospective cohort study at RSUPN Dr. Cipto Mangunkusumo Hospital was conducted in 123 T2DM patients. We followed the study subjects prospectively for three months using a validated questionnaire, health record, and laboratory data.ResultsAfter 3 months of observation, there were no significant changes, except increased BMI values (p = 0.046) in the ACE-I group, and decreased LDL value (p = 0.016) and HDL value (p = 0.004) in the ARB group. Multivariate analysis showed that the consumption of ACE-I or ARB was not associated with a decrease/constant of UACR or increase potassium level, even after adjusting by confounding variables. Interestingly, we found ARB was more likely to increase eGFR, but the significance was lost once the duration of ACE-I/ARB use was entered into the model. In addition, BMI >25 kg/m2 was a significant factor associated with decreased/constant UACR, maleness was significant for increased eGFR, and declining systolic blood pressure for increase in potassium level.ConclusionACE-I and ARB have a similar effect on UACR and blood potassium level, but ARB slightly increased eGFR compared to ACE-I within three months of consumption.

Efficacy and safety of early initiation of Sacubitril/Valsartan in patients after acute myocardial infarction: A meta‐analysis

Some randomized controlled trials have compared the effectiveness and safety outcomes between early initiation of Sacubitril/Valsartan and angiotensin‐converting enzyme inhibitors (ACEIs) in patients after acute myocardial infarction. Therefore, our current meta‐analysis aimed to clarify the confusion. Four Databases and relevant grey literature were searched for studies from inception to July 2, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias. Four studies involving 6154 patients were included to perform meta‐analysis. The results of meta‐analysis showed that the left ventricular ejection fraction in the Sacubitril/Valsartan group was higher than the ACEI group (SMD: 0.37, 95% CI: 0.19–0.55, P = .000), the incidence of major adverse cardiac events in the Sacubitril/Valsartan group was lower than the ACEI group (RR: 0.61, 95% CI: 0.46–0.82, P = .001), while the incidences of cardiac death (RR: 1.00, 95% CI: 0.81–1.24, P = 1.000) and the heart failure hospitalization (RR: 0.62, 95% CI: 0.37–1.03, P = .065) showed no difference. For the incidences of myocardial infarction and the adverse side effects, there was no obvious advantage of the Sacubitril/Valsartan group over the ACEI group, because the meta‐analysis was not performed due to the limited trials. This study indicated that early initiation of Sacubitril/Valsartan in patients after acute myocardial infarction was superior to ACEI in reducing the risks of major adverse cardiac events and left ventricular ejection fraction increasing. As for the other outcomes (the incidences of cardiac death, the heart failure hospitalization, the myocardial infarction and the adverse side effects), Sacubitril/Valsartan showed no obvious advantage than ACEI.

Effect of ACEI and ARB treatment on nitric oxide-dependent endothelial function.

Background: Angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are widely used as a first-line therapy for the treatment of cardiovascular disease. Here, ACEI modulate the bradykinin receptor (BDKRB1 and BDKRB2) system and NO-dependent endothelial function, thus determining cardiovascular health and regenerative arteriogenesis. The current study aims at evaluating nitric oxide-dependent endothelial function, and gene expression of bradykinin receptors in peripheral blood mononuclear cells (PBMC) from patients with ACEI or ARB treatment. Patients and methods: The WalkByLab has been established to screen cardiovascular patients for peripheral artery disease and coronary artery disease. In total 177 patients from WalkByLab with heterogenous disease and risk status were randomly selected, divided according to their medication history into the following groups: 1. ACEI group, 2. ARB group or 3. non-ACE/ARB group. Total plasma nitrite/nitrate (NO) levels were measured, endothelial function was evaluated by assessing flow meditated dilation (FMD). PBMC were isolated from peripheral whole blood, and gene expression (qRT-PCR) of bradykinin receptors and angiotensin converting enzyme were assessed. Results: Plasma total NO concentration in the ACEI group (24.66±16.28, µmol/l) was increased as compared to the ARB group (18.57±11.58, µmol/l, P=0.0046) and non-ACE/ARB group (16.83±8.64, µmol/l, P=0.0127) in patients between 40 to 90 years of age. However, FMD values (%) in the ACEI group (7.07±2.40, %) were similar as compared to the ARB (6.35±2.13, %) and non-ACE/ARB group (6.51±2.15, %), but significantly negatively correlated with age. Interestingly, BDKRB1 mRNA level was significantly higher and BDKRB2 mRNA level lower in the ACEI group (BDKRB1 3.88-fold±1.05, BDKRB2 0.22-fold±0.04) as compared to the non-ACE/ARB group (BDKRB1 1.00-fold±0.39, P<0.0001, BDKRB2 1.00-fold±0.45, P=0.0136). Conclusions: ACEI treatment enhances total nitrite/nitrate concentration, furthermore, upregulates BDKRB1 in PBMC, but downregulates BDKRB2 mRNA expression. FMD is a strong determinant of vascular aging and is sensitive to underlying heterogenous cardiovascular diseases.

