Prescription Of Angiotensin-converting Enzyme Inhibitors Research Articles

#3605 TREATMENT OF HYPERTENSION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PATIENTS: A COMPARISON OF POLISH AND JAPANESE MEDICATION PATTERNS

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and fourth case of kidney failure worldwide. Treatment options for ADPKD include therapy with vasopressin (ADH) receptor 2 antagonist, nephroprotection, and eventually renal replacement therapy. The earliest and most prevalent systemic complication of ADPKD is hypertension. The pathogenesis of hypertension in ADPKD is multifactorial, including endothelial dysfunction and activation of renin-angiotensin-aldosterone system (RAAS). Antihypertensive therapy with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is expected to decrease the left ventricular hypertrophy and proteinuria in ADPKD patients, according to HALT-PKD study. Data about preferences of second choice therapy and safety of other medications is lacking. Diuretics are commonly prescribed drugs in essential hypertension but carry risk of provoking ADH stimulation that may be potentially harmful in ADPKD because ADH stimulates cyst proliferation. We analyzed real-life data on antihypertensive prescriptions to determine and compare trends in treatment of hypertension in ADPKD patients in Poland and Japan. Method Patterns of antihypertensive prescriptions of ACEi, ARB, and diuretics were analyzed in patients from Poland (n = 131, median age 40 years; data 2014-2019) and Japan (n = 180, median age 44 years, data 2005-2017) diagnosed with ADPKD. The number of different medications used in combination was counted. For diuretics, even if multiple diuretics were used, they were counted as a single item. Furthermore, combination drug products were decomposed into their individual components, which were counted as either antihypertensive drugs or diuretics, respectively. Results The patterns of the number of prescriptions of antihypertensive drugs were similar in the two countries, see Figure 1. In Polish patients, the commonest pattern was no antihypertensive drugs (45.0%), followed by one (28.2%), two (16.8%), three (9.2%), and four (0.8%) prescriptions. In Japanese patients, the corresponding figures were: no antihypertensive drugs (41.1%), followed by one (32.2%), two (20.6%), three (4.4%), and four (1.7%) prescriptions in decreasing order. ACEi and ARBs were used for more than half of the patients, both Polish and Japanese. The utilization of ACEi/ARB in Polish individuals as a first-choice medication was 78.4% (75.0% in men, 81.0% in women) while in Japan 65.5% (66.7% in men, 63.2% in women). When patients were prescribed 3 or more antihypertensive drugs, ACEi/ARB was chosen in 100%, in both countries. Regarding diuretics, 15.3% of Polish patients and 6.7% of Japanese patients used them. Among patients who had one antihypertensive drug, 7.6% of Polish and 2.2% of Japanese patients also used diuretics. 44.2% of Polish and 38.9% of Japanese did not use either antihypertensive drugs or diuretics. Conclusion The patterns of number of prescriptions of antihypertensive drugs were similar among ADPKD patients in Poland and Japan while the use of diuretics was more common in Polish than in Japanese patients. In both countries, ACEi/ARB was the most frequent choice, which is in concordance with current recommendations. Unexpectedly, anti-RAAS were as frequently prescribed in women than in men, suggesting that the teratogenicity risk of the drugs did not limit access to the benefits of the treatment in both sexes.

AB022. SOH23ABS_065. Barriers to the prescription of ACE inhibitors in patients with peripheral arterial disease or related cardiovascular disease

AB022. SOH23ABS_065. Barriers to the prescription of ACE inhibitors in patients with peripheral arterial disease or related cardiovascular disease

Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Use and ICU Delirium Incidence

Background: Delirium is a form of acute brain dysfunction which is associated with longer hospital stays, cognitive decline, and increased risk of mortality. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) have been proposed to have neuroprotective effects. ACE inhibitors and ARBs both block the action of angiotensin II leading to an increase in release of acetylcholine. As acetylcholinergic failure is implicated in delirium pathophysiology, ACE inhibitors or ARBs may improve cognitive function and protect against ICU delirium.
 Objective: To study the relationship between the prescription of ACEIs or ARBs on delirium occurrence in ICU patients.Design: Observational studySetting: ICUs in three large academic hospitals in IndianapolisPatients: 4791 patients admitted to the ICU for more than 24 hours
 Methods and Main Results: The Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method for the ICU (CAM-ICU) were used to evaluate patients for the presence of delirium while in the ICU. ACEI/ARB exposure was determined if the patient had prescription for these medications 6 months prior to ICU admission. The cohort of 4791 participants had a mean age of 60.7 years (SD: 16.1), 46% were female, and 39% were African American. The most common comorbidities were hypertension (68%), hyperlipidemia (49%), and depression (43%). Delirium incidence in this cohort was 13%. Prescription of an ACEI alone (OR: 0.91, 95% CI: 0.73, 1.15, p=0.425) or ARB alone (OR: 0.64, 95% CI: 0.38, 1.07, p=0.114) were not significantly associated with decreased odds of delirium.
 Conclusion: Prescription of an ACEI or ARB 6 months prior to ICU admission was not associated with reduced incidence of ICU delirium, although further research is needed. Larger studies with medication adherence data are needed to further study the relationship among ACEI/ARBs and delirium.

