Drugs for hypertension 2012

Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 1000 Main Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Drugs for Hypertension p Important Copyright Message The Medical Letter® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF US AND INTERNATIONAL COPYRIGHT LAWS Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 10 (Issue 113) January 2012 www.medicalletter.org Updated March 2012 Tables Diuretics Renin-Angiotensin System Inhibitors Calcium Channel Blockers Beta-Adrenergic Blockers Alpha-Adrenergic Blockers and Other Antihypertensives Some Combination Products Page Pages 3-4 Page Page Page Page Drugs for Hypertension RECOMMENDATIONS: In many patients, a thiazide diuretic remains a reasonable choice for initial treatment of hypertension Chlorthalidone appears to be more effective than hydrochlorothiazide (HCTZ) in lowering blood pressure (BP) and has been shown to be as effective as a calcium channel blocker or an angiotensin-converting enzyme (ACE) inhibitor in preventing cardiovascular events in hypertensive patients with coronary risk factors An ACE inhibitor, an angiotensin receptor blocker (ARB) or a calcium channel blocker would also be a good choice for initial therapy In black patients, diuretics and calcium channel blockers are more effective than ACE inhibitors or ARBs The choice of antihypertensive agents for some patients may be dictated by concomitant conditions and their treatment Generally, if the first drug chosen is ineffective, a drug with a different mechanism of action should be substituted or added The addition of a second drug with a different mechanism of action is usually more effective in decreasing BP than raising the dose of the first drug and often allows for use of lower doses of both drugs, improving tolerability If an ACE inhibitor or an ARB was used initially, it would be reasonable to add a diuretic such as chlorthalidone For patients with resistant hypertension, adding spironolactone can be helpful Most patients eventually require or more drugs to achieve their blood pressure goals When baseline BP is >20/10 mm Hg above goal, many experts would begin therapy with drugs The use of fixed-dose combinations may facilitate adherence Drugs available in the US for treatment of chronic hypertension, with their dosages and adverse effects, are listed in the tables that begin on page Combination products are listed on page Drugs for treatment of hypertensive emergencies are not discussed here They were reviewed previously.1,2 DIURETICS Thiazide-type diuretics are the first-line therapy for many patients with hypertension Chlorthalidone and hydrochlorothiazide (HCTZ) are often prescribed at a dose of 12.5-25 mg once daily Chlorthalidone is, however, 1.5-2 times more potent than HCTZ and has a longer duration of action that persists throughout the nighttime hours.3 In a study that measured 24-hour ambulatory blood pressure (BP), chlorthalidone 25 mg was more effective than HCTZ 50 mg in lowering BP.4 HCTZ is by far the most widely used thiazide-type diuretic, even though no outcomes data are available for the most commonly used doses; studies documenting the effectiveness of HCTZ in reducing clinical outcomes used doses of >25 mg/day.5 Most studies that have shown outcome benefits of thiazide-type diuretics have used chlorthalidone In a double-blind, randomized controlled trial (ALLHAT) in more than 30,000 men and women >55 years old with hypertension and at least one risk factor for coronary heart disease, chlorthalidone 12.5-25 mg/day was as effective as the calcium channel blocker amlodipine or the angiotensin-converting enzyme (ACE) inhibitor lisinopril in preventing fatal coronary heart disease or nonfatal myocardial infarction At the end of years, about 40% of patients had required at least one additional drug to achieve the BP goal of 140/90 mm Hg.6,7 The number of fixed-dose combination products containing chlorthalidone as the diuretic is smaller than Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines Drugs for Hypertension Table Diuretics1 Some Oral Formulations Drug Usual Daily Maintenance Dosage Pregnancy Category2 Frequent or Severe Adverse Effects3 Thiazide-Type Chlorthalidone – generic Thalitone (Monarch) Chlorothiazide – generic Diuril (Salix) Hydrochlorothiazide – generic4 12.5-50 mg once B 125-500 mg once C 25, 50 mg tabs 15 mg tabs 250, 500 mg tabs 250 mg/5mL susp 12.5-50 mg once B 12.5 mg caps; 12.5, 25, 50 mg tabs 12.5 mg caps 1.25, 2.5 mg tabs 1.25-5 mg once B 2.5, 5, 10 mg tabs 1.25-5 mg once B Bumetanide – generic4 0.5, 1, mg tabs 0.5-2 mg in doses C Ethacrynic acid – Edecrin (Aton Pharma) 25 mg tabs 25-100 mg in or doses B Furosemide – generic4 20, 40, 80 mg tabs; 10 mg/mL, 40 mg/5 mL soln 20, 40, 80 mg tabs 20-320 mg in doses C 5, 10, 20, 100 mg tabs 5-20 mg in or doses B mg tabs 5-10 mg in or doses 25-100 mg in or doses 12.5-100 mg in or doses B Microzide (Watson) Indapamide – generic4 Metolazone – generic Zaroxolyn (UCB Pharma) Hyperuricemia, hypokalemia, hypomagnesemia, hyperglycemia, hyponatremia, hypercalcemia, hypercholesterolemia, hypertriglyceridemia, pancreatitis, rash and other allergic reactions, sexual dysfunction in men, photosensitivity reactions Loop Lasix (Sanofi) Torsemide – generic Demadex (Meda) Dehydration, circulatory collapse, hypokalemia, hyponatremia, hypomagnesemia, hyperglycemia, metabolic alkalosis, hyperuricemia, blood dyscrasias, rash, hypercholesterolemia, hypertriglyceridemia Potassium-Sparing Amiloride – generic Midamor (Paddock) Eplerenone – generic Inspra (Pfizer) Spironolactone – generic4 Aldactone (Pfizer) Triamterene – Dyrenium (WellSpring) 25, 50 mg tabs 25, 50, 100 mg tabs 50, 100 mg caps 50-150 mg in or doses B D C Hyperkalemia, GI disturbances, rash, headache Hyperkalemia, hyponatremia Hyperkalemia, hyponatremia, mastodynia, gynecomastia, menstrual abnormalities, GI disturbances, rash Hyperkalemia, GI disturbances, nephrolithiasis Diuretics are not recommended for treatment of gestational hypertension FDA pregnancy categories: A = controlled studies show no risk; B = no evidence of risk; C = risk cannot be ruled out; D = positive evidence of risk; X = contraindicated in pregnancy In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs A 30-day supply of some strengths is available for $4 at some discount pharmacies the number containing HCTZ A fixed-dose combination of chlorthalidone and azilsartan (Edarbyclor) has recently become available.8 Metolazone may be effective in patients with impaired renal function when the other thiazides are not, but data are lacking Indapamide with or without the ACE inhibitor perindopril was effective in one study in elderly patients (>80 years old) in reducing death from stroke or any cause.9 Loop diuretics such as furosemide are more effective than thiazides in lowering BP in patients with moder2 ate to severe renal insufficiency (CrCl 20/10 mm Hg at baseline may benefit from initiating therapy with drugs.36 By combining drugs with different mechanisms of action, lower doses can be used to effectively reduce BP and decrease the incidence of adverse effects.37 Fixed-dose combination products (see Table 6) are widely available and may improve adherence Three triple combination products are now available containing hydrochlorothiazide (12.5-25 mg) and amlodipine added to either aliskiren, olmesartan or valsartan.38,39 COST Many of the drugs commonly used to treat hypertension are available generically Some of these are available in large discount pharmacies for $4-10 for a 30-day supply 10 11 12 13 14 Clevidipine (Cleviprex) for IV treatment of severe hypertension Med Lett Drugs Ther 2008; 50:73 Cardiovascular drugs in the ICU Treat Guidel Med Lett 2002; 1:19 BL Carter et al Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability Hypertension 2004; 43:4 ME Ernst and M Moser Use of diuretics in patients with hypertension N Engl J Med 2009; 361:2153 FH Messerli and S Bangalore Half a century of hydrochlorothiazide: facts, fads, fiction and follies Am J Med 2011; 124:896 ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) JAMA 2002; 288:2981 JT Wright Jr et al ALLHAT Collaborative Research Group ALLHAT findings revisited in the context of subsequent analyses, other trials, and meta-analyses Arch Intern Med 2009; 169:832 Edarbyclor: an ARB/chlorthalidone combination for hypertension Med Lett Drugs Ther 2012; 54:17 NS Beckett et al Treatment of hypertension in patients 80 years of age or older N Engl J Med 2008; 358:1887 DA Calhoun 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 Circulation 2008; 117:e510 