Physical Activity and Inhibition of ACE Additively Modulate ACE/ACE-2 Balance in Heart Failure in Mice.

Angiotensin-converting enzyme inhibition (ACE-I) and physical activity favorably modulate the ACE/ACE-2 balance. However, it is not clear whether physical activity and ACE-I could synergistically modulate ACE/ACE-2 balance in the course of heart failure (HF). Here, we studied the effects of combined spontaneous physical activity and ACE-I–based treatment on angiotensin (Ang) pattern and cardiac function in a mouse model of HF (Tgαq*44). Tgαq*44 mice with advanced HF (at the age of 12 months) were running spontaneously in a running wheel (exercise training group, ExT) and/or were treated with ACE inhibitor (ACE-I, perindopril, 10 mg/kg) for 2 months. Angiotensin profile was characterized by an LC-MS/MS-based method. The cardiac performance was assessed in vivo by MRI. Ang-(1–7)/Ang II ratio in both plasma and the aorta was significantly higher in the combined treatment group than the ACE-I group or ExT alone, suggesting the additive favorable effects on ACE-2/Ang-(1–7) and ACE/Ang II axes’ balance induced by a combination of ACE-I with ExT. The basal cardiac performance did not differ among the experimental groups of Tgαq*44 mice. We demonstrated additive changes in ACE/ACE-2 balance in both plasma and the aorta by spontaneous physical activity and ACE-I treatment in Tgαq*44 mice. However, these changes did not result in an improvement of failing heart function most likely because the disease was at the end-stage. Ang-(1–7)/Ang II balance represents a valuable biochemical end point for monitoring therapeutic intervention outcome in heart failure.

Inhibition of the Renin-Angiotensin System Reduces Gene Expression of Inflammatory Mediators in Adipose Tissue Independent of Energy Balance.

Obesity is a growing health problem worldwide. The renin-angiotensin system (RAS) is present in adipose tissue, and evidence suggests that it is involved in both diet-induced obesity and the inflammation associated with obesity. The present experiments determined the effect of (1) different angiotensin-converting enzyme (ACE) inhibitors (captopril, perindopril, enalapril) and angiotensin receptor blockers (ARBs: telmisartan, losartan) on adiposity of mice fed a high-fat diet for 28 days (2); acute treatment with the ACE-inhibitor captopril on gene expression of inflammatory markers in mice fed a high-fat diet (HFD); and (3) short-term (2 days) and chronic (28 days) treatment of ACE-inhibition on energy expenditure (EE) and energy balance in mice fed HFD ad libitum (AL), as well as receiving HFD limited to the amount of calories eaten by controls (pair-fed (PF) group). Body weight, food intake, adiposity and plasma leptin were lower in ACE inhibitor or ARB-treated groups over 28 days compared with HFD untreated mice. Short-term treatment with captopril led to increased EE relative to the level in the PF group. After 28 days, EE was lower in both captopril-treated and PF mice compared with AL, but the effect was greater in the captopril-treated group. Adiponectin was elevated in captopril-treated mice, but not in PF mice, after both 2 and 28 days. Additionally, acute RAS blockade in HFD-fed mice reduced mRNA expression for MCP-1, IL-6, TLR4, and leptin in adipose tissue relative to values in untreated groups. These data demonstrate that ACE inhibition and angiotensin receptor blockade reduce food intake to produce weight loss and suggest that the anti-inflammatory effects of ACE inhibition may be independent of weight loss.