1234 IMPROVING HEART FAILURE MANAGEMENT WITHIN HOSPITAL AT HOME

Abstract Introduction Heart failure (HF) is a common problem managed in our West Lothian multi-disciplinary hospital at home (HaH) service, however significant variation in practice was noted with considerable resource implications. We aimed to standardise and improve this by developing a dedicated protocol. Methods We developed a protocol to guide the assessment and management of HF within HaH. We collected baseline (n=25) and follow-up data (n=10) after protocol introduction from patients referred to HaH with heart failure. Outcomes reviewed included anticipatory care planning (ACP) decisions, length of stay (LOS) and treatment strategy. We held staff education sessions and surveyed staff confidence regarding HF management. Results ACP discussion rates improved after protocol introduction, with decision rates improving for both escalation of care (28% to 80%) and resuscitation (44% to 60%). LOS reduced after protocol introduction (mean 6.3 days to 5.9 days). Titration of oral diuretics alone (71%) was associated with a shorter LOS (mean 5.4 days) compared to IV (29%, mean 8.1 days), with no difference in 28 day outcome. In those with HF with reduced ejection fraction, the rates of beta-blocker prescription increased (57% to 80%) however ACE-inhibitor prescription decreased (29% to 20%). Use of add-on therapy (e.g. thiazide diuretics) increased (12% to 30%) with a decrease in complication rates (12% to 0%). All staff found the protocol helpful with an improvement in confidence levels. Conclusions Through introducing a standardised protocol, we observed an improvement in anticipatory care discussion rates and a trend towards shorter LOS. Oral diuretic titration was less resource intensive without an adverse impact on outcome. Future plans include ongoing education and data collection, trialling a joint multi-disciplinary meeting with cardiology for discussion of complex patients and embedding a treatment strategy of oral diuretic titration with a ‘discharge with planned review' approach in appropriate patients.

598 PREVALANCE AND PREDICTORS OF LONG-TERM CARDIAC SYMPTOMS IN PATIENTS WITH TAKOTSUBO SYNDROME

Abstract Background Takotsubo syndrome (TTS) is characterized by an acute and transient left ventricular dysfunction, usually involving the apical and midventricular segments, associated with troponin elevation and often triggered by either emotional or physical stressors. Once considered a benign condition, it is now clear that TTS patients have increased long-term mortality compared with the general population. Prevalence and the determinants of long-term cardiac symptoms in TTS patients have been scarcely investigated. Methods We enrolled consecutive patients admitted to our Centre with a diagnosis of TTS . All patients underwent invasive coronary angiography with left ventriculography at admission and only those fulfilling both the Mayo Clinic and Heart Failure Association criteria for a TTS diagnosis were selected for this study. Clinical, biochemical, and instrumental data were collected at admission and before discharge, and patients were followed-up for: symptoms recurrence (i.e., presence of effort angina and/or dyspnoea in the absence of other obvious causes) and all-cause mortality. The prevalence of long-term symptoms was further compared with a control group of unselected patients admitted for acute coronary syndromes (ACS) in the same period, matched for sex, age, and left ventricular ejection fraction (LVEF) at discharge. Results We eventually enrolled 118 patients (aged 73±10 years, 91% of whom were female). Acute chest pain was the most common presenting symptom (73%), followed by dyspnoea (32%), acute heart failure (16%), cardiogenic shock (9%), and syncope (8%). Most of cases (82%) were classified as having a typical (apical) LV dysfunction. Either a physical or an emotional stressor was identified in 37 (31%) and 31 (26%) of the patients, respectively. At admission, patients showed moderate systolic dysfunction (LVEF 40±9%), which was often improved at discharge (LVEF 52±8%). Over a median follow-up of 21 (interquartile interval 11-53) months, 35% of patients complained of some cardiac symptom: 32% of patients complained of effort dyspnoea and 7% (partially overlapping with the former) complained of effort angina. When compared with ACS patients (n=55, aged 71±10 years, 94% women, LVEF 53±9%), TTS patients featured a similar mortality rate, a lower (non-significant) prevalence of angina, and a significantly higher prevalence of dyspnoea (p=0.02). Notably, while a lower age at presentation (p=0.017) and a physical trigger (p=0.015) were significantly associated with the risk of recurrent angina, the absence of chest pain (p=0.044), a lower LVEF at admission (p=0.019), and a higher troponin T concentration at discharge (p=0.018) were associated with the presence of dyspnoea at follow-up. Finally, older age, male sex, renal dysfunction, cardiogenic shock, and concomitant coronary artery disease were all associated with a higher risk of death. Prescription of ACE-inhibitors and/or beta-blockers were associated with reduced risk (p<0.05, for all), in line with previous reports. Conclusion TTS is associated with a high risk of recurrent cardiac symptoms, mostly dyspnoea, over time. Selected clinical, biochemical, and instrumental characteristics may help identify patients more at risk, who may deserve a closer follow-up and potentially tailored therapies, to be investigated in future studies.

