Drugs for hypertension 2014

Treatment GuidelinesPublished by The Medical Letter • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofi t Publication IN THIS ISSUE starts on next page Drugs for Hypertension...

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Treatment Guidelines

Published by The Medical Letter • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofi t Publication

IN THIS ISSUE (starts on next page)

Drugs for Hypertension p 31

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Treatment Guidelines

Published by The Medical Letter • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofi t Publication

Tables

3 Renin-Angiotensin System Inhibitors Page 33

4 Calcium Channel Blockers Page 34

5 Beta-Adrenergic Blockers Page 35

6 Alpha-Adrenergic Blockers and Other Antihypertensives Page 36

7 Some Combination Products Page 37

Drugs for Hypertension

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Volume 12 (Issue 141) May 2014

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DIURETICS Thiazide-type diuretics are used for initial treatment

of many patients with hypertension Most studies that have shown outcome benefi ts of thiazide-type diuretics

effective as other antihypertensive agents in reducing cardiovascular and renal risk and superior in preventing heart failure.10,11 Chlorthalidone is more potent than

hydrochlorothiazide, has a longer duration of action

that persists throughout the nighttime hours, and has been shown to be more effective.12

Metolazone may be effective in patients with impaired

renal function when the other thiazides are not, but outcomes data are lacking In one study in patients

inhibitor perindopril, reduced the incidence of death from stroke or any cause.13

Loop diuretics such as furosemide are used instead

of thiazides to lower BP in patients with moderate to severe renal impairment In patients with normal renal function, they are less effective than thiazides for treatment of hypertension Ethacrynic acid can be used

for patients allergic to sulfonamides (thiazide and loop diuretics other than ethacrynic acid contain sulfonamide moieties).

Most recent guidelines recommend a BP goal of 140/90

mm Hg.1,2,4,6 For patients >60 years old without diabetes

or chronic kidney disease, one guideline recommends

150/90 mm Hg both as the drug treatment initiation

threshold and treatment target4; this higher target is

controversial, except in patients >80 years old.9

Drugs available for treatment of chronic hypertension

in the US and their dosages and adverse effects are

listed in the tables that begin on page 32 Combination

products are listed on page 37 Drugs for treatment of

hypertensive emergencies are not discussed here.

RECOMMENDATIONS: Nearly all recent guidelines

recommend a thiazide-type diuretic (chlorthalidone is

preferred), a calcium channel blocker, an

angiotensin-converting enzyme (ACE) inhibitor, or an angiotensin

receptor blocker (ARB) as initial therapy for the

general population of hypertensive patients.1-6 For black

patients, a thiazide-type diuretic or calcium channel

blocker is recommended for initial therapy, except

for those with chronic kidney disease or heart failure,

who should receive an ACE inhibitor or an ARB.7 Beta

blockers generally are no longer recommended as initial

therapy except for patients with another indication, such

as coronary heart disease or left ventricular dysfunction

Most guidelines recommend an ACE inhibitor or an ARB

over other classes for initial treatment of hypertension in

non-black patients with diabetes.8

Many patients with hypertension need more than one

drug to control their BP Generally, if the fi rst drug

does not achieve BP goals, adding a second drug with

a different mechanism of action is more effective in

decreasing BP than increasing the dose of the fi rst drug

and often allows for use of lower, better tolerated doses

of both drugs If an ACE inhibitor or an ARB was used

initially, it would be reasonable to add a diuretic such

as chlorthalidone or a calcium channel blocker Two

renin-angiotensin system inhibitors should not be used

together.

When baseline BP is >20/10 mm Hg above goal, many

experts would begin therapy with 2 drugs.

Table 1 Initial Monotherapy

General Population

Non-black THZD, ACE inhibitor, ARB, or CCB

Chronic Kidney Disease (CKD)

Non-black ACE inhibitor or ARB Black ACE inhibitor or ARB

Diabetes

Non-black ACE inhibitor or ARB

THZD = thiazide-type diuretic; ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; CCB = calcium channel blocker

* Black patients with both diabetes and CKD should receive an ACE inhibitor

or an ARB.

