BACKGROUND Heart failure and end-stage renal disease often coexist, and management of heart failure can be challenging in patients during hemodialysis. Sacubitril-valsartan (SV) is the first drug to receive regulatory approval for use in patients with chronic heart failure with reduced ejection fraction (HFrEF) and New York Heart Association (NYHA) classification II, III, or IV. This study aimed to evaluate the efficacy and safety of SV for use in chronic heart failure patients on maintenance hemodialysis (MHD). MATERIAL AND METHODS From September 2021 to October 2022, 28 patients on MHD with chronic heart failure at the hemodialysis center of Shaanxi Second Provincial People\'s Hospital were regularly followed. During the 12-week follow-up period, all patients were administered SV at doses of 100-400 mg per day. Biochemical indicators, echocardiographic parameters, life quality scores, and adverse events were evaluated. RESULTS We enrolled 28 patients. Compared with the baseline levels, NYHA class III in these patients treated with SV was significantly decreased from 60.71% to 32.14% (P<0.05), left ventricular ejection fraction (LVEF) was significantly improved from 44.29±8.92% to 53.32±7.88% (P<0.001), the Physical Component Summary (PCS) score was significantly improved from 40.0±6.41 to 56.20±9.86 (P<0.001), and the Mental Component Summary (MCS) score was significantly improved from 39.99±6.14 to 52.59±11.0 (P<0.001). CONCLUSIONS We demonstrated that SV improved NYHA classification and LVEF values of patients on MHD with chronic heart failure and also improved their quality of life.

An angiotensin receptor/neprilysin inhibitor (ARNI), a heart failure treatment, is a combination drug made up of sacubitril, a neprilysin inhibitor, and valsartan, a vascular receptor blocker. No human or veterinary studies regarding the effect of ARNI on renal haemodynamics in the absence of cardiac or renal issues exist. Therefore, we investigated the effect of ARNI on renal haemodynamics in five healthy dogs. ARNI was administered to all five dogs at an oral dose of 20 mg/kg twice daily for 4 weeks. Renal haemodynamics were assessed on the day before ARNI administration (BL), on Day 7, and on Day 28. The glomerular filtration rate (GFR) significantly increased on Day 28 compared to BL and Day 7, whereas renal plasma flow increased on Day 7 and Day 28 compared to BL. Systolic blood pressure significantly decreased between BL and Day 28. Plasma atrial natriuretic peptide (ANP) concentrations increased on Day 7 compared to BL. Additionally, ANP concentrations increased on Day 28 in three of the five dogs. Different ANP concentrations were observed in the remaining two dogs. Both urine output volume and heart rate remained relatively stable and did not exhibit significant change. In conclusion, ARNI may enhance renal haemodynamics in healthy dogs. ARNI could be a valuable drug for treating both heart and kidney disease in dogs.

OBJECTIVE: Sacubitril/valsartan treatment reduces mortality and hospitalizations in heart failure with reduced ejection fraction but has limited application in hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the effect of sacubitril/valsartan on peak oxygen consumption (VO2) in patients with non-obstructive HCM.
RESULTS: This is a phase II, randomized, open-label multicentre study that enrolled adult patients with symptomatic non-obstructive HCM (New York Heart Association class I-III) who were randomly assigned (2:1) to receive sacubitril/valsartan (target dose 97/103 mg) or control for 16 weeks. The primary endpoint was a change in peak VO2. Secondary endpoints included echocardiographic measures of cardiac structure and function, natriuretic peptides and other cardiac biomarkers, and Minnesota Living with Heart Failure quality of life. Between May 2018 and October 2021, 354 patients were screened for eligibility, 115 patients (mean age 58 years, 37% female) met the study inclusion criteria and were randomly assigned to sacubitril/valsartan (n = 79) or control (n = 36). At 16 weeks, there was no significant change in peak VO2 from baseline in the sacubitril/valsartan (15.3 [4.3] vs. 15.9 [4.3] ml/kg/min, p = 0.13) or control group (p = 0.47). No clinically significant changes were found in blood pressure, cardiac structure and function, plasma biomarkers, or quality of life.
CONCLUSIONS: In patients with HCM, a 16-week treatment with sacubitril/valsartan was well tolerated but had no effect on exercise capacity, cardiac structure, or function.