Cardiovascular Diseases, Medications, and ALS: A Population-Based Case-Control Study

Introduction: We investigated the associations between antecedent all-cause CVD diagnoses, cause-specific CVD diagnosis, and CVD medication prescriptions with the risk of developing amyotrophic lateral sclerosis (ALS). Materials and Methods: We conducted a population-based case-control study of U.S. Medicare enrollees from 2006 to 2013. The final sample included 3,714 incident ALS cases and 18,570 controls (matched on age, sex, enrollment length, and county). Information was collected from Medicare Parts A, B, and D administrative claims data on hypertension, ischemic heart disease, heart failure, acute myocardial infarction, atrial fibrillation, prescriptions of angiotensin-converting enzyme inhibitors, angiotensin II receptors blockers, calcium channel blockers, beta blockers, and antiarrhythmics. Associations were evaluated using conditional logistic regression adjusting for age, sex, race/ethnicity, geographical location, alcohol and tobacco use, and socioeconomic status. Results: The odds ratio (OR) for having one or more ICD-9 codes for any cardiovascular disease diagnosis at least 24 months prior to the date of ALS diagnosis was 0.85 (95% confidence interval [CI]: 0.78–0.92). Cardiovascular conditions that were inversely associated with ALS included heart failure (OR = 0.79; 95% CI 0.70–0.89), atrial fibrillation (OR = 0.81; 95% CI 0.77–0.92), and hypertension (OR = 0.91; 95% CI 0.84–0.98). Exposures to several classes of cardiovascular medications were inversely associated with ALS risk even after adjusting for confounding by indication, including ACE inhibitors (OR = 0.84, 95% CI 0.77–0.91), calcium channel blockers (OR = 0.64, 95% CI 0.59–0.70), and beta blockers (OR = 0.76, 95% CI 0.71–0.83). Discussion/Conclusion: These findings merit additional research, including animal studies and pilot clinical trials, to further evaluate and evidence the effects of ACEIs, CCBs, and BBs on the risk of developing and clinical expression of ALS.

Abstract 13910: Racial/Ethnic Outcomes Following Percutaneous Coronary Intervention

Introduction: Asian-American/Pacific Islanders (AAPIs) and Hispanics are two of the most rapidly growing minorities, but both are poorly represented in the cardiovascular literature. In light of national quality improvement efforts to ensure adherence to cardiovascular therapy guidelines, this study examines guideline adherence and outcomes in AAPIs and Hispanics compared to non-Hispanic Whites (NHW) in a quaternary care center after percutaneous coronary intervention (PCI). Methods: 1,896 AAPI, Hispanics, and NHW adults from February 28, 2012 to December 30, 2020 who underwent emergent or elective PCI were included. The primary endpoint was the prescription of post-PCI guideline-directed medical therapy including aspirin, statins, P2Y12 receptor blockers, and cardiopulmonary rehabilitation. Secondary endpoints included comorbidity burden, post-PCI morbidity and mortality, and prior PCI. Analyses were adjusted for age, sex, and insurance type. Results: Hispanics had the lowest median age and the highest rates of government insurance. Hispanics had lower odds of either ACE inhibitor or ARB prescription versus NHW (OR = 0.75, p = 0.03). Odds of ticagrelor prescriptions were lower for both Hispanics (OR = 0.56, p = 0.01) and AAPIs (OR = 0.62, p = 0.02) versus NHW. However, odds of clopidogrel prescriptions were higher for Hispanics than NHW (OR = 1.57, p = 0.01), while AAPIs trended towards the same (OR = 1.42, p = 0.05). No differences were found for statin or cardiopulmonary rehabilitation prescriptions. AAPIs and Hispanics had significantly higher risks of diabetes (OR = 2.28 and 1.8 respectively, p < 0.01) and of being on dialysis (OR = 2.25 and 2.52 respectively, p < 0.01) than NHW. AAPIs also had higher odds of hypertension than NHW (OR = 1.51, p = 0.01). Hispanics had significantly higher risk of post-PCI mortality versus NHW (OR = 2.12, p < 0.01). Conclusions: AAPIs and Hispanics had lower odds of ticagrelor prescription than NHW, and Hispanics had higher odds of clopidogrel prescription. Hispanics also had higher odds of mortality post-PCI. Further, AAPIs and Hispanics had higher comorbidity burdens. This study suggests that despite quality improvement efforts, work remains to be done to narrow health disparities.