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Revised 6/24/14: See page 37

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ANGIOTENSIN-CONVERTING ENZYME

(ACE) INHIBITORS

ACE inhibitors are effective in treating hypertension and are generally well tolerated They are less effective in black patients and in those with low-renin hypertension, unless combined with a thiazide-type diuretic or calcium channel blocker, in which case the combined effect is similar to that in non-black patients ACE inhibitors have been shown to prolong survival in patients with heart failure or left ventricular dysfunction after a myocardial infarction, reduce mortality in patients without heart failure or left ventricular dysfunction who are at high risk for cardiovascular events, and reduce proteinuria in patients with either diabetic or non-diabetic nephropathy They should not

be used during pregnancy

Potassium-sparing diuretics such as amiloride and

triamterene are generally used with other diuretics

to prevent or correct hypokalemia These drugs can

cause hyperkalemia, particularly in patients with renal

impairment and in those taking ACE inhibitors, ARBs,

beta blockers, or aliskiren.

Spironolactone, a mineralocorticoid receptor

antag-onist also used as a potassium-sparing diuretic, has

been effective as an add-on in patients with

refracto-ry hypertension.14 Eplerenone, a selective

mineralo-corticoid receptor antagonist that is also effective as

an add-on in patients with refractory hypertension, is

less likely to cause gynecomastia than high doses of

spironolactone Both spironolactone and eplerenone

have been shown to reduce the risk of death in patients

with heart failure when added to standard therapy.15

Hyperuricemia, hypokalemia, hypomagnesemia, hyperglyce-mia, hyponatrehyperglyce-mia, hypercal-cemia, hypercholesterolemia, hypertriglyceridemia, pancre-atitis, rash and other allergic reactions, photosensitivity reactions

Dehydration, circulatory collapse, hypokalemia, hypo-natremia, hypomagnesemia, hyperglycemia, metabolic alkalosis, hyperuricemia, blood dyscrasias, rash, hypercholes-terolemia, hypertriglyceridemia

Usual

Some Available Maintenance Pregnancy Frequent or Severe Drug Oral Formulations Dosage 2 Category 3 Adverse Effects 4 Cost 5

Thiazide-Type

Chlorthalidone – generic 25, 50 mg tabs 12.5-25 mg B $ 6.60

once/d Chlorothiazide – generic 250, 500 mg tabs 125-500 mg C 2.60

Hydrochlorothiazide – generic 12.5 mg caps; 12.5-50 mg B 8.40

12.5, 25, 50 mg tabs once/d

Indapamide – generic 1.25, 2.5 mg tabs 1.25-2.5 mg B 6.90

Loop

Bumetanide* – generic 0.5, 1, 2 mg tabs 0.5-2 mg once/d C 13.40

or divided bid

Ethacrynic acid* – Edecrin 25 mg tabs 50-200 mg once/d B 484.20

Furosemide – generic 20, 40, 80 mg tabs; 20-80 mg once/d C 1.20

10 mg/mL, 40 mg/5 mL soln or divided bid

Torsemide – generic 5, 10, 20, 100 mg tabs 5-10 mg once/d B 9.00

Potassium-Sparing

Amiloride – generic 5 mg tabs 5-10 mg once/d B Hyperkalemia, GI disturbances, 23.90

Triamterene* – Dyrenium 50, 100 mg caps 50-150 mg once/d C Hyperkalemia, GI disturbances, 99.60

Aldosterone Antagonists

Eplerenone – generic 25, 50 mg tabs 50 mg once/d B Hyperkalemia, hyponatremia 94.20

Spironolactone – generic 25, 50, 100 mg tabs 50-100 mg once/d C Hyperkalemia, hyponatremia, 6.20

menstrual abnormalities, GI disturbances, rash

* Not FDA-approved for treatment of hypertension.

1 Diuretics are not recommended for treatment of gestational hypertension.

2 Dosage adjustments may be needed for renal or hepatic impairment.

3 FDA pregnancy categories: A = controlled studies show no risk; B = no evidence of risk in animals; no human studies; C = risk cannot be ruled out;

D = positive evidence of risk; X = contraindicated during pregnancy.

4 Class effects Some may not have been reported with every drug in the class In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs.

5 Approximate wholesale acquisition cost (WAC) for 30 days’ treatment at the lowest recommended dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) April 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher

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Treatment Guidelines from The Medical Letter • Vol 12 (Issue 141) • May 2014 33

DIRECT RENIN INHIBITOR Aliskiren, a direct renin inhibitor, is FDA-approved

alone or in combination with other antihypertensive drugs for treatment of hypertension.16 Whether aliskiren offers any advantage over ACE inhibitors or ARBs remains to be determined, and no outcomes data are available for aliskiren A randomized trial (ALTITUDE) evaluating the addition of aliskiren to an ACE inhibitor

or an ARB in patients with type 2 diabetes and chronic

ANGIOTENSIN RECEPTOR

BLOCKERS (ARBs)

ARBs are as effective as ACE inhibitors in lowering

BP, and appear to be at least equally renal and cardiac

protective, with fewer adverse effects Like ACE

inhibitors, they are less effective in black patients and

in those with low-renin hypertension, unless combined

with a thiazide-type diuretic or calcium channel blocker

ARBs should not be used during pregnancy.

