Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults.

Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension. This year, we introduce 10 new guidelines. Three previous guidelines have been revised and 5 have been removed. Previous age and frailty distinctions have been removed as considerations for when to initiate antihypertensive therapy. In the presence of macrovascular target organ damage, or in those with independent cardiovascular risk factors, antihypertensive therapy should be considered for all individuals with elevated average systolic nonautomated office blood pressure (non-AOBP) readings ≥ 140 mm Hg. For individuals with diastolic hypertension (with or without systolic hypertension), fixed-dose single-pill combinations are now recommended as an initial treatment option. Preference is given to pills containing an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in combination with either a calcium channel blocker or diuretic. Whenever a diuretic is selected as monotherapy, longer-acting agents are preferred. In patients with established ischemic heart disease, caution should be exercised in lowering diastolic non-AOBP to ≤ 60 mm Hg, especially in the presence of left ventricular hypertrophy. After a hemorrhagic stroke, in the first 24 hours, systolic non-AOBP lowering to < 140 mm Hg is not recommended. Finally, guidance is now provided for screening, initial diagnosis, assessment, and treatment of renovascular hypertension arising from fibromuscular dysplasia. The specific evidence and rationale underlying each of these guidelines are discussed.

Use, misuse and abuse of diuretics.

Resolution of edema requires a correct interpretation of body fluids-related renal function, to excrete the excess volume while restoring systemic hemodynamics and avoiding renal failure. In heart failure, the intensive diuresis should be matched by continuous fluids refeeding from interstitium to plasma, avoiding central volume depletion. The slowly reabsorbed ascites cannot refeed this contracted volume in cirrhosis: the ensuing activation of intrathoracic receptors, attended by increased adrenergic and Renin release, causes more avid sodium retention, producing a positive fluid and Na balance in the face of continuous treatment. High-dose-furosemide creates a defect in tubular Na causing diuresis adequate to excrete the daily water and electrolyte load in Chronic Renal Failure. Diuretic treatment requires care, caution and bedside "tricks" aimed at minimizing volume contraction by correctly assessing the homeostatic system of body fluids and related renal hemodynamics.

[All diuretics used in the treatment of hypertension are not the same]. / Hipertansiyon tedavisinde kullanilan tüm diüretikler ayni degildir.

Diuretics have been used for years to treat hypertension as both a monotherapy and in combination. Hydrochlorothiazide, indapamide, and chlorthalidone have frequently been considered in the same category as thiazide diuretics, but there is no evidence that their activities are similar. Studies have shown that chlorthalidone and indapamide reduce cardiovascular morbidity and mortality; however, there is no study indicating that hydrochlorothiazide has beneficial effects on cardiovascular outcomes such as myocardial infarction, renal failure, stroke, or death. Hydrochlorothiazide has less effect on blood pressure, a high risk of metabolic side effects, and may not have pleiotropic effects. As a result, it is not accurate to evaluate chlorthalidone and indapamide as similar to thiazide diuretics. Indapamide or chlorthalidone is a better choice of diuretic for use in the treatment of hypertension.

Medication adherence and persistence according to different antihypertensive drug classes: A retrospective cohort study of 255,500 patients.

BACKGROUND: Suboptimal adherence to antihypertensives leads to adverse clinical outcomes. This study aims to determine and compare medication adherence and persistence to different first-line antihypertensive drug classes in a large cohort. METHODS: A cohort study was performed using claims data for prescriptions in the German statutory health insurance scheme that insures approximately 90% of the population. A total of 255,500 patients with a first prescription of an antihypertensive were included and followed for 24months. Persistence was determined based on gaps in continuous dispensation. Adherence was analyzed by calculating the medication possession ratio (MPR). RESULTS: Within a 2-year period, 79.3% of all incident users of antihypertensive monotherapy met the classification of non-persistence (gap >0.5 times the number of days supplied with medication) and 56.3% of non-adherence (MPR<0.8). Beta-blockers (42.5%) and angiotensin-converting enzyme inhibitors (31.9%) were the most widely prescribed drug classes. Non-persistence and non-adherence were highest for diuretics (85.4%, n=6149 and 66.3%, n=4774) and lowest for beta-blockers (77.6%, n=76,729 and 55.2%, n=54,559). The first gap of antihypertensive medication occurred in median 160-250days after initiation, and the average medication possession ratio for all drug classes was less than 0.8. Fixed combinations with diuretics showed a 19.8% lower chance for non-adherence (OR=0.802, 99.9% CI=[0.715-0.900], p<0.001) and an 8.4% lower hazard for non-persistence (HR 0.916, 99.9% CI=[0.863-0.973], p<0.001) compared with monotherapies. CONCLUSIONS: This large cohort study reveals important differences in 2-year adherence and persistence between antihypertensives that were lowest for diuretics. Fixed-dose combinations with diuretics may facilitate adherence compared to single substance products. However, effective strategies to improve adherence to antihypertensives are needed regardless of drug class.

