Diuretics

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.

[1]  R. Hermida,et al.  Cardiovascular Risk of Essential Hypertension: Influence of Class, Number, and Treatment-Time Regimen of Hypertension Medications , 2013, Chronobiology international.

[2]  T. Lumley,et al.  Meta-analysis of health outcomes of chlorthalidone-based vs nonchlorthalidone-based low-dose diuretic therapies. , 2004, JAMA.

[3]  D. Gilbertson,et al.  Renal effects of conivaptan, furosemide, and the combination in patients with chronic heart failure. , 2010, Journal of cardiac failure.

[4]  J. McMurray,et al.  Eplerenone in patients with systolic heart failure and mild symptoms. , 2011, The New England journal of medicine.

[5]  Bryan Williams,et al.  Management of hypertension: summary of NICE guidance , 2011, BMJ : British Medical Journal.

[6]  T. Akasaka,et al.  Superiority of long-acting to short-acting loop diuretics in the treatment of congestive heart failure. , 2012, Circulation journal : official journal of the Japanese Circulation Society.

[7]  E. Soliman,et al.  Long-Term Effects of Chlorthalidone Versus Hydrochlorothiazide on Electrocardiographic Left Ventricular Hypertrophy in the Multiple Risk Factor Intervention Trial , 2011, Hypertension.

[8]  C. O'connor,et al.  Continuous versus bolus dosing of Furosemide for patients hospitalized for heart failure. , 2010, The American journal of cardiology.

[9]  W. Elliott Chlorthalidone Reduces Cardiovascular Events Compared With Hydrochlorothiazide: A Retrospective Cohort Analysis , 2012 .

[10]  T. Rywik [Summary of the article: Zannad F, McMurray JJV, Krum H et al.; for the EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med, 2011; 364: 11-21]. , 2011, Kardiologia polska.

[11]  M. Saklayen,et al.  Effects of Additive Therapy With Spironolactone on Proteinuria in Diabetic Patients Already on ACE Inhibitor or ARB Therapy , 2008, Journal of Investigative Medicine.

[12]  Thomas Lumley,et al.  Health outcomes associated with various antihypertensive therapies used as first-line agents , 2003 .

[13]  W. Cushman,et al.  Thiazide and Loop Diuretics , 2011, Journal of clinical hypertension.

[14]  J. Connell,et al.  A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism , 2011, Journal of hypertension.

[15]  W. Elliott Association Between Chlorthalidone Treatment of Systolic Hypertension and Long-term Survival , 2012 .

[16]  T. Holford,et al.  Chlorthalidone Compared With Hydrochlorothiazide in Reducing Cardiovascular Events: Systematic Review and Network Meta-Analyses , 2012, Hypertension.

[17]  G. Filippatos,et al.  Timing of eplerenone initiation and outcomes in patients with heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction: insights from the EPHESUS trial † , 2009, European journal of heart failure.

[18]  G. Bergus,et al.  Comparative Antihypertensive Effects of Hydrochlorothiazide and Chlorthalidone on Ambulatory and Office Blood Pressure , 2006, Hypertension.

[19]  H. Parving,et al.  Spironolactone diminishes urinary albumin excretion in patients with type 1 diabetes and microalbuminuria: a randomized placebo‐controlled crossover study , 2012, Diabetic medicine : a journal of the British Diabetic Association.

[20]  W. Cushman,et al.  Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil. , 2012, The American journal of medicine.

[21]  P. Gow,et al.  Effects of a selective vasopressin V2 receptor antagonist, satavaptan, on ascites recurrence after paracentesis in patients with cirrhosis. , 2010, Journal of hepatology.

[22]  B. Pitt,et al.  EPLERENONE POST-ACUTE MYOCARDIAL INFARCTION HEART FAILURE EFFICACY AND SURVIVAL STUDY INVESTIGATORS. EPLERENONE, A SELECTIVE ALDOSTERONE BLOCKER, IN PATIENTS WITH LEFT VENTRICULAR DYSFUNCTION AFTER MYOCARDIAL INFARCTION , 2003 .

[23]  M. Hori,et al.  Phase III Clinical Pharmacology Study of Tolvaptan , 2011, Cardiovascular Drugs and Therapy.

[24]  R. Hermida,et al.  INFLUENCE OF CIRCADIAN TIME OF HYPERTENSION TREATMENT ON CARDIOVASCULAR RISK: RESULTS OF THE MAPEC STUDY , 2010, Chronobiology international.

