Angiotensin-converting Enzyme Inhibitors/angiotensin Receptor Blockers Research Articles

Abstract 14434: Prognostic Implications of Exercise Induced Hypertension in Adults With Repaired Coarctation of Aorta

Background: The prognostic implications of exercise induced hypertension (EIH) in adults with repaired coarctation of aorta (COA) and treated hypertension are unknown. The purpose of this study was to assess the relationship between EIH and cardiovascular events, and to determine whether exercise blood pressure (BP) improved risk stratification in this population. Methods: Retrospective study of patients with COA on antihypertensive therapy that underwent exercise testing (2003-2019). BP was measured at rest in 3 different clinical settings and averaged to determine the resting BP. EIH was defined as systolic BP (SBP) >210 (males) or >190 (females) at peak exercise. Cardiovascular event was defined as atrial fibrillation, ventricular tachycardia, heart failure hospitalization, heart transplant, and cardiovascular death. Results: Of 327 patients (age 35±13 years), 116 (35%) had EIH. Although the resting BP was similar between patients with versus without EIH, the EIH group had higher pulsatile arterial load, more advanced left ventricular remodeling, and were less likely to be on angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB). EIH was associated with cardiovascular events (HR 1.06 [95%CI 1.02-1.08]) independent of resting SBP, and improved prognostic accuracy above resting SBP (C-statistic 0.671 [95%CI 0.645-0.694] to 0.727 [95%CI 0.709-0.750], p=0.01). ACEI/ARB was associated with a lower risk of cardiovascular events. Conclusions: EIH was associated with cardiovascular events independent of resting BP, and patients receiving ACEI/ARB had lower risk of EIH and cardiovascular events. These data suggest that exercise BP could be used to assess adequacy of antihypertensive therapy, and to guide titration of antihypertensive therapy.

Closing gaps in medication taking for secondary prevention of coronary heart disease patients among US adults

BackgroundThe secondary preventive medical remedies used in the U.S. general population, particularly those with numerous co-morbidities, are poorly understood. We aimed to assess health outcomes and the extent of their adherence to guideline-based secondary prevention medications among U.S. coronary heart disease (CHD) patients. MethodsWe analysed information from the U.S. National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 on people in the United States aged 18 to 85 who had a personal history of coronary heart disease (CHD). Logistic regression analyses were used to identify characteristics related to healthcare access that were linked with not taking any indicated drugs among CHD and other co-morbidity patients in the U.S. ResultsWe gathered 4256 CHD patients aged 18 and above. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), statins, and antiplatelet medications were taken by 50.94%, 48.26%, 53.41 %, and 19.78% of the population, respectively. Surprising, not received recommended drugs was reached up to 21.12%, and taking all four drugs was only 7.64%. In conclusion, the logistic regression analysis revealed that the chance of not taking prescribed drugs increased with age (18–39), race (Hispanic and Non-Hispanic Black), low income, lack of insurance, and the absence of co-morbidities (hypertension, heart failure, and diabetes mellitus). ConclusionsThe gap between the proposed secondary preventative measures and their actual execution remains sizable. In order to achieve ‘Healthy Aging’, a systematic approach for prevention of CHD is urgently needed.

Characteristics and management of very elderly patients with heart failure: a retrospective, population cohort study.

Unmet needs exist in the diagnosis and treatment of heart failure (HF) in the elderly population. Our aim was to analyse and compare data of diagnostics and management of very elderly patients (aged ≥85years) compared with younger patients (aged 18-84years) with HF in Sweden. Incidence of ≥2 HF diagnosis (ICD-10) was identified from primary/secondary care in Uppsala and Västerbotten during 2010-2015 via electronic medical records linked to data from national health registers. Analyses investigated the diagnosis, treatment patterns, hospitalizations and outpatient visits, and mortality. Of 8702 patients, 27.7% were ≥85years old, women (60.2%); most patients (80.7%) had unknown left ventricular ejection fraction; key co-morbidities comprised anaemia, dementia, and cerebrovascular disease. More very elderly patients received cardiovascular disease (CVD)-related management after diagnosis in primary care (13.6% vs. 6.5%; P<0.0001), but fewer patients underwent echocardiography (19.3% vs. 42.9%; P<0.0001). Within 1year of diagnosis, very elderly patients were less likely to be hospitalized (all-cause admissions per patient: 1.9 vs. 2.3; P<0.0001; CVD-related admissions per patient: 1.8 vs. 2.1; P=0.0004) or prescribed an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) plus a β-blocker (45.2% vs. 56.9%; P<0.0001) or an ACEI/ARB plus a β-blocker plus a mineralocorticoid receptor antagonist (15.4% vs. 31.7%; P<0.0001). One-year mortality was high in patients ≥85years old, 30.5% (CI: 28.3-32.7%) out of 1797 patients. Despite the large number of very elderly patients with newly diagnosed HF in Sweden, poor diagnostic work-up and subsequent treatment highlight the inequality of care in this vulnerable population.

