leslie bittner, pharm.d., bcps [email protected] neonp conference april 25, 2014

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 impairmentLloyd-Jones D. Circulation. 2009;119:e21-181Aronow WS. Circulation. 2011;123:2434-2506

Pathophysiology of HTN in the Elderly

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

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 yearsSHEP Research Group. JAMA. 1991;265:3255-3264.

Systolic Hypertension in the Elderly Program (SHEP)

Results Total 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)

Study Conclusion Decreasing blood pressure using low-dose

chlorthalidone as initial medication showed reduced risk of stroke and cardiovascular events over a 5-year 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 Mean age = 83.6 years Baseline average BP = 173/90.8mmHg

Intervention: 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

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

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

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 lineALLHAT 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 eventsJamerson 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

* If treatment lowers BP further (for example SBP < 140), but no adverse effects or quality of life impact – no need to adjust treatment

Age Threshold for Treatment Initiation

≥ 60 years SBP ≥ 150*DBP ≥ 90*

< 60 years SBP ≥ 140DBP ≥ 90

≥ 18 years old with Chronic Kidney Disease

SBP ≥ 140DBP ≥ 90

≥ 18 years old with Diabetes

SBP ≥ 140DBP ≥ 90

James PA. JAMA. 2014;311(5):507-520.

Trial lifestyle modification and continue throughout

Medication selection

*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

BP not at goal, Non – Black (+/- diabetes)

BP not at goal, Black (+/- diabetes)

Chronic Kidney Disease

Thiazide Diuretic (THIAZ)Ace Inhibitor (ACE-I)Angiotensin Receptor Blocker (ARB) Calcium Channel Blocker (CCB)

Alone or in Combination**

THIAZCCB

Alone or in Combination

ACE-IARB

Alone* or in Combination**

James PA. JAMA. 2014;311(5):507-520.

Some key changes from JNC 7 GuidelinesJNC 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 discussedChobanian AV. JAMA. 2003;289:2560-2572.

James PA. JAMA. 2014;311(5):507-520.

Elderly – specific guidelines

* “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

Age Threshold for Treatment Initiation**

Treatment Target

55 – 79 years SBP≥ 140DBP ≥ 90

SBP < 140DBP < 90

≥ 80 years SBP≥ 150DBP ≥ 90

SBP 140 – 145 if toleratedMay consider < 140 in some patients*Should avoid SBP < 130 and DBP < 60

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 populationSBP < 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


Special Population Treatment RecommendationsCompelling 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


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;123:2434-2506Choudry 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

pharmaciesAronow 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


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.

MANAGEMENT OF HYPERTENSION IN THE ELDERLY

Leslie Bittner, Pharm.D., BCPS

[email protected]

NEONP Conference

April 25, 2014