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1.
Heart failure drug treatment.
Rossignol, P, Hernandez, AF, Solomon, SD, Zannad, F
Lancet (London, England). 2019;(10175):1034-1044
Abstract
Heart failure is the most common cardiovascular reason for hospital admission for people older than 60 years of age. Few areas in medicine have progressed as remarkably as heart failure treatment over the past three decades. However, progress has been consistent only for chronic heart failure with reduced ejection fraction. In acutely decompensated heart failure and heart failure with preserved ejection fraction, none of the treatments tested to date have been definitively proven to improve survival. Delaying or preventing heart failure has become increasingly important in patients who are prone to heart failure. The prevention of worsening chronic heart failure and hospitalisations for acute decompensation is also of great importance. The objective of this Series paper is to provide a concise and practical summary of the available drug treatments for heart failure. We support the implementation of the international guidelines. We offer views on the basis of our personal experience in research areas that have insufficient evidence. The best possible evidence-based drug treatment (including inhibitors of the renin-angiotensin-aldosterone system and β blockers) is useful only when optimally implemented. However, implementation might be challenging. We believe that disease management programmes can be helpful in providing a multidisciplinary, holistic approach to the delivery of optimal medical care.
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2.
Effects of sartans and low-dose statins on cerebral white matter hyperintensities and cognitive function in older patients with hypertension: a randomized, double-blind and placebo-controlled clinical trial.
Zhang, H, Cui, Y, Zhao, Y, Dong, Y, Duan, D, Wang, J, Sheng, L, Ji, T, Zhou, T, Hu, W, et al
Hypertension research : official journal of the Japanese Society of Hypertension. 2019;(5):717-729
Abstract
Cerebral white matter hyperintensities (WMHs) and cognitive impairment are common in elderly hypertensive patients, and more needs to be learned about their prevention and treatment. Our aim was to investigate the effect of low-dose statins on WMH and cognitive function in elderly patients undergoing antihypertensive treatment. A total of 732 elderly hypertensive patients taking hydrochlorothiazide as their baseline medication were randomized using a 2 × 2 factorial design with antihypertensive (telmisartan vs. placebo) and lipid-modulating (low-dose rosuvastatin vs. placebo) arms. Brain magnetic resonance imaging (MRI) and cognitive function data were obtained. After a mean follow-up time of 59.8 (range 12-65) months, there were no differences in WMH progression and cognitive function decline over time between the groups in the antihypertensive arm. The risks of new-incident WMH Fazekas scale scores ≥ 2 and the incidence of cognitive impairment did not differ between the telmisartan and placebo groups. Rosuvastatin use was associated with lower risks of new-incident Fazekas scale scores ≥2 (hazard ratio = 0.500; 95% confidence interval: 0.34-0.74) and cognitive impairment (hazard ratio = 0.54; 95% confidence interval: 0.36-0.80). Telmisartan interacted with rosuvastatin on reducing WMH progression and cognitive function decline. Findings suggest that low-dose rosuvastatin could reduce WMH progression and cognitive function decline in antihypertensive patients, as demonstrated by the interaction between telmisartan and low-dose rosuvastatin to this effect.
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3.
Should we add atorvastatin to irbesartan for improving renoprotective effects in early diabetic nephropathy? A meta-analysis of randomized controlled trials.