The effect of ACE-I/ARBs and beta blockers on the development of cardiotoxicity in patients with breast cancer

Abstract Introduction Cardiovascular disease has become the leading cause of mortality among breast cancer survivors. Patients with breast cancer who receive treatment with anthracycline and trastuzumab therapies are at risk for the development of non-ischemic cardiomyopathy. The development of heart failure during chemotherapy administration often results in interruption of these life saving therapies. Purpose We aim to investigate whether ACE Inhibitors/angiotensin receptor blockers (ACE-I/ARBs) and beta-blockers can be used as primary prophylaxis to prevent the development of chemotherapy induced cardiomyopathy. Methods This was a retrospective cohort study investigating women who were diagnosed with breast cancer at our medical center from January 2000 to December 2021. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%. Cox-proportional hazard ratios were conducted to determine the impact of prophylactic ACE/ARBs and beta-blockers on the development of cardiotoxicity. Other baseline characteristics were also investigated for their potential impact on the primary endpoint. Results There were 459 patients included in the study of which 70 met criteria for chemotherapy induced cardiomyopathy. Median follow up time of included patients was 12 months and average age was 55 years. Among the included patients, 52% were treated with only trastuzumab, 34% were treated with only anthracycline, and 14% were treated with both therapies. Before chemotherapy was initiated, 15% of patients were taking only ACE-I/ARBs, 7% were taking only beta-blockers, and 5% of patients were taking a combination of ACE-I/ARBS and beta-blockers. There were no significant protective benefits noted for patients who were taking ACE-I/ARBs [HR: 0.49, 95% CI (0.17–1.4)], beta-blockers [HR: 0.50, 95% CI (0.16–1.6)], or both [HR: 1.30, 95% CI (0.44–3.9)]. Notably, there was an increased risk of cardiotoxicity noted for patients who were older [HR: 1.04, 95% CI (1.01–1.1)], smokers within the past 10 years [HR: 2.54, 95% CI (1.41–4.6)], or received a combination of both trastuzumab and anthracycline therapy [HR: 2.52, 95% CI (1.01–6.3)]. Conclusion Prophylactic use of ACE-I/ARBs and beta-blockers separately or in combination was not associated with beneficial reduction in the development of non-ischemic cardiomyopathy in patients receiving anthracycline or trastuzumab therapies. Older age, smoking within the past 10 years, and combination therapy with both anthracycline and trastuzumab were found to be associated with an increased risk. Further studies are needed to investigate the etiology of how smoking may augment the potential cardiotoxic effects in this population. Funding Acknowledgement Type of funding sources: None.

Effects of sacubitril/valsartan on life quality in chronic heart failure: A systematic review and meta-analysis of randomized controlled trials.

AimsSacubitril/valsartan has been demonstrated to have cardiovascular benefits in patients with chronic heart failure (CHF). We aimed to conduct a meta-analysis of its effects on life quality in patients with CHF, in comparison with the angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB).MethodsPubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched from inception through March 2022 for all relevant randomized controlled trials assessing the impact of sacubitril/valsartan and ACEI/ARB on health-related quality of life (HRQoL) in patients with CHF. Two reviewers independently conducted study selection, data extraction, and assessment of bias and quality of evidence. Review Manager 5.3 software was used for meta-analysis.ResultsWe included 10 clinical studies involving 10,426 patients with heart failure with reduced ejection fraction (HFrEF) and 7,689 patients with heart failure with preserved ejection fraction (HFpEF). Meta-analysis results showed that, in terms of the primary outcome, the sacubitril/valsartan group was superior than the ACEI/ARB group in improving HRQoL of HFrEF, and the difference was statistically significant (SMD 1.26; 95% CI: 0.14, 2.37; p = 0.03), while there was no significant difference between the two groups in HFpEF (SMD 0.37; 95% CI: −0.35, 1.09; p = 0.32). The effect of sacubitril/valsartan on the secondary outcome of the minimal important improvement rate of HRQoL in HFrEF was consistent with the primary outcome, while the effect in HFpEF was not clear. The descriptive analysis of individual studies indicated no significant difference in the improvement of 6-min walk distance between the two groups.ConclusionSacubitril/valsartan is beneficial to improve HRQoL outcome in patients with HFrEF with high quality of evidence. Compared with ACEI/ARB, sacubitril/valsartan was more effective. While in patients with HFpEF, this improvement was similar between the two groups.

Patients with comorbid coronary artery disease and hypertension: a cross-sectional study with data from the NHANES.

