Transcript Management of Hypertension in the Elderly

Leslie Bittner, Pharm.D., BCPS
[email protected]
NEONP Conference
April 25, 2014
Disclosure

No conflicts of interest to disclose
Objectives

Describe impact of hypertension (HTN) on the elderly

Review evidence for management of HTN in the elderly

Discuss treatment goals and medication
recommendations from current guidelines

Assess limitations to achieving treatment goals

Apply to a patient case
Impact of HTN on
the Elderly
Prevalence and Outcomes

Number of elderly Americans expected to increase

Prevalence of HTN increases with age

Framingham Heart Study


90% with normal blood pressure (BP) at age 55 years
went on to develop hypertension
Multiple end-organ effects

Cardiovascular disease, cerebrovascular disease, kidney
disease, eye impairment
Lloyd-Jones D. Circulation. 2009;119:e21-181
Aronow WS. Circulation. 2011;123:2434-2506
Pathophysiology of HTN in the Elderly
Isolated
systolic HTN
O’Rourke MF.J Am Coll Cardiol. 2007 Jul 3;50(1):1-13. Epub 2007 Jun 18.
Aronow WS. Circulation. 2011;123:2434-2506.
Isolated Systolic HTN

Increasing prevalence with age
 65%
with HTN > 60 years old
 90% with HTN > 70 years old

Changes related to aging have been noted to be
lesser in populations NOT exposed to:
 High-sodium
diet
 High-calorie diet
 Low physical activity
 High rates of obesity
Aronow WS. Circulation. 2011;123:2434-2506.
Other Factors to Consider in the Elderly

Decreased baroreflex function

Increased venous insufficiency

Increased salt sensitivity

Renal dysfunction

Lifestyle Factors
Substance use (tobacco, alcohol, caffeine, etc.)
 High-salt diet
 NSAID use

Aronow WS. Circulation. 2011;123:2434-2506
Literature Review:
Is there Benefit in
Treating the Elderly?
Systolic Hypertension in the
Elderly Program (SHEP)

Multicenter, randomized, double-blind, placebo controlled

4,736 patients, ≥ 60 years with isolated systolic HTN


Mean age = 72 years
Baseline Average SBP = 170mmHg; Average DBP = 77mmHg

Target SBP < 160mmHg if SBP > 180mmHg and goal to decrease SBP by at
least 20mmHg if SBP 160-170mmHg

Intervention:


Chlorthalidone 12.5mg – 25mg/day vs. Placebo
Chlorthalidone could be doubled, then atenolol could be added to achieve target if
needed (reserpine was used if atenolol was contraindicated)

Primary Outcome: Nonfatal and fatal stroke

Average follow-up = 4.5 years
SHEP Research Group. JAMA. 1991;265:3255-3264.
Systolic Hypertension in the
Elderly Program (SHEP)

Results
stroke: relative risk 0.64 (95% CI 0.50 – 0.82)
 Nonfatal myocardial infarction + coronary death:
relative risk 0.73 (95% CI 0.57 – 0.94)
 Total

Study Conclusion
 Decreasing
blood pressure using low-dose
chlorthalidone as initial medication showed reduced
risk of stroke and cardiovascular events over a 5year follow-up
SHEP Research Group. JAMA. 1991;265:3255-3264.
Hypertension in the Very
Elderly Trial (HYVET)

Multicenter, randomized, double-blind, placebo controlled

3845 patients, ≥ 80 years with SBP ≥ 160mmHg



Intervention:



Mean age = 83.6 years
Baseline average BP = 173/90.8mmHg
Diuretic (indapamide) vs. Placebo
Perindopril may be added to achieve target BP <150/80 mmHg
Primary Outcome: Nonfatal and fatal stroke
Beckett NS, et al. N Engl J Med. 2008;358:1887-98
Hypertension in the Very
Elderly Trial (HYVET)


Results
Hazard Ratio
95% Confidence Interval
All stroke
0.70
0.49 – 1.01
Death from Stroke
0.61
0.38 – 0.99
Cardiovascular Events
0.66
0.53 – 0.82
Total mortality
0.79
0.65 – 0.95
Study Conclusion


Trial ended early due to benefits seen at interim analysis
Treatment with indapamide +/- perindopril to a treatment goal
of < 150/80mmHg in a very elderly population showed reduced
risk of death from stroke and overall mortality.
Beckett NS, et al. N Engl J Med. 2008;358:1887-98
Literature Review:
Other Key Evidence
Guiding Treatment Choices
The Antihypertensive and Lipid-Lowering Treatment
to Prevent Heart Attack Trial (ALLHAT)