Table 3 Renin-Angiotensin System Inhibitors

Some Available Maintenance Pregnancy Frequent or Severe

Drug Oral Formulations Dosage 1 Category 2,3 Adverse Effects 4 Cost 5

Angiotensin-Converting Enzyme (ACE) Inhibitors

Benazepril – generic 5, 10, 20, 40 mg tabs 20-80 mg once/d D $ 3.60

Captopril – generic 12.5, 25, 50, 100 mg 25-50 mg bid or tid D 22.80

Enalapril – generic 2.5, 5, 10, 20 mg tabs 2.5-40 mg once/d D 3.00

Fosinopril – generic 10, 20, 40 mg tabs 10-80 mg once/d D 7.80

Lisinopril – generic 2.5, 5, 10, 20, 30, 10-40 mg once/d D 2.80

Moexipril – generic 7.5, 15 mg tabs 7.5-30 mg once/d D 27.00

Perindopril – generic 2, 4, 8 mg tabs 4-8 mg once/d D 19.80

Quinapril – generic 5, 10, 20, 40 mg tabs 10-80 mg once/d D 20.70

Ramipril – generic 1.25, 2.5, 5, 10 mg caps 2.5-20 mg once/d D 5.70

Trandolapril – generic 1, 2, 4 mg tabs 1-8 mg once/d D 12.00

Angiotensin Receptor Blockers (ARBs)

Azilsartan – Edarbi (Arbor) 40, 80 mg tabs 80 mg once/d D 118.00 Candesartan – generic 4, 8, 16, 32 mg tabs 8-32 mg once/d 77.60

Eprosartan – generic 400, 600 mg tabs 400-800 mg once/d D 82.20

Irbesartan – generic 75, 150, 300 mg tabs 150-300 mg once/d D 12.70

Losartan – generic 25, 50, 100 mg tabs 25-100 mg once/d D 3.60

Olmesartan – Benicar 5, 20, 40 mg tabs 20-40 mg once/d D 106.80 (Daiichi Sankyo)

Telmisartan – generic 20, 40, 80 mg tabs 20-80 mg once/d D 115.70

Valsartan – Diovan (Novartis) 40, 80, 160, 320 mg tabs 80-320 mg once/d D 129.00

Direct Renin Inhibitor (DRI)

Aliskiren – Tekturna (Novartis) 150, 300 mg tabs 150-300 mg once/d D Same as ARBs, but can also 115.30

2 ACE inhibitors, ARBs, and aliskiren are classifi ed as category D during the second and third trimesters Drugs that act on the renin-angiotensin system can cause fetal and neonatal morbidity and death.

4 In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs.

5 Approximate wholesale acquisition cost (WAC) for 30 days’ treatment at the lowest recommended dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) April 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher.

Cough, hypotension (par-ticularly with diuretic use or volume depletion), rash, acute renal failure in patients with bilateral renal artery stenosis

or stenosis of the artery to a solitary kidney, angioedema, hyperkalemia (particularly if also taking potassium supple-ments or potassium-sparing diuretics), mild to moderate loss of taste, hepatotoxicity, pancreatitis, blood dyscrasias and renal damage (particularly

in patients with renal dysfunc-tion)

Similar to ACE inhibitors;

seldom cause cough, rarely cause angio edema and rhab-domyolysis

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nicardipine, nisoldipine, and immediate-release nifedipine), an initial refl ex tachycardia usually occurs,

but isradipine, sustained-release nifedipine, and am-lodipine generally have less effect on heart rate The

heart rate, can slow atrioventricular (AV) conduction, and should be used with caution in patients who are also taking a beta blocker

In one meta-analysis, the risk of heart failure was higher

in patients treated with calcium channel blockers than

in those treated with ACE inhibitors, beta blockers,

kidney disease was terminated prematurely due to an

increase in adverse cardiovascular and renal events

ARBs, aliskiren should not be used during pregnancy.

