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Association between ethnicity and degree of improvement in cardiac function following initiation of sacubitril/valsartan.
Holm, N, Bromage, DI, Cannata, A, DeCourcey, J, Bhatti, P, Huang, M, McDonagh, TA
Journal of cardiovascular medicine (Hagerstown, Md.). 2022;(1):37-41
Abstract
AIMS: The aim of this study was to determine the degree of short-term improvement in left ventricular ejection fraction (LVEF), haemodynamics, NT-proBNP and quality of life following initiation of sacubitril/valsartan in black patients when compared with white patients. METHODS This was a retrospective, observational, single-centre, hypothesis-generating study of patients with symptomatic heart failure and reduced ejection fraction (HFrEF) treated with guideline recommended therapy, who were transitioned from an ACE inhibitor (ACE-I) or angiotensin receptor blocker (ARB) to sacubitril/valsartan. RESULTS Our analysis included 83 patients (mean age 57 years) with echocardiography performed before and after transition from ACE-I/ARB to sacubitril/valsartan, after excluding patients with concomitant Cardiac resynchronization therapy implantation. Overall, sacubitril/valsartan was associated with LVEF improvement from 28.8% ± 0.7 to 32.0% ± 1.1% (P = 0.0002), but no reverse remodelling was observed. The association with LVEF improvement was only observed in white patients (n = 46, P = 0.0006), but not in black patients (n = 37, P = 0.1728), and appeared to be associated with reduced blood pressure (baseline vs. 2-week blood pressure 116.5 ± 13.9 vs. 109.4 ± 14.3 mmHg, respectively, in white patients, P = 0.0449). Fifteen patients (18.1%) became ineligible for primary prevention Implantable cardioverter defibrillator implantation. CONCLUSION Sacubitril/valsartan was associated with improved LVEF, NT-proBNP concentrations and quality of life in patients with symptomatic HFrEF on guideline recommended therapy. However, in our cohort, improvement of LVEF and quality of life might be attenuated in black patients, which warrants further investigation.
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Effect of Sacubitril/Valsartan on circulating catecholamine levels during a 6-month follow-up in heart failure patients. Timeo Danaos et dona ferentes?
Chalikias, G, Kikas, P, Thomaidis, A, Rigopoulos, P, Pistola, A, Lantzouraki, A, Zisimopoulos, A, Tziakas, D
Acta cardiologica. 2021;(4):396-401
Abstract
We assessed the effect of Sacubitril/Valsartan on circulating catecholamine levels in patients with HF in an observational cohort study. We included 108 consecutive HF patients attending our HF Outpatients Clinic who were eligible to Sacubitril/Valsartan according to the PARADIGM-HF inclusion and exclusion criteria. We furthermore included 58 stable HF patients under optimal medical therapy as a control group. Norepinephrine and epinephrine were measured with immunoradiometric assays at baseline, at 3- and at 6-month time follow-up. Compared to baseline levels there was no change at three months in epinephrine (p = 0.177) or norepinephrine (p = 0.815) concentrations. At 6 months norepinephrine remained unchanged (p = 0.359). However, at 6 months we observed a significant increase in epinephrine levels compared to baseline [66 pg/mL (37-93) vs 38 pg/mL (18-74), p < 0.001]. In the control group no change was observed in epinephrine levels compared to baseline (p = 0.838). This study is the first to report on the effect of the new drug Sacubitril/Valsartan on circulating catecholamine levels in HF patients. Our data show a significant increase in epinephrine levels during a 6 month follow up in stable HF patients.
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User of angiotensin-converting-enzyme inhibitor and/or angiotensin II receptor blocker might be associated with vascular calcification in predialysis chronic kidney disease patients: a retrospective single-center observational study : ACEI/ARB and vascular calcification.
