Discontinuation Of Angiotensin-converting Enzyme Inhibitors Research Articles

Evaluation of the stopping angiotensin converting enzyme inhibitor compared to angiotensin receptor blocker (STOP ACEi trial) in advanced and progressive chronic kidney disease

In the STOP-ACEi trial, the outcome was similar whether or not renin-angiotensin system inhibitors (RASi) were discontinued. We now investigate whether the effect of withdrawing angiotensin converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARBs) differed. In this open label trial patients with estimated glomerular filtration rates (eGFR) under 30ml/min per 1.73 m2 and progressive chronic kidney disease (CKD) were randomized to stop or continue RASi. The primary outcome was eGFR at three years. The composite of kidney failure, over 50% fall in eGFR, or kidney replacement therapy (KRT) was also assessed. Of patients randomized, 99 stopped and 123 patients continued ACEi while 104 stopped and 77 continued ARB at baseline. At three years, the eGFR was similar whether or not patients were withdrawn from ACEi or from ARB. Kidney failure or initiation of KRT occurred in 65% of those stopping and 54% continuing ACEi (hazard ratio if stopped, 1.52; 95% Confidence Interval, 1.07 to 2.16) and in 60% on an ARB regardless of randomized group (hazard ratio if stopped, 1.23; 0.83 to 1.81). Kidney failure/Initiation of KRT with over 50% decline in eGFR occurred in 71% of those stopping and 59% continuing ACEi (relative risk if stopped, 1.19; 95% CI, 1.00 to 1.41) and in 65% stopping and 69% continuing ARB (relative risk if stopped, 0.96; 0.79 to 1.16). Thus, neither discontinuing ACEi nor ARB slowed the rate of decline in eGFR. Although discontinuation of ACEi appeared to have more unfavorable effects on kidney outcomes than stopping ARB, the trial was neither designed nor powered to show differences between agents.

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

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). 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. 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. 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. There is no significant difference in mortality and other outcomes between continuation and discontinuation groups.

Reinitiation and Subsequent Discontinuation of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers among New and Prevalent Users Aged 65 Years or More with Peripheral Arterial Disease

Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) are recommended in the treatment of arterial hypertension in patients with peripheral arterial disease (PAD). The aims of our study were: (a) to analyse the extent of reinitiation and subsequent discontinuation in older hypertensive PAD patients non-persistent with ACEIs/ARBs; (b) to determine patient and medication factors associated with reinitiation and subsequent discontinuation; and (c) to compare these factors between prevalent and new users. The analysis of reinitiation was performed on a sample of 1642 non-persistent patients aged ≥65 years with PAD newly diagnosed in 2012. Patients reinitiating ACEIs/ARBs were used for the analysis of subsequent discontinuation identified according to the treatment gap period of at least 6 months without any prescription of ACEI/ARB. In the group of non-persistent patients, 875 (53.3%) patients reinitiated ACEIs/ARBs during a follow-up (24.8 months on average). Within this group, subsequent discontinuation was identified in 414 (47.3%) patients. Being a new user was associated with subsequent discontinuation, but not with reinitiation. Myocardial infarction during non-persistence and after reinitiation was associated with reinitiation and lower likelihood of subsequent discontinuation, respectively. Being a prevalent or a new user is associated with the use of medication also after initial discontinuation.

Geriatric Pharmacotherapy Case Series: Recurrent Angioedema Following Discontinuation of ACE Inhibitor Therapy.

