2012 jan (113): treatment guidelines - drugs for hypertension
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Drugs for Hypertension
Drugs available in the US for treatment of chronic
RECOMMENDATIONS: In many patients, a thi-
hypertension, with their dosages and adverse effects,
azide diuretic remains a reasonable choice for
are listed in the tables that begin on page 2.
initial treatment of hypertension. Chlorthalidone
Combination products are listed on page 8. Drugs for
appears to be more effective than hydrochloro-
treatment of hypertensive emergencies are not dis-
thiazide (HCTZ) in lowering blood pressure (BP)
cussed here. They were reviewed previously.1,2
and has been shown to be as effective as a calciumchannel blocker or an angiotensin-converting
DIURETICS
enzyme (ACE) inhibitor in preventing cardiovas-cular events in hypertensive patients with coronary
Thiazide-type diuretics are the first-line therapy for
risk factors. An ACE inhibitor, an angiotensin
many patients with hypertension. Chlorthalidone and
receptor blocker (ARB) or a calcium channel
hydrochlorothiazide (HCTZ) are often prescribed
blocker would also be a good choice for initial
at a dose of 12.5-25 mg once daily. Chlorthalidone
therapy. In black patients, diuretics and calcium
is, however, 1.5-2 times more potent than HCTZ andhas a longer duration of action that persists through-
channel blockers are more effective than ACE
out the nighttime hours.3 In a study that measured
inhibitors or ARBs. The choice of antihypertensive
24-hour ambulatory blood pressure (BP), chlorthali-
agents for some patients may be dictated by con-
done 25 mg was more effective than HCTZ 50 mg in
comitant conditions and their treatment.
Generally, if the first drug chosen is ineffective,
HCTZ is by far the most widely used thiazide-type
a drug with a different mechanism of action
diuretic, even though no outcomes data are available
should be substituted or added. The addition of a
for the most commonly used doses; studies docu-
second drug with a different mechanism of action
menting the effectiveness of HCTZ in reducing
is usually more effective in decreasing BP than
clinical outcomes used doses of >25 mg/day.5 Most
raising the dose of the first drug and often allows
studies that have shown outcome benefits of thi-
for use of lower doses of both drugs, improving
azide-type diuretics have used chlorthalidone. In a
tolerability. If an ACE inhibitor or an ARB was
double-blind, randomized controlled trial (ALLHAT)
used initially, it would be reasonable to add a
in more than 30,000 men and women >55 years old
diuretic such as chlorthalidone. For patients with
with hypertension and at least one risk factor for coro-
resistant hypertension, adding spironolactone can
nary heart disease, chlorthalidone 12.5-25 mg/day was
as effective as the calcium channel blocker amlodipineor the angiotensin-converting enzyme (ACE) inhibitor
Most patients eventually require 2 or more drugs to
lisinopril in preventing fatal coronary heart disease or
achieve their blood pressure goals. When baseline
nonfatal myocardial infarction. At the end of 5 years,
BP is >20/10 mm Hg above goal, many experts
about 40% of patients had required at least one addi-
would begin therapy with 2 drugs. The use of
tional drug to achieve the BP goal of 140/90 mm Hg.6,7
fixed-dose combinations may facilitate adherence.
The number of fixed-dose combination productscontaining chlorthalidone as the diuretic is smaller
Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines. Drugs for Hypertension Table 1. Diuretics1 Usual Daily Some Oral Maintenance Pregnancy Frequent Formulations Category2 Adverse Effects3 Thiazide-Type
hypomagnesemia, hypergly-cemia, metabolic alkalosis,
Potassium-Sparing
mastodynia, gynecomastia, men-strual abnormalities, GI disturb-ances, rash
1. Diuretics are not recommended for treatment of gestational hypertension. 2. 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;
3. In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs. 4. A 30-day supply of some strengths is available for $4 at some discount pharmacies.