Cluster analysis of extracellular matrix biomarkers predicts the development of impaired systolic function within 1 year of acute myocardial infarction

The clinical utility of combining extracellular matrix (ECM) biomarkers to predict the development of impaired systolic function following acute myocardial infarction (AMI) remains largely undetermined. A combination of ELISA and multiplexing assays were performed to measure matrix metalloproteinase (MMP)-2, MMP-3, MMP-8, MMP-9, periostin, N-terminal type I procollagen (PINP) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in plasma samples from 120 AMI patients. All patients had an echocardiogram within 1 year of AMI, and were divided into impaired (n = 37, LVEF < 50%) and preserved (n = 83, LVEF ≥ 50%) systolic function groups. Exploratory factor analysis was performed on log-transformed biomarkers using principle axis analysis with Oblimin rotation. Cluster analysis was performed on log-transformed and normalised biomarkers using Ward’s method of minimum variance and the squared Euclidean distance metric. Upon univariate analysis, current smoking, prescription of ACE inhibitors at discharge, peak hsTnT > 610 ng/L (median), MMP-8 levels, Factor 1 scores and Cluster One assignment were predictive of impaired systolic function. Upon multivariate analysis, Cluster One assignment (odds ratio [95% CI], 2.74 [1.04–7.23], p = 0.04) remained an independent predictor of systolic dysfunction in combination with clinical variables. These observations support the usefulness of combining ECM biomarkers using cluster analysis for predicting the development of impaired systolic function in AMI patients.

Sex differences in acute coronary syndrome management and in 12-month case-fatality trends: data from the French MONICA registries

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Santé publique France, U1167 - RID-AGE - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France. Background Earlier studies, have reported sex differences in clinical presentation, management and outcomes of acute coronary syndrome (ACS) which have prompted the medical community to take actions to erase these differences. To our knowledge, there has been no recent analysis of sex difference trends in ACS management, to assess whether these differences have been attenuated over time. Aim To assess recent sex differences trends in ACS characteristics, management and associated mortality. Methods We assessed all men and women (aged 35-74) hospitalized for an incident (first) ACS, in the 3 distinct geographical areas covered by the MONICA registries in the north, east and south-west of France, during a 12-month period in 2006 and a 6-month period in 2016. We analyzed the patients’ clinical, biochemical, electrocardiographic and care-related data, and their vital status 12 months after the ACS. Results We analyzed 2023 incident ACSs in 2006 and 1173 in 2016. The proportion of men was three times higher than that of women in both periods. In 2016, women were younger (62.0 y in 2006 and 60.4 y in 2016; p=0.06) and men were older (57.6 y in 2006 and 59.0 y in 2016; p&amp;lt;0.01). Women had no longer more atypical symptoms than men in 2016. In both men and women, the proportion of patients with NSTEMI increased from 26% in 2006 to 39% in 2016 (p&amp;lt;0.0001), whereas the proportion of patients with unstable angina decreased from 14% in 2006 to 7% in 2016 (p&amp;lt;0.0001). Between 2006 and 2016, the proportion of thrombolysis fell from 10% to 1% (p&amp;lt;0.0001); conversely, the proportion of patients receiving angioplasty increased from 67% to 75% (p&amp;lt;0.001). However, men were still more likely than women to receive revascularization therapy (+19% in 2006 and +18% in 2016). Between 2006 and 2016, prescriptions of angiotensin-converting enzyme inhibitors at discharge decreased from 68% to 64% (p&amp;lt; 0.01), and prescriptions of statins increased from 89% to 91% (p=0.02), as did prescription of functional rehabilitation from 34% to 40% (p&amp;lt;0.0001). Despite these trends, platelet aggregation inhibitors, statins and functional rehabilitation were still less prescribed in women than men in 2016 (p&amp;lt;0.01), independently of confounders. Finally, the 12-month case fatality rate was 11% in 2006 and 10% in 2016 (p=0.15), without sex differences. Conclusions The results of the present study evidenced an improvement over time in the management of ACS. However, although there were no longer sex differences in the patients’ age and clinical presentation, women with ACS were still less likely than men to receive revascularization and pharmacological treatments in 2016.

FC082: Effects of Dapagliflozin in Patients with Chronic Kidney Disease According to Background Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Dose

Abstract BACKGROUND AND AIMS Treatment guidelines for patients with chronic kidney disease (CKD) recommend renin–angiotensin system inhibition (RASi) with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) to reduce the risk of kidney failure. However, patients with more advanced CKD do not always tolerate RASi. The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of kidney failure in patients with CKD in the DAPA-CKD trial. We performed a post hoc analysis of this trial to assess the efficacy of dapagliflozin by baseline dose level of ACEi or ARB. METHOD Participants with CKD [estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2; urinary albumin-to-creatinine ratio (UACR) 200–5000 mg/g), with or without type 2 diabetes, were randomized 1:1 to dapagliflozin 10 mg or placebo, once daily. Participants were to be treated with the recommended target dose, or a stable tolerated dose of ACEi or ARB, unless medically contraindicated, for ≥4 weeks prior to inclusion. The primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease or death from a kidney or cardiovascular cause. A prespecified kidney-specific secondary outcome was the same as the primary endpoint, but without cardiovascular death. A composite cardiovascular outcome (heart failure hospitalization or cardiovascular death), and all-cause mortality were other secondary endpoints. Time-to-event analyses were performed to assess the effects of dapagliflozin versus placebo according to baseline prescription and dose of ACEi or ARB treatment. RESULTS Of 4296 (99.9%) participants with available data on ACEi/ARB doses, 1231 (28.7%) were using the target dose, 1867 (43.5%) a dose ≥50% to &amp;lt;100% of target, 1068 (24.9%) a dose 0 to &amp;lt;50% of target and 130 (3.0%) were not using an ACEi/ARB. In the placebo group, the event rate for the primary outcome was highest among participants not using ACEi/ARBs compared to the other subgroups (figure 1). The benefit of dapagliflozin on the primary composite outcome was consistent regardless of use or non-use of the target dose of ACEi/ARBs. This consistency was maintained for the secondary outcomes (Figure 1). Dapagliflozin compared to placebo reduced the rate of eGFR decline over the study by –0.93 [95% confidence interval (95% CI) 0.61–1.25] mL/min/1.73 m2. This effect was present regardless of the use or non-use of target doses of ACEi/ARBs (P for interaction 0.877). CONCLUSION Dapagliflozin was similarly efficacious in reducing major adverse kidney and cardiovascular outcomes in participants with CKD regardless of the use or dose of ACEi/ARB.

Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Use Associated with Reduced Mortality and Other Disease Outcomes in US Veterans with COVID-19.

ObjectiveTo determine the association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) use and coronavirus disease 2019 (COVID-19) severity and outcomes in US veterans.Patients and MethodsWe retrospectively examined 27,556 adult US veterans who tested positive for COVID-19 between March to November 2020. Logistic regression and Cox proportional hazards models using propensity score (PS) for weight, adjustment, and matching were used to examine the odds of an event within 60 days following a COVID-19–positive case date and time to death, respectively, according to ACEI and/or ARB prescription within 6 months prior to the COVID-19–positive case date.ResultsThe overlap PS weighted logistic regression model showed lower odds of an intensive care unit (ICU) admission (odds ratio [OR] 95% CI 0.77, 0.61–0.98) and death within 60 days (0.87, 0.79–0.97) with an ACEI or ARB prescription. Veterans with an ARB-only prescription also had lower odds of an ICU admission (0.64, 0.44–0.92). The overlap PS weighted model similarly showed a lower risk of time to all-cause mortality in veterans with an ACEI or ARB prescription (HR [95% CI]: 0.87, 0.79–0.97) and an ARB only prescription (0.78, 0.67–0.91). Veterans with an ACEI prescription had higher odds of experiencing a septic event within 60 days after the COVID-19–positive case date (1.22, 1.02–1.46).ConclusionIn this study of a national cohort of US veterans, we found that the use of an ACEI/ARB in patients with COVID-19 was not associated with increased mortality and other worse outcomes. Future studies should examine underlying pathways and further confirm the relationship of ACEI prescription with sepsis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40265-021-01639-2.

Effects of the COVID-19 pandemic on heart failure hospitalizations in Japan: interrupted time series analysis.