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.

Comparison Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers for Incidence of Lung Cancer: A Retrospective Study.

Introduction: Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blockers (ARBs) are taken as the first treatment option for hypertensive patients. The various global trials have suggested that ACEIs and ARBs may increase risk of lung cancer; however, the results are contradictory and there is no local study available. This study is conducted to compare the incidence of lung cancers in patients on ACEIs and ARBs.Methods: This retrospective study, conducted in a major cardiology unit of a tertiary care hospital in Pakistan, included patients diagnosed with hypertension, between 2005 and 2010, who were prescribed either ACEIs or ARBs. During the period of 2005 to 2010, 47,823 naïve hypertensive patients were reported in the outpatient department of the cardiology unit. Of which, 22,241 were prescribed ACEI and 25,582 were prescribed ARBs. After sorting patient data based on our inclusion criteria, n = 14,891 participants were included in the ACEI group and n = 19,112 participants were included in the ARB group.Results: The incidence of lung cancer in the ACEI and ARB group was n = 165 and n = 160, respectively. In this study, the overall incidence rates of lung cancer in the ACEI and ARB cohorts were 12.2 and 16.6 per 10,000 person-years, respectively. The hazard ratio was 1.32 (95% confidence interval: 1.06-1.64; p-value: 0.01).Conclusion: In this study, the incidence of lung cancer was relatively more among people using ACEIs than ARBs. Hence, patients undergoing long-term treatment with ACEIs need regular follow-up and proper scanning to avoid grave complications.

Update Alert 8: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults

LettersJune 2021Update Alert 8: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in AdultsFREEKatherine Mackey, MD, MPP, Devan Kansagara, MD, MCR, and Kathryn Vela, MLIS, AHIPKatherine Mackey, MD, MPPVA Portland Health Care System, Portland, OregonSearch for more papers by this author, Devan Kansagara, MD, MCRVA Portland Health Care System, Portland, OregonSearch for more papers by this author, and Kathryn Vela, MLIS, AHIPVA Portland Health Care System, Portland, OregonSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0223 SectionsSupplemental MaterialAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In update alert 7, we summarized the state of the evidence for the key questions of this systematic review: whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) increase the risk for SARS-CoV-2 infection or worse outcomes and whether these medications are effective in the treatment of COVID-19 (1). Given our high confidence in evidence indicating that use of ACEIs or ARBs does not increase the risk for SARS-CoV-2 infection, we retired this key question from our living review. In this update alert, we provide a summary of results from 2 clinical trials addressing the question of whether continuing ACEIs or ARBs in the treatment of COVID-19 is associated with worse outcomes. We also provide an update on completed and in-progress clinical trials on the effectiveness of ACEIs or ARBs in the treatment of COVID-19 and results of our literature surveillance from 23 November 2020 to 4 April 2021 using the same search strategy as described in the original review (2).Key Question 2: Is Use of ACEIs and ARBs Associated With More Severe COVID-19 Illness?Because of high confidence based on 78 studies (77 observational studies and 1 randomized controlled trial) in the finding that ACEI or ARB use is not associated with COVID-19 severity, we ended our routine literature surveillance for this key question but planned to report on the findings of 3 in-progress clinic trials. Results are now available for 2 trials that compared COVID-19 severity and mortality in adults who continued or discontinued ACEI or ARB treatment once COVID-19 was diagnosed; the third trial was suspended because of challenges with funding and a low incidence of COVID-19 at the study site (3–5).In the REPLACE COVID (Randomized Elimination or ProLongation of ACEIs and ARBs in COronaVIrus Disease 2019) trial, a randomized, open-label multicenter trial of 152 adults, continuation of ACEIs or ARBs did not result in more severe disease as measured by a composite outcome incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction (6). Similarly, the BRACE-CORONA (Blockers of Angiotensin Receptor and Angiotensin-Converting Enzyme inhibitors suspension in hospitalized patients with coronavirus infection) trial done in Brazil of 659 adults with mild to moderate COVID-19 found no significant difference in days alive and out of the hospital in the ACEI or ARB continuation group compared with the discontinuation group (7). These findings support our conclusion that use of ACEIs or ARBs before COVID-19 illness is not associated with increased severity. Because we consider these findings to be stable (meaning that future studies are likely to have the same results), we will retire this key question from our living review.Key Question 3: What Are the Benefits and Harms of Initiating ACEI or ARB Treatment for Patients With COVID-19?We identified published results of 1 study in our search—a single-group, open-label trial on the safety of losartan initiation among 34 adults at the University of Kansas Hospital—finding that use of losartan in the intervention group was associated with a lower incidence of adverse events (defined as any untoward medical occurrence in a person during the study) compared with external, nonrandomized controls (8). This study was not designed to evaluate the effectiveness of losartan in COVID-19 treatment. We previously identified 5 planned or in-progress clinical trials evaluating ACEI or ARB initiation in COVID-19 treatment (Supplement Table) (9–13). Three of these trials remain in progress (9–11). Two are complete, but results are not published yet (11,12). We will monitor these trials for updates monthly and provide a brief status update in the fall of 2021. When results are available, we will provide an updated evidence synthesis.