Transient Hyponatremia During Hospitalization for Acute Heart Failure.

OBJECTIVE: The objective was to study whether the temporal pattern of transient hyponatremia development in acute heart failure might provide insight into its pathophysiology and prognostic relevance. METHODS: A post hoc analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) and Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE AHF) studies was performed (n = 716). Patients were stratified according to the temporal pattern of hyponatremia development: (1) no hyponatremia, (2) persistent hyponatremia, (3) decompensation hyponatremia disappearing with decongestive treatment, and (4) treatment-induced hyponatremia. RESULTS: Transient decompensation versus no hyponatremia was associated with significantly elevated blood urea nitrogen/creatinine ratio (P < .001), plasma renin activity (P < .001), and plasma aldosterone levels (P < .001) at baseline. Disease severity characteristics of such patients were intermediate between no and persistent hyponatremia. In contrast, patients with treatment-induced versus no hyponatremia had similar baseline characteristics and comparable natriuretic peptide levels, and both groups had little neurohumoral activation at baseline. Diuretic efficacy, defined as net fluid balance (milliliters) per 40 mg furosemide-equivalent dose administered, was lower in patients with persistent or treatment-induced hyponatremia versus decompensation hyponatremia or no hyponatremia, respectively. The former versus latter groups also had more pronounced neurohumoral activation with decongestive treatment. The risk for all-cause mortality (hazard ratio, 2.50; 95% confidence interval, 1.50-4.19; P < .001) and death or heart failure readmission (hazard ratio, 2.18; 95% confidence interval, 1.60-2.97; P < .001) was significantly elevated in patients with persistent versus no hyponatremia, with the risk of decompensation and treatment hyponatremia situated in between. CONCLUSIONS: Transient hyponatremia is prognostically relevant, but it has a heterogeneous cause according to its temporal pattern of development.

Intraclass differences among antihypertensive drugs.

The four major classes of antihypertensive drugs­diuretics, ß-blockers, calcium channel blockers, and renin-angiotensin system inhibitors (including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers)­have significant qualitative and quantitative differences in the adverse effects they cause. Structural and chemical differences have been identified within these classes, especially among the calcium channel blockers and, to a lesser extent, among the thiazide/thiazide-like diuretics. However, it has been more difficult to demonstrate that these differences translate into differential effects with respect to either the surrogate endpoint of blood pressure reduction or, more importantly, hypertension-related cardiovascular complications. Based on a hierarchy-of-evidence approach, differences are apparent between hydrochlorothiazide and chlorthalidone based on evidence of moderate quality. Low-quality evidence suggests atenolol is less effective than other ß-blockers. However, no significant intraclass differences have been established among the other classes of antihypertensive drugs.

Diuretic-associated electrolyte disorders in the elderly: risk factors, impact, management and prevention.

Electrolyte and acid-base disorders are commonly encountered adverse effects of various diuretic agents, which are associated with considerable morbidity and mortality especially in elderly patients. Diuretic use is associated with hyponatraemia, hypernatraemia, hypokalaemia, hyperkalaemia, hyperuricaemia and alterations in magnesium, calcium, phosphate and acid-base homeostasis. Clinical studies have provided important data on the relative frequency and risk factors for these diuretic-associated electrolyte and acid-base disorders. Old age is one of the most recognized risk factors for diuretic-associated electrolyte and acid-base disorders. Hyponatraemia and hypokalaemia are the most common electrolyte abnormalities found among the elderly population taking diuretics. Both conditions are associated with short and long-term morbidity as well as mortality. This article presents an overview of the literature on diuretic-associated electrolyte disorders and suggested risk factors for their development especially in elderly patients when evidence is available. The impact of these electrolyte disorders on patients will be discussed. Strategies to prevent adverse outcomes related to these disorders should involve careful consideration of risk factors as well as ongoing clinical and laboratory evaluations in the course of using these diuretics.

[Diuretic therapy in heart failure]. / Tratamiento diurético en la insuficiencia cardiaca.

