CLINICAL
NEWS
American College of Cardiology Extended Learning
• Is the patient taking the prescribed medications?
Poor treatment adherence, he said, accounts for
about half of all failure in BP control.
• Is the treatment failure real? He said at least
one-third of “office resistant hypertension” is
actually white-coat hypertension that can be
confirmed by ambulatory BP monitoring.3
• Is an optimal treatment regimen being prescribed? Guidelines suggest that in the absence
of a concomitant condition requiring particular
drug classes or an established contraindication,
patients with resistant hypertension should be
on all three of these agents: 1) renin–angiotensin
system blocker (angiotensin-converting enzyme
inhibitor or angiotensin receptor blocker); 2) calcium channel blockers; and 3) thiazide diuretics.
• Is the patient taking conflicting drugs? NSAIDs,
cold remedies, weight loss medications, and
antidepressants are among the drugs that can interfere with treatment and raise BP, sometimes
sharply (TABLE).4
TABLE Medications that Can Interfere with
Blood Pressure Control
Non-steroidal anti-inflammatory drugs/COX-2 inhibitors
Oral contraceptives (estrogen predominant)
While catheter-based
RDN failed spectacularly
in a sham-controlled
study, the approach may
be down but not out.
• 15 had secondary hypertension;
• 17 were controlled on four drugs;
• 40 were nonadherent (based on urinary analysis), with 30% taking none of their meds at all
and the rest taking about half of what was prescribed. (At least there was consistency: lack of
adherence was almost evenly distributed among
different classes of antihypertensive drugs.); and
Sympathomimetic agents (decongestants, diet pills, cocaine)
Stimulants (amphetamines, methylphenidate)
Alcohol
Antidepressants (tricyclic antidepressants, serotonin and
norepinephrine reuptake inhibitors)
Cyclosporine
Erythropoietin
Natural licorice
Herbal compounds (ephedra or ma huang)
• Does the patient have a secondary form of
hypertension (e.g., chronic kidney disease,
sleep apnea, aldosterone excess)? Studies have
suggested that the prevalence of idiopathic
hyperaldosteronism ranges from 17% to 22% of
individuals with resistant hypertension.
• Could an additional drug help (spironolactone can
be a good first step)? Other options: beta-blockers;
centrally acting drugs like clonidine; alpha blockers; or direct vasodilators, such as hydralazine.
To give you an idea of what you might expect from
using these individual pieces of advice in a population of patients, Dr. Weber points to one study
of 375 patients referred for specialist care due to
uncontrolled hypertension despite being on three
drugs.5 Of these:
• 267 fell out of the study by maximizing doses
and excluding white-coat hypertension;
30 CardioSource WorldNews
• 36 were true resistant hypertensives (i.e., just
10% of the 375 referred patients).
The investigators postulate
that the shorter distance of nerve
endings to the arterial lumen
in the distal segment of the
renal artery may account for the
improved treatment efficacy. In
To listen to an interan accompanying editorial comview with Michael
A. Weber, MD, on
ment,8 coauthored by Deepak
the topic of unconBhatt, MD (first author the shamtrolled hypertencontrolled trial that brought an
sion, scan the code.
The interview was
inglorious end to SYMPLICITY
conducted by David
HTN-39), “It appears that the adR. Holmes, MD.
dition of distal lesion targets may
be the most efficient approach
for improving success in renal
denervation, despite fewer nerves
surrounding the distal vessel.”
Bhatt and his coauthor Neal
N. Sawlani, MD, added that
ongoing studies in humans are currently underway
using new approaches with multielectrode catheters,
incorporating an ongoing accrual of knowledge
(NCT02439775, NCT02439749, and NCT02392351).
They concluded, “With new methodological standards
and novel preclinical studies, catheter-based renal denervation is poised to undergo significant innovation in
device application. Renal denervation appears to have
reached a new branch point in its development.”
Editor’s note: Dr. Weber recently published a paper on
RDN for the treatment of hypertension titled, Making a
new start, getting it right.10
REFERENCES:
This is not an isolated study’s findings. In one
recent trial evaluating patients before being sent for
renal denervation (RDN), top tier French specialists
searched through 1,416 referred resistant patients
to find 106 eligible subjects who truly had resistant
hypertension (7.5%).6
Once you subtract all those factors that get a patient
classified as having resistant hypertension, Dr. Weber
suspects the prevalence of resistant hypertension in
those being treated for high blood pressure is, in reality,
about 1%. “It’s a pretty rare diagnosis,” he said.
REMEMBER RDN?
While catheter-based RDN failed spectacularly in a
sham-controlled study, the approach may be down but
not out. Several reasons for the variability in response
to renal artery denervation in humans have been posited, particularly limitations with the anatomic targets
used for radiofrequency ablation in clinical trials.
Recently in JACC, Mahfoud et al. reported that
increasing the number of radiofrequency lesions in
the main renal artery was not sufficient to yield a
clear dose-response relationship. However, targeted
treatment of the renal artery branches or distal segment of the main renal artery resulted in markedly
less variability of response and significantly greater
reduction of both norepinephrine and axon density
than conventional treatment targeting only the
main renal artery for RDN.7
1. Mozaffarian D, Benjamin EJ, Go AS, et al. Circulation.
2016;133:e38-e360.
2. Weber MA. Trends in Cardiovasc Med. 2015;25:755-6.
3. de la Sierra A, Segura J, Banegas JR, et al. Hypertension.
2011;57:898-902.
4. Calhoun DA, Jones D, Textor S, et al. Hypertension.
2008;51:1403-19.
5. Jung O, Gechter JL, Wunder C, et al. J Hypertens.
2013;31:766-74.
6. Azizi M, Sapoval M, Gosse P, et al. Lancet.
2015;385:1957-65.
7. Mahfoud F, Tunev S, Ewen S, et al. J Am Coll Cardiol.
2015;66:1766-75.
8. Sawlani NN, Bhatt DL. J Am Coll Cardiol. 2015;66:1776-1778.
9. Bhatt DL, Kandzari DE, O’Neill WW, et al. N Engl J Med.
2014;370:1393-401.
10. Weber MA, Kirtane A, Mauri L, Townsend RR, Kandzari DE,
Leon MB. J Clin Hypertens (Greenwich). 2015;17:743-50.
Take-aways
• While more patients are qualifying as having
“resistant hypertension,” only a small percentage
of these patients will ultimately be determined to
have truly resistant high blood pressure.
• There are a number of discernible factors that
can be detected and lead to effective treatment
of what was originally thought to be “resistant
hypertension.”
• Renal denervation is down but not out. New
studies are suggesting that this approach may still
become an effective means of managing patients
with truly resistant hypertension.
May 2016