BackgroundHypertension (HTN) and coronary artery disease (CAD), two common cardiovascular diseases, are often comorbid and interacted. The patients with comorbid CAD and HTN have worse outcomes and prognosis, however, the prevalence remains unclear. In the cross-sectional study, we aimed to explore the prevalence and influence factors of patients with comorbid CAD and HTN in the USA.MethodsAdult patients with comorbid CAD and HTN derived from the National Health and Nutrition Examination Survey (NHANES) database in the 1999–2000 and 2017–2018 cycles were included. Demographic data, physical examination results, laboratory data, and questionnaire data were collected and compared in the two cycles. Subgroup analyses were performed between the elder (≥65 years of age) and middle-young (18–65 years of age) populations.ResultsThe age-adjusted prevalence of patients with comorbid CAD and HTN increased from 4.22% [1999–2000] to 5.40% [2017–2018] (P=0.006) and the age decreased from 71 [63–79] to 69 [61–77] years (P=0.008). The HTN control rate, the low-density lipoprotein cholesterol (LDL-C) control rate, systolic blood pressure (SBP), and the levels of blood lipids, as well as the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), β-blockers and statins improved in the 2017–2018 cycle as compared with the 1999–2000 (all P<0.05). On the other hand, the proportions complicated with diabetes mellitus (DM), obesity and chronic kidney disease (CKD), as well as the levels of serum glucose, glycohemoglobin and creatinine increased from the 1999–2000 to 2017–2018 (all P<0.01). Subgroup analyses revealed that the prevalence of middle-young patients with comorbid CAD and HTN increased more than their elder counterparts, while diastolic blood pressure (DBP), pulse, blood lipids and oral medication rates were inferior to the latter.ConclusionsThe recent prevalence of patients with comorbid CAD and HTN increased than 20 years ago, mainly caused by more morbid middle-young population. For another, the control of blood pressure (BP) and lipids were favorably affected by increased use of statins, ACEIs/ARBs and β-blockers in these patients. Nevertheless, there is still much room for strengthening medication utilization and intervention of risk factors in future.

Sacubitril/valsartan use patterns among older adults with heart failure in clinical practice: a population-based cohort study of &gt;25 000 Medicare beneficiaries.

Sacubitril/valsartan is strongly supported in guidelines for the management of heart failure, but suboptimal adherence and treatment non-persistence may limit the population-level benefit that this therapy might otherwise offer. We identified a cohort of Medicare beneficiaries (2014-2017) initiating sacubitril/valsartan after ≥6months of continuous enrolment. We assessed adherence as the proportion of days covered (PDC) and proportion of patients non-persistent (having no prescription available) at 180 days after initiation. We fit a multivariable negative binomial model with a count of adherent days to evaluate independent factors associated with of sacubitril/valsartan adherence. Among 27 063 new sacubitril/valsartan users, most (n=17 663, 65%) were prescribed low-dose at 24 mg/26 mg and most (n=19 984, 74%) were switched from prior angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) rather than being RASi treatment naïve. Median 180-day PDC was 86% (25th-75th percentiles 58-98%). Black patients, those with high comorbid disease burden (≥8 comorbidities), and patients with recent hospitalization within 30 days had fewer adherent days, while those treated with preceding ACEi/ARB had more adherent days. Thirty-four percent of patients did not have an active sacubitril/valsartan prescription at day 180. Among these, few had preceding dose down-titrations (6% among patients on 49 mg/51 mg and 9% among patients on 97 mg/103 mg) and 68% did not have a subsequent ACEi/ARB prescription. Among patients who remained persistent, dose up-titrations occurred in 29% of patients who started on 24 mg/26 mg and 27% of patients on 49 mg/51 mg. Overall adherence to sacubitril/valsartan among Medicare beneficiaries is acceptable, but is lower in Black patients, those with higher comorbidities or those who started therapy after recent hospitalization. While broad implementation of guideline-directed medical therapy is a key priority, additional focused efforts to improve adherence early after hospitalization and among at-risk patients are needed in parallel.