OBJECTIVE: The PARACOR-19 randomized controlled trial (RCT) was designed to examine the effects of sacubitril/valsartan on markers of cardiac injury, inflammation, structure, and function among patients who have recovered from acute coronavirus disease 2019 (COVID-19) infection.
RESULTS: PARACOR-19 was a single-centre, double-blind RCT of patients with cardiovascular risk factors and a history of COVID-19 infection 4-16 weeks prior to enrolment. Patients were randomized to sacubitril/valsartan (titrated to the maximum dose of 97/103 mg twice daily) versus matching placebo. Co-primary endpoints were change from baseline to 12 weeks in high-sensitivity cardiac troponin T (hs-cTnT) and soluble ST2 (sST2). Exploratory endpoints included change from baseline to 12 weeks in additional circulating biomarkers. Overall, 42 patients were randomized between August 2021 and March 2023 (n = 20 sacubitril/valsartan, n = 22 placebo). Median (25th-75th) time from COVID-19 diagnosis to enrolment was 67 (48-80) days. Median age was 67 (62-71) years, 48% were female, and 91% were White. Compared with placebo, sacubitril/valsartan did not have a significant effect on the co-primary endpoints of change from baseline in hs-TnT and sST2 (all p ≥ 0.29). In exploratory analyses, sacubitril/valsartan led to a 46% greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 51% greater reduction in C-terminal telopeptide of collagen type I (CITP). Permanent drug discontinuation occurred in four patients in the sacubitril/valsartan group and three patients in the placebo group. There were no deaths and one patient was hospitalized in each group.
CONCLUSIONS: In this pilot RCT of patients who recovered from acute COVID-19, sacubitril/valsartan did not lower hs-cTnT or sST2 compared with placebo. Exploratory analyses suggested potential benefits of sacubitril/valsartan on cardiac wall stress and collagen turnover as measured by NT-proBNP and CITP. Sacubitril/valsartan was well tolerated.
BACKGROUND: ClinicalTrials.gov NCT04883528.

UNASSIGNED: This study aimed to evaluate whether cilostazol (phosphodiesterase III inhibitor) could enhance the healing of Achilles tendon ruptures in rats.
UNASSIGNED: The Achilles tendons of 24 healthy male adult rats were incised and repaired. The rats were randomly allocated to cilostazol and control groups. The cilostazol group received daily intragastric administration of 50 mg/kg cilostazol for 28 days, while the control group did not receive any medication. The rats were sacrificed on the 30th day, and the Achilles tendon was evaluated for biomechanical properties, histopathological characteristics, and immunohistochemical analysis.
UNASSIGNED: All rats completed the experiment. The Movin sum score of the control group was significantly higher (p = 0.008) than that of the cilostazol group, with means of 11 ± 0.63 and 7.50 ± 1.15, respectively. Similarly, the mean Bonar score was significantly higher (p = 0.026) in the control group compared to the cilostazol group (8.33 ± 1.50 vs. 5.5 ± 0.54, respectively). Moreover, the Type I/Type III Collagen ratio was notably higher (p = 0.016) in the cilostazol group (52.2 ± 8.4) than in the control group (34.6 ± 10.2). The load to failure was substantially higher in the cilostazol group than in the control group (p = 0.034), suggesting that the tendons in the cilostazol group were stronger and exhibited greater resistance to failure.
UNASSIGNED: The results of this study suggest that cilostazol treatment significantly improves the biomechanical and histopathological parameters of the healing Achilles tendon in rats. Cilostazol might be a valuable supplementary therapy in treating Achilles tendon ruptures in humans. Additional clinical studies are, however, required to verify these outcomes.

