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DRUGS
FOR HIGH BLOOD PRESSURE:
WHICH ARE BEST?
Drugs
that lower high blood pressure are the cornerstone of
preventive medicine. Clearly they have prevented many
a heart attack or stroke, but it's getting harder and
harder for doctors to know who should get what drug… and
who should not be treated at all. Every few years a committee
of hypertension experts (often with strong ties to the
pharmaceutical industry) lowers the threshold for the
definition of normal hypertension, steadily expanding
the pool of people who should be on drugs.
And
every few years a study produces the bad news that a certain
anti-hypertensive drug or drug combination kills more
people than other drugs or drug combinations. Last December,
for example, a study reported that an older, supposedly
tried and true beta-blocker drug called atenolol (some
brand names: Tenoretic, Apo-Atenolol) had caused more
strokes and cardiac deaths than other commonly prescribed
anti-hypertensives.
Many
people have high blood pressure but no heart disease,
and as a group they are less likely to have a large benefit
from drug therapy than the people with heart disease.
There are exceptions, of course, such as diabetics. And
some people with high blood pressure gain nothing at all
from drug therapy. A 2003 Cochrane* review of all anti-hypertensive
drug trials that included women found that white women
under the age of 55 years showed no benefit, nor were
they harmed by the drugs.
To
complicate things further, there is a wide range of anti-hypertensive
drugs on the market. To keep them all straight, researchers
refer to them by their drug classes, for example, ACE
inhibitors, calcium channel blockers, etc. Altogether
there are six drug classes and within each, multiple brand
names [see below].
Last
month, the British journal The Lancet published a commentary
by three scientists who questioned the excessive focus
on high blood pressure when there are many other risk
factors—smoking, family history, diabetes, etc.—that determine
who will die of heart disease. Instead, they argue for
changing the focus to the prevention of blood-pressure-related
diseases. “…clear evidence now shows that several blood-pressure-lowering
drugs reduce the risks of major vascular events [e.g.
stroke] in a broad range of non-hypertensive individuals
with high-risk disorders, such as cerebrovascular disease,
diabetes, or coronary heart disease.”
The
Lancet commentary makes sense given the fact that studies
show some anti-hypertensives (ACE inhibitors) can produce
cardiovascular benefits while making only modest reductions
in blood pressure. Conversely, other drugs (calcium channel
blockers) are good at lowering blood pressure without
doing much for the odds of having a heart attack or stroke.
How
would you know whether you are taking the right drug or
drug combination for your particular circumstances? Is
your doctor able to keep up with all the new information—and,
again, how would you know?
In
2002, a major anti-hypertensive drug trial rocked the
international medical establishment with findings that
challenged widely held beliefs. It found that diuretics,
the oldest and cheapest anti-hypertensive drug class,
are just as effective and, in some circumstances, better
than the newer, expensive drugs. But just when it appeared
that, at last, there is definitive anti-hypertensive drug
news, the same study made it clear that many people with
hypertension need another drug in addition to a diuretic.
This
2002 landmark trial, known as the Antihypertensive and
Lipid-Lowering Treatment to Prevent Heart Attack Trial
(ALLHAT), included over 33,000 men and women over age
55 years with mild to moderate hypertension who were at
high risk for developing heart disease (e.g. 36% had diabetes).
The ALLHAT had randomly assigned participants to take
daily doses of a calcium channel blocker, an alpha blocker,
an ACE inhibitor, or a diuretic.
Whenever
a drug failed to control blood pressure, the study participants
were put on a second or third additional drug selected
from the other three. In other words, everyone in this
study was on anti-hypertensive drugs, often two or three
on a daily basis. The ALLHAT participants were broadly
representative of the U.S. population in terms of race,
gender, socioeconomic status, and geographical region.
Here
are some of the ALLHAT findings:
-
A
diuretic should be the first-choice treatment for high
blood pressure;
-
the
total or overall mortality—that is, the deaths from all
causes—was the same for all treatments;
-
calcium-channel-blocker
drugs increased the incidence of heart failure;
-
participants
taking the alpha-blocker (doxazosin) were stopped prior
to the intended conclusion of ALLHAT because they showed
a significantly increased rate of angina, stroke, and
congestive heart failure;
-
whether
they were treated with a diuretic, ACE inhibitor, or an
alpha blocker, the occurrences of heart-related death,
and non-fatal heart attack were virtually identical.
Because
most anti-hypertensive drug trials have combined the results
for men and women, some researchers have pointed out that
this might inflate drug therapy's benefit to women who
typically do not have heart attacks or heart-related fatalities
until they are much older than men. Also, there might
be gender-differences in harms associated with drugs that
would show up as non-cardiac deaths.
