Doctors once hesitated to prescribe medication until a patient’s
blood pressure reached 160/100. Anything below that level was deemed
“mild hypertension” and not considered dangerous, so many doctors
worried that the drugs’ potential side effects might outweigh their
benefits. These perceptions turned out to be false. Research has firmly
established the value of treating stage 1 hypertension (140/90 to
159/99 mm Hg) with drugs, if necessary.
For those with
diabetes or kidney disease, medications may be necessary at pressures
as low as 130/80. And today, blood pressure can be controlled with
lower doses of medications, meaning there is less chance of side
effects.
Doctors can choose from an abundant selection of
antihypertensive medications, including many preparations that combine
one or more drugs. Many newer antihypertensive drugs have a slightly
different chemical structure from older drugs but produce nearly
identical effects in the body. Others act in entirely different ways.
Doctors can tailor treatment to the individual patient and can often
prescribe a drug that controls blood pressure, produces few or no side
effects, and, hopefully, protects against complications. In addition,
it’s often possible to use a single medication to treat both the
hypertension and accompanying medical problems, like congestive heart
failure.
It’s also important to understand that no single
drug is superior to the others. Blood pressure control is ultimately a
numbers game: the value of any antihypertensive drug is judged on an
individual basis, depending on how significantly the medication reduces
blood pressure for the person who takes it.
Experts
recommend starting any antihypertensive drug at the lowest possible
dose and gradually increasing it until blood pressure sinks to a normal
level. If the drug causes troublesome side effects, it should be
replaced with a different medication.
The usual course of
treatment for stage 1 hypertension is to begin with one drug and add a
second if your blood pressure does not fall to desired levels (usually
less than 140/90 mm Hg, or less than 130/80 mm Hg for those with
diabetes or chronic kidney disease). You may have to try several
medications before you find a drug, or a combination, that works. The
treatment for stage 2 hypertension often begins with a two-drug
combination. Additional drugs may be added if your blood pressure
doesn’t drop to an acceptable level. With all stages of hypertension,
and even prehypertension, lifestyle changes are also an important
component of treatment.
The JNC found that blood pressure
can be adequately controlled in most people with hypertension, but many
individuals will need two or more medications to get their blood
pressure in check. Poor blood pressure control can result if the doctor
doesn’t encourage lifestyle changes, prescribe adequate doses of
medications, or add additional medications as needed.
Fast fact
In the United States, 71% of adults with hypertension don’t have their blood pressure under control.
|
Classes of hypertension drugs
Doctors
can choose from several classes of antihypertensive drugs: diuretics,
anti-adrenergics, direct-acting vasodilators, calcium-channel blockers,
angiotensin-converting–enzyme (ACE) inhibitors, and
angiotensin-receptor blockers (ARBs). In addition, researchers are
testing three potent classes: direct renin inhibitors,
endothelin-receptor antagonists, and vasopeptidase inhibitors. With so
many choices available, which medication should you and your doctor
choose? The JNC recommends that most people with hypertension start
with diuretics, but many experts disagree with this advice (see “The
right drug for the right person”). In light of the controversy, it’s
wise to talk to your doctor about which medications are best for you.
Diuretics
Diuretics,
commonly called “water pills,” are the oldest and least expensive class
of drugs used to treat hypertension (see Table 1). They help the
kidneys eliminate sodium and water from the body. This process
decreases blood volume, so your heart has less to pump with each beat,
which in turn lowers blood pressure. Loop diuretics, which act on the
part of the kidney tubules called the loop of Henle, block sodium and
chloride from being reabsorbed from the tubules into the bloodstream.
Thiazide diuretics act on another portion of the kidney tubules to stop
sodium from re-entering circulation.
One drawback of
diuretics is that they deplete potassium, so if you take these drugs
you may need potassium supplements. Doctors sometimes prescribe another
type of diuretic, called potassium-sparing, to counteract potassium
depletion. However, these drugs can cause dangerously high levels of
potassium in some patients.
Diuretics are especially
effective for salt-sensitive patients with hypertension and older
patients with isolated systolic hypertension. Aside from hypertension,
diuretics are often prescribed for fluid retention (edema) caused by
heart failure, kidney disorders, liver disease, or premenstrual
bloating.
According to the JNC report, diuretics are very
effective and underused. The JNC recommends that thiazide diuretics be
the initial drug used for most people with hypertension, and suggests
that these medications be part of treatment for most individuals taking
multiple medications to control their blood pressure.