Eplerenone (Inspra) Med Lett Drugs Ther 2003; 45:39 GS Francis and WH Tang Should we consider aldosterone as the primary screening target for preventing cardiovascular events? J Am Coll Cardiol 2005; 45:1249 Drugs for treatment of chronic heart failure Treat Guidel Med Lett 2009; 7:53 R Kunz et al Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 113) • January 2012 Drugs for Hypertension renal disease Ann Intern Med 2008; 148:30 15 LM Wing et al A comparison of outcomes with angiotensin-converting enzyme inhibitors and diuretics for hypertension in the elderly N Engl J Med 2003; 348:583 16 HH Parving et al The effect of irbesartan on the development of diabetic nephropathy in patients with type diabetes N Engl J Med 2001; 345:870 17 EJ Lewis et al Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type diabetes N Engl J Med 2001; 345:851 18 BM Brenner et al [RENAAL] Effects of losartan on renal and cardiovascular outcomes in patients with type diabetes and nephropathy N Engl J Med 2001; 345:861 19 B Dahlöf et al Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol Lancet 2002; 359:995 20 JN Cohn, G Tognoni, Valsartan Heart Failure Trial Investigators A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure N Engl J Med 2001; 345:1667 21 MA Pfeffer et al Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both N Engl J Med 2003; 349:1893 22 JB Young et al Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials Circulation 2004; 110:2618 23 S Yusuf et al Telmisartan, ramipril, or both in patients at high risk for vascular events N Engl J Med 2008; 358:1547 24 Aliskiren (Tekturna) for hypertension Med Lett Drugs Ther 2007; 49:29 25 S Oparil et al Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial Lancet 2007; 370:221 26 Blood Pressure Lowering Treatment Trialists’ Collaboration Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials Lancet 2003; 362:1527 27 S Julius et al Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial Lancet 2004; 363:2022 28 K Jamerson et al Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients N Engl J Med 2008; 359:2417 29 CS Wiysonge et al Beta-blockers for hypertension Cochrane Database Syst Rev 2007; 24 (1):CD002003 30 BM Psaty et al Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis JAMA 2003; 289:2534 31 National Clinical Guideline Centre, National Institute for Health and Clinical Excellence Hypertension: The clinical management of primary hypertension in adults: Clinical Guideline 127 www.nice.org.uk/ nicemedia/live/13561/56007.pdf Accessed December 16, 2011 32 G Mancia et al Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document J Hypertens 2009; 27:2121 33 GL Bakris et al Metabolic effects of carvedilol vs metoprolol in patients with type diabetes mellitus and hypertension: a randomized controlled trial JAMA 2004; 292:2227 34 Nebivolol (Bystolic) for hypertension Med Lett Drugs Ther 2008; 50:17 35 HB Slim et al Older blood pressure medications — they still have a place? Am J Cardiol 2011; 108:316 36 TA Kotchen Expanding role for combination drug therapy in the initial treatment of hypertension? Hypertension 2011; 58:550 37 DS Wald et al Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials Am J Med 2009; 122:290 38 In brief: another three drug combination for hypertension Med Lett Drugs Ther 2011; 53:28 39 Tribenzor for hypertension Med Lett Drugs Ther 2010; 52:70 40 Aliskiren trial terminated Med Lett Drugs Ther 2012; 54:5 10 2011 Year-End Index: For an electronic copy of the 2011 Index, go to: www.medicalletter.org/downloads/tgindex2011.pdf Coming Soon in Treatment Guidelines: Drugs for Asthma Drugs for Inflammatory Bowel Disease Treatment Guidelines Guidelines ® Treatment from The Medical Letter® from The Medical Letter EDITOR IN CHIEF: Mark Abramowicz, M.D EDITOR IN CHIEF: Mark Abramowicz, EXECUTIVE EDITOR: Gianna Zuccotti,M.D M.D., M.P.H., F.A.C.P., Harvard Medical EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., Weill Medical College School of Cornell University Pflomm, Pharm.D EDITOR: Jean-Marie EDITOR: 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Explain the current approach to the management of a patient with hypertension Discuss the pharmacologic options available for treatment of hypertension and compare them based on their mechanism of