CALCIUM CHANNEL BLOCKERS

Calcium channel blockers are a structurally and

func-tionally heterogeneous class of drugs They all cause

vasodilation and decrease total peripheral resistance

The cardiac response to decreased vascular resistance

Table 4 Calcium Channel Blockers

Usual

Dihydropyridines

Amlodipine5 – generic 2.5, 5, 10 mg tabs 2.5-10 mg once/d C $ 4.80

Felodipine – generic 2.5, 5, 10 mg ER tabs 2.5-10 mg once/d C 32.40 Isradipine – generic 2.5, 5 mg caps 5-10 mg divided bid C 42.30 Nicardipine – generic 20, 30 mg caps 60-120 mg divided tid C 58.50 extended-release

Cardene SR (EKR) 30, 60 mg ER caps 60-120 mg divided bid 99.70

extended-release

Nisoldipine – generic 8.5, 17, 20, 25.5, 30, 17-34 mg once/d C 182.70

34, 40 mg ER tabs

Non-Dihydropyridines

Diltiazem6

generic (extended-release) 180, 240, 300, 360, 420 mg 120-540 mg once/d C 106.77

ER tabs

360, 420 mg ER tabs generic (extended-release) 120, 180, 240, 300, 360 mg 120-540 mg once/d 19.40

generic (continuous-delivery) 120, 180, 240, 300, 180-360 mg once/d 27.30

Verapamil (extended-release)

generic (tabs) 120, 180, 240 mg ER tabs 120-480 mg once/d C 23.30

ER caps

extended-release (once/d)

Verelan (Elan) 120, 180, 240, 360 mg 120-480 mg once/d 144.30

Verelan PM (Elan) 100, 200, 300 mg ER caps 200-400 mg once/d 150.60

ER = extended-release; SR = sustained-release

5 Amlodipine is also available in combination with atorvastatin (Caduet, and generics).

6 Immediate-release formulation is not recommended for treatment of hypertension.

7 Dilacor XR (Actavis) is also available in 120, 180, 240 mg ER capsules.

8 Also available in 420 mg ER caps.

9 Not available in 360 mg ER caps.

Dizziness, headache, peripheral edema (more than with verapamil and diltiazem, more common

in women), fl ushing, tachycardia, rash, gingival hyperplasia

Dizziness, headache, edema, constipation (especially verapamil), AV block, bradycardia, heart failure, lupus-like rash with diltiazem

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(<60 years old) or those with hyperkinetic circulation (palpitations, tachycardia, anxiety).21 One meta-analysis

of cardiovascular outcome trials concluded that a beta blocker was less effective in preventing cardiovascular events (especially stroke) than an ACE inhibitor, an

ACE inhibitors and ARBs, beta blockers are less effective in black patients.

Acebutolol, penbutolol, and pindolol have intrinsic

sympathomimetic activity (ISA) Beta blockers without ISA are preferred for patients with angina or a history of myocardial infarction.

(ACCOMPLISH), the ACE inhibitor benazepril plus

the calcium channel blocker amlodipine was more

effective in reducing adverse cardiovascular outcomes

than benazepril plus hydrochlorothiazide.20

BETA-ADRENERGIC BLOCKERS

A beta blocker may be a good choice for treatment of

hypertension in patients with another indication for a

beta blocker, such as migraine headaches, some cardiac

arrhythmias, angina pectoris, myocardial infarction,

or heart failure, and possibly in younger patients

Table 5 Beta-Adrenergic Blockers

Atenolol5– generic 25, 50, 100 mg tabs 50-100 mg once/d D $ 1.50

Betaxolol5 – generic 10, 20 mg tabs 5-20 mg once/d C 12.80 Bisoprolol5 – generic 5, 10 mg tabs 5-20 mg once/d C 25.50

Metoprolol5 – generic 25, 50, 100 mg tabs 100-450 mg divided C 2.40

bid or tid extended-release

Nadolol – generic 20, 40, 80 mg tabs 40-320 mg once/d C 95.60

Propranolol – generic 10, 20, 40, 60, 80 mg 80-240 mg divided C 3.60

extended-release

Timolol – generic 5, 10, 20 mg tabs 20-60 mg divided bid C 39.60

Beta Blockers with Intrinsic Sympathomimetic Activity

Acebutolol5 – generic 200, 400 mg caps 200-1200 mg once/d B 8.10

Penbutolol – Levatol 20 mg tabs 10-80 mg once/d C 50.85 (Auxilium)

Pindolol – generic 5, 10 mg tabs 10-60 mg divided B 52.20

Beta Blockers with Alpha-Blocking Activity

Carvedilol – generic 3.125, 6.25, 12.5, 12.5-50 mg divided C 6.40

extended-release

ER caps Labetalol – generic 100, 200, 300 mg tabs 200-1200 mg divided C 21.00

Beta Blockers with Vasodilating Nitric Oxide-Mediated Activity

Nebivolol – Bystolic 2.5, 5, 10, 20 mg tabs 5-40 mg once/d C 78.70 (Forest)