BACKGROUND: The first angiotensin receptor/neprilysin inhibitor on the market, sacubitril-valsartan, has shown marked improvements in death and hospitalization for heart failure among adults, and is now approved for use in pediatric heart failure. While the ongoing PANORAMA-HF trial is evaluating the effectiveness of sacubitril-valsartan for pediatric patients with a failing systemic left ventricle, the enrollment criteria do not include the majority of pediatric heart failure patients. Additional studies are needed.
METHODS: Using the TriNetX database, we performed a propensity score matched, retrospective cohort study to assess the incidence of a composite of all-cause mortality or heart transplant within 1 year. The 519 patients who received sacubitril-valsartan were compared to 519 matched controls who received an angiotensin converting enzyme inhibitor (ACE) or angiotensin II receptor blocker (ARB).
RESULTS: There was no significant difference in the incidence of the composite outcome with sacubitril-valsartan over an ACE/ARB (13.3% vs 13.2%, p = 0.95), or among the components of mortality (5.0% vs 5.8%, p = 0.58) or heart transplantation (8.7% vs 7.5%, p = 0.50). Patients who were receiving full goal-directed medical therapy (14.4% vs 16.0%, p = 0.55) also showed no difference in the composite outcome. We observed a significantly increased incidence of hypotension (10% vs 5.2%, p = 0.006) and a trend toward reduced number of hospitalizations per year (mean (SD) 1.3 (4.4) vs 2.0 (9.1), p = 0.09).
CONCLUSIONS: Sacubitril-valsartan is not associated with a decrease in the composite of all-cause mortality or heart transplantation within 1 year. Future studies should evaluate the possible reduction in hospitalizations and optimal dosing to minimize hypotension.

OBJECTIVE: Sacubitril/valsartan (SV), a novel pharmacological class of angiotensin receptor neprilysin inhibitors, is effective in treating heart failure (HF) by inhibiting the degradation of natriuretic peptides and the renin-angiotensin-aldosterone system. However, no studies have observed the long-term effects of SV on patients with HF and preserved left ventricular ejection fraction (LVEF) undergoing hemodialysis (HD) over a long period.
METHODS: This single-center retrospective study of 21 months duration involved consecutive patients with HF and preserved LVEF undergoing HD, who received 50-200 mg/day. All patients were followed up regularly, and clinical, biochemical, and echocardiographic parameters were recorded at baseline and during follow-up. The efficacy and safety of SV were also analyzed.
RESULTS: This longitudinal study included nine patients, with a median age of 76 years. The median HD duration was 7 years. At baseline, the mean brain natriuretic peptide (BNP) was 133±73.6 pg/ml and that of LVEF was 66%±9%. After SV therapy, the systolic blood pressure, diastolic blood pressure, and heart rate decreased, albeit without statistical significance. BNP levels, LVEF, left atrial anteroposterior dimension, and left ventricular mass index did not change, compared to baseline values. No adverse effects were observed in any of the patients.
CONCLUSIONS: SV tended to decrease blood pressure and heart rate in patients with HF and preserved LVEF undergoing HD but did not alter cardiac function assessments, such as BNP or echocardiography.

UNASSIGNED: In a prospective open study, with intervention, conducted in Primary Health Care Units by General Practitioners (GPs) in Portugal, the effectiveness of a single pill of candesartan/amlodipine (ARB/amlodipine), as the only anti-hypertension (anti-HTN) medication, in adult patients with uncontrolled HTN (BP > 140/or > 90 mm Hg), either previously being treated with anti-HTN monotherapies (Group I), or combinations with hydrochlorothiazide (HCTZ) (Group II), or not receiving medication at all (Group III), was evaluated across 12-weeks after implementation of the new therapeutic measure.
UNASSIGNED: A total of 118 GPs recruited patients with uncontrolled HTN who met inclusion/exclusion criteria. Participants were assigned, according to severity, one of 3 (morning) fixed combination candesartan/amlodipine dosage (8/5 or 16/5 or 16/10 mg/day) and longitudinally evaluated in 3 visits (v0, v6 and v12 weeks). Office blood pressure was measured in each visit, and control of HTN was defined per guidelines (BP< 140/90 mmHg).
UNASSIGNED: Of the 1234 patients approached, 752 (age 61 ± 10 years, 52% women) participated in the study and were assigned to groups according to previous treatment conditions. The 3 groups exhibited a statistically significant increased control of blood pressure after receiving the fixed combination candesartan/amlodipine dosage. The overall proportion of controlled HTN participants increased from 0,8% at v0 to 82% at v12. The mean arterial blood pressure values decreased from SBP= 159.0 (± 13.0) and DBP= 91.1 (± 9.6) at baseline to SBP= 132,1 (± 11.3) and DBP= 77,5 (± 8.8) at 12 weeks (p < 0.01). Results remained consistent when controlling for age and sex.
UNASSIGNED: In patients with uncontrolled HTN, therapeutic measures in accordance with guidelines, with a fixed combination candesartan/amlodipine, allowed to overall achieve HTN control at 12 weeks in 82% of previously uncontrolled HTN patients, reinforcing the advantages of these strategies in primary clinical practice.
What is the context?Arterial hypertension (HTN) represents the main risk factor for cause of death from cardiovascular disease (CV). Adequate control of hypertension reduces CV risk and significantly prevents CV events and associated morbidity and mortality. This requires patients’ adherence and persistence in implemented treatment and the achievement of tension targets that are related to the reduction of CV risk. The latest international recommendations indicate that hypertension control is insufficient in most countries. In Portugal, hypertension control is <43% and a significant number of patients treated do not comply with the recommendations.What is new?In a prospective, interventional, and multicentre study, carried out by General Practitioners (GPs) in Primary Health Care Units across Portugal, the objective was to determine (i) whether the presence of uncontrolled hypertension results from non-compliance with the provisions of the recommendations and the Integrated Care Process (PAI) of the Direção Geral de Saúde (DGS), i.e. inappropriate use of monotherapies or inadequate low doses of combinations of antihypertensives, and (ii) whether the adjustment of hypertension therapies, favouring the schemes provided in the recommendations, allows adequate control of arterial hypertension, in previously uncontrolled patients, when these are closely monitored in a 12-week time period.What is the impact?When the guidelines’ therapeutic protocol is followed, as established for each identified group of patients (monotherapy, hydrochlorothiazide, and no medication), results indicate a marked and statistically significant improvements in both SBP and DBP values and hypertension control across time.