Zuo, Y, Li, T, Lei, Z
Pharmacological research. 2019;:104286
Abstract
Angiotensin II receptor blocker has exhibited their renal protective benefits in diabetic nephropathy. This meta-analysis aimed to evaluate the effects of adding atorvastatin to irbesartan in early diabetic nephropathy. A systematic literature search was performed in PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang database until March 25, 2019. Randomized controlled trials evaluating the effects of adding atorvastatin to irbesartan in early diabetic nephropathy were eligible. Primary endpoint was urinary albumin excretion rate, serum creatinine, and blood urea nitrogen. Serum level of total cholesterol, triglyceride, fasting blood glucose, interleukin-6,and C-reactive protein (CRP) as well as blood pressure were secondary endpoints. Seventeen trials involving 1,390 patients were identified. Compared with irbesartan alone, co-administration of atorvastatin and irbesartan significantly reduced urinary albumin excretion rate (weighted mean differences [WMD] -21.22 μg/min; 95% confidence interval [CI] -26.95 to -15.50), serum creatinine (WMD -6.46 μmol/L; 95%CI -8.52 to 4.39),BUN (WMD -0.46 mmol/L; 95%CI -0.64 to -0.27), total cholesterol (WMD -1.79 mmol/L; 95%CI -2.34 to -1.23), triglyceride (WMD -0.93 mmol/L; 95%CI -1.20 to -0.67),and systolic blood pressure (WMD -2.27 mmHg; 95%CI -4.01 to -0.53), CRP (standard mean difference [SMD] 1.57; 95%CI -2.24 to -0.9), and Interleukin-6 (SMD 1.53; 95%CI -2.29 to -0.78). However, there was a significantly increased risk of nausea/vomiting (risk ratio 3.15; 95% CI 1.18-8.38) on the co-administration group. In conclusion, adding atorvastatin to irbesartan achieves additional renal protective benefits in early diabetic nephropathy patients. However, these findings should be interpreted with caution due to suboptimal methodological quality of the analyzed trials.
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4.
Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.
Imaizumi, S, Shiga, Y, Ogawa, M, Sako, H, Nagata, Y, Matsunaga, A, Shirotani, T, Hoshino, F, Yahiro, E, Uehara, Y, et al
Heart and vessels. 2019;(4):698-710
Abstract
There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5 mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10 mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5 mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; - 7.9 mmHg vs. + 2.7 mmHg; p = 0.0002, diastolic BP; - 3.9 mmHg vs. + 0.6 mmHg; p = 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.
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5.
Blockade of the angiotensin system improves mental health domain of quality of life: A meta-analysis of randomized clinical trials.
Brownstein, DJ, Salagre, E, Köhler, C, Stubbs, B, Vian, J, Pereira, C, Chavarria, V, Karmakar, C, Turner, A, Quevedo, J, et al
The Australian and New Zealand journal of psychiatry. 2018;(1):24-38
Abstract
OBJECTIVE It is unclear whether blockade of the angiotensin system has effects on mental health. Our objective was to determine the impact of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor (AT1R) blockers on mental health domain of quality of life. STUDY DESIGN Meta-analysis of published literature. DATA SOURCES PubMed and clinicaltrials.gov databases. The last search was conducted in January 2017. STUDY SELECTION Randomized controlled trials comparing any angiotensin converting enzyme inhibitor or AT1R blocker versus placebo or non-angiotensin converting enzyme inhibitor or non-AT1R blocker were selected. Study participants were adults without any major physical symptoms. We adhered to meta-analysis reporting methods as per PRISMA and the Cochrane Collaboration. DATA SYNTHESIS Eleven studies were included in the analysis. When compared with placebo or other antihypertensive medications, AT1R blockers and angiotensin converting enzyme inhibitors were associated with improved overall quality of life (standard mean difference = 0.11, 95% confidence interval = [0.08, 0.14], p < 0.0001), positive wellbeing (standard mean difference = 0.11, 95% confidence interval = [0.05, 0.17], p < 0.0001), mental (standard mean difference = 0.15, 95% confidence interval = [0.06, 0.25], p < 0.0001), and anxiety (standard mean difference = 0.08, 95% confidence interval = [0.01, 0.16], p < 0.0001) domains of QoL. No significant difference was found for the depression domain (standard mean difference = 0.05, 95% confidence interval = [0.02, 0.12], p = 0.15). CONCLUSIONS Use of angiotensin blockers and inhibitors for the treatment of hypertension in otherwise healthy adults is associated with improved mental health domains of quality of life. Mental health quality of life was a secondary outcome in the included studies. Research specifically designed to analyse the usefulness of drugs that block the angiotensin system is necessary to properly evaluate this novel psychiatric target.
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6.
Association Between Change in Central Nocturnal Blood Pressure and Urine Albumin-Creatinine Ratio by a Valsartan/Amlodipine Combination: A CPET Study.
