New Recommendations for Treating Hypertension in Black Patients

Editorial Commentary
New Recommendations for Treating Hypertension in
Black Patients
Evidence and/or Consensus?
Jackson T. Wright, Jr, Lawrence Y. Agodoa, Lawrence Appel, William C. Cushman, Anne L. Taylor,
Gbenga G. Obegdegbe, Kwame Osei, James Reed
H
evidence and, moreover, are inconsistent with the most recent
results of large randomized clinical outcome trials in black
hypertensive patients.
While acknowledging that less than one third of black
hypertensive patients are controlled to ⬍140/90 mm Hg, the
ISHIB statement recommends substantially lower BP goals in
patients already ⬍140/90 mm Hg. In uncomplicated hypertensive patients without target organ damage, preclinical
cardiovascular disease (CVD), or history of CVD, it recommends lowering the target BP from ⬍140/90 to ⬍135/
85 mm Hg. The selection of this new BP target appears both
arbitrary and unfounded. To support the new lower goal, the
authors cite evidence from observational studies and the
results from 3 clinical trials: the Treatment of Mild Hypertension Study (TOMHS) (n⫽902 with 177 blacks); CardioSis, a European trial (n⫽1111, no blacks identified); and the
Trial of Preventing Hypertension (TROPHY) (n⫽772, 79
blacks).3–5 Only the TOMHS and CardioSis reported clinical
outcomes; more than half of the outcomes in the TOMHS
were based on a screening questionnaire for angina (the Rose
questionnaire). In CardioSis, the primary outcome was ECG
evidence of left ventricular hypertrophy.
The ISHIB statement also references end-of-study,
achieved BP data from the Antihypertensive and Lipid
Lowering Heart Attack Prevention Trial (ALLHAT) to support the ⬍135/85-mm Hg target in uncomplicated hypertensive patients. However, the ALLHAT BP goal was ⬍140/
90 mm Hg, and trial participants were, by trial design,
extremely high risk patients: mean age was 67 years, more
than half had CVD, ⬎25% had coronary heart disease, 35%
had diabetes mellitus, and ⬇60% met criteria for the metabolic syndrome.6 Entry into CardioSis also required ⱖ1
additional risk factor. Thus, both CardioSis and the ALLHAT
studied populations substantially different from the low-risk
patients for which the lower BP target is recommended.
Even more problematic is the recommendation for a BP
goal of ⬍130/80 mm Hg in those with diabetes mellitus,
prediabetes, high Framingham risk, left ventricular hypertrophy, metabolic syndrome, or glomerular filtration rate ⬍60.
This recommendation would mean that the majority of black
hypertensive patients would have a goal BP of ⬍130/80 mm Hg.
Data from clinical outcome trials designed to compare BP goals
of ⬍130/80 mm Hg with those ⬍140/90 mm Hg in hypertensive
patients with left ventricular hypertrophy, high Framingham
risk, or metabolic syndrome are not available. However, we now
do have such data in black patients with chronic kidney disease
or diabetes mellitus.
ypertension is the major cause of morbidity, mortality,
and disability in black populations in the United States
and increasingly worldwide. Its greater severity, resistance to
treatment, and more frequent financial challenges to achieve
control in this population make it critical that populationspecific recommendations for hypertension management be
based on the very best evidence. In 2003, the International
Society of Hypertension in Blacks (ISHIB) published its first
consensus statement.1 The 2003 Statement has been widely
promoted as the authoritative guideline for managing hypertension in black patients. The consensus statement2 in this
issue of Hypertension updates the 2003 statement, and,
although the authors are careful not to call it a guideline, it
may become viewed similarly. Thus, it could dramatically
impact the management of hypertension in this population.
The ISHIB statement has a number of commendable
features. Written by a very impressive group of experts, it is
a well-organized, comprehensive document providing an
excellent update on the epidemiology, significance, and
pathophysiology of hypertension in the black population, as
well as substantial practical advice on its management. A
particularly worthwhile feature is the discussion of psychosocial factors influencing blood pressure (BP) control in this
population, including those related to patient-provider interaction. However, it makes several sweeping recommendations that are both unsupported by randomized clinical trial
The opinions expressed in this editorial are not necessarily those of the
editors or of the American Heart Association.