P181 CARDIAC PROTECTION BY PIRFENIDONE AFTER MYOCARDIAL INFARCTION: A BIOINFORMATIC ANALYSIS

Abstract Purpose Left ventricular (LV) remodeling after myocardial infarction (MI) is promoted by an intense fibrotic response, which could be targeted by an anti–fibrotic drug such as pirfenidone. Methods We explored the relationship between protein modulation by pirfenidone and post–MI remodeling, based on publicly available molecular information and transcriptomic data from a swine model of MI. We also compared the effects of pirfenidone and angiotensin–converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB), mineralocorticoid receptor blockers (MRA) and beta–blockers. Results We identified 6 causative motives of post–MI remodeling (cardiomyocyte cell death, impaired myocyte contractility, extracellular matrix remodeling and fibrosis, hypertrophy, renin–angiotensin–aldosterone system activation, and inflammation), 4 pirfenidone targets and 21 bioflags (indirect effectors). When considering both targets and bioflags, pirfenidone showed a broad relationship encompassing all 6 motives. p38γ–MAPK12 blockade inhibits cardiomyocyte apoptosis, cardiomyocyte hypertrophy and inflammation. Furthermore, pirfenidone can modulate extracellular matrix remodeling and cardiac fibrosis by targeting the TGFβ1–SMAD2/3 pathway and other effector proteins such as matrix metalloproteases 2 and 14, PDGFA/B, and IGF1, which promote myocardial fibrosis, cardiomyocyte hypertrophy and impaired contractility. All the gold standard drugs were found to be important for specific clinical motives, but pirfenidone had a more widespread action on the molecular pathways active in the post–MI setting. Conclusion A bioinformatic approach allowed to identify several possible mechanisms of action of pirfenidone with beneficial effects in the post–MI LV remodeling, and suggests additional effects over guideline–recommended therapies. These findings support clinical studies evaluating the beneficial effects of pirfenidone in patients with MI.

PO-628-03 ASSOCIATION OF MINERALOCORTICOID RECEPTOR ANTAGONIST USE WITH MORTALITY AND VENTRICULAR ARRHYTHMIA RISK IN PATIENTS WITH IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS

Heart failure (HF) patients with implantable devices have improved outcomes on optimal Guideline-Directed Medical Therapy (GDMT), yet few studies have evaluated the impact of mineralocorticoid receptor antagonists (MRA) on mortality and arrythmia risk in patients who may be unable to tolerate optimal GDMT. To assess the impact of MRA use on the risk of all-cause mortality and ventricular tachyarrhythmia (VTA) in HF patients with an ICD or CRT-D who were not concomitantly treated with both beta blockers (BB) and ACE-inhibitors/angiotensin receptor blockers (ACE/ARB) in 4 MADIT (Multicenter Automatic Defibrillator Implantation Trial; MADIT-II, MADIT-CRT, MADIT-RIT, MADIT-RISK) and Ranolazine in High-Risk Patients with ICD (RAID) clinical trials. We included 5504 patients enrolled in 5 landmark ICD clinical trials. Patients were categorized by MRA use in addition to baseline BB and/or ACE/ARB use into subgroups of those who were prescribed both BB and ACE/ARB (2-drug GDMT) and those who were prescribed only one of the two drugs (1-drug GDMT) at enrollment. Cox proportional hazards regression models and Fine and Gray regression models, stratified by studies, were performed to assess the association between time-dependent MRA use and risks of all-cause mortality and VTA. VTA was defined as any treated or monitored sustained ventricular tachycardia (≥170 bpm) or ventricular fibrillation. Among 5504 study patients, 4392 (80%) were prescribed 2-drug GDMT and 1016 (18%) were prescribed 1-drug GDMT. MRA was prescribed to 1656 (30%) patients. Multivariate analysis demonstrated that MRA use was associated with a 52% reduction in mortality risk when prescribed in patients on 1-drug GDMT (HR=0.48 [95% CI: 0.27-0.86], p=0.014). The mortality benefit of MRA therapy was attenuated among patients on 2-drug GDMT (HR=1.05 [95% CI: 0.82-1.34], p=0.7) (Figure 1). Further, MRA use was associated with a 36% reduction in VTA risk in patients on 1-drug GDMT (HR=0.64 [95% CI: 0.40-1.01], p = 0.05), while among patients on 2-drug GDMT the association of MRA use with VTA risk was also attenuated (HR=1.09 [95% CI: 0.93-1.29], p=0.28) (Figure 2). In HF patients with an ICD or CRT-D who are unable to tolerate 2-drug GDMT, MRA use is associated with a reduction in the risk of mortality and VTA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Development of a Cardio-Oncology Service in Lithuania: Prediction, Prevention, Monitoring and Treatment of Cancer Treatment-Induced Cardiotoxicity.