BACKGROUND: Effectiveness of candesartan in migraine prevention is supported by two randomized controlled trials. We aimed to assess the effectiveness, tolerability, and response predictors of candesartan in the preventive treatment of migraine.
METHODS: Observational, multicenter, prospective cohort study. The 50%, 75% and 30% responder rates, between weeks 8-12 and 20-24, were compared with the baseline. Treatment emergent adverse effects were systematically evaluated. Response predictors were estimated by multivariate regression models.
RESULTS: Eighty-six patients were included, 79.1% females, aged 39.5 (inter-quartile range [IQR] 26.3-50.3), with chronic migraine (43.0%), medication overuse headache (55.8%) and a median of two (inter-quartile range: 0.75-3) prior preventive treatments. At baseline patients had 14 (10-24) headache and 8 (5-11) migraine days per month. The 30%, 50% and 75% responder rates were 40%, 34.9% and 15.1% between weeks 8-12, and 48.8%, 36%, and 18.6% between weeks 20-24. Adverse effects were reported by 30 (34.9%) and 13 (15.1%) patients between weeks 0-12 and 12-24, leading to discontinuation in 15 (17.4%) patients. Chronic migraine, depression, headache days per month, medication overuse headache, and daily headache at baseline predicted the response between weeks 20-24.
CONCLUSIONS: Candesartan effectiveness and tolerability in migraine prevention was in line with the clinical trials\' efficacy.Trial registration: The study protocol is registered in ClinicalTrials.gov (NCT04138316).

OBJECTIVE: To investigate differences in the incidence of enteropathy or intestinal malabsorption in patients taking angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), and beta blockers (BBs) at a single center in Korea.
METHODS: In this retrospective study, we utilized data from the Yangsan electronic medical records to identify 129,169 patients. These individuals were prescribed olmesartan, other ARBs, ACEI, CCB, and BBs between November 2008 and February 2021.
RESULTS: Of the 44,775 patients, 51 (0.11%) were observed to have enteropathy or intestinal malabsorption. Compared with the ACEI group, the adjusted odds ratios (ORs) for enteropathy and intestinal malabsorption were OR=1.313 (95% confidence interval [CI]: [0.188-6.798], p=0.893) for olmesartan, OR=0.915 (95% CI: [0.525-1.595], p=0.754) for the other ARBs, OR=0.928 (95% CI: [0.200-4.307]; p=0.924) for the CCB, and OR=0.663 (95% CI: [0.151-2.906]; p=0.586) for the BBs group. These findings were adjusted for factors such as age, gender, duration of antihypertensive medication, and comorbidities.
CONCLUSIONS: In a retrospective cohort study of patients on antihypertensive medications, no significant difference was found in the incidence of enteropathy or intestinal malabsorption when ACEI was compared to olmesartan, other ARBs, CCB, and BBs.