Randomized, double-blind, active control trial

> 33,000 enrolled, ≥ 55 years old with hypertension

Interventions:

Chlorthalidone vs. Amlodipine vs. Lisinopril vs. Doxazosin

Outcome: Combined fatal CHD or non-fatal MI

Results
 Doxazosin arm terminated early
 Thiazide found to be superior in preventing 1 or more forms of
cardiovascular disease and has low cost  considered 1st line
ALLHAT Study Group. JAMA. 2002;288:2981-97.
ACCOMPLISH

Randomized, double-blind study

11,506 enrolled, ≥ 55 years with HTN & high risk for cardiac event

Intervention:
 Benazepril + Amlodipine vs. Benazepril + Hydrochlorothiazide
 Target BP < 140/90mmHg (or 130/80mmHg if diabetes or kidney disease)

Primary outcome: Composite of cardiovascular (CV) disease states

Results
 Study terminated early at interim analysis
 Benazepril + amlodipine combination was superior in reducing CV events
Jamerson KA, et al. N Engl J Med. 2008;359:2417-28.
Relationship Between BP and
Cardiovascular Outcome (from INVEST)
Denardo S. Am J Med. 2010;123:719-26.
Systolic Blood Pressure
Intervention Trial (SPRINT)

STUDY UNDERWAY

Study Question: "Will lower blood pressure reduce
the risk of heart and kidney diseases, stroke, or
age-related declines in memory and thinking?”

Will compare SBP target <120mmHg vs. 140mmHg

SUBGROUPS:
SPRINT – MIND  will look at memory and cognition
 SPRINT – SENIOR  Will include patients 75 and older

https://www.sprinttrial.org
Guideline Update

Target Blood Pressure Recommendations
Age
Threshold for Treatment Initiation
≥ 60 years
SBP ≥ 150*
DBP ≥ 90*
< 60 years
SBP ≥ 140
DBP ≥ 90
≥ 18 years old with
Chronic Kidney Disease
SBP ≥ 140
DBP ≥ 90
≥ 18 years old with
Diabetes
SBP ≥ 140
DBP ≥ 90
* If treatment lowers BP further (for example SBP < 140), but no adverse effects or quality
of life impact – no need to adjust treatment
James PA. JAMA. 2014;311(5):507-520.

Trial lifestyle modification and continue throughout

Medication selection
BP not at goal,
Non – Black (+/- diabetes)
BP not at goal,
Black (+/- diabetes)
Chronic Kidney
Disease
Thiazide Diuretic (THIAZ)
THIAZ
Ace Inhibitor (ACE-I)
CCB
Angiotensin Receptor Blocker (ARB)
Calcium Channel Blocker (CCB)
ACE-I
ARB
Alone or in Combination**
Alone* or in
Combination**
Alone or in
Combination
*Guideline states no evidence for use in age > 75; may be beneficial in age group but THIAZ or CCB also option
**Avoid use of ACE-I and ARB together
James PA. JAMA. 2014;311(5):507-520.

Some key changes from JNC 7 Guidelines
JNC 7
2014 HTN Guidelines
General population treatment threshold
140/90 regardless of age
Different treatment thresholds for general
population based on age
Treatment threshold 130/80 for DM
or CKD
Treatment threshold 140/90 for DM
or CKD
HTN stages discussed
Treatment initiation thresholds discussed
Thiazide diuretics recommended as
initial drug for most in general population
Initial drug options broadened to multiple
classes and also dependent on race
Beta blocker included as alternative first
line drug choice in general population
Beta blocker not included as first line
drug choice in general population
Treatment selection for many compelling
indications discussed
Treatment selection for CKD and DM
only discussed
Chobanian AV. JAMA. 2003;289:2560-2572.
James PA. JAMA. 2014;311(5):507-520.

Elderly – specific guidelines
Age
Threshold for
Treatment Initiation**
Treatment Target
55 – 79 years
SBP≥ 140
DBP ≥ 90
SBP < 140
DBP < 90
≥ 80 years
SBP≥ 150
DBP ≥ 90
SBP 140 – 145 if tolerated
May consider < 140 in some patients*
Should avoid SBP < 130 and DBP < 60
* “In those elderly patients in whom a SBP < 150mmHg is readily and safely obtained with just 1 or 2 drugs, a further modest
intensification of treatment to achieve a value < 140mmHg could be considered, even though there is no firm evidence to support
this target.”
** “There is no evidence in older people to support the use of lower BP targets in patients at high risk because of conditions such as
diabetes mellitus, CKD, or CAD.”

