Managing Hypertension in the Elderly: How to Best Achieve Control

Objectives
Review the pathophysiology of

hypertension in the elderly

Review the benefits of treatment
Relate unique aspects of management for

older patients

Epidemiology
Most common primary care diagnosis

35 million office visits per year

Improved awareness, treatment and

control over last 25 years

51 31 10 70 percent aware of HTN 59 percent treated for their HTN 34 percent with controlled HTN

Goal is to achieve 50 percent in control More important to control SBP > 50 years

Epidemiology
HTN affects 50 million US, 1 billion

world If normotensive at 55, 90% lifetime risk to develop HTN The higher the BP, the greater the risk of MI, CHF, stroke, kidney disease. Age 40-70, BP 115/75 to 185/115
Increase in 20 mm SBP doubles CVD risk Increase in 10 mm DBP doubles CVD risk

BP Measurement
Home BP checks Helpful >135/85 = HTN Check for accuracy

Ambulatory BP Evaluate white-coat HTN etc HTN = 135/85 awake HTN = 120/75 asleep Normal BP falls 10-20% Better correlation with endorgan injury

Case #1
68 year Afri-Amer male Type 2 diabetes mellitus for 5 years No nephropathy No CV history On atorvastatin 80 mg and LDL is 80 BP is 148/98 last visit and now 150/98 Diagnosis? Stage 1 hypertension

Classification of BP
Normal <120 and <80 Prehypertension Rx for DM or CRF 120-139 or 80-89 Stage 1 Hypertension begin Rx here 140-159 or 90-99

Stage 2 Hypertension > 160 or > 100

Classification
Isolated systolic hypertension Systolic BP of > 140 mm Hg AND Diastolic BP < 90 mm Hg 76 percent of HTN patients Widened pulse pressure (more than 50) Independent CV risk factor Low diastolic BP (lower than 70) Independent CV risk factor

Pathophysiology
Hypertension in the Elderly Increase in arterial stiffness (large arteries) Sympathetic activation Large arteries dilate and thicken Intimal hyperplasia Leads to increased systolic BP and

widened pulse pressure and morbidity

CV mortality

Pathophysiology
Hypertension in the Elderly
Increased total PVR Decrease in cardiac output Lability of BP due to decreased baroreceptor function Dysfunction of autoregulation in brain, heart and kidneys

Affects choice of treatment for HTN

Pathophysiology
Hypertension in the Elderly Average BP 65-94 years old
Men = 133 +/- 19 / 77 +/- 11 Women = 134 +/- 19 / 76 +/- 10

White coat hypertension Occurs in 42 % of patients over 65 Hypertension at an outpatient clinic and documented BP readings below 134/90 out of clinic Prognosis and end-organ damage same as normotensive patients

Pathophysiology
Hypertension in the Elderly Pseudohypertension
Advanced arterial stiffness Arteries not compressed by arm cuff BP readings higher than direct

Oslers sign
Pump arm cuff and feel brachial artery If palpable but without beats, may indicate pseudohypertension Difficult to reproduce

Treatment
Goals of therapy
Reduce CV and renal morbidity and mortality

Reduce vascular dementia in elders

Focus on reducing SBP Goal is <140/90, <130/80 with diabetes, renal disease

Benefits of Therapy
Treatment decreases Stroke by 35-40% MI by 20-25% CHF by 50%

NNT for stage 1 11 patients in 10 years with a 12 mm decrease in SBP to prevent 1 death.
NNT with CVD etc. 9 patients

Evidence for Elderly and ISH

Treat 19 for 5 years
Prevent 1 CV event

Treat 50 for 5 years

Prevent 1 CV death

Treat 63 for 5 years

Prevent 1 all cause death

Benefits of Therapy
Outcome CV mortality CBV mortality CHD mortality CV M & M CBV M & M CHD M & M Total mortality Age >60 5y NNT 58 193 88 21 46 68 72 Age <60 5y NNT 205 365 NS -468 184 167

Treatment
Treatment goals in elderly Controversial How low is too low? HOT trial 1998 (mean age 61.5)
Best effect at 130-140/80-85

SHEP trial 2000 (mean age 71.6)

No increase stroke protection from 150-140 SBP DBP <55 twice the rate of CV events

PATE-Hypertension 2000
SBP <130 increase CV events

Treatment
Possible goals
Age (years) 60-69 70-79 >80

SBP

140

150

160

DBP

90

90

90

Ogihara et al. Guidelines for treatment of hypertension in the elderly - 2002 revised version. Hypertens Res 2003;26:1-36.

Case #1
68 year Afri-Amer male Type 2 diabetes mellitus for 5 years No nephropathy No CV history On atorvastatin 80 mg and LDL is 80 BP is 148/98 last visit and now 150/98 Treatment? Lifestyle, medications

Treatment
Lifestyle modifications
Weight reduction - C
DASH eating plan (rich in K+ and Ca++) www.nhlbi.nih.gov - A

Reduce dietary sodium

Increase physical activity - A Moderate alcohol consumption Smoking cessation - A

DASH eating plan is similar to

monotherapy for BP reduction

Treatment
Paced breathing

14/8 mm Hg reduction after 4 weeks

Evidence Case reports Uncontrolled studies Not better than placebo with T2DM All studies small Very low risk!