Many of the primary clinical manifestations of heart failure (HF) are due to fluid retention, and treatments targeting congestion play a central role in HF management. Diuretic therapy remains the cornerstone of congestion treatment, and diuretics are prescribed to the majority of HF patients. Despite this ubiquitous use, there is limited evidence from prospective randomized studies to guide the use of diuretics. With the chronic use of diuretic and usually in advanced stages of HF, diuretics may fail to control salt and water retention. This review describes the mechanism of action of available diuretic classes, reviews their clinical use based on scientific evidence and discusses strategies to overcome diuretic resistance.

[Diuretics]. / Leki moczopedne.

Diuretics are an important class of medicine used to treat a wide variety of acute and chronic conditions, like: heart failure, hypertension and renal diseases. They act by increasing urinary excretion of water, sodium, and some others electrolytes, at different sites in the nephron. In this paper the mechanisms of action, use, dosing and adverse effects of the commonly used diuretics are reviewed.

Diuretic use, increased serum urate levels, and risk of incident gout in a population-based study of adults with hypertension: the Atherosclerosis Risk in Communities cohort study.

OBJECTIVE: To quantify the role of diuretic use in gout development in an adult population with hypertension. METHODS: The Atherosclerosis Risk in Communities study, a prospective population-based cohort from 4 US communities, consisted of 4 visits over a 9-year period. Participants were included in this analysis if they answered a query about gout, were free of gout at baseline, and had hypertension (defined as taking medication to treat hypertension or having blood pressure of ≥140/90 mm Hg). Trained interviewers recorded use of antihypertensive drugs. Incident gout was defined as self-reported onset of gout after baseline. Using a time-dependent Cox proportional hazards model, we estimated hazard ratios (HRs; with 95% confidence intervals [95% CIs]) for incident gout by time-varying diuretic use, both adjusted for confounders and tested for mediation by serum urate level. RESULTS: There were 5,789 participants with hypertension; 37% were treated with a diuretic. Use of any diuretic (HR 1.48 [95% CI 1.11, 1.98]), a thiazide diuretic (HR 1.44 [95% CI 1.00, 2.10]), or a loop diuretic (HR 2.31 [95% CI 1.36, 3.91]) was associated with incident gout as compared with not using any diuretic, not using a thiazide diuretic, or not using a loop diuretic, respectively. After adjusting for serum urate level, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR 0.64 [95% CI 0.49, 0.86]) compared to untreated hypertension. The longitudinal change in serum urate levels was 0.72 mg/dl (95% CI 0.57, 0.87) higher in those who began treatment with a diuretic than in those who did not (P<0.001). CONCLUSION: Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate levels.

Meta-analysis: impact of drug class on adherence to antihypertensives.

BACKGROUND: Observational studies suggest that there are differences in adherence to antihypertensive medications in different classes. Our objective was to quantify the association between antihypertensive drug class and adherence in clinical settings. METHODS AND RESULTS: Studies were identified through a systematic search of English-language articles published from the inception of computerized databases until February 1, 2009. Studies were included if they measured adherence to antihypertensives using medication refill data and contained sufficient data to calculate a measure of relative risk of adherence and its variance. An inverse-variance-weighted random-effects model was used to pool results. Hazard ratios (HRs) and odds ratios were pooled separately, and HRs were selected as the primary outcome. Seventeen studies met inclusion criteria. The pooled mean adherence by drug class ranged from 28% for ß-blockers to 65% for angiotensin II receptor blockers. There was better adherence to angiotensin II receptor blockers compared with angiotensin-converting enzyme inhibitors (HR, 1.33; 95% confidence interval, 1.13 to 1.57), calcium channel blockers (HR, 1.57; 95% confidence interval, 1.38 to 1.79), diuretics (HR, 1.95; 95% confidence interval, 1.73 to 2.20), and ß-blockers (HR, 2.09; 95% confidence interval, 1.14 to 3.85). Conversely, there was lower adherence to diuretics compared with the other drug classes. The same pattern was present when studies that used odds ratios were pooled. After publication bias was accounted for, there were no longer significant differences in adherence between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors or between diuretics and ß-blockers. CONCLUSION: In clinical settings, there are important differences in adherence to antihypertensives in separate classes, with lowest adherence to diuretics and ß-blockers and highest adherence to angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. However, adherence was suboptimal regardless of drug class.

Diuretic management in heart failure.