Common
side effects of these drugs include frequent urination,
lightheadedness, fatigue, diarrhea or constipation, and muscle cramps.
Men may occasionally experience erectile dysfunction. Diuretics can
cause gout, a painful form of arthritis caused by the buildup of uric
acid in the body, because they elevate blood levels of this substance.
Thiazide
diuretics may cause an elevated blood sugar level. In some people, this
may be enough to cause diabetes or to make their diabetes worse. Blood
sugar levels therefore should be monitored in people taking diuretics
for blood pressure control.
Table 1: Diuretics
|
|
Class
|
Generic name
|
Brand name
|
Side effects
|
|
Thiazide diuretics
|
chlorothiazide
|
Diuril
|
Weakness,
confusion, potassium depletion, gout, fatigue, thirst, frequent
urination, lightheadedness, muscle cramps, diarrhea or constipation,
increased sensitivity to sunlight, allergic reaction in people allergic
to sulfa drugs, impotence.
|
|
chlorthalidone
|
Hygroton
|
|
hydrochlorothiazide
|
Esidrix, HydroDiuril, Microzide
|
|
indapamide
|
Lozol
|
|
metolazone
|
Mykrox, Zaroxolyn
|
|
Loop diuretics
|
bumetanide
|
Bumex
|
Weakness,
confusion, potassium depletion, gout, fatigue, thirst, diarrhea or
constipation, increased sensitivity to sunlight, allergic reaction in
people allergic to sulfa drugs, impotence.
|
|
ethacrynic acid
|
Edecrin
|
|
furosemide
|
Lasix
|
|
torsemide
|
Demadex
|
|
Potassium-sparing diuretics/ aldosterone-receptor blockers*
|
amiloride
|
Midamor
|
Excessive
potassium levels, especially in patients with kidney disease; breast
enlargement and erectile dysfunction in men; menstrual irregularities
in women.
|
|
spironolactone
|
Aldactone
|
|
triamterene
|
Dyrenium
|
|
eplerenone
|
Inspra
|
Headache, dizziness, diarrhea, fatigue, upset stomach, and breast enlargement or tenderness.
|
|
*Note:
Potassium-sparing diuretics also directly or indirectly block
aldosterone, a hormone that raises blood pressure by causing the
kidneys to conserve sodium and water. As a result, these four
medications are sometimes also known as aldosterone-receptor blockers.
Amiloride (Midamor), spironolactone (Aldactone), and triamterene
(Dyrenium) also affect other hormones and thus carry some unwanted side
effects, such as breast enlargement and impotence in men and menstrual
irregularities in women. Eplerenone (Inspra) is the only one of these
medications that affects solely aldosterone and not other hormones.
|
Anti-adrenergics
Anti-adrenergics
lower blood pressure by limiting the action of the hormones epinephrine
and norepinephrine, thereby relaxing the blood vessels and reducing the
speed and force of the heart’s contractions. This class includes a
variety of different agents that work in slightly different ways (see
Table 2).
Peripheral adrenergic-receptor blockers.
These drugs work by preventing neurotransmitters from attaching to
cells and stimulating the heart and blood vessels. They are divided
into two major groups: beta blockers and alpha blockers (see “Receptor
blockers: Fooling the body,” below).
Beta blockers, which
have been used since the 1960s, lock on to cell structures called beta
receptors — the same receptors that certain neurotransmitters
(primarily epinephrine) normally attach themselves to in order to
stimulate the heart. Thus, by preventing the neurotransmitters from
activating heart cells, beta blockers cause the heart rate to slow and
blood pressure to fall.
Beta blockers come in two varieties:
cardioselective and nonselective. Cardioselective beta blockers attach
primarily to beta-1 receptors in the heart. Nonselective beta blockers
attach not only to beta-1 receptors but also to beta-2 receptors, which
are found in the lungs, blood vessels, and other tissues.
Either
type of beta blocker can worsen asthma or other chronic lung disorders,
but the nonselective agents are potentially more dangerous for people
with respiratory problems. Beta blockers can also worsen heart failure
in some patients while improving it in others. They can mask the
warning signs of hypoglycemia (low blood sugar) in patients with
diabetes. The most common side effects of beta blockers are fatigue,
depression, erectile dysfunction, shortness of breath, insomnia, and
reduced tolerance for exercise.