AimsThe Coronavirus Disease 2019 (COVID‐19) pandemic has had unprecedented effects on health care utilization for acute cardiovascular diseases. Although hospitalizations for acute coronary syndrome decreased during the COVID‐19 pandemic, there is a paucity of data on the trends and management of heart failure (HF) cases. Furthermore, concerns have been raised that angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase susceptibility to COVID‐19. This study aimed to elucidate changes in HF hospitalizations from the COVID‐19 state of emergency in Japan and investigated changes in the prescription of ACEIs and ARBs, and in‐hospital mortality.Methods and resultsWe performed an interrupted time series analysis of HF hospitalizations in Japan to verify the impacts of the COVID‐19 state of emergency. Changes in the weekly volume of HF hospitalizations were taken as the primary outcome measure. Between 1 April 2018 and 4 July 2020, 109 429 HF cases required admission. After the state of emergency, an immediate decrease was observed in HF cases per week [−3.6%; 95% confidence interval (CI): −0.3% to −6.7%, P = 0.03]. There was no significant change in the prescription of ACEIs or ARBs after the state of emergency (4.2%; 95% CI: −0.3% to 8.9%, P = 0.07). The COVID‐19 pandemic had no effect on in‐hospital mortality among HF patients (5.3%; 95% CI: −4.9% to 16.6%, P = 0.32).ConclusionsWe demonstrated a decline in HF hospitalizations during the COVID‐19 pandemic in Japan, with no clear evidence of a negative effect on the prescription of ACEIs and ARBs or in‐hospital mortality.

Rate of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Use and the Number of COVID-19–Confirmed Cases and Deaths

The novel coronavirus SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor as an entry point to the cell. Cardiovascular disease (CVD) is a risk factor for COVID-19 with poor outcomes. We tested the hypothesis that the rate of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use is associated with the rate of COVID-19–confirmed cases and deaths. We conducted a geospatial, ecological study using publicly available county-level data. The Medicare ACEI and ARB prescription rate was exposure. The COVID-19–confirmed case and death rates were outcomes. Spatial autoregression models were adjusted for the rate of births and deaths; Group Quarters population; percentage of female; percentage of Native American, Pacific Islander, Hispanic, and Black; percentage of children and older (>65 years) adults; percentage of uninsured; percentage of those living in poverty; percentage of those who are obese, smoking, admitting insufficient sleep, and those with at least some college degree; median household income; air quality index; CVD hospitalization rate in Medicare beneficiaries; and CVD death rate in a total county population. After adjustment for confounders, the ACEI use rate did not associate with COVID-19–confirmed case rate (direct county-own effect + 0.027%; 95% confidence interval [CI] −1.080 to 1.134; p = 0.962; indirect spillover effect + 0.26%; 95% CI −70.0 to 70.5; p = 0.994). Similarly, the ARB use rate was not associated with COVID-19–confirmed case rate (direct effect + 0.029%; 95% CI −0.803 to 0.862; p = 0.945; indirect effect + 0.19%; 95% CI −52.8 to 53.2; p = 0.994). In both unadjusted and adjusted Bayesian zero inflation Poisson analysis, neither ACEI nor ARB use rates were associated with COVID-19 death rates. In conclusion, ACEI and ARB use rates were not associated with COVID-19 infectivity and death rate in this ecological study.

Meta-analysis of the association between angiotensin pathway inhibitors and COVID-19 severity and mortality

BackgroundConflicting findings and the analysis of unpublished and retracted data have led to controversy on the safety of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in people with COVID-19 infection. This meta-analysis examined the association of prescription of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) with the outcome from COVID-19.MethodsA systematic search was conducted to find published studies that reported the outcome of COVID-19 in relation to prescription of ACEI or ARB. Two authors (MF and AD) independently screened and extracted data and assessed study quality and strength of association using standardised tools. The endpoints for the meta-analyses were severe or critical disease outcome and mortality based on standardised criteria.ResultsTwenty-six studies including 8389 people prescribed ACEI or ARB and 20,989 people not prescribed these medications were included. The quality of studies varied, and the overall strength of association was poor with a high risk of confounding bias. Patients prescribed ACEI or ARB had a greater prevalence of risk factors. Meta-analysis found an association between prescription of ACEI or ARB with severe or critical disease outcome (risk ratio, RR, 1.23, 95% confidence interval, CI, 1.06 to 1.42, p = 0.006, I2 = 88%) but this association was lost in sensitivity analyses. There was no association between ACEI or ARB prescription and mortality (RR 1.18, 95% CI 0.92 to 1.50, p = 0.19, I2 = 82%).ConclusionsThis meta-analysis suggests that people prescribed ACEI or ARB more commonly had severe or critical disease outcome, but not mortality, in published cohorts of patients diagnosed with COVID-19. This finding is most likely due to a greater prevalence of risk factors in these patients rather than due to exposure to angiotensin pathway inhibitors.