Background: Advances in cancer therapy have dramatically improved outcomes for cancer pa-tients. However, cancer treatment can cause several cardiovascular (CV) complications, increasing cardiac mortality and morbidity in cancer patients and survivors. As a result, a new cardiology subspecialty—cardio-oncology (CO)—has been developed. The goals of CO are to understand the mechanism of the cardiotoxicity (CTX) of cancer therapies and invent the best monitoring and treatment strategies to improve the survival of cancer patients. Methods: We performed a retro-spective observational study reporting on the 6-year experience of the first CO service in Vilnius, Lithuania. Cancer patients were consulted by a single part-time specialist at Vilnius University Hospital. All new patients underwent blood tests, including cardiac biomarkers and advanced transthoracic echocardiogram (TTE) with stress protocol if indicated. During a follow-up, we evaluated the association of patient survival with such variables as age, gender, reasons for re-ferral, cancer location and stage, cardiovascular (CV) risk factors (RF), and rates and stage of CTX and treatment strategies. Results: 447 patients were consulted (70% females), and the median age was 64 years. Cardiovascular (CV) RF was common: 38.5% of patients had hypertension, almost 38% had dyslipidemia, 29% were obese, 10% were smokers, and 9% had diabetes. Nearly 26% of patients had a history of HF. Early biochemical cardiotoxicity was determined in 27%, early functional cardiotoxicity was seen in 17%, and early mixed cardiotoxicity—in 45% of referred patients treated with cardiotoxic cancer therapies. In addition, reduced left ventricular ejection fraction (LVEF) was found in 7% of patients. Beta-blockers (BB) were administered to 61.1% of patients, while angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) to 54.1% of patients. In addition, 18.3% of patients received loop diuretics and almost 12% mineralocorticoid receptor antagonists (MRA), respectively. A total of 143 patients died during the 6-year follow-up period. The leading cause of death was primarily cancer (92.3%). Only in 5.6% of patients, cardiovascular complications were reported as the cause of death, and 2.1% of deaths were due to the COVID–19 infection. We found that age (HR 1.020 [95% CI: (1.005–1.036)] p = 0.009); LV diastolic dysfunction (HR 1.731 [95% CI: 1.115–2.689] p = 0.015; NYHA stage II (HR 2.016 [95% CI: 1.242–3.272] p = 0.005; NYHA stage III (HR 3.545 [95% CI: 1.948–6.450] p < 0.001; kidney dysfunction (HR 2.085 [95% CI: 1.377–3.159] p = 0.001; previous cancer (HR 2.004 [95% CI: 1.219–3.295] p = 0.006); tumor progression (HR 1.853 [95% CI: 1.217–2.823] p = 0.004) and lung cancer (HR 2.907 [95%CI: 1.826–4.627] p < 0.001) were statistically significantly associated with the increased risk of all-cause death. Conclusions: CO is a rapidly growing subspecialty of cardiology that aims to remove cardiac disease as a barrier to effective cancer treatment by preventing and reversing cardiac damage caused by cancer therapies. Establishing a CO service requires a cardiologist with an interest in oncology. Continuous education, medical training, and clinical research are crucial to success. Age, previous cancer, tumor progression, kidney dysfunction, left ventricular diastolic dysfunction, and NYHA stages were associated with increased mortality.

Empagliflozin and incidence of events consistent with acute kidney injury: Pooled safety analysis in more than 15 000 individuals.

Empagliflozin and incidence of events consistent with acute kidney injury: Pooled safety analysis in more than 15 000 individuals.

Validation Of A Computable Algorithm For Medication Optimization In Heart Failure With Reduced Ejection Fraction

Background Guideline-directed medical therapy (GDMT) optimization can improve outcomes in heart failure with reduced ejection fraction (HFrEF) but often does not occur in clinical practice. The objective of this study was to assess the prescribing of GDMT in clinical trial data using a novel algorithm to identify opportunities for medication optimization. Methods Clinical trial data from GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure), a study using natriuretic peptides to guide medical therapy in HFrEF, was passed through a computable medication optimization algorithm to output GDMT recommendations. Algorithm-based recommendations were compared to actual medication changes at GUIDE-IT visits. Results Data were analyzed from 5733 GUIDE-IT visits in 841 unique patients. In patients not on therapy, the algorithm recommended initiation of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB), beta-blockers, and mineralocorticoid receptor antagonists (MRA) in 480 (52.8%), 51 (34.9%), and 1421 (68.1%) visits, respectively. Initiation of the agents only occurred in 100 (20.8%), 29 (56.9%), and 224 (15.8%) of those visits. The algorithm also recommended increasing doses in an additional 1475 (48.8%) visits for ACEi/ARBs and 1158 (39.4%) visits for beta-blockers. The dose increases only occurred in 358 (24.3%) of these visits for ACEi/ARBs and 426 (36.8%) visits for beta-blockers leaving many opportunities for medication optimization (Figure 1). The medication optimization score (MOS) increased over time (Figure 2). As the MOS increased over time, the hazard ratio for time to first CV death or HF hospitalization decreased. Conclusions The algorithm accurately identified patients that met the criteria for GDMT initiation and titration. Even in a clinical trial with robust protocols, GDMT could have been further optimized in a meaningful number of visits. The MOS generated from the algorithm may correlate with clinical outcomes. Implementation of algorithms into electronic health records could help identify suboptimal GDMT and improve HFrEF care. Guideline-directed medical therapy (GDMT) optimization can improve outcomes in heart failure with reduced ejection fraction (HFrEF) but often does not occur in clinical practice. The objective of this study was to assess the prescribing of GDMT in clinical trial data using a novel algorithm to identify opportunities for medication optimization. Clinical trial data from GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment in Heart Failure), a study using natriuretic peptides to guide medical therapy in HFrEF, was passed through a computable medication optimization algorithm to output GDMT recommendations. Algorithm-based recommendations were compared to actual medication changes at GUIDE-IT visits. Data were analyzed from 5733 GUIDE-IT visits in 841 unique patients. In patients not on therapy, the algorithm recommended initiation of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB), beta-blockers, and mineralocorticoid receptor antagonists (MRA) in 480 (52.8%), 51 (34.9%), and 1421 (68.1%) visits, respectively. Initiation of the agents only occurred in 100 (20.8%), 29 (56.9%), and 224 (15.8%) of those visits. The algorithm also recommended increasing doses in an additional 1475 (48.8%) visits for ACEi/ARBs and 1158 (39.4%) visits for beta-blockers. The dose increases only occurred in 358 (24.3%) of these visits for ACEi/ARBs and 426 (36.8%) visits for beta-blockers leaving many opportunities for medication optimization (Figure 1). The medication optimization score (MOS) increased over time (Figure 2). As the MOS increased over time, the hazard ratio for time to first CV death or HF hospitalization decreased. The algorithm accurately identified patients that met the criteria for GDMT initiation and titration. Even in a clinical trial with robust protocols, GDMT could have been further optimized in a meaningful number of visits. The MOS generated from the algorithm may correlate with clinical outcomes. Implementation of algorithms into electronic health records could help identify suboptimal GDMT and improve HFrEF care.