ER = extended-release

5 Cardioselective.

Fatigue, depression, bradycardia, erectile dysfunction, decreased exercise tolerance, heart failure, worsening of peripheral arterial insuffi ciency, may aggravate al-lergic reactions, bronchospasm, may mask symptoms of and delay recovery from hypoglycemia, Raynaud’s phenomenon, insom-nia, vivid dreams or hallucinations, acute mental disorder, increased serum triglycerides, decreased HDL cholesterol, increased inci-dence of diabetes, sudden with-drawal may lead to exacerbation of angina and myocardial infarction

or precipitate thyroid storm

Similar to other beta-adrenergic blocking drugs, but with less rest-ing bradycardia and lipid changes;

acebutolol has been associated with a positive antinuclear anti-body test and occasional drug-in-duced lupus

Similar to other beta-adrenergic blocking drugs, but may not cause impotence, and may improve erec-tile dysfunction

Similar to other beta-adrenergic blocking drugs, but more

orthostat-ic hypotension; hepatotoxorthostat-icity with labetalol

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(ALLHAT) Alpha blockers provide symptomatic relief from benign prostatic hyperplasia in men, but may cause stress incontinence in women and postural hypotension in elderly patients.

CENTRAL ALPHA-ADRENERGIC AGONISTS

decrease sympathetic outfl ow, but do not inhibit refl ex responses as completely as sympatholytic drugs that act peripherally They may, however, cause sedation, dry mouth, and erectile dysfunction Clonidine is often used for treatment of hypertensive urgencies Once-daily guanfacine (half-life ~17 hours) may be a reasonable add-on for treatment of refractory hypertension; at doses

of 1 mg, which provide all or most of the drug’s blood pressure-lowering effect, it is generally well tolerated.

Labetalol combines beta receptor blockade with

alpha-adrenergic receptor blockade Carvedilol is another beta

blocker with alpha-blocking properties; compared to

metoprolol, it may be less likely to interfere with glycemic

control in patients with type 2 diabetes and hypertension.23

Nebivolol does not have alpha-blocking properties, but

does have nitric oxide-mediated vasodilating activity.24

ALPHA-ADRENERGIC BLOCKERS

Doxazosin, prazosin, and terazosin cause less

tachy-cardia than direct vasodilators (hydralazine, minoxidil),

but more frequent postural hypotension, especially

after the fi rst dose Treatment of essential hypertension

with doxazosin has been associated with an increased

incidence of heart failure, stroke, and combined

cardio-vascular disease compared to treatment with a diuretic

Table 6 Alpha-Adrenergic Blockers and Other Antihypertensives

Alpha-Adrenergic Blockers

Doxazosin – generic 1, 2, 4, 8 mg 1-16 mg once/d C $16.20

extended-release

Terazosin – generic 1, 2, 5, 10 mg 1-20 mg once/d or C 4.60

Central Alpha-Adrenergic Agonists

Clonidine – generic 0.1, 0.2, 0.3 mg 0.2-0.6 mg divided C 3.60

(Boehringer Ingelheim)

Guanfacine – generic 1, 2 mg tabs 1-3 mg once/d5 B Similar to clonidine, but milder 8.30

bid or qid

Direct Vasodilators

Hydralazine – generic 10, 25, 50, 100 mg 40-200 mg divided C Tachycardia, aggravation of angina, 22.60

tabs bid or qid headache, dizziness, fl uid retention,

nasal congestion, lupus-like

Minoxidil – generic 2.5, 10 mg tabs 5-40 mg once/d C Tachycardia, aggravation of angina, 20.10

or divided bid marked fl uid retention, pericardial

effusion, hair growth on face and body

ER = extended release

* Not FDA-approved for treatment of hypertension.

2 FDA pregnancy categories: A = controlled studies show no risk; B = no evidence of risk in animals, no human studies; C = risk cannot be ruled out;

4 Approximate wholesale acquisition cost (WAC) for 30 days’ treatment at the lowest recommended dosage Source: Analy$ource® Monthly (Selected from

Actual retail prices may be higher

5 The fi rst dose is 1 mg at bedtime.

Syncope with fi rst dose (less likely with terazosin and doxazosin), dizziness and vertigo, headache, palpitations, fl uid retention, drows-iness, weakness, anticholinergic effects, priapism, thrombocyto-penia, atrial fi brillation

CNS reactions similar to meth-yldopa, but more sedation and dry mouth; bradycardia, heart block, rebound hypertension (less likely with patch), contact dermatitis from patch

Sedation, fatigue, depression, dry mouth, orthostatic hypotension, bradycardia, heart block, auto-immune disorders (including colitis, hepatitis), hepatic necrosis, Coombs-positive lupus-like syn-drome, thrombocytopenia, red cell aplasia, impotence, hemolytic anemia

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should generally be avoided in patients with coronary artery disease Hydralazine maintenance dosage should

be limited to 200 mg per day to decrease the possibility

of a lupus-like reaction Minoxidil, a potent drug that

rarely fails to lower blood pressure, should be reserved for severe hypertension refractory to other drugs It may cause hirsutism and tachycardia and can also cause severe fl uid retention.