[25]  R. Wachter,et al.  Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial. , 2013, JAMA.

[26]  C. Orlandi,et al.  A multicenter, randomized, double-blind, placebo-controlled study of tolvaptan monotherapy compared to furosemide and the combination of tolvaptan and furosemide in patients with heart failure and systolic dysfunction. , 2011, Journal of cardiac failure.

[27]  Thomas Lumley,et al.  Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. , 2003, JAMA.

[28]  B. Pitt,et al.  Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction , 2003 .

[29]  Daniel W. Jones,et al.  A Scientific Statement From the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research , 2008 .

[30]  B. Davis,et al.  Mortality and Morbidity During and After the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial , 2012, Journal of clinical hypertension.

[31]  S. Werns Diuretic Strategies in Patients with Acute Decompensated Heart Failure , 2012 .

[32]  Yong Peng,et al.  The Effect of Aldosterone Antagonists for Ventricular Arrhythmia: A Meta‐Analysis , 2010, Clinical cardiology.

[33]  S. Mikami,et al.  Effect of Renin-Angiotensin-Aldosterone System Triple Blockade on Non-Diabetic Renal Disease: Addition of an Aldosterone Blocker, Spironolactone, to Combination Treatment with an Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker , 2008, Hypertension Research.

[34]  M. Mani,et al.  The comparison of the diuretic and natriuretic efficacy of continuous and bolus intravenous furosemide in patients with chronic kidney disease , 2008, Nephrology.

[35]  B. Adams-Huet,et al.  Differential effects of chlorthalidone versus spironolactone on muscle sympathetic nerve activity in hypertensive patients. , 2009, The Journal of clinical endocrinology and metabolism.

[36]  R. Hermida,et al.  Comparison of the Effects on Ambulatory Blood Pressure of Awakening versus Bedtime Administration of Torasemide in Essential Hypertension , 2008, Chronobiology international.

[37]  R. Brůha,et al.  Clinical trial: short‐term effects of combination of satavaptan, a selective vasopressin V2 receptor antagonist, and diuretics on ascites in patients with cirrhosis without hyponatraemia – a randomized, double‐blind, placebo‐controlled study , 2010, Alimentary pharmacology & therapeutics.

[38]  N J Wald,et al.  Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies , 2009, BMJ : British Medical Journal.

[39]  J. DiNicolantonio Should torsemide be the loop diuretic of choice in systolic heart failure? , 2012, Future cardiology.

[40]  S. Nesbitt,et al.  Management of high blood pressure in Blacks: an update of the International Society on Hypertension in Blacks consensus statement. , 2010, Hypertension.

[41]  B. Pitt,et al.  The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. , 1999, The New England journal of medicine.

[42]  B. Adams-Huet,et al.  Spironolactone Prevents Chlorthalidone-Induced Sympathetic Activation and Insulin Resistance in Hypertensive Patients , 2012, Hypertension.

[43]  B. Pitt,et al.  The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure , 2000 .

[44]  B. Rutkowski,et al.  Triple pharmacological blockade of the renin-angiotensin-aldosterone system in nondiabetic CKD: an open-label crossover randomized controlled trial. , 2008, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[45]  H. Nakano,et al.  Comparative analysis of the therapeutic effects of long‐acting and short‐acting loop diuretics in the treatment of chronic heart failure using 123I‐metaiodobenzylguanidine scintigraphy , 2011, European journal of heart failure.

[46]  S. Campbell,et al.  Diuretics for hypertension – an inconsistency in primary care prescribing behaviour , 2011, Current medical research and opinion.

[47]  S. Strandgaard,et al.  Moderate Antiproteinuric Effect of Add-On Aldosterone Blockade with Eplerenone in Non-Diabetic Chronic Kidney Disease. A Randomized Cross-Over Study , 2011, PloS one.

[48]  D. Goff,et al.  Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. , 2008, Circulation.

[49]  M. Ernst,et al.  Renewed Interest in Chlorthalidone: Evidence From the Veterans Health Administration , 2010, Journal of clinical hypertension.

[50]  Li-sheng Liu,et al.  Treatment of hypertension in patients 80 years of age or older. , 2008, The New England journal of medicine.

[51]  M. Burnier,et al.  Neurohormonal consequences of diuretics in different cardiovascular syndromes. , 1992, European heart journal.

[52]  Tara Gomes,et al.  Chlorthalidone Versus Hydrochlorothiazide for the Treatment of Hypertension in Older Adults , 2013, Annals of Internal Medicine.