Takaori, K, Iwatani, H, Yamato, M, Ito, T
BMC nephrology. 2021;(1):7
Abstract
BACKGROUND Vascular calcification is a prominent feature in chronic kidney disease (CKD) and diabetes mellitus. A recent report suggests that angiotensin II is protective to vascular calcification. Therefore, we investigated the relationship between vascular calcification and use of angiotensin-converting-enzyme inhibitor (ACEI) and/or angiotensin II receptor blocker (ARB) from a cross-sectional view. METHODS A total of 121 predialysis CKD patients (age 71 ± 12 y; male 72; estimated glomerular filtration rate (eGFR) 20.2 (11.8 - 40.3) mL/min/1.73 m2) who underwent thoracoabdominal plain computed tomography scan were included in this study. The total vascular calcification volume (Calc) was calculated with a three-dimensional imaging software and standardized by body surface area (BSA). The relevance between log [Calc/BSA] and ACEI/ARB use was investigated by multivariate linear regression analyses with or without a time-duration factor of ACEI/ARB use. RESULTS The Calc/BSA was 5.62 (2.01 - 12.7) mL/m2 in 121 patients. In multivariate analyses adjusted with age, sex, ACEI/ARB and log [eGFR], ACEI/ARB use is significantly and positively associated with log [Calc/BSA] (β = 0.2781, p = 0.0007). Even after the adjustment by age, sex, log [eGFR], phosphate, diabetes mellitus, systolic blood pressure, warfarin, hypertension, dyslipidemia, low-density lipoprotein cholesterol, diuretics and ACEI/ARB, ACEI/ARB use is significantly and positively associated with log [Calc/BSA] (β = 0.1677, p = 0.0487). When 90 patients whose time-duration of ACEI/ARB use was clear in medical records were studied, a multivariate analysis adjusted with age, sex, log [eGFR], and ACEI/ARB duration factors showed that the longer use of ACEI/ARB more than 2 years was significantly, independently and positively associated with log [Calc/BSA] (β = 0.2864, p = 0.0060). CONCLUSIONS ACEI/ARB user was associated with vascular calcification in predialysis patients with low eGFR. Prospective studies with larger numbers of patients or more in vitro studies are needed to confirm whether this phenomenon is due to the use of ACEI/ARB itself, the underlying disease condition or the prescription bias.
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Angiotensin receptor neprilysin inhibitor for patients with heart failure and reduced ejection fraction: Real-world experience from Turkey (ARNi-TR).
Ekici, B, Yaman, M, Küçük, M, Dereli, S, Yenerçağ, M, Yiğit, Z, Baş, MM, Karavelioğlu, Y, Çakmak, HA, Kıvrak, T, et al
Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir. 2021;(5):357-367
Abstract
OBJECTIVE Heart failure (HF) is a growing public health problem with high morbidity and mortality. Recently, angiotensin receptor neprilysin inhibitor (ARNi) has emerged as a promising treatment for HF with reduced ejection fraction (HFrEF). Here, we shared our experience with the use of ARNi in HFrEF from multiple centers in Turkey. METHODS The ARNi-TR is a multicenter, noninterventional, retrospective, observational study. Overall, 779 patients with HF from 22 centers in Turkey who were prescribed sacubitril/valsartan were examined. Initial clinical status, biochemical and echocardiographic parameters, and New York Heart Association functional class (NYHA-FC) values were compared with follow-up values after 1 year of ARNi use. In addition, the effect of ARNi on number of annual hospitalizations was investigated, and the patients were divided into 2 groups, depending on whether ARNi was initiated at hospitalization or under outpatient clinic control. RESULTS N-terminal pro-brain natriuretic peptide (NT-proBNP), left-ventricle ejection fraction (LV-EF), and NYHA-FC values improved significantly in both groups (all parameters, p<0.001) within 1-year follow-up. In both groups, a decrease in hemoglobin A1c (HbA1c) values was observed in ARNi use (p<0.001), and a decrease in daily diuretic doses and hospitalizations owing to HF were observed after ARNi use (all comparisons, p<0.001). Hypotension (16.9%) was the most common side effect in patients using ARN. CONCLUSION The ARNi-TR study offers comprehensive real-life data for patients using ARNi in Turkey. The use of ARNi has shown significant improvements in FC, NT-proBNP, HbA1c levels, and LV-EF. Likewise, reductions in the number of annual hospitalizations and daily furosemide doses for HF were seen in this study.
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Renin-angiotensin-aldosterone system inhibitors and SARS-CoV-2 infection: an analysis from the veteran's affairs healthcare system.
Sandhu, AT, Kohsaka, S, Lin, S, Woo, CY, Goldstein, MK, Heidenreich, PA
American heart journal. 2021;:46-57
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BACKGROUND Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are known to impact the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The association between chronic therapy with these medications and infection risk remains unclear. OBJECTIVES The objective was to determine the association between prior ACEI or ARB therapy and SARS-CoV-2 infection among patients with hypertension in the U.S. Veteran's Affairs health system. METHODS We compared the odds of SARS-CoV-2 infection among three groups: patients treated with ACEI, treated with ARB, or treated with alternate first-line anti-hypertensives without ACEI/ARB. We excluded patients with alternate indications for ACEI or ARB therapy. We performed an augmented inverse propensity weighted analysis with adjustment for demographics, region, comorbidities, vitals, and laboratory values. RESULTS Among 1,724,723 patients with treated hypertension, 659,180 were treated with ACEI, 310,651 with ARB, and 754,892 with neither. Before weighting, patients treated with ACEI or ARB were more likely to be diabetic and use more anti-hypertensives. There were 13,278 SARS-CoV-2 infections (0.8%) between February 12, 2020 and August 19, 2020. Patients treated with ACEI had lower odds of SARS-CoV-2 infection (odds ratio [OR] 0.93; 95% CI: 0.89-0.97) while those treated with ARB had similar odds (OR 1.02; 95% CI: 0.96-1.07) compared with patients treated with alternate first-line anti-hypertensives without ACEI/ARB. In falsification analyses, patients on ACEI did not have a difference in their odds of unrelated outcomes. CONCLUSIONS Our results suggest the safety of continuing ACEI and ARB therapy. The association between ACEI therapy and lower odds of SARS-CoV-2 infection requires further investigation.