DIRECT VASODILATORS

Direct vasodilators frequently produce refl ex

tachy-cardia (especially early in treatment) and rarely cause

orthostatic hypotension They should usually be given

with a beta blocker or a centrally-acting drug to minimize

the refl ex increase in heart rate and cardiac output, and

with a diuretic to avoid sodium and fl uid retention They

Table 7 Some Combination Products

Drug Formulations Cost 1

ACE Inhibitors and Diuretics

Benazepril/HCTZ 5/6.25, 10/12.5,

generic 20/12.5, 20/25 mg tabs $48.60

Captopril/HCTZ 25/15, 25/25, 50/15,

generic 50/25 mg tabs 8.70

Enalapril/HCTZ

generic 5/12.5, 10/25 mg tabs 14.70

Fosinopril/HCTZ 10/12.5, 20/12.5 mg tabs

Lisinopril/HCTZ 10/12.5, 20/12.5,

Zestoretic (AstraZeneca) 43.80

Moexipril/HCTZ 7.5/12.5, 15/12.5,

Quinapril/HCTZ 10/12.5, 20/12.5,

ARBs and Diuretics

Azilsartan/chlorthalidone 40/12.5, 40/25 mg tabs

Candesartan/HCTZ 16/12.5, 32/12.5,

Atacand HCT (AstraZeneca) 119.10

Eprosartan/HCTZ 600/12.5, 600/25 mg

Teveten HCT (Abbvie) tabs 134.10

Irbesartan/HCTZ 150/12.5, 300/12.5 mg

Losartan/HCTZ 50/12.5, 100/12.5,

Olmesartan/HCTZ 20/12.5, 40/12.5,

Benicar HCT 40/25 mg tabs 106.80

(Daiichi Sankyo)

Telmisartan/HCTZ 40/12.5, 80/12.5,

(Boehringer Ingelheim)

Valsartan/HCTZ 80/12.5, 160/12.5, 160/25,

generic 320/12.5, 320/25 mg tabs 104.00

Direct Renin Inhibitor and Diuretic

Aliskiren/HCTZ 150/12.5, 150/25,300/12.5,

Tekturna HCT (Novartis) 300/25 mg tabs 114.30

Beta-Adrenergic Blockers and Diuretics

Atenolol/chlorthalidone 50/25, 100/25 mg tabs

Tenoretic (AstraZeneca) 51.60

Beta-Adrenergic Blockers and Diuretics (cont)

Bisoprolol/HCTZ 2.5/6.25, 5/6.25, generic 10/6.25 mg tabs $ 6.10

Metoprolol/HCTZ 50/25, 100/25, generic 100/50 mg tabs 27.90

Lopressor HCT (Validus) 50/25 mg tabs 62.10 Nadolol/bendrofl umethiazide 40/5, 80/5 mg tabs

Calcium Channel Blockers and ACE Inhibitors

Amlodipine/benazepril 2.5/10, 5/10, 5/20, 5/40 generic 10/20, 10/40 mg caps 40.90

Verapamil ER/trandolapril 180/2, 240/1, 240/2,

Tarka (Abbvie) 240/4 mg tabs 127.20

Calcium Channel Blockers and ARBs

Amlodipine/telmisartan – 5/40, 5/80, 10/40, generic 10/80 mg tabs 127.30

(Boehringer Ingelheim) Amlodipine/valsartan 5/160, 5/320, 10/160,

Exforge (Novartis) 10/320 mg tabs 151.90 Amlodipine/olmesartan 5/20, 5/40, 10/20,