From the Department of Medicine, Division of Nephrology and
Hypertension, Case Western Reserve University (J.T.W.), Cleveland,
Ohio; National Institute of Diabetes and Digestive and Kidney Diseases
(L.Y.A.), Bethesda, Md; Welch Center for Prevention, Epidemiology and
Clinical Research, Johns Hopkins University (L.A.), Baltimore, Md; Veterans Affairs Medical Center, Medical Service, Preventive Medicine Section
(W.C.C.), Memphis, Tenn; Department of Medicine, Division of Cardiology, Columbia University (A.L.T.), New York, NY; Division of General
Internal Medicine, Department of Medicine, New York University School of
Medicine (G.G.O.), New York, NY; Department of Medicine, Division of
Endocrinology, Diabetes and Metabolism, Ohio State University (K.O.),
Columbus, Ohio; Department of Medicine, Division of Endocrinology,
Morehouse College of Medicine (J.R.), Atlanta, Ga.
Correspondence to Jackson T. Wright, Jr, Department of Medicine,
Division of Nephrology and Hypertension, Case Western Reserve University, William T. Dahms Clinical Research Unit, Clinical and Translational Science Collaborative, Clinical Hypertension Program, Bolwell
Suite 2200, 11100 Euclid Ave, Cleveland, OH 44106-6053. E-mail
[email protected]
(Hypertension. 2010;56:801-803.)
© 2010 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org
DOI: 10.1161/HYPERTENSIONAHA.110.159566
801
802
Hypertension
November 2010
The African American Study of Kidney Disease and
Hypertension (AASK) trial studied black hypertensive patients with hypertensive renal disease. It was as large
(n⫽1094) as any of the 3 trials that were used to justify the
lower BP goals, and the number of black participants in
AASK far exceed the cumulative number in all 3 of the trials.
Although it was a trial of kidney disease progression and not
powered to assess CVD outcomes, it still had more than twice
the number of CVD events of those other studies, and it was
a direct test of a BP goal approximating 140/90 mm Hg
versus a lower goal in a black hypertensive population.
Despite maintaining a 13/7-mm Hg BP difference (141/85
versus 128/78 mm Hg) over 3 years of mean follow-up, no
benefit on renal (or CVD) outcomes was seen in those
randomized to the lower goal either overall or in the subgroup
of patients with baseline urine protein/urine creatinine ⬍0.22
(equivalent to ⬇300 mg/d).7,8 Long-term (⬇10 years) posttrial follow-up suggests potential benefit of the lower BP goal
on chronic kidney disease progression but not CVD events in
the subgroup of patients with baseline urine protein/urine
creatinine ⬎0.22; however, there was no apparent benefit
overall or in participants with urine protein/urine creatinine
ⱕ0.22.9
The National Heart, Lung, and Blood Institute–funded
Action to Control Cardiovascular Risk in Diabetes Trial
results were published recently comparing systolic BP goals
of ⬍140 mm Hg versus ⬍120 mm Hg in diabetic hypertensive patients.10,11 Overall, in this trial of ⬇5000 participants,
24% black (n⫽1142) and mean follow-up of 4.7 years, there
was no difference in the primary composite outcome consisting of nonfatal myocardial infarction, stroke, or CVD death,
although a significant benefit of the lower BP goal was
observed for stroke, one of the components of the primary
outcome and a prespecified secondary outcome. The Action
to Control Cardiovascular Risk in Diabetes Trial retinopathy
BP results also reported no benefit of this lower BP goal on
diabetic retinopathy progression.11 Importantly, although the
stroke subgroup data have not yet been reported, the subgroup
data by race for the primary composite CVD outcome shows
that nonwhite participants (61% black) in the trial were not
more likely to benefit from the lower BP goal (hazard ratio:
0.97 [95% CI: 0.71 to 1.33]; P⫽0.87). Thus, it is very
difficult to make the case that black hypertensives with
diabetes mellitus would benefit from a lower BP goal. The
authors of the ISHIB statement appear to accept the results on
CVD outcomes and retinopathy of the much smaller Appropriate Blood Pressure Control in Diabetes normotensive trial
with only 480 participants as rebuttal to the Action to Control
Cardiovascular Risk in Diabetes results, although the similarly small Appropriate Blood Pressure Control in Diabetes
hypertensive trial (n⫽470) reported no benefit for renal,
retinopathy, or CVD outcomes.12 The National Institutes of
Health–funded Systolic Blood Pressure Intervention Trial
will provide a definitive test of this question in high-risk
nondiabetic patients.