Abstract P121: Combining Extracellular Matrix Biomarkers Using Cluster Analysis More Accurately Predicts The Development Of Systolic Dysfunction In Acute Myocardial Infarction Compared To Single Biomarker Analysis

Introduction: The extracellular matrix (ECM) is central to cardiac repair following acute myocardial infarction (AMI), and pathological ECM activity may result in adverse ventricular remodeling. Systolic dysfunction is a manifestation of adverse remodeling, and the utility of combined biomarker analysis for prognosis remains undetermined. Cluster analysis is a statistical methodology that can combine biomarkers, while also accounting for collinearity. Hypothesis: In this study, we assessed the hypothesis that combining biomarkers using cluster analysis may more accurately predict the development of systolic dysfunction in AMI patients when compared to single biomarker analysis. Methods: In a cohort of 120 AMI patients, plasma levels of matrix metalloproteinase (MMP) -3, -8, -9 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured using ELISA and multiplexing assays during hospital admission. All patients had an echocardiogram within 1 year of AMI (median [IQR], 145 [89 - 252] days). Patients were divided into impaired (n=37, LVEF &lt;50%) and preserved (n=83, LVEF ≥50%) systolic function. Hierarchical clustering was performed using Ward’s method of minimum variance. Mann-Whitney U and Chi-Squared testing was performed for univariate analysis, and binary logistic regression was performed for multivariate analysis. Results: Upon univariate analysis, current smoking, prescription of ACE inhibitor at discharge, peak Troponin T &gt; 610 ng/L (median), and MMP-8 levels were predictive of impaired systolic function. Cluster analysis partitioned patients into two clusters (Cluster One, n=31; Cluster Two, n=89). Cluster One comprised a higher proportion of patients with impaired systolic function when compared to Cluster Two (15 out of 31 [48.4%] versus 22 out of 89 [24.7%]). Upon multivariate analysis, Cluster One assignment (odds ratio [95% CI], 2.74 [1.04-7.23], p=0.04) remained an independent predictor of systolic dysfunction in combination with clinical variables, while MMP-8 levels did not (3.43 [0.32-36.68], p=0.308). Conclusion: Findings from our study demonstrate a combined biomarker approach outperforms single biomarker analysis for predicting the development of systolic dysfunction following AMI.

Prescription Patterns for the Use of Antihypertensive Drugs for Primary Prevention Among Patients With Hypertension in the United Kingdom.

Several antihypertensive drugs are available for the primary prevention of cardiovascular disease (CVD). However, existing evidence on prescription patterns was primarily generated among patients at high CVD risk with short-term follow-up, and failed to capture impacts of time and patient characteristics. Our objective was therefore to describe longitudinal prescription patterns for antihypertensive drugs for the primary prevention of CVD among patients with arterial hypertension in the United Kingdom. This population-based cohort study used data from the Clinical Practice Research Datalink, included 660,545 patients with hypertension who initiated an antihypertensive drug between 1998 and 2018. Antihypertensive treatments were measured by drug class and described overall and in subgroups, focusing on first-line therapy (first antihypertensive drug(s) recorded after a diagnosis of hypertension) and second-line therapy (antihypertensive drug(s) prescribed as part of a treatment change following first-line therapy). Angiotensin-converting enzyme (ACE) inhibitors (29.0%), thiazide diuretics (22.1%), and calcium-channel blockers (CCBs) (21.0%) were the most prescribed first-line therapies. ACE inhibitors have been increasingly prescribed as first-line therapy since 2001. Men were more likely to be prescribed ACE inhibitors than women (43.5% vs. 32.1%; difference: 11.4%; 95% confidence interval [CI], 11.0%-11.8%), and Black patients were more likely to be prescribed CCBs than White patients (63.6% vs. 37.0%; difference: 26.6%; 95% CI, 24.8%-28.4%). Antihypertensive prescription patterns for the primary prevention of CVD among patients with hypertension are consistent with treatment guidelines that were in place during the study period, providing reassurance regarding the use of evidence-based prescribing.

Angiotensin-Converting Enzyme Inhibitors Used Concomitantly with Insulin Secretagogues and the Risk of Serious Hypoglycemia.