Azor (Daiichi Sankyo) 10/40 mg tabs 133.20

Calcium Channel Blocker and Direct Renin Inhibitor

Amplodipine/aliskiren 5/150, 10/150, 5/300,

Tekamlo (Novartis) 10/300 mg tabs 114.00

Diuretic Combinations

HCTZ/spironolactone 25/25 mg tabs

Aldactazide (Pharmacia) 25/25, 50/50 mg tabs 39.90 HCTZ/triamterene 25/37.5, 50/75 mg tabs,

generic 25/37.5, 25/50 mg caps 6.40

Maxzide (Mylan) 25/37.5, 50/75 mg tabs 40.50 HCTZ/amiloride 50/5 mg tabs

Central Alpha-Adrenergic Agonist and Diuretic

Clonidine/chlorthalidone 0.1/15, 0.2/15,

Clorpres (Mylan) 0.3/15 mg tabs 59.40

Triple Drug Combinations

Aliskiren/amlodipine/HCTZ 150/5/12.5, 300/5/12.5,

Amturnide (Novartis) 300/5/25, 300/10/12.5, 103.70

300/10/25 mg tabs Valsartan/amlodipine/HCTZ 160/5/12.5, 160/5/25,

Exforge HCT (Novartis) 160/10/12.5, 160/10/25, 151.90

320/10/25 mg tabs Olmesartan/amlodipine/HCTZ 20/5/12.5, 40/5/12.5,

Tribenzor (Daiichi Sankyo) 40/5/25, 40/10/12.5, 133.20

40/10/25 mg tabs

Drug Formulations Cost 1

ARB = angiotensin receptor blocker; HCTZ = hydrochlorothiazide

1 Approximate wholesale acquisition cost (WAC) for 30 of the lowest strength tablets or capsules Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) April 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher

Revised 6/24/14: Valturna has been deleted from Table 7 because it is no longer available.

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Treatment Guidelines from The Medical Letter ®

EDITOR IN CHIEF: Mark Abramowicz, M.D

EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School EDITOR: Jean-Marie Pfl omm, Pharm.D

ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D.,

Corinne Z Morrison, Pharm.D., Michael P Viscusi, Pharm.D.

CONSULTING EDITORS: Brinda M Shah, Pharm.D., F Peter Swanson, M.D CONTRIBUTING EDITORS:

Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School Eric J Epstein, M.D., Albert Einstein College of Medicine

Jane P Gagliardi, M.D., M.H.S., F.A.C.P Duke University School of Medicine Jules Hirsch, M.D., Rockefeller University

David N Juurlink, BPhm, M.D., Ph.D., Sunnybrook Health Sciences Centre Richard B Kim, M.D., University of Western Ontario

Hans Meinertz, M.D., University Hospital, Copenhagen Sandip K Mukherjee, M.D., F.A.C.C., Yale School of Medicine Dan M Roden, M.D., Vanderbilt University School of Medicine Esperance A.K Schaefer, M.D., M.P.H., Harvard Medical School

F Estelle R Simons, M.D., University of Manitoba Neal H Steigbigel, M.D., New York University School of Medicine Arthur M F Yee, M.D., Ph.D., F.A.C.R., Weill Medical College of Cornell University SENIOR ASSOCIATE EDITOR: Amy Faucard

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Copyright and Disclaimer: The Medical Letter is an independent nonprofi t organization that provides health care professionals with unbiased drug prescribing recommendations The editorial process used for its publications relies on a review of published and unpublished liter-ature, with an emphasis on controlled clinical trials, and on the opinions of its consultants The Medical Letter is supported solely by subscription fees and accepts no advertising, grants, or donations No part of the material may be reproduced or transmitted by any process in whole

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1 National Institute for Health and Clinical Excellence Hypertension: clinical