The use of ace inhibitors influences the risk of progression of BD-IPMNs under follow-up

BackgroundChemoprevention's ability to slow down or prevent the progression of BD-IPMNs is extremely appealing. Aspirin (ASA), Ace Inhibitors/Angiotensin Receptor Blockers (ACEIs/ARBs) and Statins (STATs) are frequently prescribed drugs with a possible beneficial effect on different cancer types. Their effect on IPMNs is largely unknown. AimTo evaluate the association between the use of ASA, ACEIs/ARBs and STATs and the risk of progression of BD-IPMNs in follow-up.Materials and methods: multicenter, retrospective cohort study on patients with presumed BD-IPMNs without relative or absolute indication for surgery. Pharmacological exposures and risk factors were collected. We identified clinically relevant progression (occurrence of radiological absolute or relative indication for surgery) and any progression (occurrence of clinically relevant progression OR any dimension increase OR the occurrence of new cysts). ResultsOverall 594 patients were included. ACEIs were associated with a lower occurrence of any progression (HR = 0.70; 95% CI 0.49–0.98, p = 0.04) and clinically relevant progression, HR = 0.42 (95% CI 0.20–0.88; p = 0.02). No significant effect was shown for factors associated with the occurrence of pancreas cancer such as smoking, alcohol consumption and 1st degree family history of pancreas cancer. Among pharmacological exposures, no convincing effect was shown for the chronic use of ASA, ARB and STAT. ConclusionsACEIs might have an effect in slowing the progression of BD-IPMNs. ASA, STAT and ARBs show no convincing effect on the progression of BD-IPMNs. Further, prospective, and long-term multicenter studies are needed to verify such association and to define the potential underlying mechanisms.

Risk factor control among heart failure patients in the United States: Results from the NHANES 1999–2018

BackgroundCompliance with recommended pharmacological and non-pharmacological treatments to modify risk factors is associated with improved outcomes for patients with heart failure (HF). MethodsWe conducted an analysis of the National Health and Nutrition Examination Survey (NHANES) years 1999–2018 to evaluate the adequacy of risk factor control and compliance with recommended lifestyle and medications according to the clinical guidelines for the management of HF. Demographic, clinical, and healthcare-access factors associated with having risk factors uncontrolled or not receiving recommended medications were determined using logistic regression analyses. ResultsWe collected 1906 participants aged 18 years or older with a self-reported history of HF. The majority were at target goals for blood pressure (45.07%), low-density lipoprotein cholesterol (22.04%), and glycated hemoglobin (72.15%), whereas only 19.09% and 27.38% were at targets for body mass index and waist circumference respectively. Besides, 79.49% and 67.23% of respondents reported smoking cessation and recommended alcohol consumption, whereas only 11.54% reported adequate physical activity. Proportion of taking beta blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) and diuretics was 54.77%, 52.62% and 49.37%, respectively. Finally, the logistic regression analysis showed that metabolic syndrome and diabetes mellitus were associated with a higher likelihood of having risk factor uncontrolled, while metabolic syndrome, diabetes mellitus, and chronic kidney disease were predictors for not receiving recommended medications. ConclusionsRisk factor control and adherence to recommended lifestyle and medications are non-ideal among HF patients in the USA. A systematic approach for risk factor optimization in people with HF is urgently needed.