Introduction Angiotensin-converting enzyme inhibitors (ACEIs) are first-line pharmaceutical agents in common chronic conditions such as hypertension and heart failure with reduced ejection fraction. When angioedema occurs, if secondary to ACEIs, discontinuation of the ACEI is necessary to mitigate the risk of recurrent angioedema. While angioedema is a well-known adverse effect of ACEIs, it is not well-known that angioedema may recur even after ACEI discontinuation. Additionally, only few reports in the literature describe this phenomenon. This case describes an older man with a history of chronic obstructive pulmonary disease, hypothyroidism, diabetes mellitus, hypertension, and heart failure who presented from an assisted living facility with recurrent angioedema 12 days after an initial episode of angioedema where his ACEI therapy (enalapril) was discontinued. Assessment Empiric methylprednisolone, diphenhydramine, intramuscular epinephrine, intravenous C1 esterase inhibitor Berinert®, and two units of fresh frozen plasma was given in the emergency department. The patient was monitored in the intensive care unit because of mild airway compromise but did not require invasive airway protection. Serum C4 level was normal, ruling out hereditary angioedema. Outcome Patient was discharged after five days in stable condition with resolution of symptoms. Conclusion ACEIs are the most common cause of drug-induced angioedema in the United States. Angioedema is self-limiting swelling that requires close airway monitoring. While health professionals recognize the risk for angioedema with active ACEI use, it is not well known that the risk of angioedema may occur for months following cessation of ACEI therapy. Increased awareness of delayed ACEI-induced angioedema following ACEI discontinuation is important for both providers and pharmacists to provide appropriate diagnosis and monitoring. Improved awareness would also allow patients with a history of ACEI-induced angioedema to be cognizant of the potential for recurrence following drug discontinuation.

Long‑term follow‑up of a case of recurrent angioedema due to acquired C1‑inhibitor deficiency – clinical and therapeutic aspects

Angioedema (AE) is a frequent pathology in medical practice, raising significant diagnostic and therapeutic problems. Angioedema due to acquired C1-inhibitor esterase (C1-INH) deficiency is a rare form of AE without urticaria, with life-threatening potential outcome, often associated with lymphoproliferative or autoimmune diseases. We report the long-term outcome of an 80-year-old female patient, diagnosed in 2014 with AE due to acquired C1-INH deficiency, with good response to attenuated androgens, who has been constantly monitored in our clinic for 12 years. The onset of AE attacks was six years before diagnosis confirmation, and was considered first induced by angiotensin-converting enzyme inhibitors (ACEIs) therapy, but she continued to have AE attacks after the discontinuation of ACEI. No underlying disease could be identified, despite extended medical evaluation. AE episodes stopped after the initiation of treatment with danazol in September 2014 and the C1-INH and C4 plasma levels became normal after one month. We have closely monitored the possible side effects of danazol and the occurrence of other clinical and laboratory manifestations. Danazol therapy was well tolerated and we could not find any causal disease for the C1-INH deficiency. During the last three years, moderate blood hypereosinophilia was recorded, with no clinical manifestations and clear cause, still under investigation.

Angiotensin-Converting Enzyme (ACE) Inhibitors May Moderate COVID-19 Hyperinflammatory Response: An Observational Study with Deep Immunophenotyping.

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARB), the most commonly prescribed antihypertensive medications, counter renin-angiotensin-aldosterone system (RAAS) activation via induction of angiotensin-converting enzyme 2 (ACE2) expression. Considering that ACE2 is the functional receptor for SARS-CoV-2 entry into host cells, the association of ACEi and ARB with COVID-19 outcomes needs thorough evaluation. We conducted retrospective analyses using both unmatched and propensity score (PS)-matched cohorts on electronic health records (EHRs) to assess the impact of RAAS inhibitors on the risk of receiving invasive mechanical ventilation (IMV) and 30-day mortality among hospitalized COVID-19 patients. Additionally, we investigated the immune cell gene expression profiles of hospitalized COVID-19 patients with prior use of antihypertensive treatments from an observational prospective cohort. The retrospective analysis revealed that there was no increased risk associated with either ACEi or ARB use. In fact, the use of ACEi showed decreased risk for mortality. Survival analyses using PS-matched cohorts suggested no significant relationship between RAAS inhibitors with a hospital stay and in-hospital mortality compared to non-RAAS medications and patients not on antihypertensive medications. From the analysis of gene expression profiles, we observed a noticeable up-regulation in the expression of 1L1R2 (an anti-inflammatory receptor) and RETN (an immunosuppressive marker) genes in monocytes among prior users of ACE inhibitors. Overall, the findings do not support the discontinuation of ACEi or ARB treatment and suggest that ACEi may moderate the COVID-19 hyperinflammatory response.

Angiotensin-Converting Enzyme Inhibitor-Induced Non-allergic Perioral Angioedema: A Case-Based Scoping Review.

