Altman, Lawrence K. "Use of Some Hypertension Drugs Questioned," New York Times, 29

Altman, Lawrence K. "Use of Some Hypertension Drugs Questioned," New York Times, 29
August 2000, p. A17.

The second most popular kind of drug used to lower high blood pressure is less effective than
other drugs in preventing heart attacks and heart failure, according to a study being reported

The use of such drugs, known as calcium channel blockers, is leading to nearly 85,000
unnecessary heart attacks and cases of heart failure each year worldwide, with half the cases in
the United States, the study's authors are reporting at a meeting in Amsterdam of the European
Cardiology Society. The findings seem likely to extend a long and bitter debate over the safety
and effectiveness of calcium channel blockers to treat high blood pressure, which is also called

Calcium channel blockers are not harmful. By blocking calcium's role in contracting muscles in
the heart and arteries, the drugs relax muscles and thus directly lower blood pressure. But
because the drugs are less effective, users do not gain the benefits they would by using other
types of antihypertensive drugs, and the reason is unknown, said the scientific team that was led
by Dr. Curt D. Furberg of the Wake Forest University School of Medicine in Winston-Salem,

Patented calcium channel blockers are also much more expensive than other antihypertensive
drugs, Dr. Furberg said in an interview. He cited costs of $740 to $990 a year for calcium channel
blockers, compared with $60 for low doses of a diuretic drug. Wider use of more effective
antihypertensive drugs could reduce the cost of health care in the United States by up to $5
billion a year, Dr. Furberg said.

The Food and Drug Administration does not list all calcium channel blocker drugs marketed in
the United States, a spokeswoman said. Those listed in the Physicians' Desk Reference include:
Adalat, Calan, Cardene, Cardizem, Covera, Dilacor, Isoptin, Nimotop," Norvasc, Plendil,
Procardia, Sular, Tiazac, Vascor and Verelan.

Such drugs should not be taken off the market, Dr. Furberg said. But, he stressed, doctors should
be more cautious in prescribing them as first-line drug therapy for high blood pressure and to
prevent its complications. Dr. Furberg's team urged doctors to limit use of calcium channel
blockers to patients who have not responded to or cannot tolerate other standard drugs. Low-dose
diuretics should continue to be considered as the standard therapy for hypertension, and all new
classes of drugs should be compared with diuretics, Dr. Furberg's team said. Dr: Furberg and
other experts stressed that patients should not stop taking calcium channel blockers without first
discussing any change with their doctor.

An estimated 28 million people worldwide, including 12.7 million in this country, take calcium
channel blockers to lower high blood pressure and for other reasons like relieving the vain of

Millions more take antihypertensive drugs that belong to other classes. They work by different
mecanisms and include: ACE inhibitors, the most popular antihypertensive drugs, which block a
cascade of hormones, beginning with one produced by the kidneys; diuretics, which reduce the
amount of fluid in the blood vessels; beta-blockers, which reduce the force and rate of the heart's
contractions; and alpha blockers, which slow the brain's action on the sympathetic nervous

Dr. Robert Temple, a top official of the Food and Drug Administration said the agency would
pay close attention to the new findings. "It hasn't been possible to do this before be cause there
wasn't a great deal of comparative data," he said.

Dr. Temple said he expected that additional important information would come from a study that
is the largest involving a calcium channel blocker. It is sponsored by the National Heart, Lung
and Blood Institute. But the study will not end untie 2002, said Dr. Furberg, who is the study's
chief investigator.

That study and a number of other large-scale trials should provide evidence supporting the
benefits of calcium channel blockers for hypertension, said Dr. Rob Scott, a vice president of
Pfizer, which make: Procardia XL and Norvasc. "All the data we have tells us that blood pressure
lowering is a good ting to do." Dr. Scott said. "We need to try not to start making
recommendations that could turn out to be wrong until we have the results of those trials."

Calcium channel blockers have been marketed for more than two decades .in the United States,
and critics have said that their long-term. safety was never documented, unlike that of some other
antihypertensive drugs.

Dr. Furberg's team began challenging the drugs' safety and effectiveness in 1995. The team
focused first on the short-acting form of calcium channel blockers that many American doctors
had prescribed for high blood pressure despite lacking F.D.A. approval for such use. In 1995
federal health officials warned that short-acting calcium channel blackens should be prescribed
"witth great caution, if at all." Since then their use in this country has fallen. In 1995, Dr.
Furberg's team also challenged the safety and effectiveness of the long-acting form of calcium
channel blockers. But critics contended that they were safer because they lowered blood pressure
more gradually than the short-acting form The debate could not be resolved because of a lack of
information from scientifically controlled trials.

In 1998, The New England Journal of Medicine Published a study from the University of
Toronto concerning the debate over the safety of calcium channel blockers. The study found that
doctors who wrote articles in medical journals supporting the use of calcium channel blockers
were much more likely to have financial relationships with drug companies than authors who
were critical of such use or had neutral positions on the issue.

Dr. Furberg said his team responded to the criticism by doing what is known as a meta- analysis.
It combines a number of small studies to provide a greater statistical power than any of the
smaller ones can provide.

Dr. Furberg's team analyzed information on 27,000 patients who participated in nine studies. All
the studies had been publied in peer-reviewed medical journals that directly compared calcium
channel and other antihyertensive drugs.

The researchers found th the risk of heart attack was 27 percent higher and the risk of heart
failure 26 percent higher among users of calcium channel blockers. There was no difference in
risk of stroke or total number of deaths from all causes between those taking channel blockers
and other drugs, and no evidence of differences among the various calcium channel blocker
drugs in the study. The meta-analysis also found that all drugs lowered the blood pressure by the
same amount.

The aim of lowering high blood pressure is to prevent damage to blood vessels that can lead to
complications like heart attacks, heart failure and stroke.

Conventional medical wisdom has held that lowering blood pressure to normal levels was all
that-mattered in preventing complications. But doctors are beginning to understand that such
prevention is much more complicated than simply reducing blood pressure to normal levels, said
Dr. Michael H. Alderman, a co-author of the study from Albert Einstein College of Medicine in
the Bronx and a former president of the American Society of Hypertension.

The risk of developing complications is now thought to involve the interplay of a number of
hormones and factors in the walls of blood vessels and the actions of drugs on them. Thus, drugs
that have an equal effect on lowering blood pressure may vary in their ability to prevent heart
attacks and heart failure, and mechanisms that do not involve blood pressure may be important in
determining the therapeutic effects of antihypertensive drugs, Dr. Alderman said.