Hot Line IV Hypertension
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Hot Line IV Hypertension

September 7, 2019

JESSUP: Hi, I’m Mariell Jessup from the American Heart Association, and I’m here with our president of the American Heart
Association, Mark Creager. We’re in London, not so sunny today, at the European
Society of Cardiology. We’re very interested and excited about so much
that’s been presented at the Hot Line trials. I believe, Mark, that you were very
interested in the hypertension trials of Hot Line 4. CREAGER: I was indeed. This was really a very important Hot Line session, as you mentioned Mariell, focusing on high
blood pressure and really will be of considerable interest to the
cardiovascular community and primary care physicians, and I’d like to talk about
three trials. Two of them came from the British Heart Foundation and the
National Institute for Heart Research right here in the United Kingdom. The
first of the ones I want to speak about is called PATHWAY-2, and PATHWAY-2
focused on patients with resistant hypertension. So these were patients who
still had an elevated blood pressure even though they were taking a renin
angiotensin system inhibitor, a calcium channel blocker , and a diuretic. And
the question that the investigators posed was does an aldosterone
antagonist improve blood pressure control better than perhaps other
classes of drugs that we would have considered the next line of therapy. So
those classes would be beta-blockers and they used bisoprolol or alpha-blockers and they used doxazosin.
So in a crossover trial which was placebo-controlled, they studied over 300
patients with resistant hypertension, and the important findings from this trial
was that the aldosterone antagonist spironolactone was more effective than
placebo, more effective than bisoprolol, and more effective than doxazosin,
and by a substantial margin, really confirming what we have seen in smaller
trials that aldosterone antagonists are very
effective forms of therapy in patients with resistant hypertension. So I think
that the use of an aldosterone antagonist is really going to enter
everyone’s therapeutic armamentarium for treating patients with resistant
hypertension. So the second trial from the same group was called PATHWAY-3,
and this was in patients with essential hypertension who did not have adequate
blood pressure control. Their drug pressure regimen did not yet include a
diuretic, and the question that was being a was does a lower dose combination of a thiazide diuretic hydrochlorothiazide and potassium sparing diuretic amiloride
is that combination more effective in reducing the risk of an elevated blood
sugar or in reducing the risk of high potassium and in lowering blood pressure
than either higher doses of hydrochlorothiazide alone or higher
doses of amiloride alone. And what they found was, it really was, it was almost like
a Goldilocks and the three bears effect. It was right there in the middle so
hydrochlorothiazide tended to increase glucose in our oral glucose tolerance test,
amiloride alone tended to reduce it, and the combination was right in the middle,
and the opposite was true with the potassium. So amiloride tended to increase
potassium when given alone, hydrochlorothiazide reduced it, and the
combination of the two, it was more in the middle. But in terms
of blood pressure control, the combination of lower doses of
hydrochlorothiazide plus lower doses of amiloride were better than higher doses
of hydrochlorothiazide again or higher doses of amiloride. JESSUP: Yeah, I love that trial. Less is more in this case,… [CREAGER: There you go.] …and they’re inexpensive, easily available
drugs. CREAGER: Right. And the amiloride, amiloride hydrochlorothiazide combination has not
been used much in recent years. Now the third trial was called the PARAMETER
trial. Now the PARAMETER trial used a drug whose initials and number is LCZ696,
and what this is is an angiotensin receptor neprilysin inhibitor going
by the acronym ARNI, and this trial was looking at patients who were elderly
with systolic hypertension, a very tough group of patient in whom to get
their blood pressure under control. And to be eligible for this trial you had to have a systolic blood pressure greater than 150 and a wide pulse pressure more than 60
millimeters of mercury indicative of vascular, increased vascular stiffness. So
the combination, the ARNI was compared to an angiotensin receptor blocker olmesartan, and the primary endpoints were markers of vascular stiffness, in this
case, central aortic pulse pressure and central aortic systolic pressure. And the
important findings from this trial was that indeed the combined neprilysin
inhibitor angiotensin receptor blocker was more effective at lowering central
aortic systolic pressure, central aortic pulse pressure than olmesartan. And this has very important implications because when vascular stiffness is increased and
central pressures are increased, you’re increasing the load on the heart, you’re
increasing their risk for heart failure, you’re increasing the risk for atrial
fibrillation, you’re increasing the risk of stroke. So although this was not an
outcome trial per se in terms of cardiovascular event, it certainly shows
promise of more effective blood pressure control in this very vulnerable
population. JESSUP: And this new class ARNI that we heard so much about last year at
this meeting in the PARADIGM trial which was looking at this ARNI class in patients with low EF heart failure was a real
blockbuster last year. This is now more mechanistic rationale for using this
class of drug in in other kinds of patients, and I think if nothing else the excitement and so far positive effects of a new class I think paves the way for other new classes, so more hope for our
patients. CREAGER: Terrific hope. JESSUP: Yes. CREAGER: Yeah, I’m very optimistic of this field moving forward with the trials that I saw today. I
think they’ll be very applicable right off the bat. JESSUP: Well, thank you, Mark. I know that you’ve been stimulated by being here at this meeting as I have, and
it’s more great news for our patients and lots of learning for our clinicians.

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