Patients with angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema (ACEIIA) may visit family physicians. The aim of this article was to describe a case of delayed-onset ACEIIA and to present a concise scoping review. Using a case report and a scoping review study design, we report a case of ACEIIA, with clinically confirmed diagnosis. The symptoms resolved after replacing the offending ACEI with another antihypertensive agent. After excluding other causes of perioral swelling and discontinuation of ACEI, the patient was symptom-free within a few days thereafter. Based on this case presentation, we performed a meta-narrative scoping review including up-todate diagnosis and management of ACEIIA, based on published data in English, French, and German from inception to April 1, 2021. Patients with angioedema of unknown origin should be cautiously examined to rule out oral diseases, including allergy to dental materials and drug-induced angioedema. Clinicopathological aspects and current treatment guidelines for ACEI-associated angioedema are also presented.

RECURRENT ANGIOEDEMA FOLLOWING ANGIOTENSIN CONVERTING ENZYME INHIBITOR DISCONTINUATION

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Angiotensin converting enzyme inhibitors (ACEIs) are guideline recommended first-line treatment for hypertension. Angioedema is a recognized side effect of ACEI therapy, yet clinicians are often unaware that limited case reports describe recurrent angioedema following ACEI discontinuation. This is a case of ACEI-induced angioedema occurring after discontinuing ACEI therapy. CASE PRESENTATION: An elderly male with medical history of hypothyroidism, hypertension, and heart failure presented from his long-term care facility complaining of face, tongue, and throat swelling with dysphagia and voice changes starting 24 hours prior. Examination showed normal vital signs and edema of aforementioned areas. He denied family history of similar occurrences. It was reported 12 days prior he was seen for unilateral lip swelling and his enalapril was discontinued without further treatment. Medication administration record review showed ACEI was appropriately discontinued by his care facility. He was given methylprednisolone, diphenhydramine, intramuscular epinephrine, C1 esterase inhibitor, and 2 units of fresh frozen plasma prior to admission. The patient was monitored in the intensive care unit due to mild airway compromise but did not require invasive airway protection. A serum complement factor 4 level was checked and returned normal. He was discharged after 5 days in stable condition with resolution of symptoms. DISCUSSION: ACEIs are the most common cause of drug induced angioedema in the United States. ACEI-induced angioedema is a self-limiting swelling that may involve the lips, tongue, upper airway, and rarely intestinal wall. Swelling is said to occur because of ACEI inhibition on the angiotensin converting enzyme preventing degradation of vasoactive substances such as bradykinin (1). Recurrence of angioedema after ACEI discontinuation was reported in 46% of cases in one retrospective study (2). The precise etiology of this delayed reaction is not well described, though it is reasonable to hypothesize in part, a drug washout period must occur. The adverse drug reaction probability scale score was 5 (probable) in this patient (3). Recurrence has been documented more commonly in elderly male patients (2). The mainstay of treatment for non-allergic angioedema caused by ACEIs is discontinuation of the offending drug and acute airway management if needed. No drug therapy has been proven effective in the treatment of this condition (1). CONCLUSIONS: Increased awareness of delayed ACEI-induced angioedema following ACEI discontinuation is important among health care providers for appropriate diagnosis and monitoring. While self-limiting without a known effective treatment, close airway monitoring is critical for patient survival. Improved awareness would also allow patients with a history of ACEI-induced angioedema to be cognizant of the potential for recurrence early following drug discontinuation. REFERENCE #1: Erickson DL, Coop CA. Angiotensin-converting enzyme inhibitor-associated angioedema treated with c1-esterase inhibitor: A case report and review of the literature. Allergy Rhinol (Providence). 2016;7(3):168-171. REFERENCE #2: Beltrami L, Zanichelli A, Zingale L, Vacchini R, Carugo S, Cicardi M. Long-term follow-up of 111 patients with angiotensin-converting enzyme inhibitor-related angioedema. J Hypertens. 2011 Nov;29(11):2273-7. REFERENCE #3: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Adverse Drug Reaction Probability Scale (Naranjo) in Drug Induced Liver Injury. [Updated 2019 May 4]. DISCLOSURES: No relevant relationships by Mark Malesker, source=Web Response No relevant relationships by Shraddha Narechania, source=Web Response No relevant relationships by Bryton Perman, source=Web Response