action, efficacy, dosage and administration, potential adverse effects and drug interactions Determine the most appropriate therapy given the clinical presentation of an individual patient Privacy and Confidentiality: The Medical Letter guarantees our firm commitment to your privacy We not sell any of your information Secure server software (SSL) is used for commerce transactions through VeriSign, Inc No credit card information is stored IT Requirements: Windows 98/NT/2000/XP/Vista/7, Pentium+ processor, Mac OS X+ w/ compatible process; Microsoft IE 6.0+, Mozilla Firefox 2.0+ or any other compatible Web browser Dial-up/high-speed connection Have any questions? Call us at 800-211-2769 or 914-235-0500 or e-mail us at: custserv@medicalletter.org Questions start on next page Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 113) • January 2012 DO NOT FAX OR MAIL THIS EXAM To take this exam, go to: medicalletter.org/cme Issue 113 Questions Most studies that have shown outcome benefits of a diuretic in treating hypertension have used: a hydrochlorothiazide b chlorthalidone c metolazone d furosemide Issue 113 Among calcium channel blockers, an initial reflex tachycardia is to be expected with: a felodipine b verapamil c diltiazem d all of the above Issue 113 A 64-year-old man with fairly well-controlled hypertension and chronic heart failure who is being treated with hydrochlorothiazide has developed hypokalemia One reasonable option would be to add: a chlorthalidone b furosemide c spironolactone d none of the above Issue 113 Alpha-adrenergic blockers are especially likely to cause: a rash b postural hypotension c cough d hepatic toxicity Issue 113 Which of the following antihypertensive drugs are less effective in black patients? a ACE inhibitors b ARBs c beta blockers d all of the above Issue 113 One advantage of ARBs over ACE inhibitors for treatment of hypertension is that they: a are more effective b are safer for use in pregnancy c have fewer adverse effects d all of the above Issue 113 A 53-year-old woman with hypertension being treated with an ARB is told by her next-door neighbor, who also has hypertension, that she is being treated with aliskiren, which is more effective and safer Which of the following statements about aliskiren is true? a It has been shown to be more effective than an ARB in lowering blood pressure b It has fewer side effects than an ARB c It has been shown to lead to better outcomes than ARBs d Whether it offers any advantage over ACE inhibitors or ARBs remains to be determined Issue 113 Use of a beta blocker to treat hypertension has been found less effective in preventing cardiovascular events than: a an ACE inhibitor b a diuretic c a calcium channel blocker d all of the above Issue 113 Minoxidil is highly effective in lowering blood pressure, but it can cause: a hirsutism b tachycardia c edema d all of the above Issue 113 10 The diuretic found in most antihypertensive combination products is: a hydrochlorothiazide b chlorthalidone c furosemide d spironolactone Issue 113 11 The triple drug combinations available in the US for hypertension all contain: a an ACE inhibitor b an ARB c a calcium channel blocker d all of the above Issue 113 12 Use of drugs with different mechanisms of action for treatment of hypertension: a is usually more effective in decreasing BP than raising the dose of a single drug b often allows for use of lower doses of both drugs c should be considered for initial therapy in patients with a baseline BP >20/10 mm Hg above goal d all of the above Issue 113 ACPE UPN: 379-0000-11-113-H01-P; Release: December 2011, Expire: December 2012 Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 113) • January 2012 ... drug combination for hypertension Med Lett Drugs Ther 2011; 53:28 39 Tribenzor for hypertension Med Lett Drugs Ther 2010; 52:70 40 Aliskiren trial terminated Med Lett Drugs Ther 2012; 54:5 10 2011... January 2012 Drugs for Hypertension renal disease Ann Intern Med 2008; 148:30 15 LM Wing et al A comparison of outcomes with angiotensin-converting enzyme inhibitors and diuretics for hypertension. .. combination for hypertension Med Lett Drugs Ther 2012; 54:17 NS Beckett et al Treatment of hypertension in patients 80 years of age or older N Engl J Med 2008; 358:1887 DA Calhoun et al Resistant hypertension: