Resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. The antihypertensive drugs should be administered at maximum or maximally tolerated daily doses. RH also includes patients whose BP achieves target values on ≥4 antihypertensive medications. The diagnosis of RH requires assurance of antihypertensive medication adherence and exclusion of the "white-coat effect" (office BP above goal but out-of-office BP at or below target). The importance of RH is underscored by the associated risk of adverse outcomes compared with non-RH. This article is an updated American Heart Association scientific statement on the detection, evaluation, and management of RH. Once antihypertensive medication adherence is confirmed and out-of-office BP recordings exclude a white-coat effect, evaluation includes identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. Management of RH includes maximization of lifestyle interventions, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and, if BP remains elevated, stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower BP. If BP remains uncontrolled, referral to a hypertension specialist is advised.

Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association.

Major findings and recent advances in virus-like particle (VLP)-based vaccines.

Importance
Hypertension, defined as persistent systolic blood pressure (SBP) at least 130 mm Hg or diastolic BP (DBP) at least 80 mm Hg, affects approximately 116 million adults in the US and more than 1 billion adults worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (coronary heart disease, heart failure, and stroke) and death.


Observations
First-line therapy for hypertension is lifestyle modification, including weight loss, healthy dietary pattern that includes low sodium and high potassium intake, physical activity, and moderation or elimination of alcohol consumption. The BP-lowering effects of individual lifestyle components are partially additive and enhance the efficacy of pharmacologic therapy. The decision to initiate antihypertensive medication should be based on the level of BP and the presence of high atherosclerotic CVD risk. First-line drug therapy for hypertension consists of a thiazide or thiazidelike diuretic such as hydrochlorothiazide or chlorthalidone, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker such as enalapril or candesartan, and a calcium channel blocker such as amlodipine and should be titrated according to office and home SBP/DBP levels to achieve in most people an SBP/DBP target (<130/80 mm Hg for adults <65 years and SBP <130 mm Hg in adults ≥65 years). Randomized clinical trials have established the efficacy of BP lowering to reduce the risk of CVD morbidity and mortality. An SBP reduction of 10 mm Hg decreases risk of CVD events by approximately 20% to 30%. Despite the benefits of BP control, only 44% of US adults with hypertension have their SBP/DBP controlled to less than 140/90 mm Hg.


Conclusions and Relevance
Hypertension affects approximately 116 million adults in the US and more than 1 billion adults worldwide and is a leading cause of CVD morbidity and mortality. First-line therapy for hypertension is lifestyle modification, consisting of weight loss, dietary sodium reduction and potassium supplementation, healthy dietary pattern, physical activity, and limited alcohol consumption. When drug therapy is required, first-line therapies are thiazide or thiazidelike diuretics, angiotensin-converting enzyme inhibitor or angiotensin receptor blockers, and calcium channel blockers.

pdf/treatment-of-hypertension-a-review-17nb15zyg1.pdf

Treatment of Hypertension: A Review.

Diuretics have been recommended as first-line treatment of hypertension and are also valuable in the management of hypervolemia and electrolyte disorders. This review summarizes the key features of the most commonly used diuretics. We then provide an update of clinical trials for diuretics during the past 5 years. Compared to other classes of medications, thiazide diuretics are at least as effective in reducing cardiovascular events (CVEs) in patients with hypertension and are more effective than β-blockers and angiotensin-converting enzyme inhibitors in reducing stroke. Observational cohort data and a network analysis have shown that CVEs are lowered by one-fifth from chlorthalidone when compared to the commonly used thiazide, hydrochlorothiazide. Relative to placebo, chlorthalidone increases life expectancy. In those aged 80 years and older, the diuretic, indapamide, lowers CVEs relative to placebo. The aldosterone antagonist, eplerenone, lowers total mortality in early congestive heart failure. The benefit of eplerenone following acute myocardial infarction (MI) is limited to administration within 3 to 6 days post-MI. Aldosterone antagonists have been shown to lower the incidence of sudden cardiac death and to reduce proteinuria. In the setting of heart failure, long acting loop diuretics azosemide and torasemide are more effective in improving heart failure outcomes than the far more commonly used short acting furosemide. Evening dosing of diuretics appears to lower CVEs relative to morning dosing. In conclusion, diuretics are a diverse class of drugs that remain extremely important in the management of hypertension and hypervolemic states.

Diuretics: a review and update.

Recent Progress on the Versatility of Virus-Like Particles

Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil.

Background. Noroviruses pose a significant public health risk, particularly in very young individuals, older adults, and individuals with underlying conditions. We assessed 2 bivalent norovirus virus-like particle (VLP) vaccine candidate formulations in healthy adults aged 18–49 years.

Methods. Enrolled subjects (n = 454) randomly assigned among 3 groups received intramuscular placebo (saline) or vaccines containing either 15 µg or 50 µg of GI.1 VLP and 50 µg GII.4 VLP (15/50 and 50/50 formulations) adjuvanted with monophosphoryl lipid A and Al(OH)3. We present safety and immunogenicity assessments up to 28 days after vaccination.

Results. No vaccine-related serious adverse events or adverse events of special interest were reported. Reactions were mainly mild to moderate, the most frequent being transient pain, in 8%, 64%, and 73% of placebo, 15/50, and 50/50 groups, respectively; transient myalgia, headache, and fatigue were the commonest systemic adverse events. Subjects assessed per protocol (n = 442) displayed rapid immune responses to vaccination, peaking by days 7–10 and persisting through day 28. GI.1 responses were highest with the 50/50 formulation, but GII.4 responses were higher with the 15/50 formulation.

Conclusions. Both candidate VLP vaccines were well tolerated and elicited robust immune responses by 7–10 days that persisted through day 28. The 15/50 formulation displayed the best balance of tolerability and immunogenicity.

Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT02142504","term_id":"NCT02142504"}}NCT02142504.

Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial.

Background: Azilsartan medoxomil (AZL-M), a novel angiotensin receptor blocker, lowers blood pressure (BP) more effectively than olmesartan (OLM) and valsartan (VAL) in patients with hypertension. Post hoc analyses of 3 randomized, placebo- and/or active-controlled trials were conducted to compare the BP-lowering effects of AZL-M, OLM and VAL in black patients with stage 1 and 2 hypertension, using ambulatory (ABPM) and clinic BP monitoring. Methods: Data were pooled from 3 trials that randomized patients to AZL-M (40 and 80 mg), OLM 40 mg, VAL 320 mg, or placebo daily for 6 to 24 weeks. Major endpoints included changes from baseline in 24-hour ambulatory and clinic systolic BP (SBP) and clinic SBP following 6 to 8 weeks. Results: Most (>90%) black patients were enrolled in the USA. Mean age was 51–53 yr, with 45–58% men. Baseline (BL) 24-h SBP was 145–148 mm Hg; BL clinic SBP was 156–159 mm Hg. Reductions from BL in 24-h mean and clinic SBP were significantly or numerically greater with 40 and 80 mg AZL-M versus each comparator (Table). The proportion of patients achieving goal BP also was higher for subjects receiving AZL-M compared with OLM or VAL (Table). Safety and tolerability measures were similar for AZL-M, active comparators, and placebo. Conclusions: These data indicate that AZL-M has greater SBP lowering efficacy in black patients with hypertension compared to OLM and VAL at their maximum approved doses. Table. No title available.

558 azilsartan medoxomil vs olmesartan and valsartan: effects on ambulatory and clinic bp in hypertensive black patients

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Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil.

Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial.

558 azilsartan medoxomil vs olmesartan and valsartan: effects on ambulatory and clinic bp in hypertensive black patients