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Stopping Renin-Angiotensin System Inhibitors in Patients with Advanced CKD and Risk of Adverse Outcomes: A Nationwide Study.
Fu, EL, Evans, M, Clase, CM, Tomlinson, LA, van Diepen, M, Dekker, FW, Carrero, JJ
Journal of the American Society of Nephrology : JASN. 2021;(2):424-435
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BACKGROUND It is unknown whether stopping renin-angiotensin system (RAS) inhibitor therapy in patients with advanced CKD affects outcomes. METHODS We studied patients referred to nephrologist care, listed on the Swedish Renal Registry during 2007-2017, who developed advanced CKD (eGFR<30 ml/min per 1.73 m2) while on RAS inhibitor therapy. Using target trial emulation techniques on the basis of cloning, censoring, and weighting, we compared the risks of stopping within 6 months and remaining off treatment versus continuing RAS inhibitor therapy. These included risks of subsequent 5-year all-cause mortality, major adverse cardiovascular events, and initiation of kidney replacement therapy (KRT). RESULTS Of 10,254 prevalent RAS inhibitor users (median age 72 years, 36% female) with new-onset eGFR <30 ml/min per 1.73 m2, 1553 (15%) stopped RAS inhibitor therapy within 6 months. Median eGFR was 23 ml/min per 1.73 m2. Compared with continuing RAS inhibition, stopping this therapy was associated with a higher absolute 5-year risk of death (40.9% versus 54.5%) and major adverse cardiovascular events (47.6% versus 59.5%), but with a lower risk of KRT (36.1% versus 27.9%); these corresponded to absolute risk differences of 13.6 events per 100 patients, 11.9 events per 100 patients, and -8.3 events per 100 patients, respectively. Results were consistent whether patients stopped RAS inhibition at higher or lower eGFR, across prespecified subgroups, after adjustment and stratification for albuminuria and potassium, and when modeling RAS inhibition as a time-dependent exposure using a marginal structural model. CONCLUSIONS In this nationwide observational study of people with advanced CKD, stopping RAS inhibition was associated with higher absolute risks of mortality and major adverse cardiovascular events, but also with a lower absolute risk of initiating KRT.
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Clinical characteristics, prescription patterns, and persistence associated with sacubitril/valsartan adoption: A STROBE-compliant study.
Chen, W, Liu, Y, Tang, L, Li, Z, Liu, Y, Dang, H
Medicine. 2021;(30):e26809
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Sacubitril/valsartan (sac/val) was launched in China in 2018; however, the adoption of sac/val in real-world clinical practice has yet to be described.This study aimed to analyze real-world treatment patterns of sac/val using data from 3 tertiary hospitals in China.A non-interventional, retrospective cohort study of patients with Heart failure (HF) prescribed sac/val from 3 tertiary hospitals in China between January 1, 2018 and June 30, 2020 was conducted. The analysis included sac/val dose titration patterns and persistence during 6 months post-index.A total of 267 patients were included, with a mean age of 63.9 ± 13.1 years. At index, 27% of patients were prescribed sac/val 12/13 mg b.i.d., 63.7% were prescribed 24/26 mg b.i.d., 4.5% were prescribed the target dose of 49/51 mg b.i.d., and 4.8% were not prescribed according to the recommended dose. During the 6 months post-index, 8.3% of patients had only 1 dose titration record. Good therapeutic persistence was observed across sac/val doses, and only 15.7% of patients discontinued sac/val during the 6 months post-index.In China, the majority of patients prescribed sac/val are not initiated on the recommended dose nor up-titrated according to drug instruction. Notably, good persistence with sac/val is observed in the real-world cohort study.
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Comparative Effectiveness of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in Individuals With Advanced CKD: A Nationwide Observational Cohort Study.