Alpha blockers are similar
in action to beta blockers, but they work on alpha receptors — the
sites where neurotransmitters that cause vessel constriction (primarily
norepinephrine) attach themselves. Drugs called alpha-1 blockers block
alpha receptors in the heart and blood vessels. They may be especially
useful for hypertensive patients with high cholesterol. In addition to
reducing blood pressure, alpha-1 blockers also reduce “bad” LDL
cholesterol levels and increase “good” HDL cholesterol. They may
improve insulin sensitivity in patients with glucose intolerance and
hyperglycemia (high blood sugar). They are also prescribed for men with
benign prostatic hyperplasia, a noncancerous enlargement of the
prostate gland, because these drugs relax smooth muscles surrounding
the prostate, relieving the constriction of the urethra and easing
urine flow.
Side effects of alpha blockers include
orthostatic hypotension (a drop in blood pressure upon standing up),
heart palpitations, dizziness, nasal congestion, headaches, and dry
mouth. These drugs can also cause erectile dysfunction, although not as
frequently as some other blood pressure medications.
Receptor blockers: Fooling the body
The
discovery of the “lock and key” system of cell communication opened the
door to a new world of drug research. The search began with a simple
question: why do some cells react to particular chemicals, but not
others? The answer is both maddeningly complex and extremely simple.
Chemicals
circulating through the blood, such as hormones and neurotransmitters,
stimulate cells. At any given moment, a cell may come in contact with
hundreds of different chemicals, so it must be selective about which
ones it responds to. To do this, cells have special structures on their
outer surfaces called receptors. A receptor operates much like a car’s
ignition switch. Only a chemical with the right molecular configuration
(the key) will fit the receptor (the lock) and start up biological
activity inside the cell.
Researchers have used
their knowledge of this system to formulate drugs that prevent cells
from responding to certain substances. Beta blockers, which are used to
treat hypertension, are a prime example. At times of stress and during
exercise, your nerve cells release the neurotransmitters epinephrine
and norepinephrine. When epinephrine attaches to beta receptors on
cells in your heart, the heart cells become activated, increasing your
heart rate and the strength of your heart’s contractions. This raises
your blood pressure. But beta blockers attach to the same receptors,
because their structure has been carefully designed to fit neatly into
the same “lock.” With this spot filled, epinephrine and norepinephrine
are unable to connect to the receptor, thus breaking the chain of
chemical communication that would otherwise stimulate the heart and
spark an increase in blood pressure.
|
Some
patients require both alpha and beta blockers to control their blood
pressure. The drugs labetalol (Normodyne) and carvedilol (Coreg) have
properties of both.
Centrally acting agents. These
agents block the neurotransmitters that activate the sympathetic
nervous system to increase blood pressure. They include clonidine
(Catapres) and methyldopa (Aldomet). Like peripheral nerve–acting
agents (see below), they are generally used in combination with other
blood pressure medicines. Common side effects include abnormally low
blood pressure when standing up, dry mouth, depression, erectile
dysfunction, and sedation.
Peripheral nerve–acting agents.
These anti-adrenergics (now used far less often because of frequent
side effects) deplete the autonomic nerves of norepinephrine, a
substance that causes vessels to contract and raises blood pressure.
Such drugs are usually prescribed along with other antihypertensives
since they are more effective this way. Reserpine (Serpalan) can cause
depression, nightmares, nasal stuffiness, and indigestion, while
guanethidine (Ismelin) is more apt to bring on orthostatic hypotension
and slow the heart rate.
Table 2: Anti-adrenergic drugs
|
|
Class
|
Generic name
|
Brand name
|
Side effects
|
|
Beta blockers (cardioselective)
|
atenolol
|
Tenormin
|
Wheezing,
dizziness, depression, impotence, fatigue, insomnia, decreased HDL
cholesterol levels, lower exercise tolerance. Can worsen peripheral
vascular disease and heart failure. Abrupt withdrawal may trigger
angina or a heart attack in patients with heart disease.
|
|
metoprolol
|
Lopressor
|
|
metoprolol extended release
|
Toprol-XL
|
|
nebivolol
|
Bystolic
|
|
Beta blockers (nonselective)
|
nadolol
|
Corgard
|
|
pindolol
|
Visken
|
|
propranolol
|
Inderal, Inderal LA
|
|
sotalol
|
Betapace
|
|
timolol
|
Blocadren
|
|
Alpha-1 blockers
|
doxazosin
|
Cardura
|
A drop in blood pressure upon standing up, fainting, weakness, heart palpitations, headache, nasal congestion, dry mouth.