Perioperative Care Standards in Cardiac Surgery Patients Aiming at Enhancing Recovery: A Nationwide Survey in the Netherlands and Belgium

The aim of this survey was to describe existing perioperative care standards and best practices in the Netherlands and Belgium. An online survey was followed up by an in-depth personal interview. The main outcomes were the existing standards of perioperative care for patients undergoing cardiac surgery. The online survey and subsequent interviews were targeted to one representative in the intensive care unit (ICU), cardiac surgery, and anesthesiology department from each cardiac surgical center in the Netherlands and Belgium. A representative intensive care physician, cardiac surgeon, and cardiac anesthesiologist. None. The response rate was 60% (71% for the Netherlands, and 44% in Belgium). Agreement across centers was found for discontinuation of proton-pump inhibitors (80%) and avoiding intra- and postoperative (92%) nonsteroidal antiinflammatory drugs. Additionally, 98% of respondents stated that physiotherapy should be started immediately in the ICU. Major divergence was found for elements such as the discontinuation of angiotensin-converting enzyme inhibitors (55%) or the postoperative use of chest support vests (44%). The authors demonstrated a wide range of different local protocols. Strategies differed among disciplines, hospitals, and countries. This emphasized the need for the implementation of a more universal protocol to further reduce variance and improve recovery practices. This nationwide survey was the first of its kind simultaneously studying best practices for cardiac surgery through the entire care pathway at the advent of Enhanced Recovery After Surgery (ERAS) Cardiac implementation. A multinational randomized controlled trial to test the implementation of an evidence-based ERAS Cardiac protocol is the next step to pave the way for further outcome improvements in this high-risk population.

Heart failure drug titration, discontinuation, mortality and heart failure hospitalization risk: a multinational observational study (US, UK and Sweden)

Use and dosing of guideline-directed medical therapy (GDMT) in patients with heart failure (HF) have been shown to be suboptimal. Among new users of GDMT in HF, we followed the real-life patterns of dose titration and discontinuation of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), beta-blockers, mineralocorticoid receptor antagonists (MRA) and angiotensin receptor-neprilysin inhibitors (ARNI). New users were identified in health care databases in Sweden, UK and US between 2016-2019. Inclusion criterion was a recent HF hospitalization (HHF) triggering the initiation of GDMT. Patients were grouped by GDMT, i.e. ACEi, ARB, beta-blocker, MRA and ARNI, and stratified by initial dose. Follow-up was 12 months, until death or study end. Outcomes were dose titration within each drug class, discontinuation and first HHF or death. Dose/discontinuation follow-up was assessed daily based on the coverage length of a filled prescription and reported on day 365. New users of ACEi (n=8426), ARB (n=2303), beta-blockers (n=10 476), MRA (n=17 421), and ARNI (n=29 546) were identified. Over 12 months, target dose achievement was 15%, 10%, 12%, 30%, and discontinuation was 55%, 33%, 24% and 27% for ACEi, ARB, beta-blockers and ARNI, respectively. MRA was rarely titrated and discontinuation rates were high (40%). Event rates for HHF or death ranged from 40.0-86.9 per 100 patient-years across the treatment groups. Despite high risk of clinical events following HHF, new initiation of GDMT was followed by consistent patterns of low up-titration and early GDMT discontinuation in three countries with different health care and economies. Our data highlight the urgent need for moving away from long sequential approach when initiating HF treatment and for improving just-in-time decision support for patients and health care providers.

Impact of in-hospital discontinuation with angiotensin receptor blockers or converting enzyme inhibitors on mortality of COVID-19 patients: a retrospective cohort study