Many of the primary clinical manifestations of heart failure are due to fluid retention and congestion, and therefore treatments targeting congestion play a central role in heart failure management. Diuretic therapy remains the cornerstone of congestion treatment, and diuretics are prescribed to the majority of heart failure patients. Despite this ubiquitous use, there is limited evidence from prospective randomized studies to guide the use of diuretics. Some observational data have suggested that diuretics may actually be harmful in heart failure, potentially contributing to worsening renal function, neurohormonal activation, and even heart failure progression. Recent clinical trial data have provided new insights into the balance of risks and benefits from diuretics. This review describes the mechanism of action of available diuretic classes, reviews their clinical use based on current guidelines, and briefly discusses evolving alternatives to diuretic therapy in the management of congestion in heart failure patients.

[Effects of various diuretics on cardiac function in rats with heart failure].

Torasemide is a long-acting loop diuretic that combines the effects of both furosemide and spironolactone. It has been reported that torasemide but not furosemide might attenuate myocardial remodeling accompanied by left ventricular (LV) dysfunction. However, nothing is known about the effect of torasemide, long-acting loop diuretic and spironolactone, an aldosterone receptor antagonist in a rat model of chronic heart failure (CHF). Therefore, we compared the therapeutic effects of torasemide, furosemide and spironolactone on the progression of LV remodeling in a rat model of CHF after experimental autoimmune myocarditis (EAM). EAM was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, rats were treated for 28 days with torasemide, furosemide and spironolactone. Diuretic actions, heart weight/body weight, heart rate, mean blood pressure, myocardial function by echocardiography, cardiac fibrosis, myocyte diameter and cardiac aldosterone synthetase (CYP11B2) were evaluated. Increased cardiac CYP11B2, severe LV remodeling and resultant cardiac dysfunction was found in CHF rats, whereas decreased cardiac CYP11B2, less remodeling and improvement of cardiac function were found in torasemide- and spironolactone-treated CHF rats. Our results indicate that torasemide and spironolactone treatment significantly improved cardiac function and LV remodeling compared with furosemide treatment.

[Diuretic-based therapy]. / Thérapeutique diurétique.

Diuretics are pharmacological agents that increase natriuresis through inhibition of tubular re-absorption of sodium. The mechanisms and site of this inhibition differ with each drug class, accounting for their additive effects on natriuresis increase and their hydroelectrolytic side effects. The response to a given diuretic dose depends on the diuretic concentration on the urine at its action site. This concentration may be decreased by pharmacokinetic factors such as encountered in renal insufficiency or in nephrotic syndrome. These resistance mechanisms of diuretics may be corrected by dose increase, previous diuretic fixation on albumin or warfarin administration. Once these mechanisms are opposed, the diuretic concentration for maximal efficacy is reached at is action site and the natriuresis obtained as the normal maximal plateau. This is not the case when an oedematous systemic disease with effective hypovolemia is present, like in heart failure or cirrhosis, or when chronic use of loop diuretics has induced a hypertrophy of the more distant part of the tubule. In theses cases, a pharmacodynamic resistance exists, resulting in a lower maximal natriuresis plateau in spite of adequate concentration of the diuretic at its action site, even in the absence of pharmacokinetic resistance factors. The main indications of diuretics are systemic oedematous disease and hypertension. In the oedematous diseases, diuretics indication is both straightforward and sufficient only if effective hypervolemia is present. The therapeutic approach is discussed according to the various clinical conditions and pathophysiological background. In uncomplicated hypertension, diuretics are the cornerstone of the therapy. The most suitable diuretic treatment for hypertension is an association of low doses thiazide (12.5-50 mg/day) with potassium sparing diuretics. Rare indications of diuretics are also reviewed.

[Sex-specific antihypertensive drug therapy]. / Geschlechtsspezifische medikamentöse Therapie der Hypertonie.

BACKGROUND: Hypertension is a leading cause of cardiovascular diseases. To evaluate sex-specific differences in the prescription pattern of antihypertensive therapy, registry data from the regional health insurance fund "Burgenländische Gebietskrankenkasse" (BGKK) were analyzed. MATERIAL AND METHODS: In a retrospective cross sectional cohort study data from 41499 individuals covered by the BGKK in 2003, and who had been treated with cardiovascular drugs were analyzed. Data were evaluated according to drug classifications. RESULTS: Among subjects treated with cardiovascular medication 38.3 % were males and 61.7 % females. The drug classes acting on the renin-angiotensin-system were prescribed more frequently than beta-blockers, calcium channel blockers, diuretics and antihypertensives. Women were treated more often with diuretics and beta-blockers, whereas men received more antihypertensives and drugs acting on the renin angiotensin system (p < 0.01 between groups of sexes). CONCLUSION: Sex-specific differences exist regarding the prevalence of antihypertensive drug prescriptions between men and women. Further, the prescription pattern of equivalently effective medications differs between sexes.