Therapeutic effects and safety of early use of sacubitril/valsartan after acute myocardial infarction: a systematic review and meta-analysis.

infarction (AMI) can be reduced by the use of sacubitril/valsartan. However, the therapeutic effects of sacubitril/valsartan in clinical settings are inconsistent. In this paper, the related research on the application of sacubitril/valsartan in AMI was comprehensively searched, in order to explore the clinical efficacy and safety of early application of sacubitril/valsartan after AMI. English databases, including American National Library of Medicine, Medline, and Embase, and Chinese databases, including Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure (CNKI), Wanfang, and VIP, were searched using a combination of the following search terms: AMI, acute ST-segment elevation myocardial infarction (STEMI), acute non-ST-segment elevation myocardial infarction (NSTEMI), sacubitril/valsartan sodium tablets, and angiotensin receptor enkephalinase inhibitors. The experimental group was given Sacubitril/Valsartan sodium tablets, while the control group was given angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB). Cochrane Handbook 5.0 risk assessment table were used for quality assessment and bias risk assessment. A total of 5 articles were included in the meta-analysis. The total incidence of adverse cardiovascular events in the sacubitril/valsartan group was significantly lower than that in the control group {relative risk (RR) =0.61 [95% confidence interval (CI): 0.46, 0.82], significance testing Z=3.36, and P=0.0008}. The difference between the rehospitalization rate of the sacubitril/valsartan group and control group was statistically significant [RR =0.67 (95% CI: 0.47, 0.95), significance testing Z=2.23, and P=0.03]. The difference in low blood pressure between the sacubitril/valsartan group and the control group was statistically significant [RR =1.28 (95% CI: 1.18, 1.40), significance testing Z=5.58, and P<0.00001]. The difference in left ventricular ejection fraction (LVEF) between the sacubitril/valsartan group and control group was statistically significant [mean difference (MD) =3.09 (95% CI: 1.69, 4.49), significance testing Z=4.33, and P<0.0001]. Sacubitril/valsartan was found to inhibit ventricular remodeling after AMI, improve cardiac function, and reduce the incidence of adverse cardiovascular events after myocardial infarction, the rehospitalization rate, and the mortality rate.

A CROSS-SECTIONAL STUDY OF ANTIHYPERTENSIVE DRUG UTILIZATION PATTERN IN RURAL POPULATION OF SOUTHERN INDIA

Objectives: The objective of the study is to study the antihypertensive drug utilization pattern, demographic profile, and associated comorbid conditions of hypertensive patients in the rural population of Southern India. Methods: This study was a cross-sectional, community-based, door-to-door survey of hypertensive patients. The details of the patients which include age, sex, body mass index (BMI), past medical history, usage of drugs for hypertension (HTN), any other related drugs, and comorbid conditions were collected in this study. Results: As per the results, the mean age of study participants was 54.68 years, men were 62.31% women were 37.68%, mean BMI was 30.48 kg/m2. In associated comorbidities with HTN, Diabetes was the most common with 19.4%. As per usage of antihypertensive drugs, In Monotherapy, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) occupy 16.4% followed by beta-blockers (BB) 13.4%.In 2+ drug therapy, Diuretics were 26.8% followed by BB 22.7% and in drug combinations, the combination of ACE/ARB + Diuretics were 11.5% followed by ACE/ARB + calcium channel blocker at 8.2%. Conclusion: HTN was more common in Men and the BMI was also on the higher side in hypertensive patients. In associated comorbidities with HTN, Diabetes was the most common disease. Antihypertensive drugs usage pattern shows that in monotherapy, ACE inhibitors/ARBs were the most commonly used drugs. In 2+ therapy, the most common add-on drugs were diuretics. In combination therapy, the most common combination was ACE/ARB + Diuretics.

Use of Guideline-Based Therapy for Diabetes, Coronary Artery Disease, and Chronic Kidney Disease After Acute Kidney Injury: A Retrospective Observational Study.