Fujiwara, T, Yano, Y, Hoshide, S, Kanegae, H, Hashimoto, J, Kario, K
American journal of hypertension. 2018;(9):995-1001
Abstract
BACKGROUND We aimed to assess the association of changes in brachial or central nocturnal systolic blood pressure (SBP) with change in urine albumin-creatinine ratio (UACR) by a valsartan/amlodipine combination (80/5 mg) therapy in hypertensive patients. METHODS Twenty-three patients (age range, 47-78 years; mean, 68.0 years; 35% men, 65% with chronic kidney disease) with clinic brachial BP ≥140/90 mm Hg were treated with valsartan/amlodipine combination therapy for 16 weeks. At baseline and 16 weeks later, we measured brachial and central nocturnal SBP using an oscillometric Mobil-O-Graph device and UACR by spot urine in 23 patients. RESULTS The changes in brachial nocturnal SBP (r = 0.445, P = 0.033) and those in central nocturnal SBP (r = 0.616, P = 0.002) were significantly associated with change in UACR by intervention. In multivariable-adjusted multiple regression analyses including changes in both brachial and central nocturnal SBP jointly, only central nocturnal SBP change retained a statistically significant association with change in UACR (β = 0.919, P = 0.020). CONCLUSIONS Lowering central nocturnal SBP by a valsartan/amlodipine combination therapy was associated with reduction of UACR, independently of brachial nocturnal SBP reduction. Central nocturnal SBP may be a therapeutic target to protect the kidney. A larger scale interventional study will be needed to confirm the kidney protection conferred by lowering central nocturnal SBP. CLINICAL TRIALS REGISTRATION Trial Number UMIN000013519.
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7.
Hydrochlorothiazide treatment increases the abundance of the NaCl cotransporter in urinary extracellular vesicles of essential hypertensive patients.
Pathare, G, Tutakhel, OAZ, van der Wel, MC, Shelton, LM, Deinum, J, Lenders, JWM, Hoenderop, JGJ, Bindels, RJM
American journal of physiology. Renal physiology. 2017;(6):F1063-F1072
Abstract
The thiazide-sensitive NaCl cotransporter (NCC), located apically in distal convoluted tubule epithelia, regulates the fine-tuning of renal sodium excretion. Three isoforms of NCC are generated through alternative splicing of the transcript, of which the third isoform has been the most extensively investigated in pathophysiological conditions. The aim of this study was to investigate the effect of different anti-hypertensive treatments on the abundance and phosphorylation of all three NCC isoforms in urinary extracellular vesicles (uEVs) of essential hypertensive patients. In uEVs isolated from patients (n = 23) before and after hydrochlorothiazide or valsartan treatment, the abundance and phosphorylation of the NCC isoforms was determined. Additionally, clinical biochemistry and blood pressure of the patients was assessed. Our results show that NCC detected in human uEVs has a glycosylated and oligomeric structure, comparable to NCC present in human kidney membrane fractions. Despite the inhibitory action of hydrochlorothiazide on NCC activity, immunoblot analysis of uEVs showed significantly increased abundance of NCC isoforms 1 and 2 (NCC1/2), total NCC (NCC1-3), and the phosphorylated form of total NCC (pNCC1-3-T55/T60) in essential hypertensive patients treated with hydrochlorothiazide but not with valsartan. This study highlights that NCC1/2, NCC1-3, and pNCC1-3-T55/T60 are upregulated by hydrochlorothiazide, and the increase in NCC abundance in uEVs of essential hypertensive patients correlates with the blood pressure response to hydrochlorothiazide.
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8.
Sacubitril and valsartan fixed combination to reduce heart failure events in post-acute myocardial infarction patients.
Zaid Iskandar, M, Lang, CC
Drugs of today (Barcelona, Spain : 1998). 2017;(10):545-551
Abstract
Heart failure is a term used to define a constellation of symptoms and signs that are commonly attributed to the inability of the heart to produce a cardiac output that meets the demands of the body. It remains a deadly disease, affecting between 1-2% of the population, and is more common in the elderly, with around 6-10% of patients over 65 suffering from the condition. Sacubitril/valsartan (LCZ-696) is a combined neprilysin inhibitor and angiotensin AT1 receptor blocker approved in recent years for the treatment of chronic heart failure with reduced ejection fraction. In an area where there have been limited pharmacological advances in the last 10 years, this drug was a game changer and a much welcomed addition to contemporary heart failure therapy. It is currently being studied in patients with heart failure with preserved ejection fraction and for the reduction of heart failure events post-acute myocardial infarction. Results from the ongoing PARADISE-MI study are awaited by the global cardiology community with great interest.