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.

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.

Onset of Hyperkalemia following the Administration of Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker.

Introduction In spite of the established importance of detecting angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker- (ARB-) induced hyperkalemia, there have not been many studies on the time of its occurrence. Methods We retrospectively analyzed electronic medical records to determine the onset time and incidence rate of hyperkalemia (serum potassium > 5.5 mEq/L or 6.0 mEq/L) among hospitalized patients newly started on a 15-day ACEI or ARB therapy. Results Among 3101 hospitalized patients, hyperkalemia incidence was 0.5%–0.9% and 0.8%–2.1% in the ACEI and ARB groups, respectively. However, it was not significantly different among different ARB types. Hyperkalemia's onset was distributed throughout 15 days, without any trend. Hyperkalemia incidence was 7.3 and 35.1 times higher at 5.5 mEq/L (hazard ratio (HR) = 7.31, 95%confidence interval (CI) = 4.19–12.76, p < 0.001) and 6.0 mEq/L (HR = 35.11, 95%CI = 8.25–149.52, p < 0.001), respectively, than the baseline creatinine level. Hyperkalemia incidence in patients with chronic renal failure was 5.7 and 9.2 times higher at 5.5 mEq/L (HR = 5.72, 95%CI = 3.24–10.12, p < 0.001) and 6.0 mEq/L (HR = 9.16, 95%CI = 4.02–20.88, p < 0.001), respectively. Conclusions It is unlikely that it is necessary to monitor hyperkalemia immediately after administration of ACEI or ARB. However, when prescribed for patients with abnormal kidney function, clinicians should always consider the possibility of developing hyperkalemia.

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.

The impact of angiotensin-converting-enzyme inhibitors versus angiotensin receptor blockers on 3-year clinical outcomes in 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 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 = 4,053 patients and the ARB group, n = 4,107 patients. During the 3-year clinical follow-up, the cumulative incidences of MACE (hazard ratio [HR], 0.843; 95% confidence interval [CI], 0.740–0.960; p = 0.010), any repeat revascularization (HR, 0.856; 95% CI, 0.736–0.995; p = 0.044), stroke (HR, 0.613; 95% CI, 0.417–0.901; p = 0.013), and re-hospitalization due to heart failure (HF) (HR, 0.399; 95% CI, 0.294–0.541; p <0.001) in the ACEI group were significantly lower than in the ARB group. In Korean patients with AMI without a history of hypertension, the use of ACEI was significantly associated with reduced incidences of MACE, any repeat revascularization, stroke, and re-hospitalization due to HF than those with the use of ARB.

