Transcript Management of Hypertension

Management of
Hypertension
Laura Fitzpatrick, MD, MPH
Intern Academics
Friday the 13th, August 2004
Background
The JNC VII guidelines are issued
periodically from the National Heart, Lung,
and Blood Institute. (NHLBI)
 Many new observational studies and
clinical trials since JNC VI in 1997.
 JNC VII published in 2003: express
format in JAMA, full report in
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Hypertension.
What are the differences between
JNC VI and JNC VII?
A new category added called “prehypertension”; this combines normal and
borderline.
 Previous stage 2 and 3 were combined.
 Lower threshhold for starting therapy.
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Blood pressure classifications
BP class
SBP
DBP
Lifestyle
Changes
Initial
Drug
therapy
Normal
<120
<80
Encourage
None
Pre-HTN
120-139
80-89
Yes
No drug if no
DM/CKD
Stage 1
140-159
90-99
Yes
Thiazides
first-line
Stage 2
>=160
>=100
Yes
2-drug
combination
for most
BP increases with age
How does one measure BP?
Auscultatory method
 Person seated at least 5 min with feet on
the floor, arms supported at heart level.
 Use a cuff bladder that encircles at least
80% of the arm to ensure accuracy.
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What are the target organs of injury?
Cardiac: LVH, angina, CAD, CHF
 Neuro: CVA/TIA
 Renal: CKD
 PVD
 Retinopathy
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What components of history are
important in a newly diagnosed pt?
h/o smoking
 h/o hyperlipidemia
 physical activity
 h/o diabetes
 age
 family history of premature CAD defined
as males < 55 and females < 65
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What PE components should be
performed in a newly diagnosed pt?
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checking BP in both arms
examination of the optic fundi
documenting the BMI
listening for carotid, abdominal, and femoral bruits
palpating the thyroid
detailed cardiac/pulmonary exam
assessing for enlarged kidneys on abdominal exam
documenting peripheral pulses
neurologic exam
What labs should we obtain?
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EKG
U/A
glucose
hematocrit
K+
creatinine
Calcium
Lipid profile
optional: albumin/creatinine ratio or urinary albumin
excretion
What is the goal BP in patients with
hypertension?
Goal is <140/90
 In patients with DM or CKD, goal is
<130/80
 In patients with >1g proteinuria, the goal
is <125/75
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When do you follow up?
Why these goals?
HOT (Hypertension Optimal Treatment)
Trial.
 The National Kidney Foundation (NKF)
Kidney Disease Outcome Quality Initiative
(K/DOQI) clinical practice guidelines.
 ADA recommendations
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Hypertension Optimal Treatment Trial
(HOT)
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Goal was to determine the optimal level of BP to reduce
CV morbidity/ mortality. ? J-curve existence.
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Randomized 19,000 pts with HTN (mean 170/105 mm
Hg) to 3 different goal diastolic bp arms: <= 90, <= 85,
<= 80 mm Hg.
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Felodipine 5 mg was given as baseline therapy, with
addition of other agents according to a 5-step regimen.
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Half were randomized to receive aspirin.
Hypertension Optimal Treatment Trial
(HOT)
DBP was reduced to 85.2, 83.2, and 81.1
mm Hg.
 Outcomes: CV events, MI, CVA, CV
mortality, total mortality.
 No significant differences among the 3
arms with respect to any outcome.
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Hypertension Optimal Treatment Trial
(HOT)
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Trial did not prove/ disprove the J-curve.
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Lower bp further did not appear to enhance risk.
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ASA 75 mg significantly reduced MI and CV
events (by 15%).
Lancet 1998 Jun 13;351(9118):1755-62
What are the lifestyle modifications
suggested by the JNC VII?
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weight loss to BMI 18-24 (decrease of 5-20 mm Hg for
every 10 kg wt. loss)
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DASH diet rich in potassium and calcium (lead to 8-14
mm Hg reduction in SBP)
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limit Na intake (a 2.4 g Na diet lead to 2-8 mm Hg
reduction in SBP)
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physical activity at least 30 min/day 7 days a week
(lead to 4-9 mg Hg reduction in BP)
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limit etoh intake
What are the different classes of BP
lowering medications available?