Special circumstances for SBP goal of ≥ 150mmHg:



Already on 4 well-selected and appropriately dosed drugs
Unacceptable side effects, especially postural changes
DBP drops to ≤ 65 in effort to achieve SBP goal
Aronow WS. Circulation. 2011;123:2434-2506

Consider general health & frailty when deciding whether to treat

Trial lifestyle modification first

Medication selection in the general population
SBP < 160 and DBP < 100
SBP > 160 or DBP > 100
Ace Inhibitor (ACE-I)
Angiotensin Receptor Blocker (ARB)
Calcium Channel Blocker (CCB)
Thiazide (THIAZ)
Combination
Combination therapy with 2 drugs
likely needed if 20mmHg/10mmHg or
more above target
Amlodipine + ACE-I or ARB may be
preferred to diuretic combination, but
either is acceptable
Aronow WS. Circulation. 2011;123:2434-2506

Special Population Treatment Recommendations
Compelling Indication
Initial Therapy Options
Heart Failure
THIAZ, beta blocker (BB), ACE-I, ARB, CCB,
aldosterone antagonist (ALDO ANT)
Post MI
BB, ACE-I, ALDO ANT, ARB
CAD or high risk for CVD
THIAZ, BB, ACE-I, CCB
Angina
BB, CCB
Aoropathy/Aortic aneurysm
BB, ARB, ACE-I, THIAZ, CCB
Diabetes
ACE-I, ARB, CCB, THIAZ, BB
Chronic Kidney Disease
ACE-I, ARB
Early Dementia
Blood pressure control
Aronow WS. Circulation. 2011;123:2434-2506
Limitations to Achieving
Treatment Goals
The Statistics

Almost half of patients become non-adherent
to their antihypertensive medication within 1
year of initiating therapy

In patients with hypertension, 10% of poor
compliance was due to adverse effects of
prescribed medication
Aronow WS. Circulation. 2011;123:2434-2506
Choudry NK. Circulation. 2011;123:1584-1586.
What may influence a patient?







Adverse effects (actual or fear of experiencing)
Complexity of therapeutic regimen
Cognitive impairment
Misperceptions of benefits or risks of treatment
Poor provider–patient relationship
Cost
Difficulties accessing physicians or pharmacies
Aronow WS. Circulation. 2011;123:2434-2506
Choudry NK. Circulation. 2011;123:1584-1586.
Adverse Effects
Medication Class
Adverse Effects
Thiazide and Loops Diuretics
Hypokalemia, hyponatremia, hypomagnesemia, renal
impairment, hypotension, hyperuricemia, hyperglycemia
Aldosterone antagonists
Hyperkalemia, hypotension
Beta blockers
Sinus bradycardia, fatigue, AV nodal heart block,
bronchospasm, intermittent claudication, confusion,
aggravation of acute heart failure, hyperglycemia
Ace Inhibitors
Cough, hyperkalemia, angioedema, rash, altered taste
sensation, renal impairment
Angiotension receptor blockers
Hyperkalemia, renal impairment
Calcium channel blockers
(non – dihydropyridine)
Rash, exacerbation of GERD symptoms, sinus
bradycardia, heart block, heart failure, constipation,
gingival hyperplasia
Calcium channel blockers
(dihydropyridine)
Peripheral edema, heart failure, tachycardia, orthostatic
hypotension, headache, aggravation of angina pectoris
Aronow WS. Circulation. 2011;123:2434-2506
Ways to Help Promote Adherence

ASK: about adherence and any difficulties the
patient may be having with their medication

CONSIDER: possible patient concerns such as
complexity or cost. Try to use once – daily
regimens and lower cost generics/formulary items
if able.

REMIND: the patient about possible, but transient
side effects to reduce unnecessary discontinuation
Choudry NK. Circulation. 2011;123:1584-1586.
Equip Patients with Equipment

Assess if patient may benefit from equipment.
Make recommendations or supply if possible.
 Pillbox
to help manage medications
 Pill splitter if regimen calls for halving tablets
 Pill crusher if unable to swallow whole tablets
 Blood pressure cuff to monitor home pressures

If patient expresses concerns with remembering,
try to tie dosing to another routine daily event
Consider the Risk for Polypharmacy

Always monitor for the prescribing cascade
Pain NSAID started Develops HTN Anti-HTN started
 HTN + Hx Gout HCTZ started  Gout flare Allopurinol



Ask patients to bring medication bottles and any list to
their visits including any herbals or vitamins
“Any symptom in an elderly patient should be
considered a drug side effect until proved otherwise.”
Rochon PA. BMJ 1997;315:1096–9.
Gurwitz J. Long-Term Care Quality Letter. Providence (RI): Brown University, 1995.
Clinical Application
Case Study

BB is an 82 year old African American male presenting to your
outpatient clinic for a follow-up. Initial blood pressure on
presentation is 170/90.