BackgroundIn the first wave of the COVID-19 pandemic, the hypothesis that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) increased the risk and/or severity of the disease was widely spread. Consequently, in many hospitals, these drugs were discontinued as a “precautionary measure”. We aimed to assess whether the in-hospital discontinuation of ARBs or ACEIs, in real-life conditions, was associated with a reduced risk of death as compared to their continuation and also to compare head-to-head the continuation of ARBs with the continuation of ACEIs.MethodsAdult patients with a PCR-confirmed diagnosis of COVID-19 requiring admission during March 2020 were consecutively selected from 7 hospitals in Madrid, Spain. Among them, we identified outpatient users of ACEIs/ARBs and divided them in two cohorts depending on treatment discontinuation/continuation at admission. Then, they were followed-up until discharge or in-hospital death. An intention-to-treat survival analysis was carried out and hazard ratios (HRs), and their 95%CIs were computed through a Cox regression model adjusted for propensity scores of discontinuation and controlled by potential mediators.ResultsOut of 625 ACEI/ARB users, 340 (54.4%) discontinued treatment. The in-hospital mortality rates were 27.6% and 27.7% in discontinuation and continuation cohorts, respectively (HR=1.01; 95%CI 0.70–1.46). No difference in mortality was observed between ARB and ACEI discontinuation (28.6% vs. 27.1%, respectively), while a significantly lower mortality rate was found among patients who continued with ARBs (20.8%, N=125) as compared to those who continued with ACEIs (33.1%, N=136; p=0.03). The head-to-head comparison (ARB vs. ACEI continuation) yielded an adjusted HR of 0.52 (95%CI 0.29–0.93), being especially notorious among males (HR=0.34; 95%CI 0.12–0.93), subjects older than 74 years (HR=0.46; 95%CI 0.25–0.85), and patients with obesity (HR=0.22; 95%CI 0.05–0.94), diabetes (HR=0.36; 95%CI 0.13–0.97), and heart failure (HR=0.12; 95%CI 0.03–0.97).ConclusionsThe discontinuation of ACEIs/ARBs at admission did not improve the in-hospital survival. On the contrary, the continuation with ARBs was associated with a trend to a reduced mortality as compared to their discontinuation and to a significantly lower mortality risk as compared to the continuation with ACEIs, particularly in high-risk patients.

Acute Kidney Injury after Heart Valve Surgery in Elderly Patients: any Risk Factors to Modify?

IntroductionPostoperative acute kidney injury contributes to longer hospital stays and increased costs related to cardiac surgery in the elderly. We analyse the influence of the patient’s age on risk factors for acute kidney injury after cardiac valve surgery.MethodsWe evaluated the prevalence and risk factors for acute kidney injury in 939 consecutive patients undergoing valve surgery, between 2013 and 2018.ResultsThe prevalence of acute kidney injury was 19.5%. Hypertension (P=0.017); RR (95% CI): 1.74 (1.10-3.48), age ≥70 years (P=0.006); RR (95% CI): 1.79 (1.17-2.72), preoperative haematocrit <33% (P=0.009); RR (95% CI): 2.04 (1.19-3.48), glomerular filtration rate <60 ml/min/1.73 m2 (P<0.0001); RR (95%) CI: 2.36 (1.54-3.62) and cardiac catheterization <8 days before surgery (P=0.021); RR (95% CI): 2.15 (1.12-4.11) were identified as independent risk factors. In patients older than 70 years, with no kidney disease diagnosed preoperatively, glomerular filtration rate <70 ml/min/1.73 m2, male gender, cardiopulmonary bypass time, preoperative haematocrit <36% and preoperative therapy with angiotensin-converting enzyme inhibitors were risk factors for acute kidney injury after valve surgery.ConclusionsIn elderly patients, postoperative acute kidney injury develops with higher values of preoperative glomerular filtration rate than those observed in a younger population. Preoperative correction of anaemia, discontinuation of angiotensin-converting enzyme inhibitors and surgical techniques reducing cardiopulmonary bypass time would be considered to reduce the prevalence of renal failure.

Molecualr Association of Coronavirus with Diabetes Mellitus Type 2 in Pakistan

Patients with COVID-19 who have elevated blood sugar levels without a previous diagnosis of diabetes may be at a high risk of death and an increased risk of severe complications from the infectious disease, a new study says. We aimed to briefly review the general characteristics of the novel coronavirus (SARSCoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: “SARS-CoV-2”, “COVID-19”, “infection”, “pathogenesis”, “incubation period”, “transmission”, “clinical features”, “diagnosis”, “treatment”, and “diabetes”, with interposition of the Boolean operator “AND”. The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers or thiazolidinedione’s because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. Suggestions are made on the possible pathophysiological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients With Coronavirus Disease 2019: Friend or Foe?