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Thiazides
Other diuretics (loop, K+ - sparing)
Beta-blockers
Combined alpha and beta- blockers (carvedilol, labetalol)
ACE inhibitors
Angiotensin-receptor blockers
CCB’s (non-dihydropyridine) – verapamil, dilt
CCB’s (dihydropyridines) – amlodipine, felodipine
Central-acting agents
Direct vasodilators
What to use when
Ischemic heart
disease
Beta-blockers and ACE-I’s
CHF
ACE-inhibitors, beta-blockers,
aldosterone antagonists
Diabetes Mellitus
ACE-I’s/ ARB’s first choice,
slow the progression of
diabetic nephropathy
CKD
Consider ACE-I/ ARB; can
tolerate up to increase of
35% Cr or until hyperkalemia.
Cerebrovasc.
disease
Combination of ACE-I/ TD can
decrease recurrence
Pregnancy
Methyldopa, b-blocker (not
atenolol) and direct
vasodilators; avoid ACE/ARB’s
What to use when
Congestive Heart Failure
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SOLVD (1991)
 randomized
pts with CHF-EF<35% to
enalapril vs. placebo and followed for 41
months.
 16% risk reduction in mortality (p=.0036)
 26% risk reduction for hospitalization
(p<.0001)
 XSOLVD showed that this gap narrowed over
time.
N Engl J Med 1991 Aug 1;325(5):293-302
Congestive Heart Failure
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MERIT-HF (1999)
~4000 patients with class II-IV CHF and EF<40%
randomized to metoprolol XL/CR vs. placebo.
Followed for ~1 yr.
 All-cause mortality lowered with metoprolol
(RR=0.66)
 Also decreased sudden deaths, deaths from
worsening heart failure, and hospitalization.
 Study terminated prematurely.
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Lancet 1999 Jun 12;353(9169):2001-7
Congestive Heart Failure
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United States Carvedilol Heart Failure Program
(NEJM, 1996)
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1100 pts already receiving dig, diuretics, ACE
randomized to carvedilol vs. placebo.
Decreased total mortality
Decreased hospitalizations
Increased event-free survival
Study terminated prematurely
N Engl J Med 1996 May 23;334(21):1349-55
Ischemic Heart Disease
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SAVE trial (1992)
 2231
patients with EF<40% but no overt HF
signs/symptoms, 3-16 days post-MI
randomized to placebo vs. captopril.
 All-cause mortality decreased 19% (P=.019)
 Major CV events decreased 21%
 Recurrent MI decreased 25%
N Engl J Med 1992 Sep 3;327(10):669-77
Cerebrovascular Disease
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SHEP (Systolic HTN in the Elderly, 1991)
 4736
pts 60 yrs and over with isolated systolic
HTN (mean 170/77) randomized to
chlorthalidone vs. placebo. Atenolol added, if
needed, to achieve a goal reduction of 20
mmHg.
 Primary outcome: CVA; Secondary: CV M/M,
all-cause mortality, QOL measures.
JAMA 1991 Jun 26;265(24):3255-64
SHEP trial
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Outcomes
 Risk
of stroke significantly lower in the
treatment group. (RR=0.64; p=.0003)
 Risk of CV events was reduced, but NS.
High-risk for coronary disease
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LIFE (2002)
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Randomly assigned 9193 pts with severe HTN and EKG
evidence LVH to losartan vs. atenolol.
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Outcomes were death, MI or stroke.
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RR of primary composite endpoint was 0.87 (p=.021)
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Decreased stroke RR=0.75 (p=.001)
Lancet 2002 Mar 23;359(9311):995-1003
LIFE trial
LIFE trial
High-risk for coronary disease
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HOPE (2000)
 9451
high-risk pts without acute MI, HF or LV
dysfunction.
 High-risk: either evidence of vascular disease
OR diabetes + another CV RF.
 Pts randomly assigned to ramipril vs. placebo.
 Endpoints were CV death, MI, or CVA
N Engl J Med 2000 Jan 20;342(3):145-53
HOPE trial
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Study terminated after a 4.5 year followup when it showed the following:
 Reduction
in primary endpoint (RR=0.78)
 Reduction in nonfatal MI (RRR=23%)
 Reduction in Stroke (RR=0.68)
HOPE trial
ALLHAT
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A RCT of high-risk pts with HTN, designed to determine
if occurrence of fatal CHD or nonfatal MI is lower with a
CCB, ACE-I, alpha-blocker vs. thiazide diuretic.
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Secondary outcomes included all-cause mortality, CVA,
and CVD events.
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A subtrial included moderately hyperlipidemic patients
randomized to pravastatin vs. placebo to determine
differences in mortality.
ALLHAT
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42,000 patients >55 years (men and women)
with stage 1 or 2 HTN and >=1 additional CVD
risk factor.
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Randomized to 4 arms: tx with amlodipine,
chlorthalidone, lisinopril or doxazosin.
