CLINICAL
NEWS
American College of Cardiology Extended Learning
ACCEL interviews and topical summaries of cardiology’s
most interesting research areas
PATHWAY for Prevention and Treatment of Hypertension
T
here are many options for treating hypertension and, to some extent, that’s the problem.
Trying to determine the best treatment for an
individual patient may require a lot of trial and error.
Of the estimated 80 million American adults with
high BP, 76.5% are currently being treated, but only
54.1% of hypertensives in the U.S. have it controlled.1
One of several organizations trying to make a
dent in the problem is the British Hypertension Society and, specifically, their PATHWAY research project. The program consists of three complementary
studies. The unifying themes are that measurement
and interpretation of a patient’s renin status permit
more rational and less empirical treatment decisions
than have been traditional in hypertension; and
that with hypertension now clearly recognized as a
complex disorder, rational therapy in most patients
means choosing the appropriate combinations.
The first study—monotherapy versus combination
for initial treatment—tests the hypothesis that patients
treated with a single drug never catch up with the BP
control achieved with initial combination because of compensatory vasoconstriction or sodium retention. While
only the study design has been published as of this
writing,2 the results have been presented and they suggest that two drugs were significantly better than one.
According to Tom MacDonald, MD, first author of the
paper and the current president of the British Hypertension Society, this was true even when the best single
medicine at optimal dose was chosen using the best predictors of effectiveness. (Professor Morris Brown, MD, of
Cambridge spearheads the overall PATHWAY program.)
Dr. MacDonald added, “An understandable concern
was that two medicines might have unacceptably more
side effects such as dizziness compared with singlemedicine therapy. But we did not find this; so, we are
reassured that we can now recommend combined medicines for the initial treatment of
patients with high blood pressure
which will reduce blood pressure
and result in fewer strokes, heart
attacks, and sudden deaths.”
The second study—optimal
therapy of resistant hypertenTo listen to an
sion—evaluated the theory that
interview with Morris
spironolactone is the best overall
Brown, MSc, MD, on
treatment for patients with resisthe PATHWAY results,
scan the code. The
tant hypertension.3 PATHWAY 2
interview was conwas the first randomized clinical
ducted by Patricia
trial to directly compare spironoPallikka, MD.
lactone with other active BPlowering treatments in patients
with well characterized resistant
hypertension. It showed that spironolactone (25–50 mg daily) is
overwhelmingly the most effective
ACC.org/CSWN
drug treatment for resistant hypertension. It controlled
BP in almost 60% of patients with resistant hypertension—and was three times as likely to be the patient’s
best drug versus doxazosin or bisoprolol.
The result in favor of spironolactone was,
according to the investigators, “unequivocal”—
“Spironolactone is the most effective treatment for
resistant hypertension, and these results should influence treatment guidelines globally.” The authors
even went so far as to add that patients should not
be defined as having resistant hypertension unless
their BP remains uncontrolled on spironolactone.
Spironolactone was well tolerated with no significant excess adverse effects with the caveat that
serum potassium levels and renal function should be
monitored on treatment and treatment duration was
too short to assess incident gynecomastia (~ 6% in
longer-term studies).
PATHWAY 3
The third study—single versus combination diuretic
in patients with low-renin hypertension—tested the
hypotheses that multiple nephron blockade is more
effective than single and that the addition of potassiumsparing diuretic to or substitution for thiazide in patients with features of metabolic syndrome will prevent
deterioration of glucose tole &