JNC 8
Update on Hypertension
Guidelines
Alan Cementina, MD
Associate Clinical Professor
Family Medicine Center at Asylum Hill
DISCLOSURE
I have not had nor do I currently have any
financial relationships with the manufacturers of
health care products.
I will not discuss any pharmaceuticals, medical
procedures, or devices that are investigational or
unapproved for their stated use by the FDA.
JNC 8?
JNC “Late”
JNC “Wait”
JNC…….
Not!
NHLBI adopts new collaborative
partnership model for clinical practice
guidelines development
Gary H. Gibbons, M.D. - June 19, 2013
In June 2012, the NHLBAC recommended that the Institute transition to a
new model in accordance with the best practice standards established by
the IOM, in which the Institute focuses its primary effort on the generation
of high-quality systematic evidentiary reviews and supports the
development of clinical practice guidelines through partnerships with
professional societies and other organizations.
GOALS
Identify Highlights of JNC7.
Understand evidence influencing
recommendations for new BP goals.
Understand evidence influencing the
recommendations for choice of first line
therapy.
Identify concerns about Beta-Blockers.
Be aware of the role of spirinolactone.
2003
Measuring BP
Seated quietly for 5 min in chair.
Feet on floor, arm supported at heart level.
No caffeine, exercise or smoking for 30min.
Cuff bladder encircle at least 80% arm circ.
At least 2 measurements and average.
Measuring BP
Inflate 20-30mmHg above pulse extinction.
Deflate at rate of 2mmHg/sec.
SBP = onset of 1st Karotkoff sound.
DBP = disappearance of Karotkoff sounds.
Study drug
Add on drug
BP achieved
Population
End Points
Psaty B, JAMA, 1997, 277(9)
Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial
JAMA 2002;288:2981-97
33,357 pts age >55 with stage 1-2 HTN and 1
other CHD risk factor.
Randomized, double-blind, active-controlled
clinical trial.
Randomized to amlodipine or lisinopril, v.
chlorthalidone. (doxazosin)
Goal BP <140/90.
Mean follow-up 4.9 years.
Copyright restrictions may apply.
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, JAMA 2002;288:2981-2997.
Cumulative Event Rates for All-Cause Mortality, Stroke, Combined Coronary Heart Disease, Combined Cardiovascular Disease, Heart Failure, and Hospitalized Plus Fatal Heart Failure by
Treatment Group
A
L
C
JNC7 Summary
Lowering SBP as close to 120 mmHg as is feasible is the single most important goal.
Traditional agents (thiazide diuretics) are the most cost effective choice for initial Rx.
Few of your patients will be adequately treated using whatever you choose first.
Certain drug classes confer particular benefit for selected patients with specific co-morbid conditions.
JNC7 Summary
ACEI/ARB should be included for patients
with DM.
ACEI/ARB/BB/HCTZ should be included for
patients with CAD.
ACEI/ARB/BB/AA/diuretic should be used
for patients with impaired LV systolic function.
CCB not recommended in HF.
2013
Is a BP <140/90 a universal goal for
all patients?
Is SBP<120 ideal?
Antihypertensive Therapy in the Elderly
Antihypertensive Therapy in the Elderly
HYVET Hypertension in the Very Elderly Trial
NEJM 2008; 358: 1887-98.
3,485 patients from Europe, China*, Australasia, and Tunisia aged 80 and older with SBP 160 mmHg
Randomized to indapamide SR (Lozol) 1.5 mg vs placebo
After 3 mo, perindopril (Aceon) 2/4 mg could be added
Target BP 150/80 mmHg
Primary endpoint = fatal or nonfatal stroke
* 95% of patients from Eastern Europe or China
NEJM 2008; 358: 1887-98
NEJM 2008; 358: 1887-98
Benazepril plus HCTZ or amlodipine
Journal of Hypertension 2009, 27:1360–1369
ONTARGET
Composite of CV
death, MI, stroke or
hospitalization for
heart failure.
Telmisartan, Ramipril, or both in high risk patients
ACCORD BP
NEJM 2010; 362: 1575-85.
4733 pts with type 2 DM at high CV risk.
Randomized to SBP <120mmHg or SBP
<140mmHg.
Primary endpoint: nonfatal MI, nonfatal stroke,
or CV death.
4.7 yr mean follow up.
Am J Cardiol 2007;99[suppl]:44i–55i
N Engl J Med 2010;362:1575-85.
N Engl J Med 2010;362:1575-85.
Event rate
in the
Standard
Rx group
was 50%
lower than
expected
Summary of Recent Studies Evaluating
Goal BP
2008 HYVET Low risk > 80y/o: SBP<150 is still beneficial
2008 ACCOMPLISH High risk 68.4y/o: SBP<130 no better than <140
2009 ONTARGET High risk 66.4y/o: SBP =130 is optimal
2010 ACCORD BP High risk Diabetics 62.2y/o: SPB<120 no better than <140
2013
Are all thiazide diuretics equivalent?
Are they still the best choice for
initial therapy?
Chlorthalidone vs HCTZ Estimated Dosing
Equivalence based on Estimated Equivalent
BP Reduction
6.5
12
20
28
6.4
18
3.8
24
18
23
0
5
10
15
20
25
30
3 6 12.5 25 50 100 200
HCTZ Chlor.
Red
ucti
on
in
SB
P (
mm
Hg
)
Carter BL, Ernst ME, Cohen JD. Hypertension 2004;43:4-9.