Goal: <140/90
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Doxazosin arm discontinued due to higher rates
of CVD and CHF.
ALLHAT
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Patient population was diverse
 Mean
 36%
 47%
 35%
 19%
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age: 67 years
had diabetes
female
black
Hispanic
Populations virtually identical at baseline
ALLHAT results
ALLHAT results
No significant difference among the 3 arms with
respect to the primary outcome.
 The amlodipine group had a 38% higher risk of
CHF compared with chlorthalidone group.
(p<.001)
 Lisinopril group had a 15% higher risk of CVA
(p=.02), a 10% higher risk of combined CVD
(p<.001); 19% higher risk of HF.
 The efficacy of chlorthalidone compared to
lisinopril was higher in blacks than in whites.
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Secondary HTN
What are the identifiable causes of
HTN?
chronic kidney disease
 aortic coarctation
 cushing syndrome/ chronic steroid therapy
 drug-related (ex. Cocaine, amphetamines,
decongestants)
 Pheochromocytoma
 primary aldosteronism
 renovascular hypertension
 sleep apnea
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thyroid/ parathyroid disease
When is a workup of secondary HTN
appropriate?
In patients whose history, PE, severity of
HTN or initial labs suggest secondary causes
 BP responds poorly to drug therapy
 BP begins to increase without explanation
after being well-controlled
 Onset of HTN is sudden
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Cases
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A 54 y.o. WF with PMH of HTN, fibromyalgia, recently diagnosed type 2 DM
presents for her regular diabetes visit. Baseline EKG shows no
abnormalities, and urinary dipstick showed trace proteinuria. Her bp is
147/92, and her current regimen consists of HCTZ 12.5 mg daily and
atenolol 50 mg daily.
 (1) What is her goal bp?
 (2) What is the next step in the management of her bp?
 (3) What agents would you consider if the EKG had shown evidence of
LVH?
 (4) You place her on ramipril, and her creatinine bumps from its
baseline of 1.2 to 1.5, where it stabilizes. Do you stop the ACE-I?
Answers
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(1) What is her goal bp? 130/ 80 in a patient with DM. Her trace proteinuria is
not likely to exceed 1g/day, but if it did, her goal would be 125/ 75 mm Hg.
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(2) What is the next step in the management of her bp? Add another agent. You
could titrate up one of her existing medications, however, given her proteinuria
you should consider the addition of an ACE-I or ARB.
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(3) What agents would you consider if the EKG had shown evidence of LVH?
You could consider an ARB (or ACE-I). The LIFE trial compared losartan and
atenolol in hypertensive patients with LVH; losartan was superior, mainly due to
its reduction of stroke risk.
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(4) Serum creatinine should be carefully monitored with ACE-I initiation, but
creatinine increases up to 35% are acceptable. Increases over 20% may be a
clue to the presence of renal artery stenosis.
Cases
A 48 y.o. WM presents to your office with no significant PMH. His bp is
168/92. This has been confirmed on two other separate occasions. He is on
no meds at present. He has no DM, no known heart disease, no history of
CVA/ TIA. His family history is unremarkable. He does not smoke, and
drinks minimal alcohol.
(1) What class of hypertension does he have?
(2) How would you manage his blood pressure?
(3) What labs would you order now?
Answers
(1) What class of hypertension does he have? He has stage 2
hypertension, as his systolic value places him in that category.
(2) How would you manage his blood pressure? Start 2 agents. HCTZ would
be a good choice for one of the agents.
(3) What labs would you order now? 12-lead EKG, fasting lipid panel,
glucose, serum Cr and U/A. A Hct and electrolytes may be helpful.
Cases
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A 87 y.o. AAM has never visited a physician in his life and comes to see you.
His bp is 180/75. He states he has never had any health problems. Your
workup of target end-organ damage, along with all bloodwork, is
completely negative.
 (1) Would you start 1 or 2 agents?
 (2) What would be the first agent you would choose and why?
Answers
(1) Would you start 1 or 2 agents? Although he falls under the
category of stage 2 HTN (and therefore needs to be started on 2
agents), given his advanced age (and likely decreased metabolism), you
could consider starting 1 agent, then bringing him back soon (within 24 weeks) to start a second agent. Ultimately, he will very likely need 2
agents.
 (2) What agent(s) would you choose and why? According to the SHEP
trial, elderly patients with isolated systolic HTN had a significant
decrease in stroke risk when patient were placed on chlorthalidone. You
could therefore consider a thiazide diuretic as initial therapy.
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