than the number containing HCTZ. A fixed-dose
Loop diuretics such as furosemide are more effective
combination of chlorthalidone and azilsartan
than thiazides in lowering BP in patients with moder-
(Edarbyclor) has been approved by the FDA.8
ate to severe renal insufficiency (CrCl <30 mL/min). In patients with normal renal function, they are less
Metolazone may be effective in patients with impaired
effective than thiazides for treatment of hypertension.
renal function when the other thiazides are not, but
Ethacrynic acid can be used in patients allergic to
data are lacking. Indapamide with or without the ACE
sulfonamides (thiazide and other loop diuretics contain
inhibitor perindopril was effective in one study in eld-
erly patients (>80 years old) in reducing death from
Potassium-sparing agents such as amiloride and tri- amterene are generally used with other diuretics to Treatment Guidelines from The Medical Letter • Vol. 10 ( Issue 113) • January 2012 Drugs for Hypertension
prevent or correct hypokalemia. These drugs can cause
unless combined with a thiazide diuretic or calcium
hyperkalemia, particularly in patients with renal
channel blocker. ACE inhibitors have been shown to
impairment and in those taking ACE inhibitors,
prolong survival in patients with heart failure or left
angiotensin receptor blockers (ARBs), beta blockers or
ventricular dysfunction after a myocardial infarction,
reduce mortality in patients without heart failure orleft ventricular dysfunction who are at high risk for
Spironolactone, a mineralocorticoid receptor antago- nist also used as a potassium-sparing diuretic, has been
cardiovascular events, and reduce proteinuria in
effective as an add-on in patients with resistant hyper-
patients with either diabetic or non-diabetic nephropa-
tension.10 Eplerenone, a selective mineralocorticoid
thy.14 In an open-label trial (ANBP2) among more
receptor antagonist,11 is less likely than higher doses of
than 6000 mostly white patients with a low incidence
spironolactone to cause gynecomastia. Aldosterone
of diabetes, ACE inhibitor-treated male patients had
antagonism may provide cardiovascular benefits
an 11% lower incidence of cardiovascular events or
beyond minimizing hypokalemia.12 Both spironolac-
all-cause mortality than those treated with various
tone and eplerenone have been shown to reduce
doses of thiazide diuretics, despite similar reductions
mortality in patients with heart failure when added to
in BP.15 However, among 15,700 mostly white
patients in the double-blind ALLHAT study, treatmentof hypertension with an ACE inhibitor did not
ANGIOTENSIN-CONVERTING ENZYME
improve cardiovascular outcomes compared to
(ACE) INHIBITORS
chlorthalidone 12.5-25 mg. In black hypertensiveparticipants in ALLHAT, the ACE inhibitor regimen
ACE inhibitors are effective in treating hypertension
was less effective than the diuretic in lowering BP and
and are well tolerated. They are less effective in black
less effective in reducing the incidence of stroke and
patients and others with low-renin hypertension,
Table 2. Renin-Angiotensin System Inhibitors Usual Daily Some Oral Maintenance Pregnancy Frequent or Severe Formulations Category1,2 Adverse Effects3 Angiotensin-Converting Enzymes (ACE) Inhibitors
tion), rash, acute renal failure inpatients with bilateral renal artery
taking potassium supplements or potassium-sparing diuretics),
dysfunction), increased fetal mal-formations and mortality with use
Trandolapril – generic 1, 2, 4 mg tabs 1-8 mg in C/D
1. ACE inhibitors, ARBs and aliskiren are rated category C during the first trimester and category D during the second and third trimesters. Drugs that
act on the renin-angiotensin system can cause fetal and neonatal morbidity and death.