Fu, EL, Clase, CM, Evans, M, Lindholm, B, Rotmans, JI, Dekker, FW, van Diepen, M, Carrero, JJ
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021;(5):719-729.e1
Abstract
RATIONALE & OBJECTIVE It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrology practice who were initiating either RAS inhibitor or CCB therapy. STUDY DESIGN Observational study in the Swedish Renal Registry, 2007 to 2017. SETTINGS & PARTICIPANTS 2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates<30mL/min/1.73m2 (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a positive control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60mL/min/1.73m2) were evaluated. EXPOSURES RAS inhibitor versus CCB therapy initiation. OUTCOME Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke). ANALYTICAL APPROACH HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demographic, clinical, and laboratory covariates. RESULTS Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The positive control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs. LIMITATIONS Potential confounding by indication. CONCLUSIONS Our findings provide evidence from real-world clinical practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection.
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Clinical evidence of initiating a very low dose of sacubitril/valsartan: a prospective observational analysis.
Kim, H, Oh, J, Lee, S, Ha, J, Yoon, M, Chun, KH, Lee, CJ, Park, S, Lee, SH, Kang, SM
Scientific reports. 2021;(1):16335
Abstract
Sacubitril/valsartan is superior to enalapril in reducing the risks of cardiovascular death and preventing hospitalization in patients with heart failure and reduced ejection fraction (HFrEF). However, patients often do not receive sacubitril/valsartan because of concerns about hypotension. We examined the feasibility of initiating sacubitril/valsartan at a very low dose (VLD) in potentially intolerant patients with HFrEF and subsequent dose up-titration, treatment persistence and outcomes. We analyzed 206 patients with HFrEF grouped according to starting sacubitril/valsartan dose. The VLD group (n = 106) commenced 25 mg twice daily, and the standard-dose (SD) group (n = 100) started on ≥ 50 mg twice daily. Baseline systolic blood pressure was 103 ± 12 mmHg vs. 119 ± 14 mmHg in the SD group (P < 0.001). The maximal target dose achievement rate was higher in the SD group (27.0% vs 9.4%, p = 0.001) and the VLD group experienced more dose up-titrations and fewer down-titrations than the SD group. The VLD group had a decrease in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) similar to the SD group and a similar increase in left ventricular ejection fraction. There were no significant differences in symptomatic hypotension, worsening renal function, hyperkalemia, cardiovascular mortality, and rehospitalization due to HF between the two groups during follow-up period. In patients considered by the treating physician likely to be intolerant of sacubitril/valsartan, initiation with 25 mg twice daily was generally possible and patients remained in therapy, with similar decreases in NT-proBNP and increases in left ventricular ejection fraction to those observed in patients receiving SD sacubitril/valsartan.
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Comparison of Percutaneous Coronary Intervention, Coronary Artery Bypass Grafting and Medical Therapy in Non-ST Elevation Acute Coronary Syndrome Patients With 3-Vessel Disease.
Jia, S, Zhang, C, Jiang, L, Xu, L, Tian, J, Zhao, X, Feng, X, Wang, D, Zhang, Y, Sun, K, et al
Circulation journal : official journal of the Japanese Circulation Society. 2020;(10):1718-1727
Abstract
BACKGROUND The aim of this study is to compare the long-term prognosis of non-ST elevation acute coronary syndrome (NSTE-ACS) patients with 3-vessel disease (3VD) who underwent percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or medical therapy (MT).Methods and Results:Overall, 3,928 NSTE-ACS patients with 3VD were consecutively enrolled from April 2004 to February 2011 at Fu Wai Hospital. Patients were followed up for a median of 7.5 years, and were divided into PCI, CABG or MT groups according to their treatment. Compared with patients undergoing PCI, CABG patients had lower rates of myocardial infarction (MI), unplanned revascularization, major adverse cardiovascular and cerebrovascular events (MACCE) and a higher rate of stroke (all P<0.05). Compared with MT, PCI and CABG had lower incidences of all adverse outcomes (all P<0.05), except for a similar rate of stroke between PCI and MT. Kaplan-Meier analysis showed similar results. After adjusting for confounders, CABG was independently associated with a lower risk of cardiac death, revascularization and MACCE compared with PCI (all P<0.05). Compared with MT, PCI reduced long-term risk of death, whereas CABG reduced long-term risk of death, revascularization and MACCE events (all P<0.05). CONCLUSIONS In NSTE-ACS patients with 3VD, CABG is independently associated with a lower risk of long-term cardiac death, revascularization and MACCE compared with PCI. Patients who received MT alone had the highest risk of long-term MACCE.