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9.
A randomised controlled trial evaluating renal protective effects of selenium with vitamins A, C, E, verapamil, and losartan against extracorporeal shockwave lithotripsy-induced renal injury.
El-Nahas, AR, Elsaadany, MM, Taha, DE, Elshal, AM, El-Ghar, MA, Ismail, AM, Elsawy, EA, Saleh, HH, Wafa, EW, Awadalla, A, et al
BJU international. 2017;(1):142-147
Abstract
OBJECTIVE To evaluate the protective effects of selenium with vitamins A, C and E (selenium ACE, i.e. antioxidants), verapamil (calcium channel blocker), and losartan (angiotensin receptor blocker) against extracorporeal shockwave lithotripsy (ESWL)-induced renal injury. PATIENTS AND METHODS A randomised controlled trial was conducted between August 2012 and February 2015. Inclusion criteria were adult patients with a single renal stone (<2 cm) suitable for ESWL. Patients with diabetes, hypertension, congenital renal anomalies, moderate or marked hydronephrosis, or preoperative albuminuria (>300 mg/L) were excluded. ESWL was performed using the electromagnetic DoLiS lithotripter. Eligible patients were randomised into one of four groups using sealed closed envelopes: Group1, control; Group 2, selenium ACE; Group 3, losartan; and Group 4, verapamil. Albuminuria and urinary neutrophil gelatinase-associated lipocalin (uNGAL) were estimated after 2-4 h and 1 week after ESWL. The primary outcome was differences between albuminuria and uNGAL. Dynamic contrast-enhanced magnetic resonance imaging was performed before ESWL, and at 2-4 h and 1 week after ESWL to compare changes in renal perfusion. RESULTS Of 329 patients assessed for eligibility, the final analysis comprised 160 patients (40 in each group). Losartan was the only medication that showed significantly lower levels of albuminuria after 1 week (P < 0.001). For perfusion changes, there was a statistically significant decrease in the renal perfusion in patients with obstructed kidneys in comparison to before ESWL (P = 0.003). These significant changes were present in the control or antioxidant group, whilst in the losartan and verapamil groups renal perfusion was not significantly decreased. CONCLUSIONS Losartan was found to protect the kidney against ESWL-induced renal injury by significantly decreasing post-ESWL albuminuria. Verapamil and losartan maintained renal perfusion in patients with post-ESWL renal obstruction.
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10.
Impact of Renin-Angiotensin Aldosterone System Inhibition on Serum Potassium Levels among Peritoneal Dialysis Patients.
Ribeiro, SC, Figueiredo, AE, Barretti, P, Pecoits-Filho, R, de Moraes, TP, ,
American journal of nephrology. 2017;(2):150-155
Abstract
BACKGROUND The chronic use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker has been associated with hyperkalemia in patients with reduced renal function even after the initiation of hemodialysis. Whether such medications may cause a similar effect in peritoneal dialysis patients is not well established. So, the aim of our study was to analyze the impact of renin-angiotensin-aldosterone inhibitors on the serum levels of potassium in a national cohort of peritoneal dialysis patients. METHOD A prospective, observational, nationwide cohort study was conducted. We identified all incident patients on peritoneal dialysis that had angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) prescribed for at least 3 months and a similar period of time without these medications. Patients were divided into 4 groups: Groups I and III correspond to patients using, respectively, an ACEi or ARB and then got the drug suspended; Groups II and IV started peritoneal dialysis without the use of any renin-angiotensin aldosterone system inhibitor and then got, respectively, an ACEi or ARB introduced. Changes in potassium serum levels were compared using 2 statistical approaches: (1) the non-parametric Wilcoxon test for repeated measures and (2) a crossover analysis. RESULTS Mean potassium serum levels at the first phase of the study for Groups I, II, III, and IV were, respectively, 4.46 ± 0.79, 4.33 ± 0.78, 4.41 ± 0.63, and 4.44 ± 0.56. Changes in mean potassium serum levels for Groups I, II, III, and IV were -0.10 ± 0.60, 0.02 ± 0.56, -0.06 ± 0.46, and 0.03 ± 0.50, respectively. CONCLUSION The use of ACEi and ARB was not associated with a greater risk for hyperkalemia in stable peritoneal dialysis patients independently of residual renal function.