2. 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;
3. In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs. 4. A 30-day supply of some strengths is available for $4 at some discount pharmacies. 5. Not available as 2.5 or 30 mg tablets. Treatment Guidelines from The Medical Letter • Vol. 10 ( Issue 113) • January 2012 Drugs for Hypertension Table 2. Renin-Angiotensin System Inhibitors (continued) Usual Daily Some Oral Maintenance Pregnancy Frequent or Severe Formulations Category1,2 Adverse Effects3 Angiotensin Receptor Blockers (ARBs) Direct Renin Inhibitor (DRI)
Aliskiren – Tekturna (Novartis) 150, 300 mg tabs
1. ACE inhibitors, ARBs and aliskiren are rated category C during the first trimester and category D during the second and third trimesters. Drugs that
act on the renin-angiotensin system can cause fetal and neonatal morbidity and death.
2. 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;
3. In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs. ANGIOTENSIN RECEPTOR BLOCKERS DIRECT RENIN INHIBITOR Aliskiren, a direct renin inhibitor (DRI), is FDA-
ARBs are as effective as ACE inhibitors in lowering
approved alone or in combination with other
BP, and appear to be equally reno- and cardioprotec-
antihypertensive drugs for treatment of hyperten-
tive, with fewer adverse effects. Like ACE inhibitors,
sion.24 Whether aliskiren offers any advantage over
they are less effective in black patients and others with
ACE inhibitors or ARBs remains to be determined,
low-renin hypertension, unless combined with a thi-
and no outcomes data are available for aliskiren. In an
azide diuretic or calcium channel blocker. Irbesartan
8-week study, concurrent use of aliskiren and the ARB
treatment delayed development of overt diabetic
valsartan was significantly more effective in lowering
nephropathy in hypertensive patients with type 2
diabetes.16 In diabetic patients who already had overt nephropathy, irbesartan
and losartan CALCIUM CHANNEL BLOCKERS
progression of the renal disease.17,18 In patients withhypertension and left ventricular hypertrophy, with or
Calcium channel blockers are a structurally and func-
without diabetes (LIFE), losartan was more effective
tionally heterogeneous class of drugs. They all cause
in decreasing stroke, than the beta blocker atenolol, but
vasodilatation, which decreases peripheral resistance.
not in black patients.19 The ARBs valsartan and can-
The cardiac response to decreased vascular resistance
desartan have been shown to slow disease progression in patients with chronic heart failure (Val-HeFT,
is variable; with some dihydropyridines (felodipine,
VALIANT, CHARM).20-22 Telmisartan was as effec- nicardipine, nisoldipine and immediate-release
tive as the ACE inhibitor ramipril in preventing
nifedipine), an initial reflex tachycardia usually
cardiovascular events in high-risk hypertensive
occurs, but isradipine, sustained-release nifedipine
patients with diabetes or vascular disease
and amlodipine generally cause little increase in heart
(ONTARGET); the combination of an ACE inhibitor
rate. The non-dihydropyridines verapamil and dilti-
and an ARB provided no additional benefit on cardio-
azem slow heart rate, can affect atrioventricular (AV)
vascular or renal outcomes compared to either agent
conduction and should be used with caution in patients
alone, but was more effective in lowering BP.23
Treatment Guidelines from The Medical Letter • Vol. 10 ( Issue 113) • January 2012 Drugs for Hypertension Table 3. Calcium Channel Blockers Usual Daily Some Oral Maintenance Pregnancy Frequent Formulations Category1 Adverse Effects2 Dihydropyridines
genericAdalat CC (Bayer)Procardia XL (Pfizer)
8.5, 17, 25.5, 34 mg ER tabs 17-34 mg once
Non-Dihydropyridines
generic (sustained-release) 120, 180, 240, 300, 360
generic (continuous-delivery)120, 180, 240, 300,
1. 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;
2. In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs. 3. Amlodipine is also available in combination with atorvastatin (Caduet – Pfizer). 4. A 30-day supply of some strengths is available for $4 at some discount pharmacies. 5. Diltia XT and Dilacor XR (both manufactured by Watson) are also ER capsules (available in 120, 180, 240 mg ER capsules). 6. Also available in 420 mg ER caps. 7. Not available in 360 mg ER caps.