management of primary hypertension in adults National Institute for

Health and Clinical Excellence 2011 Available at: http://www.nice.org.uk/

nicemedia/live/13561/56008/56008.pdf Accessed April 7, 2014

2 WS Aronow et al ACCF/AHA 2011 expert consensus document

on hypertension in the elderly: a report of the American College of

Cardiology Foundation Task Force on Clinical Expert Consensus

documents developed in collaboration with the American Academy

of Neurology, American Geriatrics Society, American Society for

Preventive Cardiology, American Society of Hypertension, American

Society of Nephrology, Association of Black Cardiologists, and

European Society of Hypertension J Am Coll Cardiol 2011; 57:2037

3 G Mancia et al 2013 ESH/ESC Guidelines for the management of

arterial hypertension: the Task Force for the management of arterial

hypertension of the European Society of Hypertension (ESH) and of the

European Society of Cardiology (ESC) J Hypertens 2013; 31:1281

4 PA James et al 2014 evidence-based guideline for the management of

high blood pressure in adults: report from the panel members appointed

to the Eighth Joint National Committee (JNC 8) JAMA 2014; 311:507

5 MA Weber et al Clinical practice guidelines for the management of

hypertension in the community: a statement by the American Society

of Hypertension and the International Society of Hypertension J Clin

Hypertens (Greenwich) 2014; 16:14

6 The 2014 Canadian Hypertension Education Program (CHEP)

recommendations Available at http://www.hypertension.ca/en/chep

Accessed April 7, 2014

7 KDIGO clinical practice guideline for the management of blood pressure

in chronic kidney disease Available at: http://www.kdigo.org/clinical_

practice_guidelines/pdf/KDIGO_BP_GL.pdf Accessed April 7, 2014

8 Executive summary: standards of medical care in diabetes — 2014

Diabetes Care 2014; 37(Suppl 1):S5

9 JT Wright Jr et al Evidence supporting a systolic blood pressure goal

of less than 150 mm Hg in patients aged 60 years or older: the minority

view Ann Intern Med 2014; 160:499

10 JB Kostis et al Association between chlorthalidone treatment of systolic

hypertension and long-term survival JAMA 2011; 306:2588

11 JT Wright Jr et al ALLHAT fi ndings revisited in the context of

subsequent analyses, other trials, and meta-analyses Arch Intern Med

2009; 169:832

12 ME Ernst and M Moser Use of diuretics in patients with hypertension

N Engl J Med 2009; 361:2153

13 NS Beckett et al Treatment of hypertension in patients 80 years of age

or older N Engl J Med 2008; 358:1887

14 DA Calhoun et al Refractory hypertension: determination of prevalence, risk

factors, and comorbidities in a large, population-based cohort Hypertension

2014; 63:451

15 Drugs for chronic heart failure Treat Guidel Med Lett 2012; 10:69

16 Aliskiren (Tekturna) for hypertension Med Lett Drugs Ther 2007;

49:29

17 HH Parving et al Cardiorenal end points in a trial of aliskiren for type 2

diabetes N Engl J Med 2012; 367:2204

18 Aliskiren trial terminated Med Lett Drugs Ther 2012; 54:5

19 F Turnbull et al Effects of different blood-pressure-lowering regimens

on major cardiovascular events: results of prospectively-designed

overviews of randomised trials Lancet 2003; 362:1527

20 K Jamerson et al Benazepril plus amlodipine or hydrochlorothiazide for

hypertension in high-risk patients N Engl J Med 2008; 359:2417

21 WH Frishman and E Saunders ß-adrenergic blockers J Clin Hypertens

(Greenwich) 2011; 13:649

22 CS Wiysonge et al Beta-blockers for hypertension Cochrane Database

Syst Rev 2012; 8:CD002003

23 GL Bakris et al Metabolic effects of carvedilol vs metoprolol in patients

with type 2 diabetes mellitus and hypertension: a randomized controlled

trial JAMA 2004; 292:2227

24 Nebivolol (Bystolic) for hypertension Med Lett Drugs Ther 2008;

50:17

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The mission of The Medical Letter’s Continuing Medical Education Program is to support the professional development of healthcare professionals including physicians, nurse practitioners, pharmacists and physician assistants by providing independent, unbiased drug information and prescribing recommendations that are free of industry infl uence The program content includes current information and unbiased reviews of FDA-approved and off-label uses of drugs, their mechanisms of action, clinical trials, dosage and administration, adverse effects and drug interactions The Medical Letter delivers educational content in the form of self-study material.

The expected outcome of the CME Program is to increase the participant’s ability to know, or apply knowledge into practice after assimilating, information presented in

materials contained in Treatment Guidelines.

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in supporting the professional development of healthcare professionals through Core Competencies by providing continuing medical education that is unbiased and free

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GOAL:

Through this program, The Medical Letter expects to provide the healthcare community with unbiased, reliable and timely educational content that they will use to make independent and informed therapeutic choices in their practice.

LEARNING OBJECTIVES:

The objective of this activity is to meet the need of healthcare professionals for unbiased, reliable and timely information on treatment of major diseases The Medical Letter expects to provide the healthcare community with educational content that they will use to make independent and informed therapeutic choices in their practice Participants will be able to select and prescribe, or confi rm the appropriateness of the prescribed usage of the drugs and other therapeutic modalities discussed in

Treatment Guidelines with specifi c attention to clinical evidence of effectiveness, adverse effects and patient management.

Upon completion of this program, the participant will be able to:

1 Explain the current approach to the management of a patient with hypertension.

2 Discuss the pharmacologic options available for patients with hypertension and compare them based on their effi cacy, dosage and administration, and potential adverse effects.

3 Determine the most appropriate therapy given the clinical presentation of an individual patient.

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Treatment Guidelines from The Medical Letter • Vol 12 (Issue 141) • May 2014

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