Past Medical History





Dyslipidemia
Benign prostatic hyperplasia
Hypertension
Diabetes
Current medications:




Glipizide 5mg daily
Terazosin 4mg at bedtime
Atorvastatin 10mg at bedtime
Aspirin 81mg daily
Question 1


On recheck BB’s blood pressure is 172/90
What would be your threshold for initiation of
pharmacotherapy for BB?
 A.
130/80
 B. 140/90
 C. 150/90
Question 2

Based on multiple, appropriately checked blood
pressures above threshold and a trial of lifestyle
modification, you decide to treat.

Which treatment option would you choose?
A. Increase terazosin
 B. Hydrochlorothiazide
 C. Lisinopril + Hydrochlorothiazide
 D. Lisinopril + Amlodipine
 E. Amlodipine + Hydrochlorothiazide
 F. Lisinopril + Losartan

Question 3

BB expresses concerns regarding managing his
new medications at home.

What suggestions can you make to help him to
remember to take his medications?
Question 4 – Part 1


After several weeks on therapy, BB telephones
you to follow-up with home BP readings.
He reports the following:
 140/68,

145/72, 146/80, 142/76
What other questions would you want to ask BB
before making decisions regarding treatment?
Question 4 – Part 2

What is your response to BB’s blood pressure
readings from home?
 A.
Blood pressures are at target, continue therapy
 B. Blood pressures not yet at target, titrate therapy
 C. Blood pressures too low, decrease dose
Putting It All Together
Summary of Guidelines and Evidence

Treatment of hypertension in the very elderly has shown significant benefits
on stroke and cardiovascular risk

A treatment threshold of 150/90 appears to be reasonable in the elderly

Thiazide diuretic remains a good first-choice option for most

Lowering blood pressure likely more important than choice of add-on agent

Start low and go slow, monitor closely for adverse effects

Consider factors which may impact adherence to medication when choosing
the initial medication and add-on therapies
References

Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics—2009 update:
a report from the American Heart Association Statistics Committee and Stroke Statistics
Subcommittee. Circulation. 2009;119:e21–181.

Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 Expert Consensus Document on
Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task
Force on Clinical Expert Consensus Documents. Circulation. 2011;123:2434-2506.

O’Rourke MF, Hashimoto J. Mechanical Factors in Arterial Aging: a Clinical Perspectives. J Am
Coll Cardiol. 2007 Jul 3;50(1):1-13. Epub 2007 Jun 18.

SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in
older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in
the Elderly Program (SHEP). JAMA. 1991; 265 (24):3255-64.

Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age
or older. N Engl J Med. 2008;358:1887-1898.

ALLHAT Study Group. Major outcomes in high-risk hypertensive patients randomized to
angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. JAMA.
2002;288:2981–97.
References

Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide
for hypertension in high-risk patients. N Engl J Med. 2008;359:2417–28.

Denardo S, Gong Y, Nichols WW, et al. Blood pressure and outcomes in very old hypertensive
coronary artery disease patients: an INVEST substudy. Am J Med. 2010;123:719 –26.

Systolic Blood Pressure Intervention Trial. Sprint Trial Website. http://www.sprinttrial.org.
Accessed April 1, 2014.

James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of
High Blood Pressure in Adults Report from the Panel Members Appointed to the Eighth Joint
National Committee (JNC 8). JAMA. 2014;311(5):507-520.

Chobanian AV, Bakris GL, Black HR, et al. and the National High Blood Pressure Education
Program Coordinating Committee. The Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.
JAMA. 2003;289:2560-2572.

Choudry NK. Promoting Persistence: Improving Adherence Through Choice of Drug Class.
Circulation. 2011;123:1584-1586.

Rochon PA, Gurwitz JH. Optimizing Drug Treatment for Elderly People: the Prescribing
Cascade. BMJ. 1997; 315: 1096-9.

Gurwitz J, et al. Long-Term Care Quality Letter. Providence (RI): Brown University, 1995.
Leslie Bittner, Pharm.D., BCPS
[email protected]
NEONP Conference
April 25, 2014