In one meta-analysis, the risk of heart failure was
with amlodipine and the ARB valsartan.27 In one large
higher in patients treated with calcium channel block-
outcomes trial, a combination of the ACE inhibitor
ers compared to those treated with ACE inhibitors,
benazepril with the calcium channel blocker amlodip-
beta blockers or diuretics.26 One large double-blind
ine was more effective in preventing adverse
trial (VALUE Trial) in more than 15,000 high-risk
cardiovascular outcomes than benazepril with HCTZ
patients found similar rates of cardiovascular events
Treatment Guidelines from The Medical Letter • Vol. 10 ( Issue 113) • January 2012 Drugs for Hypertension Table 4. Beta-Adrenergic Blockers Usual Daily Some Oral Maintenance Pregnancy Frequent or Severe Formulations Category1 Adverse Effects2
dia, erectile dysfunction, decr-eased exercise tolerance,
Beta Blockers with Intrinsic Sympathomimetic Activity
acebutolol has been associatedwith a positive antinuclear anti-
Beta Blockers with Alpha-Blocking Activity Beta Blockers with Vasodilating Nitric-Oxide-Mediated Activity
blocking drugs but may not cause impotence and may improve erectile dysfunction.
1. 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;
2. In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs. 3. Cardioselective4. A 30-day supply of some strengths is available for $4 at some discount pharmacies. Treatment Guidelines from The Medical Letter • Vol. 10 ( Issue 113) • January 2012 Drugs for Hypertension Table 5. Alpha-Adrenergic Blockers and Other Antihypertensives Usual Daily Maintenance Pregnancy Frequent or Severe Formulations Category1 Adverse Effects2 Alpha-Adrenergic Blockers Doxazosin – generic3
pitations, fluid retention, drowsiness, weakness, anticholinergic effects,
Central Alpha-Adrenergic Agonists
mouth, orthostatic hypotension, bradycardia, heart block, autoim-mune disorders (including colitis, hepatitis), hepatic necrosis, Coombs-positive hemolytic anemia, lupus-like syndrome, thrombocy-topenia, red cell aplasia, impotence
Direct Vasodilators
marked fluid retention, pericardial effusion, hair growth on face and body
Peripheral Adrenergic Neuron Antagonists
disturbances, bradycardia, depression, nightmares with high doses, tardive dyskinesia
1. 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;
2. In addition to the adverse effects listed, antihypertensive drugs may interact adversely with other drugs. 3. A 30-day supply of some strengths is available for $4 at some discount pharmacies. 4. The first dose is 1 mg at bedtime. BETA-ADRENERGIC BLOCKERS
found a beta blocker less effective in preventingcardiovascular events (especially stroke) than an ACE
A beta blocker may be a good choice for treatment of
inhibitor, an ARB, a calcium channel blocker or a
hypertension in patients with another indication for a
diuretic.29,30 Two guideline panels have recommended
beta blocker, such as migraine, angina pectoris,
not using a beta blocker for initial therapy of hyperten-
myocardial infarction or heart failure. In other high-
sion.31,32 Like ACE inhibitors and ARBs, beta blockers
risk patients, large cardiovascular outcome trials have
are less effective in black patients. Treatment Guidelines from The Medical Letter • Vol. 10 ( Issue 113) • January 2012 Drugs for Hypertension Table 6. Some Combination Products Strengths (mg) Drug Strengths (mg) ACE Inhibitors and Diuretics Beta-Adrenergic Blockers and Diuretics (cont) Calcium Channel Blockers and ACE Inhibitors Calcium Channel Blockers and ARBs Calcium Channel Blockers and Direct Renin Inhibitor Angiotensin Receptor Blockers and Diuretics Diuretic Combinations Direct Vasodilator and Diuretic Central Alpha Adrenergic Agonist and Diuretic ARB and Direct Renin Inhibitor Triple Drug Combinations Direct Renin Inhibitor and Diuretic Beta-Adrenergic Blockers and Diuretics