When the coronavirus disease 2019 (COVID-19) wreaked an unprecedented havoc of an escalating number of deaths and hospitalization in the United States, clinicians were faced with a myriad of unanswered questions, one of the them being the implication of the renin-angiotensin-aldosterone system in patients with COVID-19. Animal data and human studies have shown that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the expression of ACE2. ACE2 is an enzyme found in the heart, kidney, gastrointestinal tract, and lung and is a coreceptor for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV2), the virus responsible for COVID-19. Therefore, one can speculate that discontinuing ACE inhibitor or ARB therapy may lead to decreased ACE2 expression, thereby attenuating the infectivity of SARS-CoV-2, and mitigating the disease progression of COVID-19. However, several studies have also shown that ACE2 exhibits reno- and cardioprotection and preserves lung function in acute respiratory distress syndrome, which would favor ACE inhibitor or ARB therapy. This article is to examine and summarize the 2 opposing viewpoints and provide guideline recommendations to support the use or discontinuation of ACE inhibitors and ARBs in patients with COVID-19.

Frequency of Intraoperative Hypotension After the Induction of Anesthesia in Hypertensive Patients with Preoperative Angiotensin-converting Enzyme Inhibitors.

IntroductionThe renin-angiotensin-aldosterone system (RAAS) is an important target in the treatment of hypertension. Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II. ACE inhibitors not only treat hypertension but also decrease morbidity and mortality in heart failure patients and in patients with acute myocardial infarction. The discontinuation of ACE inhibitors before the surgery is still controversial. To assess the current magnitude of the problem in our population, we aimed to conduct this study, which evaluated the frequency of intraoperative hypotension after the induction of anesthesia in controlled hypertensive patients with preoperative ACE inhibitors.Material and methodsThis descriptive case series study was conducted at a tertiary hospital in a developing country after approval from the Ethics Review Committee. A total of 115 adult patients, from 16 to 60 years of age, who have undergone elective surgery, have controlled hypertension on the desired drugs for at least six months, have no history of any cardiac event, and have taken the drug on the morning of the surgery, were included in the study after written consent. The demographic data of the patients were entered into the proforma. Preoperative systolic, diastolic, and mean arterial pressure were recorded by the researcher or an assignee in the preoperative holding area. The patients were followed in the recovery room by the team conducting the study until 10 minutes after the arrival of the patient in the recovery room. All statistical analyses were performed using Statistical Packages for the Social Sciences version 19 (SPSS Inc., Chicago, IL). p-value ≤0.05 was considered significant.ResultsOf the 115 patients, 56 (48.7%) patients were in the age group between 51 and 60 years of age; 38 patients were between the ages of 41 and 50 years and only 21 patients were 40 years or less. On gender, 68 patients were female and 47 were male. According to body mass index (BMI), the majority of the patients were in the overweight group, amounting to 53 (46%), and 86 (74.78%) patients were known diabetics. Overall, 77 (66.96%) of the patients developed intraoperative hypotension with 41 (35.65%) patients requiring the use of vasopressors in order to correct the hypotension. No statistically significant difference was found between demographic and clinical variables.ConclusionIntraoperative hypotension is more frequent in patients with controlled hypertension on ACE inhibitors although more studies need to be conducted on a larger population in order to determine a more definitive result.

Psoriasis After Exposure to Angiotensin-Converting Enzyme Inhibitors: French Pharmacovigilance Data and Review of the Literature.

Angiotensin-converting enzyme inhibitors (ACEIs) can induce or aggravate psoriasis. This risk is not specified in the Summary of Product Characteristics (SmPC) of some drugs of this class, such as captopril or enalapril. We aimed to investigate the association between psoriasis and ACEI exposure. We analyzed spontaneous reports recorded in the French national Pharmacovigilance Database (FPVD) from 1985 to 31 December 2018. The association between psoriasis and ACEI exposure was assessed using the case/non-case method. We also reviewed literature reports. One hundred reports of psoriasis after ACEI exposure were registered in the FPVD. The reporting odds ratio (ROR) was 2.40 (95% CI 1.96-2.95). Time to onset was < 1year in 67% of reports. Outcome was favorable in 73% of reports after ACEI discontinuation. Almost all ACEIs were concerned. In the literature, we found 21 published reports of psoriasis with ACEIs. Time to onset ranged from 1week to 4months. Outcome was also favorable after ACEI discontinuation in over half of the literature reports. We found a statistically significant association between psoriasis and ACEI, which constitutes a potential safety signal. The risk of psoriasis is a class effect, time to onset is less than1year, and outcome is favorable after ACEI discontinuation. Psoriasis should be mentioned in the SmPCs of all ACEIs, and healthcare professionals should be informed about this risk.