A
2003 Cochrane review of all trials that included women
concluded that in white women over 55 years, drugs reduced
the rate of fatal and non-fatal cerebrovascular “events”
(e.g., stroke, trans ischemic attacks), and fatal and
non-fatal cardiovascular events, but they do not reduce
the cardiovascular or overall mortality. Black women of
any age , however, benefited on all counts (except
overall mortality) from drug therapy because their cardiovascular
risk is higher to begin with. Black women tend to develop
hypertension earlier in life than white women. In the
trials included in this Cochrane review, they also were
more likely to be smokers and diabetics than white women.
Another
attempt to clarify things was an all-woman study published
at the end of 2004 in JAMA, the Journal of the American
Medical Association. A research team led by S. Wassertheil-Smoller
evaluated different drug combinations in over 30,000 older
women—50 to 79 years—with hypertension but no heart disease
or diabetes. They had been followed for almost six years.
This is what researchers call an observational study because
it looked at the different ways women with hypertension
are treated in “the real world” as opposed to a clinical
trial based at an academic medical center where researchers
determine the treatments and assign them randomly to participants.
Here
are some of the findings:
-
Of
the women taking only a diuretic, this drug was equal
to or superior to other drugs taken singly in preventing
cardiovascular disease complications;
-
of
the women taking only one drug: those on a calcium channel
blocker had a higher rate of death from heart disease
than those taking only a diuretic;
-
the
women who took only a calcium channel blocker had a higher
rate of death from heart disease compared with those who
took a diuretic plus a beta-blocker;
-
and
women taking a diuretic plus a calcium channel blocker
had a greater rate of cardiovascular death than those
on a diuretic plus a beta blocker or a diuretic plus an
ACE inhibitor.
Who
has hypertension?
In
all the anti-hypertensive drug studies described in this
article, the definitions of hypertension were roughly
similar. Study participants were diagnosed as having high
blood pressure when they had a systolic that is higher
than 140 mm HG (millimeters of mercury) or a diastolic
more than 90 mm Hg.
Bottom
Line:
Diuretics
are the first-choice drug for men and women. While it
would seem reasonable to conclude that the calcium channel
blocker should be avoided, hypertension researchers see
it as a “drug of last resort”. The ALLHAT did not include
low-risk people with hypertension—that is, healthy adults
whose only risk for heart disease is high blood pressure.
When trials show a reduction in cardiovascular deaths
but not in overall deaths, this suggests that the heart-related
survival benefit may be canceled by treatment-related
deaths. Anti-hypertensive drug trials follow people five
or six years, at most, whereas people are expected to
take these drugs for life.
Many
heart disease researchers believe that physicians should
not focus solely on high blood pressure when deciding
drug therapy. Instead, a person's entire risk profile
should be taken into consideration. And finally, this
from the authors of the all-woman study: “An important
question is whether it is the blood pressure lowering
effect of anti-hypertensive drug therapy that is the critical
element in preventing cardiovascular disease sequelae
or whether particular drug classes offer benefits beyond
their effects in lowering blood pressure.”
--
*Abstracts
generated by The Cochrane Collaboration are available
at www.thecochranelibrary.com
, see “Pharmacotherapy for Hypertension in Women of
Different Races”.
Box
insert
SIX
ANTI-HYPERTENSIVE DRUG CLASSES AND BRAND-NAMED MEMBERS
Alpha
Blockers or Alpha-Adrenergic Blockers
Cardura,
Minipress, Hytrin, Doxaloc, Apa-Doxazosin, Gen-Doxazosin,
Med-Doxazosin
ACE
(angiotensin-converting enzyme) Inhibitors
Lotensin,
Benicar, Capoten, Vasotec, Monopril, Prinivil, Zestril,
Univasc, Aceon, Accupril Altace, Renormax, Mavik
Angiotensin-2-Receptor
Antagonists, also known as ARBs
Atacand,
Teveten, Avapro, Cozaar, Micardis, Diovan
Beta
Blockers (beta-adrenergic-blocking drugs)
Sectral,
Atenolol, Tenormin, Kerlone, Zebeta, Ziac, Cartrol, Coreg,
Normodyne, Trandate, Lopressor, Corgard, Levatol, Visken,
Inderal, Blocadren
Calcium
Blockers or Calcium-Channel-Blocking Drugs
Norvasc,
Vascor, Cardizem, Tiazac, Plendil, DynaCirc, Cardene,
Adalat CC, Procardia XL, Nimotop, Sular, Calan, Isoptin,
Verelan
Thiazide
Diuretics
Naturetin,
Aquatag, Exna, Marazide, Diuril, Anhydron, Esidrix, HydroDiuril,
Diucardin, Saluron, Enduron, Aquatensen, Renese, Metahydrin,
Naqua
---
Maryann
Napoli, Center for Medical Consumers © April 2005
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