Abstract 14077: One-year Outcome After PCI in Patients Treated Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers - Subanalysis From Multicenter Registry -

Background: The prescription of inhibitors for renin-angiotensin-aldosterone system (RAAS) is associated with improved prognosis but have respectively different mechanisms of action in patients with coronary artery disease (CAD). We aimed to compare the clinical outcomes between angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) therapy in patients with CAD undergoing percutaneous coronary intervention (PCI). Methods: This study is a subanalysis from the TWINCRE registry that is a multicentral prospective cohort including patients who underwent PCI. After excluding 18 patients who received both ACEi and ARB from 2,896 registered patients, we ultimately evaluated 369 patients treated with ACEi, 492 with ARB and 541 without ACEi or ARB. The primary endpoint was a major adverse cardiovascular and cerebrovascular events (MACCE) including death from any cause, acute coronary syndrome, stent thrombosis, stroke and hospitalization for heart failure. The impact of RAAS inhibitors on all-cause mortality alone was also evaluated. Results: During the observation period with 366 days of a median follow-up, Kaplan-Meier analysis revealed that the ARB group had the lowest rate of MACCE than other two groups (Log-rank for trend, p&amp;lt; for &lt; 0.0001, Figure). Regarding all-cause mortality, the ARB group and ACEi group had comparable rates for MACCE, which were lower than the no-ACEi/ARB group (p&amp;lt; for &lt; 0.0001). In a Cox regression analysis, after adjusting with age, gender, comorbidities, multivessel disease, acute myocardial infarction, and medications at discharge including dual antiplatelet therapy and statins, ARB therapy was still had a superiority to ACEi therapy regarding with MACCE (hazard ratio: 0.54, 95% confidence interval: 0.30-0.98). Conclusion: In the multicenter cohort study, ARB therapy was associated with better one-year clinical outcomes compared to ACEi therapy in patients undergoing PCI.

Influence of different anti‐hypertensive drugs on gingival overgrowth: A cross‐sectional study in a Turkish population

The purpose of this study was to evaluate the occurrence rate of drug-induced gingival overgrowth (DIGO) in patients treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) such as amlodipine, lercanidipine, and benidipine, as well as to assess the relationship of those mentioned above with medication variables and oral hygiene. Sociodemographic details, DIGO, and clinical periodontal parameters were obtained from one hundred and thirty-one patients receiving ACE inhibitors, ARBs, and CCBs for a period of at least 2years. The occurrence rate of DIGO was 19.6% in patients using CCB, 12.5% in the ARB group, and 7.5% in the ACE inhibitor group. In a subgroup analysis of CCBs, DIGO was found to be 31.8% in the amlodipine group, 13.3% in the lercanidipine group, and 7.1% in the benidipine group. While there was a significant relationship between amlodipine drug dosage and DIGO, no association was found between the duration of therapy and DIGO in all CCB subgroups. There was no difference between the groups in terms of DIGO. Duration of therapy and drug dosage did not affect the severity of DIGO in both ACE inhibitors and ARB groups.

Angiotensin Receptor 1 Blockers Prolong Time to Recurrence after Radiofrequency Ablation in Hepatocellular Carcinoma patients: A Retrospective Study.

Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. Aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation. Data on 215 patients were reviewed. The study population was classified into three groups: 113 (52.5%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 59 (27.4%) patients treated with angiotensin-converting enzyme inhibitors (group 2) and 43 (20.1%) patients treated with sartans (group 3). Survival outcomes were analyzed using Kaplan–Meier analysis and compared with log-rank test. In the whole study population, 85.6% of patients were in Child-Pugh A-class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30 mm (10–40 mm) and alpha-fetoprotein was 25 (1.1–2100) IU/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (42–51) in group 1, 51 months (42–88) in group 2, and 63 months (51–84) in group 3 (p = 0.15). Child-Pugh stage and Model for End-staging Liver Disease (MELD) score resulted as significant predictors of overall survival in multivariate analysis. Median time to recurrence was 33 months (24–35) in group 1, 41 (23–72) in group 2 and 51 months (42–88) in group 3 (p = 0.001). Number of nodules and anti-angiotensin treatment were confirmed as significant predictors of time to recurrence in multivariate analysis. Sartans significantly improved time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients but did not improve overall survival.