Rather than setting new lower BP goals, we suggest a
greater focus on increasing the number of patients controlled
to the conventional goal of ⬍140/90 mm Hg. At present, less
than half of treated black hypertensive patients are controlled
to even this level.13 There are several reasons to resist
recommending lower BP goals not demonstrated to confer
major benefits in randomized clinical outcome trials. Adherence to a more complex regimen and other proven effective
therapies may be compromised. Furthermore, far more resources will be expended to reach lower goals, for example,
more medications, more monitoring, more frequent clinic
visits, and, consequently, higher costs.
The recommended approach to treatment is also a strength
of the document, with one exception. The recommendation
for the initiation of multiple drugs in those ⬎15 mm Hg
above their target systolic BP and/or ⬎10 mm Hg above their
target DBP (an innovation first proposed in the first ISHIB
guideline) has been retained. The recommendation for this
population of a renin-angiotensin-aldosterone system inhibitor as initial therapy in those without a compelling indication,
a weakness of the 2003 document, has been deleted in this
update. However, the recommendation in this update of a
renin-angiotensin-aldosterone system inhibitor/calcium channel blocker combination over other possible 2-drug regimens
in those receiving combination therapy has few data to
support it. It currently recommends including diuretics for
initial combination therapy only in those with edema or fluid
overload.
This recommendation is based on the results of a single
trial, the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension
(ACCOMPLISH) trial,14 with results in blacks thus far only
referenced by a personal communication. There are several other
inconsistencies in this recommendation. The ACCOMPLISH
trial compared an angiotensin-converting enzyme inhibitor
(ACEI)/calcium channel blocker with only 1 other 2-drug
regimen, ACEI/hydrochlorothiazide (HCTZ), but the latter used
a dose of HCTZ substantially lower than that used in other
clinical trials demonstrating CVD outcome benefits with HCTZ.
It also provides no evidence comparing it with other 2-drug
regimens. Furthermore, this recommendation treats all thiazidetype diuretics as one class, although in other places, it recommends a preference for chlorthalidone over HCTZ and a higher
dose of HCTZ than was used in ACCOMPLISH. In recommending the renin-angiotensin-aldosterone system inhibitor/
calcium channel blocker combination, it treats ACEIs, angiotensin receptor blockers, and direct renin inhibitors as a
group, yet ACCOMPLISH only provided data comparing an
ACEI/calcium channel blocker versus an ACEI plus a very
low-dose diuretic. Finally, the recommendation ignores the
vast clinical outcome trial literature from the first Veterans
Administration Cooperative Trials to ALLHAT demonstrating the benefit of thiazide-type diuretics in preventing major
clinical outcomes in black hypertensive patients in favor of
the results of a single study.
In summary, the new ISHIB consensus document presents
useful, practical information to guide practitioners in the
diagnosis, prevention, and treatment of hypertension in black
patients. However, there is insufficient evidence to support
the recommendations for the lower BP goals and the preferential use of 1 combination drug therapy.
Wright et al
Disclosures
J.T.W. is a consultant/advisory board member for Sanofi-Aventis
(modest), Novartis (modest), Daiichi-Sanyo (modest), Take Care
Health (at least $10 000), Noven Pharmaceuticals (modest), NiCox
Pharmaceuticals (modest), and CVRx DSMB (modest). W.C.C.
received other research support from Novartis (modest) and Glaxo
Smith Kline (modest) and is a consultant/advisory board member for
Novartis (at least $10 000), Takeda (at least $10 000), SanofiAventis (modest), Bristol Myers Squibb (modest), Noven Pharmaceuticals (modest), and Daiichi-Sanyo (modest). A.L.T. received
other support from CVRx DSMB (modest). K.O. received research
grants from Eli-Lilly (modest), is on the Speakers Bureau of
Novo-Nordisk (modest), received honoraria from Novo-Nordisk
(modest), and is a consultant/advisory board member with Eli-Lilly
(modest) and Daiichi-Sankyo (modest). J.T.W., L.A., W.C.C., and
K.O. are all NIH funded.
6.
7.
8.
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