1. A 30-day supply of some strengths is available for $4 at some discount pharmacies. 2. Only available in 10/12.5 and 20/12.5 mg tabs
Pindolol, acebutolol, penbutolol and carteolol have Labetalol combines beta blockade with alpha-adrenergic
intrinsic sympathomimetic activity (ISA). Beta block-
receptor blockade. Carvedilol is another beta blocker
ers without ISA are preferred in patients with angina or
with alpha-blocking properties; compared to metopro-
lol, it is less likely to interfere with glycemic control in
Treatment Guidelines from The Medical Letter • Vol. 10 ( Issue 113) • January 2012 Drugs for Hypertension
patients with type 2 diabetes and hypertension.33
rently recommended) it can cause severe depression.35
Nebivolol does not have alpha-blocking properties but Guanadrel (no longer available in the US) decreases
does have nitric-oxide-mediated vasodilating activity.34
cardiac output and may lower systolic pressure morethan diastolic; postural and exertional hypotension
ALPHA-ADRENERGIC BLOCKERS
occur commonly and are aggravated by vasodilatationcaused by heat, exercise or alcohol. Prazosin, terazosin and doxazosin cause less tachycardia than direct vasodilators (hydralazine, COMBINATION THERAPY
minoxidil), but more frequent postural hypotension,especially after the first dose. Treatment of essential
Most patients with hypertension eventually need more
hypertension with doxazosin has been associated with
than one drug to control their BP. Patients with a BP
an increased incidence of heart failure, stroke and
>20/10 mm Hg at baseline may benefit from initiating
combined cardiovascular disease compared to treat-
therapy with 2 drugs.36 By combining drugs with dif-
ment with a diuretic (ALLHAT). Alpha-blockers
ferent mechanisms of action, lower doses can be used
provide symptomatic relief from prostatism in men,
to effectively reduce BP and decrease the incidence of
but may cause stress incontinence in women and pos-
adverse effects.37 Fixed-dose combination products
tural hypotension in elderly patients.
(see Table 6) are widely available and may improveadherence. Three triple combination products are now
CENTRAL ALPHA-ADRENERGIC AGONISTS
available containing hydrochlorothiazide (12.5-25 mg)and amlodipine added to either aliskiren, olmesartan or
Drugs such as clonidine, guanfacine and methyldopa
decrease sympathetic outflow, but do not inhibit reflexresponses as completely as sympatholytic drugs that
act peripherally. They do, however, frequently causesedation, dry mouth and erectile dysfunction.
Many of the drugs commonly used to treat hyperten-
Clonidine is often used for treatment of hypertensive
sion are available generically. Some of these are
urgencies. Due to its short half-life (~7 hours), it must
available in large discount pharmacies for $4-10 for a
be taken 2 to 3 times a day for adequate long-term
management of chronic hypertension. Once daily
guanfacine (half-life ~17 hours) is more convenient for
treatment of chronic hypertension; at doses of 1 mg,
which provide all or most of the drug’s blood pressure-
lowering effect, it is generally well tolerated. DIRECT VASODILATORS
Direct vasodilators frequently produce reflex tachycar-
dia and rarely cause orthostatic hypotension. They
should usually be given with a beta blocker or a cen-
trally-acting drug to minimize the reflex increase in
heart rate and cardiac output, and with a diuretic to
avoid sodium and water retention. They should gener-
ally 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
causes hirsutism and tachycardia and can also cause
PERIPHERAL ADRENERGIC NEURON ANTAGONISTS Reserpine is an effective antihypertensive but is sel-
dom used now because (in doses much higher than cur-