2631 Angiotensin Converting Enzyme Inhibitor-Induced Isolated Angioedema of Small Bowel

INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEi) are generally known to cause angioedema, with the face, tongue, and pharynx primarily involved. ACEi-induced small bowel angioedema is relatively rare occurring in 0.1 to 0.7% patients on ACEi. CASE DESCRIPTION/METHODS: Our case report is about a 34-year-old woman who was recently started on lisinopril and diagnosed with angioedema of the stomach and duodenum. The patient presented to our hospital with a 3-week history of nausea and a 2-day history of worsening epigastric pain. She also had one episode of non-bilious emesis and one episode of watery diarrhea. Her home medications included lisinopril 20 mg daily for hypertension, which she started taking 3 weeks ago. She was hemodynamically stable and physical examination revealed mild epigastric tenderness with no organomegaly, guarding or rebound tenderness. Laboratory values were significant for leukocytosis of 12,000, and normal complement and lipase levels. Abdominal computed tomography (CT) scan showed signs of findings of acute severe enteritis involving the duodenum and proximal jejunum, with no pancreatitis. Endoscopy revealed edema of the duodenum. Given the high suspicion for ACEi induced angioedema of the small bowel, her lisinopril was discontinued and the patient showed complete symptom resolution within 24 hours. DISCUSSION: ACEi-induced angioedema of the small bowel is a rare clinical presentation, however, it is an important differential diagnosis to consider when a patient taking an ACEi presents with nausea and abdominal pain. It is important to highlight angioedema of the small bowel can occur at any time after a patient starts taking an ACEi. Although ACEi-induced small bowel angioedema is relatively rare, its recognition is important as ACEi use is high and misdiagnosis can lead to frequent hospital visits and unnecessary surgery. The first line treatment being discontinuation of ACEi, there are other pharmacological options including icaibant, ecallantide which have unproven efficacy from the current trails. Fresh frozen plasma has shown to have success in cases where nothing has worked. The usual dose being used to treat are 2 to 4 units of fresh frozen plasma.

Discontinuation of angiotensin-converting enzyme inhibitors or beta-blockers and the impact on heart failure hospitalization rates.

Adherence to evidence-based therapy is essential for optimal management of heart failure. Yet, medication adherence is poor in heart failure patients. The Ascertaining Barriers to Compliance Project decomposed the medication adherence process into initiation, implementation, and discontinuation stages, but electronic monitoring-based adherence analyses usually do not consider this process. The aim of this study was to describe individual-patient patterns of medication adherence from electronic monitoring data among adults with chronic heart failure, adherence types, and risk factors for increased all-cause hospitalization including measures of poor adherence such as discontinuation. Data from two prospective studies of adherence measured with electronic monitoring for heart failure patients were combined and restricted to monitoring of angiotensin-converting enzyme inhibitors and beta-blockers over an initial three-month period. Hospitalizations were recorded for this period as well as for a three-month follow-up period. Analyses were conducted using adaptive modeling methods to identify individual-patient adherence patterns, adherence types, and risk factors for an increased hospitalization rate. Using electronic monitoring data for 254 heart failure patients, four adherence types were identified: highly consistent, consistent but variable, moderately consistent, and poorly consistent. Sixteen individually significant risk factors for increased hospitalization rates were identified and used to generate a multiple risk factors model. Medication discontinuation was the most important individual risk factor and most important in the multiple risk factors model. Discontinuation of angiotensin-converting enzyme inhibitors or beta-blockers increases hospitalization rates for heart failure patients. Interventions that effectively address this problem are urgently needed.