|
|
prazosin
|
Minipress
|
|
terazosin
|
Hytrin
|
|
Alpha and beta blockers
|
carvedilol
|
Coreg
|
Wheezing,
depression, insomnia, diarrhea, lightheadedness, dizziness, unusual
tiredness or weakness, drying of the eyes, erectile dysfunction,
headache, dry mouth, nasal congestion, decreased HDL cholesterol
levels, lower exercise tolerance, a drop in blood pressure upon
standing up, fainting, heart palpitations. Can worsen peripheral
vascular disease and heart failure. Abrupt withdrawal may trigger
angina or a heart attack in patients with heart disease.
|
|
labetalol
|
Normodyne, Trandate
|
|
Centrally acting agents
|
clonidine
|
Catapres, Catapres-TTS
|
A
drop in blood pressure upon standing up, drowsiness, sedation, dry
mouth, fatigue, erectile dysfunction, depression, dizziness.
Catapres-TTS (a patch) may cause a rash.
|
|
methyldopa
|
Aldomet
|
|
Peripheral nerve–acting agents
|
guanethidine
|
Ismelin
|
A
drop in blood pressure upon standing up, depression, nasal stuffiness,
nightmares. Guanethidine may slow heart rate and reserpine may cause
indigestion.
|
|
reserpine
|
Serpalan
|
Direct-acting vasodilators
Direct-acting
vasodilators (see Table 3) relax the arteries. They act quickly and are
often used in emergencies. However, they can cause fluid retention and
tachycardia (fast heart rate), so doctors usually prescribe them in
combination with another blood pressure medication that slows heart
rate, such as a cardioselective beta blocker. Hydralazine and
minoxidil, the direct-acting vasodilators most commonly used to treat
hypertension, can cause headaches, weakness, flushing, and nausea. In
addition, minoxidil can cause hair growth, fluid retention, and
hyperglycemia (increased blood sugar).
Table 3: Direct-acting vasodilators
|
|
Generic name
|
Brand name
|
Side effects
|
|
hydralazine
|
Apresoline
|
Headaches,
palpitations, weakness, flushing, nausea. Minoxidil may cause hair
growth, fluid retention, and increased blood sugar.
|
|
minoxidil
|
Loniten
|
Calcium-channel blockers
Calcium-channel
blockers (see Table 4) slow the movement of calcium into the
smooth-muscle cells of the heart and blood vessels. This weakens heart
muscle contractions and dilates blood vessels, lowering blood pressure.
Because calcium-channel blockers also slow nerve impulses in the heart,
they are often prescribed for arrhythmias (irregular heartbeat). Common
side effects of calcium-channel blockers are headache, edema,
heartburn, bradycardia (slow heart rate), and constipation.
Table 4: Calcium-channel blockers
|
|
Generic name
|
Brand name
|
Side effects
|
|
amlodipine
|
Norvasc
|
Headache,
dizziness, edema, and heartburn. Nifedipine can cause palpitations.
Diltiazem and verapamil can cause constipation and a slowed heartbeat.
|
|
diltiazem
|
Cardizem, Dilacor, others
|
|
felodipine
|
Plendil
|
|
isradipine
|
DynaCirc
|
|
nicardipine
|
Cardene, Cardene SR
|
|
nifedipine
|
Adalat CC, Procardia XL
|
|
verapamil
|
Calan, Isoptin, others
|
ACE inhibitors
This
class of drugs, introduced in 1981, has proved widely effective in
treating hypertension. These agents prevent your kidneys from retaining
sodium and water by deactivating angiotensin-converting enzyme, which
converts inactive angiotensin I to the active angiotensin II.
Angiotensin II raises blood pressure by triggering sodium and water
retention and constricting the arteries.
ACE inhibitors (see
Table 5) reduce blood pressure in most patients and produce fewer side
effects than many other antihypertensive drugs. In addition, ACE
inhibitors protect the kidneys of people with diabetes and kidney
dysfunction and the hearts of people with congestive heart failure.
