Angiotensin receptor-neprilysin inhibitors (ARNIs) are a new class of cardiovascular agents characterized by their dual action on the major regulators of the cardiovascular system, including the ...renin-angiotensin system (RAS) and the natriuretic peptide (NP) system. The apparent clinical benefit of one ARNI, sacubitril/valsartan, as shown in clinical trials, has positioned the drug class as a first-line therapy in patients with heart failure, particularly with reduced ejection fraction. Accumulating evidence also suggests that sacubitril/valsartan is superior to conventional RAS blockers in lowering blood pressure in patients with hypertension. To decide whether to apply an ARNI to treat hypertension clinically, it is important to understand the potential properties of the drug in modulating multiple factors inside and outside the cardiovascular system beyond its effect on reducing peripheral blood pressure. In this context, ARNIs are distinct from preexisting antihypertensive medications in terms of the multiple actions of NPs in various organs and the pharmacological potential of neprilysin inhibitors to modulate multiple cardiac and noncardiac peptides. In particular, analysis of the clinical trials of sacubitril/valsartan implies that ARNIs can provide additional clinical benefits independent of their original purpose, including alleviation of glycemic control and renal impairment in patients with heart failure. Understanding the potential mechanisms of action of ARNIs will help interpret the relevance of their additional benefits beyond lowering blood pressure in hypertension. This review summarizes the comprehensive clinical evidence and relevance of ARNIs by specifically focusing on the potential properties of this new drug class in treating patients with hypertension.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Japan's population is aging more rapidly than that of any other country. Frailty has recently been recognized as an important priority. Understanding the basic epidemiology of frailty in Japan, which ...is an example of a rapidly aging society, will be beneficial for Japan as well as other countries expecting an aging population. A systematic literature search of 11 electronic databases was conducted in March 2016 using a comprehensive set of Medical Subject Heading and text terms for any studies published in 2000 or later that report the prevalence of frailty among Japanese community-dwelling older people aged 65 years or older. A total of 1529 studies were identified in the systematic search, of which five studies were included in this review. The pooled prevalence of frailty, prefrailty, and robustness was 7.4% (95% confidence interval CI, 6.1%–9.0%), 48.1% (95% CI, 41.6%–54.8%), and 44.4% (95% CI, 37.2%–51.7%), respectively. A significant degree of heterogeneity was observed. There was no evidence of publication bias. Age-stratified meta-analyses of four studies showed the pooled prevalence of frailty was 1.9%, 3.8%, 10.0%, 20.4%, and 35.1% for those aged 65–69, 70–74, 75–79, 80–84, and ≥85 years, respectively. Pooled prevalence of frailty was 8.1% for women and 7.6% for men. This review showed an overall pooled prevalence of frailty among Japanese community-dwelling older people of 7.4%. The age-stratified analysis suggested that Japanese older people are less frail before their late 70's but frailer in later life than older people in other countries. These findings provide important basic information for all parties involved in Japanese frailty research.
•Frailty is an important priority in Japan, where the population is aging rapidly.•Japan is a good example of a rapidly aging society for frailty research.•Five studies were included in this systematic review and meta-analysis study.•Pooled prevalence of frailty in Japanese in the community aged >65 years is 7.4%.