Serious hypoglycemia is a major adverse event associated with insulin secretagogues. Previous studies have suggested a potential relationship between angiotensin-converting enzyme inhibitors (ACEIs) used with sulfonylureas and serious hypoglycemia, and widely used drug compendia warn of this potential drug-drug interaction. We investigated the association between serious hypoglycemia and concomitant use of ACEIs in patients receiving insulin secretagogues, using the self-controlled case series design and Medicaid claims data from 5 US states linked to Medicare claims from 1999-2011. The exposure of interest was active prescription for ACEIs during insulin secretagogue or metformin (negative control object drug) episodes. The outcome was hospital presentation for serious hypoglycemia, identified by discharge diagnosis codes in inpatient and emergency department claims (positive predictive value ~78-89%). We calculated confounder-adjusted rate ratios (RRs) and 95% confidence internals (CIs) of outcome occurrence during ACEI-exposed vs. ACEI-unexposed time using conditional Poisson regression. The RRs for ACEIs were not statistically elevated during observation time of glipizide (RR, 1.06; CI, 0.98-1.15), glyburide (RR, 1.05; CI, 0.96-1.15), repaglinide (RR, 1.15; CI, 0.94-1.41), or metformin (RR, 1.02; CI, 0.97-1.06); but was modestly elevated with glimepiride (RR, 1.23; CI, 1.11-1.37) and modestly reduced with nateglinide (RR, 0.73; CI, 0.56-0.96). The overall pattern of results do not suggest that ACEIs used with insulin secretagogues were associated with increased rates of serious hypoglycemia, with the possible exception of glimepiride.

Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy-analysis of registry data

To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD). We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34–0.72] and 0.47 (95% CI 0.31–0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17-0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04–0.62). All other sensitivity analyses yielded similar results. Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.

Retrospective evaluation of a dose‐dependent effect of angiotensin‐converting enzyme inhibitors on long‐term outcome in dogs with cardiac disease

BackgroundAngiotensin‐converting enzyme inhibitors (ACEIs) are commonly prescribed in dogs, but the ideal dosage is unknown.Hypothesis/ObjectivesIn dogs with cardiac disease, a dose‐response relationship exists for ACEIs with respect to long‐term outcome.AnimalsOne hundred forty‐four dogs with cardiac disease, 63 with current or prior congestive heart failure.MethodsRetrospective medical record review. Cox proportional hazards models were used to determine variables associated with 2‐year survival or survival from first‐onset congestive heart failure (CHF).ResultsMedian initial ACEI dosage was 0.84 (interquartile range [IQR], 0.56‐0.98) mg/kg/day, and 108/144 (75%) of dogs received q12h dosing. No clinically relevant changes in renal function test results, serum electrolyte concentrations, or blood pressure occurred between initial prescription of ACEI and first reevaluation (median, 14 days later). In univariable analysis, higher ACEI dose was associated with increased survival from first‐onset CHF (P = .005), and within the subgroup of dogs in CHF at the time of ACEI prescription, higher ACEI dose was associated with improved survival at 2 years (P = .04). In multivariable analysis, q12h dose frequency of ACEI (hazard ratio [HR], 0.30; 95% CI, 0.10‐0.88; P = .03) and higher serum potassium concentration at visit 1 (HR, 0.39; 95% CI, 0.16‐0.97; P = .04) were predictive of 2‐year survival. The ACEIs were well‐tolerated, with only 8/144 (5.6%) dogs having ACEI dose decreased or discontinued because of adverse effects.Conclusions and Clinical ImportanceTwice daily dose frequency might optimize the cardioprotective benefit of ACEIs.

Variability of discharge medical therapy for secondary prevention among patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) in the United States.

BackgroundOptimal medical therapy after myocardial infarction with nonobstructive coronary arteries (MINOCA; <50% stenosis) is uncertain. We evaluated variability in discharge prescription of angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACEI/ARB) and beta-blockers (BB) to MINOCA patients between hospitals to assess physician equipoise about secondary prevention.MethodsPatients with MINOCA between 2007–2014 were identified in the NCDR Chest Pain–MI Registry. Those with prior revascularization or missing demographic, angiographic, or medication data were excluded. Analysis was limited to high-volume hospitals with ≥20 MINOCA total discharges. Discharge prescriptions for ACEI/ARB and BB after MINOCA were analyzed for each hospital. Clinical data on left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and diabetes mellitus status were extracted to identify other indications for ACEI/ARB or BB.ResultsClinical data were available for 17,849 MINOCA patients, of whom 8,752 (49%) had LVEF <40%, GFR ≤60 mL/min, and/or diabetes. 5,913 patients without one of these indications for ACEI/ARB or BB were discharged from 156 high-volume hospitals. At discharge, ACEI/ARB was prescribed to between 16.0% and 88.8% of MINOCA patients (median 45.6%, IQR 38.0%-56.5%) and BB to between 28.0% and 97.5% (median 74.1%, IQR 64.7%-80.0%).ConclusionThere is marked variability between hospitals in the proportions of patients receiving ACEI/ARB and BB after hospitalization for MINOCA, suggesting clinical equipoise about the routine use of these agents. Randomized clinical trials are necessary to establish the benefit of ACEI/ARB and BB to improve outcomes after MINOCA.