The
most common side effects of these medications are a reduced sense of
taste and a dry cough. Rarely, a patient can have difficulty breathing
because of a swelling of the lips, tongue, and throat. ACE inhibitors
can also cause potassium retention; therefore, people with poor kidney
function must use them cautiously. Because these drugs can cause fetal
abnormalities, women who are pregnant or trying to get pregnant should
not take them.
Table 5: ACE inhibitors
|
|
Generic name
|
Brand name
|
Side effects
|
|
benazepril
|
Lotensin
|
Cough,
rash, fluid retention, high potassium levels, and loss of taste. May
cause low blood pressure and fainting. Can worsen kidney impairment if
narrowed arteries feed both kidneys. May cause fetal abnormalities.
|
|
captopril
|
Capoten
|
|
enalapril
|
Vasotec
|
|
fosinopril
|
Monopril
|
|
lisinopril
|
Prinivil, Zestril
|
|
quinapril
|
Accupril
|
|
ramipril
|
Altace
|
Angiotensin-receptor blockers (ARB)
This
class of medication, approved for treating hypertension since 1995,
blocks angiotensin II from constricting the blood vessels and
stimulating salt and water retention. Because ARBs are highly effective
and well tolerated by most people who take them, these medications have
become quite popular (see Table 6). They don’t produce any of the
traditional side effects of other antihypertensive medications, and
they’re less likely than ACE inhibitors to cause a cough. In addition,
like ACE inhibitors, they benefit patients with diabetes, congestive
heart failure, or both.
Table 6: Angiotensin-receptor blockers (ARB)
|
|
Generic name
|
Brand name
|
Side effects
|
|
candesartan
|
Atacand
|
Muscle cramps, dizziness.
|
|
eprosartan
|
Teveten
|
|
irbesartan
|
Avapro
|
|
losartan
|
Cozaar
|
|
olmesartan
|
Benicar
|
|
telmisartan
|
Micardis
|
|
valsartan
|
Diovan
|
Direct renin inhibitors
These
drugs, in development since the 1980s, represent a newer generation of
blood pressure medications. Renin inhibitors work, as the name would
suggest, by inhibiting the activity of renin, the enzyme largely
responsible for angiotensin II levels. In clinical trials, renin
inhibitors have proven effective in not only lowering blood pressure,
but also keeping blood pressure levels steadier throughout the day.
(Fluctuations throughout the day have been linked with heart problems.)
One renin inhibitor, aliskiren (Tekturna), was approved by the FDA in
2007. Other drugs in this class are in development.
Table 7: Combination antihypertensive drugs
|
|
Class
|
Generic name
|
Brand name
|
|
Potassium-sparing and thiazide diuretics
|
amiloride + HCTZ*
|
Moduretic
|
|
spironolactone + HCTZ
|
Aldactazide, Spironazide, Spirozide
|
|
triamterene + HCTZ
|
Dyazide, Maxzide
|
|
Alpha blocker and diuretic
|
prazosin + polythiazide
|
Minizide
|
|
Beta blocker and diuretic
|
atenolol + chlorthalidone
|
Tenoretic
|
|
bisoprolol + HCTZ
|
Ziac
|
|
metoprolol + HCTZ
|
Lopressor HCT
|
|
nadolol + bendroflumethiazide
|
Corzide
|
|
propranolol + HCTZ
|
Inderide, Inderide LA
|
|
timolol + HCTZ
|
Timolide
|
|
ACE inhibitor and diuretic
|
benazepril +HCTZ
|
Lotensin HCT
|
|
captopril + HCTZ
|
Capozide
|
|
enalapril + HCTZ
|
Vaseretic
|
|
fosinopril + HCTZ
|
Monopril HCT
|
|
lisinopril + HCTZ
|
Prinzide, Zestoretic
|
|
moexipril + HCTZ
|
Uniretic
|
|
quinapril + HCTZ
|
Accuretic
|
|
ARB and diuretic
|
candesartan + HCTZ
|
Atacand HCT
|
|
eprosartan + HCTZ
|
Teveten HCT
|
|
irbesartan + HCTZ
|
Avalide
|
|
losartan + HCTZ
|
Hyzaar
|
|
telmisartan + HCTZ
|
Micardis HCT
|
|
valsartan + HCTZ
|
Diovan HCT
|
|
Calcium-channel blocker and ACE inhibitor
|
amlodipine + benazepri
|
Lotrel
|
|
diltiazem + enalapril
|
Teczem
|
|
felodipine + enalapril
|
Lexxel
|
|
verapamil + trandolapril
|
Tarka
|
|
Other combinations
|
methyldopa + HCTZ
|
Aldoril
|
|
reserpine + chlorothiazide
|
Diupres
|
|
reserpine + HCTZ
|
Hydropres
|
|
aliskiren + HCTZ
|
Tekturna HCT
|
|
Calcium-channel blocker and ARB
|
amlodipine + valsartan
|
Exforge
|
|
amlodipine + olmesartan
|
Azor
|
|
*HCTZ=hydrochlorothiazide
|
Drug combinations
Because
having to take several different pills often presents an obstacle for
people sticking to their blood pressure treatment program, some of the
most common drug combinations are now available in a single pill.