50 mg HCTZ ~ 25 to 37.5 mg
chlorthalidone
We conducted a literature search
from 1960 to 2003 to identify
studies that evaluated the
pharmacokinetic and blood
pressure–lowering effects of these
2 agents.
Major U.S. Diuretic Trials
VA Cooper (3) HCTZ 50-100 mg
PHS trial Chlorothiazide 500-1000 mg
HDFP Chlorthalidone 50-100 mg
MRFIT HCTZ 50-100mg(BID) or
Chlorthalidone 50-100 mg
EWPHBPE HCTZ 25-50 mg
MRC HCTZ 25-50 mg
SHEP Chlorthalidone 25-50 mg
TOMHS Chlorthalidone 15-30 mg
ALLHAT Chlorthalidone 12.5-25 mg
Outcomes in Diuretic Trials
HDFP
MRFIT
SHEP
TOMHS
ALLHAT
VA II (beat placebo, with help)
MRFIT (lost to chlorthalidone)
EWPHBPE (beat or tied placebo)
HAPPHY (tied b-blockers)
MAPPHY (lost to metoprolol)
MRC-E (beat placebo, atenolol)
MIDAS (tied CCB)
INSIGHT (tied nifedipine)
PATS (beat placebo)
ANBP-2 (lost to, or tied with, enalapril)**
ACCOMPLISH (lost in combo with benazepril to amlodipine/benazepril)**
Chlorthalidone Hydrochlorothiazide
**12.5-25 mg HCTZ
dosing
No comparator proven
superior
ACCOMPLISH
NEJM 2008; 359: 2417-28.
11,506 pts with HTN at high CV risk.
Randomized to benazepril + amlodiopine or benazepril + HCTZ.
Primary endpoint: composite of CV death, non-fatal MI, non-fatal stroke, hospitalization for angina, resuscitation after SCA and coronary revascularization.
3 year mean follow up
n engl j med 359;23
n engl j med 359;23
n engl j med 359;23
Perspective on ACCOMPLISH A typical drug company study (Novartis)
Selection of an inferior comparator (HCTZ) at suboptimal dose (used the excuse that it is the most commonly prescribed agent and dose)
Comparison is essentially amlodipine vs HCTZ Amlodipine t1/2 = 38-50 hrs
Benazepril t1/2 = 8-12 hrs, trough:peak 0.4 (>0.5 recommended by FDA)
HCTZ t1/2 = 8-15 hrs
Other important points: Heart failure not included in primary composite
Predict ABPM substudy will yield revealing results (e.g. HOPE substudy) Likely that nighttime control better in amlodipine group (only need to see 4-6 mmHg
diff based on epi studies to explain 20% diff in outcome)
Office BP overestimates response to HCTZ (Finkielman Am J Hypertens 2005;18:398-402)
Findings will likely be overemphasized to demote importance of diuretic-based regimens
Ernst ME, Carter BL, Basile JN. All thiazide-like diuretics are not chlorthalidone:
Putting the ACCOMPLISH study into perspective. Journal of Clinical
Hypertension 2009;11:5-10
2013
Are all Beta-Blockers Equivalent?
JACC, 2006;47 (suppl):361A
ATENOLOL
2013
What drug to add in resistant HTN
after ACE/ARB, BB, CB and
Thiazide Diuretic?
Resistant HTN
Failure to reach goal BP taking
at least 3 drugs, one of which is a
diuretic.
JNC 7, 2003
Options for Treatment of Resistant
Hypertension
Identify and treat secondary causes.
Centrally acting alpha agonists.
Direct vasodilators.
Aldosterone antagonists (ENaC).
Renal artery denervation.
The Role of Spironolactone in
Resistant HTN
At least 5 studies from 2002 to 2007.
Patient populations poorly characterized.
Differed with respect to both nature and number of baseline therapies.
1 study did not attempt to characterize primary hyperaldosteronism.
All but 1 study were open and not controlled.
None assessed hard clinical endpoints.
Low-dose Spironolactone in
Resistant Hypertension
Lane, et. al., Journal of Hypertension 2007; 25: 891-894.
Open observational study, 25-50mg of spirinolactone added to ACE-I/ARB + (3 drugs)
N = 119, after 11 dropout due to “side effects” (no trend), 6 mo follow up.
Excluded hyper-aldosterone, renal HTN, CKD, CHF.
21.7 mmHg drop in SBP*
8.5 mmHg drop in DBP*
0.3 mmol/L rise in K+
2 patients with K+ above 6.0 mmol/L
48 (31%) achieved target BP of <140/90
* Likely overestimated.
Inhibition of Epithelial Sodium
Channel in Blacks with HTN
Saha, et. al., Hypertension 2005; 46: 481-487.
Prospective randomized placebo-controlled
doubled-blind trial.
2-by-2 factorial design: amiloride 10mg,
spironolactone 25mg, both or placebo added to
diuretic and CCB.
N=98, 9 wk follow up, excluded if PRA
elevated.
-4.6mmHg, P=0.006
-1.8mmHg, P=0.07
Hypertension. 2005;46:481-487
No hyperkalemia
JNC 8?
Hypothetical JNC 8
Recommendations
Goal BP likely to be refined (relaxed) for population subgroups,
particularly for those >80 and those with DM.
Chlorthalidone recommended over HCTZ, but pre-eminence as
first line therapy might be challenged.
Reduced role for Beta-Blockers as initial therapy (still pre-
eminent for HFrEF and CAD), particularly atenolol.
Recommendation for low dose aldosterone antagonist as add-on
therapy in resistant HTN.
Introduction of renal artery sympathetic denervation.
? Delineation of role for ambulatory/home BP monitoring.