Treatment Guidelines from The Medical Letter • Vol. 10 ( Issue 113) • January 2012 Drugs for Hypertension 2011 Year-End Index:
For an electronic copy of the 2011 Index, go to:
Coming Soon in Treatment Guidelines: EDITOR IN CHIEF: Mark Abramowicz, M.D. EDITOR IN CHIEF: EXECUTIVE EDIT Mark Abramo wicz, M.D Gianna Zuccotti
, M.D., M.P.H., F.A.C.P., Harvard Medical
EXECUTIVE EDIT OR: Gianna Zuccotti, M.D., M.P.H., Weill Medical College Jean-Marie Pflomm, Pharm.D. ASSIST Jean-Marie Pflomm ANT EDITORS, DR UG INFORMATION: Susan M. Daron, Pharm.D., ASSISTANT EDIT Blaine M. Houst OR, DR UG INFORMA
m.D., Corinne E.TION: Susan More Zanone, Pharm.D. y, Pharm.D. CONTRIBUTING EDITOR: Eric J. Epstein, M.D. Albert Einstein College of Medicine CONSULTING EDITORS: Brinda M. Shah, Pharm.D., F. Peter Swanson, M.D. CONTRIBUTING EDITOR, DRUG INTERACTIONS: Philip D. Hansten, Pharm.D., UTING EDITORS: Bazil, ARD:
M.D., Ph.D., Columbia University College of Physicians and Surgeons
Jules Hir anessa K. h, M.D., Roc Dalton, M.D kefeller Univ
.H., University of Michigan Medical School
Juurlink,
., PhD, Sunnybrook Health Sciences Centre
ules Hir Kim Gerald L. David N. Mandell uurlink,
BPhm, M.D., PhD Virginia School of Medicine
Hans Meiner Richard B. Dan M. Roden Hans Meiner , M.D F. Estelle R. Sandip K. Simons, M.D Mukherjee, Dan M. Steigbig Roden el, M.D SENIOR ASSOCIA F. Estelle R. Simons, M.D ORS:
., Univ Donna Goodstein, Amy Faucard Smoller, Cynthia Macapa gal Covey EDITORIAL FELLO Neal H. Steigbigel W:
, M.D., New York University School of Medicine
Lauren K. thur M.F. Yhwar
., Ph.D., F.A.C.R, Weill Medical College of Cornell University
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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 andadministration, 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 do 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 com- patible 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: [email protected] 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: Issue 113 Questions
1. Most studies that have shown outcome benefits of a diuretic in
7. Among calcium channel blockers, an initial reflex tachycardia is to
2. A 64-year-old man with fairly well-controlled hypertension and
8. Alpha-adrenergic blockers are especially likely to cause:
chronic heart failure who is being treated with hydrochlorothiazide
has developed hypokalemia. One reasonable option would be to
9. Minoxidil is highly effective in lowering blood pressure, but it can
3. Which of the following antihypertensive drugs are less effective in
10. The diuretic found in most antihypertensive combination products
4. One advantage of ARBs over ACE inhibitors for treatment of
c. have fewer adverse effectsd. all of the above
11. The 3 triple drug combinations available in the US for hyperten-
5. A 53-year-old woman with hypertension being treated with an
ARB is told by her next-door neighbor, who also has hyperten-
sion, that she is being treated with aliskiren, which is more effec-
tive and safer. Which of the following statements about aliskiren is
a. It has been shown to be more effective than an ARB in low-
12. Use of 2 drugs with different mechanisms of action for treatment
b. It has fewer side effects than an ARB.
a. is usually more effective in decreasing BP than raising the
c. It has been shown to lead to better outcomes than ARBs.
d. Whether it offers any advantage over ACE inhibitors or ARBs
b. often allows for use of lower doses of both drugs
c. should be considered for initial therapy in patients with a
6. Use of a beta blocker to treat hypertension has been found less
effective in preventing cardiovascular events than:
a. an ACE inhibitorb. a diureticc. a calcium channel blockerd. all of the above
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
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