Frequently prescribed combination medications include pills in which
the diuretic hydrochlorothiazide (HCTZ) is added to a beta blocker such
as atenolol or metoprolol or an ACE inhibitor such as benazepril or
lisinopril. Some of the most commonly used combination medications are
listed in Table 7. (For side effects, see the listings for the
individual drugs in the previous tables.)
Tips to help you remember to take your blood pressure medicine
-
Take your medicine after you brush your teeth. Keep it with your toothpaste as a reminder.
-
Put self-stick notes in visible places to remind yourself.
-
Use a weekly pillbox to store your medicines so you can see at a glance whether you’ve taken the current day’s dose.
-
Keep your medicine on the nightstand next to your bed to remind yourself to take your evening medications.
-
Ask
a friend or relative to call your telephone answering machine to remind
you to take your medicine; then don’t erase the message.
-
Establish a buddy system with a friend who also takes a medication each day.
|
The right drug for the right person
If
you can’t control your blood pressure by adopting healthier habits —
such as limiting salt, increasing exercise, and quitting smoking — then
it’s time for medications. Although the JNC recommended thiazide
diuretics as the first medications to try, several studies have
provided evidence that other drugs might be better choices, especially
if you have other health conditions. For instance, diabetes and heart
disease often accompany hypertension, and newer drugs, such as ACE
inhibitors or ARBs, perform double duty by helping to treat these
conditions while lowering blood pressure.
Several major
studies have attempted to differentiate among the many categories of
hypertension drugs, to determine which are best and under what
circumstances. For example, the Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial (ALLHAT) examined blood
pressure control and cardiovascular events in more than 42,000 men and
women, ages 55 and older, who had mild to moderate hypertension. For
five years, the participants took one of three drugs: chlorthalidone (a
diuretic), amlodipine (a calcium-channel blocker), or lisinopril (an
ACE inhibitor).
The findings were reported in 2002 in The Journal of the American Medical Association.
To many people’s surprise, the diuretic seemed to perform as well as or
slightly better than the newer drugs in controlling blood pressure and
preventing complications such as stroke and heart failure. These
results and the low cost of diuretics prompted the JNC to recommend
thiazide diuretics as the first line of treatment for most people with
hypertension. And a 2005 subgroup analysis of the ALLHAT data found
that diuretics were just as effective for people with diabetes as they
were for the other study participants.
Even so, the
consensus is growing that diuretics are not always the best first
choice, especially for people with certain health problems, including
diabetes, kidney disease, or heart failure, as evidenced by several
studies. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) involved
more than 19,000 people with hypertension who were between the ages of
40 and 79. ASCOT was designed to see whether using a combination of two
drugs — a calcium-channel blocker (amlodipine) with an ACE inhibitor
(perindopril) added, if necessary — was better at preventing heart
attack and stroke than the more traditional approach of using a beta
blocker (in this case, atenolol) with a thiazide diuretic added, if
necessary. As reported in 2005 in The Lancet, the researchers
found that compared with the older drug combination, the
amlodipine-perindopril combination reduced the risk of major cardiac
events (such as heart attacks) by an additional 16%, the risk of stroke
by an additional 23%, and the risk of dying from cardiovascular disease
by an additional 24%.
However, experts have cautioned
against interpreting this study as evidence that the newer drugs trump
the old. Instead, the picture is more complex. One clear take-home
message is that lowering blood pressure in whatever way you can
provides real benefits: people who took the calcium-channel blocker–ACE
inhibitor combination lowered their systolic blood pressure by an
average of 2.7 mm Hg more than people taking the beta blocker–diuretic
combination — and some experts think that perhaps the blood pressure
reduction helps explain the reduction in heart disease risk. Second,
the calcium-channel blocker–ACE inhibitor combination significantly
lowered the risk of developing diabetes, and may have had other
heart-healthy benefits as well — a reminder that tackling multiple risk
factors at once is good for your heart.