Nine year follow-up of a rare case of angioedema due to acquired C1-inhibitor deficiency with late onset and good response to attenuated androgen

BackgroundAngioedema due to acquired deficiency of C1-inhibitor (C1-INH-AAE) is a rare disease sharing some clinical and laboratory similarities with hereditary angioedema, but with late onset and no positive family history. The underlining cause may be malignant or due to autoimmune diseases, but some cases remain idiopathic.Case presentationWe report a case of a 75 year old woman suffering from recurrent episodes of angioedema since the age of 66, considered first induced by treatment with angiotensin-converting-enzyme inhibitors (ACEI). She continued to have angioedema attacks during 6 years after discontinuation of ACEI, until evaluation in our clinic in 2014, when C1 inhibitor esterase (C1-INH) deficiency was confirmed. The extended medical evaluation for inflammatory, allergic, autoimmune and neoplasic diseases was negative. C1-INH and complement fraction C4 plasma levels were significantly decreased at all measurements, but no diagnostic criteria for diseases known to induce C1-INH deficiency could be found. We first initiated daily prophylactic treatment with tranexamic acid, with no amelioration after 3 months. During the last and most severe attack, with the first facial and laryngeal edema, we have switched to attenuated androgen danazol. The evolution was very good, with prompt remission of angioedema and significant increase of C1-INH and C4 plasma levels after 2 weeks of daily danazol use. She completed 3 years of continuous treatment with low daily maintenance dose of danazol (ongoing), with no angioedema attack. We closely monitored C1-INH and C4 plasma levels, possible danazol side effects and any signs suggesting late onset of C1-INH deficiency causal disease.ConclusionWe reported a particular case of rare angioedema due to acquired deficiency of C1-inhibitor, which has no clear cause after long follow-up, but good response to attenuated androgen. We concluded that the awareness of angioedema due to C1-INH deficiency should be increased within medical community and therapeutic options should be more clearly indicated and available for all diagnosed cases.

Incidence of and Risk Factors for Severe Adverse Events in Elderly Patients Taking Angiotensin‐Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers after an Acute Myocardial Infarction

To assess the incidence of and risk factors associated with severe adverse events in elderly patients who used angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) after an acute myocardial infarction (AMI). Retrospective cohort study. Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse (Medicare service claims database), American Community Survey of the U.S. Census Bureau, and Multum Lexicon Drug database. A total of 101,588 eligible Medicare fee-for-service beneficiaries 66 years or older, who were hospitalized for AMI between January 1, 2008, and December 31, 2009, and used ACEIs or ARBs within 30 days after discharge. Primary outcomes were hospitalizations for acute renal failure (ARF) and hyperkalemia. The secondary outcome was discontinuation or suspension of ACEI/ARB therapy after a visit to a health care provider. The primary risk factors of interest were age, sex, race/ethnicity, and chronic kidney disease (CKD). Cumulative incidence curves and multivariable Fine-Gray proportional hazards models with 95% confidence intervals (CIs) were used with death as a competing risk in both intention-to-treat (ITT) and as-treated (AT) analyses. In the study cohort, 2.8% experienced ARF, 0.5% experienced hyperkalemia, and 63.7% discontinued ACEI/ARB therapy within 1 year after hospital discharge. Approximately half of the incidence of ARF and hyperkalemia occurred within 6 months after hospital discharge, but the cumulative incidence increased after 6 months. Patients older than 85 years had a higher rate of ARF (ITT hazard ratio [HR] 1.15, 95% CI 1.04-1.28) and hyperkalemia (ITT HR 1.33, 95% CI 1.05-1.68) compared with those aged 65-74 years. Patients with baseline CKD had higher rates of ARF (ITT HR 1.61, 95% CI 1.42-1.82), hyperkalemia (ITT HR 1.41, 95% CI 1.11-1.77), and ACEI/ARB therapy discontinuation or suspension (ITT HR 1.05, 95% CI 1.02-1.09). We found a low incidence of ARF and hyperkalemia in elderly patients treated with ACEIs or ARBs after AMI hospitalization. However, a high rate of treatment discontinuation might prevent a higher rate of occurrence of these events. Long-term careful monitoring of severe adverse events and timely discontinuation of ACEIs or ARBs among elderly patients with advancing age and CKD after an AMI is warranted in clinical practice.