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FFLJ, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The number of people with dementia is rapidly growing along with the aging of society and is becoming a social issue worldwide. The results of recent clinical and basic studies have suggested that ...vascular risk factors, such as hypertension and diabetes mellitus, affect the pathogenesis of dementia. Cerebrovascular damage due to vascular risk factors directly triggers vascular dementia, and it is becoming more apparent that vascular risk factors also increase the risk of neurodegenerative Alzheimer's disease, which is associated with the accumulation of neurotoxic proteins in the brain. Although disease-modifying therapy for dementia has not yet been established, several studies have shown that the management of vascular risk factors could possibly contribute to reducing the risk of developing dementia, thus making them important targets for dementia prevention. In this article, we review recent findings regarding the relationship between vascular risk factors and dementia, especially focusing on Alzheimer's disease, the underlying molecular mechanisms, and the potential strategies targeting these modifiable risk factors to prevent cognitive decline.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The nonsteroidal mineralocorticoid receptor (MR) blocker esaxerenone has demonstrated good antihypertensive activity in a variety of patients, including those with uncomplicated grade I-III ...hypertension, hypertension with moderate renal dysfunction, hypertension with type 2 diabetes mellitus with albuminuria, and hypertension associated with primary aldosteronism. Hyperkalemia has long been recognized as a potential side effect occurring during treatment with MR blockers, but there is a lack of understanding and guidance about the appropriate management of hyperkalemia during antihypertensive therapy with MR blockers, especially in regard to the newer agent esaxerenone. In this article, we first highlight risk factors for hyperkalemia, including advanced chronic kidney disease, diabetes mellitus, cardiovascular disease, age, and use of renin-angiotensin-aldosterone system inhibitors. Next, we examine approaches to prevention and management, including potassium monitoring, diet, and the use of appropriate therapeutic techniques. Finally, we summarize the currently available data for esaxerenone and hyperkalemia. Proper management of serum potassium is required to ensure safe clinical use of MR blockers, including awareness of at-risk patient groups, choosing appropriate dosages for therapy initiation and dosage titration, and monitoring of serum potassium during therapy. It is critical that physicians take such factors into consideration to optimize MR blocker therapy in patients with hypertension.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This phase III study assessed the efficacy and safety of sacubitril/valsartan compared with those of olmesartan in Japanese patients with essential hypertension. Patients (n = 1161, aged ≥20 years) ...with mild to moderate hypertension (mean sitting systolic blood pressure msSBP ≥150 to <180 mmHg) were randomized to receive sacubitril/valsartan 200 mg (n = 387), sacubitril/valsartan 400 mg (n = 385), or olmesartan 20 mg (n = 389) once daily for 8 weeks. The primary assessment was a reduction in msSBP from baseline with sacubitril/valsartan 200 mg vs. olmesartan 20 mg at Week 8. Secondary assessments included msSBP reduction with sacubitril/valsartan 400 mg vs. olmesartan at Week 8 and reductions in mean sitting diastolic blood pressure (msDBP), mean sitting pulse pressure (msPP), and overall blood pressure (BP) control rate for all treatment groups at Week 8. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP from baseline than olmesartan at Week 8 (between-treatment difference: -5.01 mmHg 95% confidence interval: -6.95 to -3.06 mmHg, P < 0.001 for noninferiority and superiority). Greater reductions in msSBP with sacubitril/valsartan 400 mg vs. olmesartan, as well as in msDBP and msPP with both doses of sacubitril/valsartan vs. olmesartan (P < 0.05 for all), were also observed. Patients treated with sacubitril/valsartan achieved an overall higher BP control rate. The safety and tolerability profiles of sacubitril/valsartan were generally comparable to those of olmesartan. The adverse event rate with sacubitril/valsartan was not dose-dependent. Treatment with sacubitril/valsartan was effective and provided superior BP reduction, with a higher proportion of patients achieving target BP goals than treatment with olmesartan in Japanese patients with mild to moderate essential hypertension.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Renin-angiotensin system inhibitors are recommended for treating hypertension with chronic kidney disease. The addition of a mineralocorticoid receptor blocker may be one option to achieve target ...blood pressure. We investigated the efficacy and safety of esaxerenone, a mineralocorticoid receptor blocker, in Japanese hypertensive patients with moderate kidney dysfunction. Two multicenter, open-label, nonrandomized dose escalation studies were conducted to investigate esaxerenone monotherapy and add-on therapy to renin-angiotensin system inhibitor treatment. Esaxerenone therapy was initiated at 1.25 mg/day and titrated to 2.5 and then 5 mg/day for a treatment duration of 12 weeks. Primary endpoints were changes from baseline in sitting systolic and diastolic blood pressure. Safety, pharmacokinetics, and urinary albumin-to-creatinine ratios were also assessed. Thirty-three patients received monotherapy, and 58 received add-on therapy; the mean baseline estimated glomerular filtration rates were 51.9 and 50.9 mL/min/1.73 m
, respectively. The esaxerenone dosage was increased to ≥2.5 mg/day in 100% (n = 33) and 93.1% (n = 54) of patients receiving monotherapy and add-on therapy, respectively. Reductions in sitting blood pressure from baseline to the end of treatment were similar (monotherapy: -18.5/-8.8 mmHg; add-on therapy: -17.8/-8.1 mmHg; both P < 0.001). The antihypertensive effects of esaxerenone were consistent across patient subgroups. A serum K
level ≥5.5 mEq/L was observed in seven patients (12.1%) receiving add-on therapy but in none receiving monotherapy. All increases in serum K
levels were transient, and no patient met predefined serum K
level criteria for dose reduction or therapy discontinuation. No patient discontinued treatment owing to kidney function decline. Esaxerenone was effective and well tolerated in hypertensive patients with moderate kidney dysfunction.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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