Indeed, this
two-pronged message — about the value of lowering blood pressure while
also reducing diabetes risk — was also underscored by the 2004
Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. The
VALUE trial compared valsartan (an ARB) to the calcium-channel blocker
amlodipine in order to determine which was better at reducing the risk
of cardiovascular events such as heart attack and stroke. The study
involved more than 15,000 hypertensive patients ages 50 and older who
were at high risk of cardiovascular problems because of underlying
disease or a history of heart attack or stroke.
As with the
ASCOT trial, the VALUE study results were complicated. On the one hand,
the calcium-channel blocker lowered blood pressure more significantly
than the ARB, especially initially: in the first few months of the
study, amlodipine lowered systolic blood pressure by 4 mm Hg more than
valsartan, while beyond six months, the extra decrease in systolic
blood pressure was a less dramatic but still significant 2 mm Hg.
Amlodipine also significantly reduced the risk of suffering a heart
attack. But the people who took valsartan were less likely to develop
diabetes. And — in a surprise — both drugs provided the same protection
against actually dying from a heart attack.
Clearly the
ASCOT and VALUE studies both underscore the importance of controlling
blood pressure to reduce the risk of heart attack and stroke. But these
two trials have led experts to question the JNC’s advice to start with
thiazide diuretics. It now appears that people should use whatever drug
is most likely to work for them, given their other cardiac risk
factors. In particular, both the ASCOT and VALUE trials provide
additional evidence that reducing your risk of diabetes may also help
protect you against cardiac events.
So what do all of these
studies mean for you? To put it simply, there is clearly no
cookie-cutter approach to protecting yourself from cardiovascular
disease. Designing an effective medication program for hypertension is
like fitting together the pieces of a jigsaw puzzle. Matching the
benefits and side effects of the dozens of available drugs to a
particular person’s risk factors, health conditions, and lifestyle
considerations is often a trial-and-error process. What may work well
for your neighbor or cousin may not be right for you. It may take some
time to find a medication that offers you the best blood pressure
control with the fewest side effects.
So talk with your
doctor about which medications are best for you. The best regimen is
one that’s tailored to your needs and is based on your medical history,
any coexisting diseases, your preferences about how and when to take
medications, and your concerns about side effects. Some general
recommendations for particular subgroups of people, found in the
following pages, may also be helpful.
African Americans
Developing
healthy habits is particularly important among African Americans
because they have higher rates of smoking, obesity, diabetes, and salt
sensitivity. They are also more likely to incur complications such as
stroke or kidney damage as a result of unchecked hypertension.
Diuretics work especially well in this population because of their
effectiveness in treating hypertension in patients who are
salt-sensitive. On the other hand, ACE inhibitors seem to be less
effective at low doses when prescribed as a single medication.
Ultimately, many African Americans have such severe hypertension that
two or more drugs are needed to bring their blood pressure under
control.
Older people
For older people, the JNC
recommends thiazide diuretics, either alone or in combination with beta
blockers, but calcium-channel blockers are also often used. Older
people should not use medications that are prone to cause orthostatic
hypotension (a sudden drop in blood pressure upon standing up), such as
anti-adrenergics and alpha blockers, because these drugs can lead to
fainting and falls, a common cause of hip fractures. Older adults
should also avoid combination medications that contain alpha blockers
such as labetalol. ACE inhibitors and ARBs may also be appropriate in
the elderly because of the high incidence of diabetes.
Can you reduce your need for medication?
Controlling
your stress and learning to make healthful lifestyle choices can help
lower your blood pressure. But can these steps actually reduce your
need to take blood pressure medicine?
To answer this
question, investigators conducted a randomized trial to determine the
impact of the relaxation response on both blood pressure and the need
for medication. (The relaxation response is a physiological state that
can be elicited through a variety of mental and physical techniques
aimed at reducing stress.) The study involved 122 people ages 55 and
over, with systolic blood pressure between 140 and 159 mm Hg, who took
at least two antihypertensive medications. Participants were divided
into two groups: one that would practice the relaxation response for
eight weeks, and one that would receive health education about blood
pressure.
