Two large analyses estimating the cardiovascular and stroke benefit with initial
drug treatment for hypertension showed that only angiotensin receptor blockers
(ARBs) were not significantly better than placebo for the prevention of coronary
events, while all antihypertensive drugs were better than placebo for the
prevention of stroke.

Regarding the lack of cardiovascular protection with ARBs, investigators suggest
that this is the result of a limited number of studies and cardiovascular
outcomes in these trials compared with the other drug classes.

"People should feel very comfortable that when their doctor is giving them a
certain medication they don't have to worry," said lead investigator Dr William
Elliott (Rush Medical College, Chicago, IL). "The concern we have with the ARBs
is probably because we simply don't have enough data at this time. . . . There
really aren't enough data with ARBs to make a really strong statement."

The two meta-analyses were presented here this week at the American Society of
Hypertension (ASH) 2009 Scientific Meeting.

Meta-Analysis Includes Recent Hypertension Trials

During a press conference with assembled media, Elliott said that the last
meta-analysis estimating outcomes with initial hypertensive therapy was
performed in 2003, before the publication of Seventh Report of the Joint
National Committee on Prevention, Detection, Evaluation, and Treatment of High
Blood Pressure (JNC 7). In that analysis, researchers concluded there was a
reduction in stroke with any hypertensive drug but that low-dose diuretics were
the most effective first-line agents for preventing cardiovascular disease.

However, with the publication of the Avoiding Cardiovascular Events in
Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH),
a study showing the ACE inhibitor benazepril plus the calcium-channel blocker
amlodipine was more effective than treatment with the ACE inhibitor and diuretic
in reducing major fatal and nonfatal cardiovascular events, there is some
uncertainty if this is still true, said Elliott.

In the two new meta-analyses, investigators included all published
outcomes-based clinical trials with minimum follow-up of one year. All subjects
included in the analysis were required to have hypertension, thereby excluding
studies such as HOPE, PROGRESS, EUROPA, PEACE, and ONTARGET, among others, and
the drug used must have been prescribed as initial antihypertensive therapy. The
reference drug in the two analyses was diuretic therapy.

In an analysis estimating the reduction in stroke risk with the hypertensive
medications, which included nearly 270 000 hypertensive patients in 60 clinical
trials, all medications were significantly better than placebo for reducing the
risk of stroke. Diuretics and calcium-channel blockers were slightly more
protective than ARBs but were significantly better than ACE inhibitors and beta
blockers.

Investigators noted that the results were identical whether the reference
diuretic was chlorthalidone or hydrochlorothiazide and that the overall network
findings were confirmed by Bayesian analysis. Moreover, the data are robust to
numerous changes in the data set, which included the addition of ACCOMPLISH to
the analysis as well as different studies that included add-on drug therapy for
the treatment of hypertension and studies that didn't include patients with high
blood pressure.

"The fact is that it doesn't really matter when you add in these other studies,
you get the same answer," said Elliott.

Cardiovascular Risk Reduction With Antihypertensive Drugs

In the second meta-analysis examining coronary heart disease risk reduction with
the different antihypertensive drugs, the researchers used the same entry
criteria and included 57 clinical trials involving 276 000 patients. In that
analysis, all drugs, except ARBs, were significantly better than placebo or no
treatment for reducing the risk of coronary events.

"The good news is that all of the generically available medicines are
significantly better than placebo, and the take-home message for patients and
doctors is that you can be sure whatever generic medicine you're taking does
protect you better than placebo or no treatment for heart attack and sudden
cardiac death," said Elliott.

The findings also showed that ACE inhibitors were significantly better than ARBs
and beta blockers for coronary heart disease risk reduction, which echoes
previous reports suggesting ACE inhibitors have pleiotropic effects independent
from blood-pressure lowering that protect patients from cardiovascular events.

Like the stroke findings, the results were similar when different studies were
added to the analysis and when the different diuretics were used as the
reference drugs.

Speaking with the media, Elliott noted that the results have been heralded as a
"tempest in a teapot" because most patients with hypertension are treated with
multiple antihypertensive drugs, whereas this analysis was concerned primarily
with looking at risk reduction with initial hypertension therapy. However, since
treatment in the US follows "road maps," and patients are typically started with
one drug, it is important to know the differences with the different pathways
that lead to getting blood pressure down, he said.

Elliott reports serving as a consultant to Novartis Pharmaceuticals and is on
the speakers' bureau for Novartis, Pfizer, a Bristol
Myers-Squibb/Sanofi-Synthelabo partnership, and Sanofi-Aventis.

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Authors and Disclosures
Journalist
Michael O'Riordan
Michael O'Riordan is a journalist for Medscape. Before becoming a journalist for
theheart.org, now part of the WebMD Professional Network, he worked for WebMD
Canada. Michael studied at Queen's University in Kingston and the University of
Toronto and has a master's degree in journalism from the University of British
Columbia, where he specialized in medical reporting. He can be contacted at
MORiordan@....
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Information
Authors and Disclosures
Michael O'Riordan
Michael O'Riordan is a journalist for Medscape. Before becoming a journalist for
theheart.org, now part of the WebMD Professional Network, he worked for WebMD
Canada. Michael studied at Queen's University in Kingston and the University of
Toronto and has a master's degree in journalism from the University of British
Columbia, where he specialized in medical reporting. He can be contacted at
MORiordan@....


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