Background:Survivors of acute kidney injury (AKI) are at a high risk for cardiovascular complications. An underrecognition of this risk may contribute to the low utilization of relevant guideline-based therapies in this population.Objective:We sought to assess accordance with guideline-based recommendations for survivors of AKI with diabetes, coronary artery disease (CAD), and preexisting chronic kidney disease (CKD) in a post-AKI clinic, and identify factors that may be associated with guideline accordance.Design:Retrospective cohort study.Setting:Post-AKI clinics at 2 tertiary care centers in Ontario, Canada.Patients:We included adult patients seen in both post-AKI clinics between 2013 and 2019 who had at least 2 clinic visits within 24 months of an index AKI hospitalization.Measurements:We assessed accordance to recommendations from the most recent North American and international guidelines available at the time of study completion for diabetes, CAD, and CKD.Methods:We compared guideline accordance between visits using the Cochran Mantel Haenszel test. We used multivariable Poisson regression to identify prespecified factors associated with accordance.Results:Of 213 eligible patients, 192 (90%) had Kidney Disease Improving Global Outcomes Stage 2-3 AKI, 91 (43%) had diabetes, 76 (36%) had CAD, and 88 (41%) had preexisting CKD. From the first clinic visit to the second, there was an increase in angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-I/ARB) use across all disease groups—from 33% to 46% (P = .028) in patients with diabetes, from 30% to 57% (P = .002) in patients with CAD, and from 16% to 35% (P < .001) in patients with preexisting CKD. Statin use increased in patients with preexisting CKD from 64% to 71% (P = .034). Every 25 μmol/L rise in the discharge serum creatinine was associated with a 19% (95% confidence interval [CI], 8%-28%) and 12% (95% CI, 2%-21%) lower likelihood of being on an ACE-I/ARB in patients with diabetes and preexisting CKD, respectively.Limitations:The study lacked a comparison group that received usual care. The small sample and multiple comparisons make false positives possible.Conclusion:There is room to improve guideline-based cardiovascular risk factor management in survivors of AKI, particularly ACE-I/ARB use in patients with an elevated discharge serum creatinine.

545 Cardiac protection by pirfenidone after myocardial infarction: a bioinformatic analysis

Abstract Aims Left ventricular (LV) remodelling after myocardial infarction (MI) is promoted by an intense fibrotic response, which could be targeted by an anti-fibrotic drug such as pirfenidone. Methods and results We explored the relationship between protein modulation by pirfenidone and post-MI remodelling, based on publicly available molecular information and transcriptomic data from a swine model of MI. We also compared the effects of pirfenidone and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB), mineralocorticoid receptor blockers (MRA) and beta-blockers. We identified six causative motives of post-MI remodelling (cardiomyocyte cell death, impaired myocyte contractility, extracellular matrix remodelling and fibrosis, hypertrophy, renin–angiotensin–aldosterone system activation, and inflammation), 4 pirfenidone targets and 21 bioflags (indirect effectors). When considering both targets and bioflags, pirfenidone showed a broad relationship encompassing all six motives. p38γ-MAPK12 blockade inhibits cardiomyocyte apoptosis, cardiomyocyte hypertrophy and inflammation. Furthermore, pirfenidone can modulate extracellular matrix remodelling and cardiac fibrosis by targeting the TGFβ1-SMAD2/3 pathway and other effector proteins such as matrix metalloproteases 2 and 14, PDGFA/B, and IGF1, which promote myocardial fibrosis, cardiomyocyte hypertrophy and impaired contractility. All the gold standard drugs were found to be important for specific clinical motives, but pirfenidone had a more widespread action on the molecular pathways active in the post-MI setting. Conclusions A bioinformatic approach allowed to identify several possible mechanisms of action of pirfenidone with beneficial effects in the post-MI LV remodelling, and suggests additional effects over guideline-recommended therapies. These findings support clinical studies evaluating the beneficial effects of pirfenidone in patients with MI.

Abstract 13186: A Machine Learning Evaluation of Patient Characteristics Associated With Guideline-Directed Prescribing for Heart Failure and Reduced Ejection Fraction

Introduction: Patients with heart failure and reduced ejection fraction (HFrEF) are consistently under-prescribed guideline-directed medications. Many barriers to prescribing are known, including patient characteristics (e.g., higher potassium values within normal limits predict under-prescribing of some medications). However, identification of these barriers has relied on traditional a priori hypotheses or qualitative methods. To overcome the limitations of traditional methods, we used a supervised machine learning (ML) approach to identify potential new barriers to prescribing. Methods: We used electronic health record data to evaluate characteristics of adults with HFrEF within the UCHealth system. Characteristics evaluated included insurance type, medications, diagnoses and lab values. We evaluated the predictive performance of ML algorithms and statistical models based on area under the receiver operating characteristic curve (AUC) to predict prescription of 4 types of medications: angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACE/ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta blocker (BB), or mineralocorticoid receptor antagonist (MRA). We identified top characteristics associated with prescribing each medication type from the models with the best predictive performance. Results: For 3,835 patients meeting inclusion criteria, 70% were prescribed an ACE/ARB, 8% an ARNI, 75% a BB and 40% a MRA. The best-predicting model for each medication type was a random forest. Figure 1 describes the top characteristics associated with each medication type. Conclusions: In this hypothesis generating ML study, we identified additional patient characteristics that may be associated with under-prescribing for HFrEF. These results also align with some patient characteristics that are known barriers to prescribing. Additional research is needed to further elucidate barriers to prescribing for HFrEF.

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

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