After eight weeks, 34 of the people who
practiced the relaxation response — a little more than half — had
achieved a systolic blood pressure reduction of more than 5 mm Hg, and
were therefore eligible for the next phase of the study, in which they
could reduce levels of the medication they were taking. During that
second phase, 50% were able to eliminate at least one blood pressure
medicine, while 35% were able to reduce the dosage of their medication.
People
randomized to the health education group also saw improvement, although
it was not as dramatic as in the relaxation response group. In the
education group, 24 people (a little more than a third of those who
started) were able to reduce their blood pressure enough to progress to
the second phase of the study. During that second phase, 19% eliminated
medication, and 50% reduced their dosage.
The study
thus demonstrated that both practicing the relaxation response and
undergoing health education can enable some people to reduce systolic
pressure by about 10 mm Hg, but those who practiced the relaxation
response were more likely to successfully eliminate or reduce their
antihypertensive medications. Subsequent studies are planned to examine
whether people at risk of developing high blood pressure can use
relaxation techniques to stave off full-blown hypertension and the use
of medications altogether. While the results of this study are
compelling, just remember that any reduction or elimination of
medication must be done on your doctor’s recommendation and under his
or her supervision.
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People with coronary artery disease
People
with hypertension complicated by angina often benefit from beta
blockers and calcium-channel blockers. The JNC recommends beta blockers
for those who have had heart attacks because these medications reduce
the risk of having another one.
People with congestive heart failure
Because
ACE inhibitors help prevent the progression of heart failure, the JNC
recommends these drugs — either alone or in combination with a diuretic
— for people who have congestive heart failure and high blood pressure.
Beta blockers and ARBs may also be helpful.
People with left ventricular hypertrophy
The
JNC found that all antihypertensive drugs except direct-acting
vasodilators (hydralazine and minoxidil) reduce left ventricle wall
thickness. ACE inhibitors, however, are generally considered to be the
most effective. Weight loss and salt restriction are also effective
strategies for patients with this condition.
People with kidney disease
All
types of antihypertensive drugs are effective in patients with kidney
disease, and in many cases more than one type of medication will be
needed. People with kidney disease or diabetes respond favorably to ACE
inhibitors because these drugs can slow the rate of progression of
kidney failure. But ACE inhibitors can promote a dangerous buildup of
potassium, especially when taken with nonsteroidal anti-inflammatory
drugs (NSAIDs) such as aspirin, ibuprofen, and many prescription
painkillers. Consequently, potassium levels and kidney function tests
must be closely monitored.
People with chronic kidney
failure often develop hypertension because they retain too much sodium
and water. Frequently, loop diuretics are required to help control
hypertension in these patients, but the JNC cautions that
potassium-sparing diuretics can be dangerous.
People with diabetes
ACE
inhibitors or ARBs are the preferred choices for patients with diabetes
because these drugs slow the rate of kidney disease. Several
antihypertensive drugs can be dangerous for people with diabetes. For
example, thiazide diuretics may elevate blood sugar levels, and beta
blockers can mask the symptoms of hypoglycemia.
People with high cholesterol
If
you need medication to control high cholesterol, alpha-1 blockers may
slightly reduce your total cholesterol and raise your levels of
protective HDL. The harmful effect of some other hypertension
medications on blood lipids has raised concern among doctors about
prescribing these drugs to people with high cholesterol. Beta blockers
can increase triglyceride levels and reduce beneficial HDL. In high
doses, thiazide and loop diuretics can raise overall cholesterol
levels, “bad” LDL cholesterol, and triglycerides. Calcium-channel
blockers, ACE inhibitors, and ARBs do not affect blood lipids.
People with respiratory disease
Because
beta blockers can aggravate symptoms of chronic bronchitis, emphysema,
and asthma, they aren’t recommended as initial therapy for anyone with
these conditions. Most other antihypertensive agents can be used safely
for patients with respiratory ailments.
Because many
over-the-counter asthma preparations and cold remedies contain
vasoconstrictors, which can raise both heart rate and blood pressure,
you should consult your doctor before taking these medications.
People with gout
High
blood levels of uric acid can trigger gout, a painful joint disorder.
Diuretics can increase uric acid levels, making gout attacks more
likely. For this reason, diuretics aren’t recommended for people with
gout unless they take other measures to control their uric acid levels.