Treatment
Pharmacologic treatment These meds have been shown to work
ACE inhibitors

Thiazide diuretics
Beta blockers Calcium channel blockers Angiotensin-receptor blockers

Treatment
Thiazide diuretics
Basis of most outcome trials Unsurpassed in preventing CV complications of HTN. JNC VII Enhance the efficacy of multidrug regimens

Do not widen pulse pressure in ISH

Affordable but underused

Treatment
First line medications uncomplicated

hypertension
THIAZIDE DIURETICS!!! Consider
ACE Inhibitor ARB CCB Beta-blocker Combination

Treatment
Second line medications THIAZIDE DIURETICS!!! Addition of
ACE Inhibitor ARB CCB Beta-blocker

Consider 2 drugs initially when BP is

more than 20/10 above goal

Treatment Trials
ALLHAT Double blind RCT Sponsored by NHLBI 42,418 age >55 with one CHD risk factor Amlodipine or lisinopril or doxazosin
VS.

Chlorthalidone Step 2 Atenolol or clonidine or reserpine Step 3 - Hydralazine

Treatment Trials
ALLHAT Doxazosin terminated early due to much higher incidence of CHF Nearly 5 year follow up of other arms No difference in primary endpoint of combined fatal CHD or nonfatal MI Diverse population, high percent with DM
35% African American 47% women

Treatment Trials
ANBP2 Open label RCT Sponsored by Australian Dept of Health and Merck, Sharp, Dohme 6083 65-84 with low CV risk profile ACEI (enalapril) vs. Diuretic (HCTZ) Step 2 blocker or blocker or CCB Step 3 Nonstep 2 drugs or diuretic in ACEI Step 4 Nonstep 2 or 3 drugs

Treatment Trials
ANBP2 Followed for median 4.1 years Primary endpoint changed
Initial protocol Total CV events including CV death; secondary endpoints-death & CHD events Final pub All CV events and all cause death

Marginally lower primary endpoint for ACEI

56.1 vs 59.8 per 1000 patient years Lower stroke rate for diuretic
Sawicki. Have ALLHAT, ANBP2 ASCOT-BPLA, and so forth improved our knowledge about better hypertension care? Hypertension 2006;48:1-7.

Treatment Trials
ANBP2
Validity issues
Question of primary endpoints measured

Open label design may have induced bias as data collection supported by sponsor/maker of ACEI
Diuretic use was permitted in the ACEI group

Superiority of ACEI over diuretics not demonstrated

Treatment Trials
ASCOT-BPLA Open label RCT
Sponsored by Pfizer 19,257 40-79, > 3 CV risk factors

Amlodipine vs. atenolol

Step 2 Add perindopril vs. thiazide + K

Step 3 - Doxazosin

Treatment Trials
ASCOT-BPLA Followed for 5.5 years, terminated early Primary endpoint nonfatal MI + fatal CHD
Amlodipine 8.2 per 1000 PY vs. atenolol 9.1 per 1000 PY, p = 0.105

Reduction noted in all cause mortality secondary endpoint

Amlodipine 13.9 per 1000 PY vs. atenolol 15.5 per 1000 PY, p = 0.025 Improved BP control in amlodipine arm led to better stroke, CV mortality, PAOD, total coronary endpoint and total CV events

Treatment Trials
ASCOT BPLA Validity issues
Protocol listed statistical significance for secondary endpoints as 0.01 Lipophilic blocker less effective Only 55% of patients with blocker + diuretic Open label design may have introduced bias Premature termination of trial may influence outcome

Does not prove superiority of amlodipine

based regimen
Sawicki. Have ALLHAT, ANBP2, ASCOT-BPLA and so forth improved our knowledge about better hypertension care? Hypertension 2006;48:1-7.

Thiazide Diuretics
Bendroflumethiazide Chlorothiazide

Chlorthalidone Hydrochlorothiazide

Hydroflumethiazide Methyclothiazide Metolazone Polythiazide Quinethazone Trichlormethiazide

Thiazide Diuretics
Chlorthalidone vs HCTZ
Chlorthalidone basis of landmark studies HCTZ more commonly prescribed

Chlorthalidone longer acting

Chlortalidone 1.5-2 times more potent
More effective BP control

No head to head studies

Treatment Trials in Elderly

12 Studies reviewed

Average BP drop 17/8 mm Hg

~30 % decrease in relative risk for CV disease CAD CHF Total CV diseases

Treatment Trials in Elderly

SHEP 1991, 4739 patients, 57% women
SBP 160-190, DBP<90 72 years

177/77

143/68, p<0.001

NNT to prevent stroke is 50 NNT to prevent CV event is 20 Agents

Chlorthalidone, atenolol, reserpine

Treatment Trials in Elderly

Sys-Eur 1997, 4695 patients, 67% women
SBP 160-219, DBP<95 70 years

174/85

151/78, p<0.001

NNT to prevent stroke is 100 NNT to prevent CV event is 50 Agents

Nitrendipine, enalapril, HCTZ

Treatment Trials in Elderly

Sys-China 1998, 2394 patients, 35% women SBP 160-219, DBP<95 66 years 170/86 150/81, p<0.001 NNT to prevent stroke is 50 NNT to prevent CV event is 50 Agents
Nitrendipine, captopril, HCTZ

Choice of Medications
STOP 2 - 2000 6614 patients, 70-84 years old Diuretics/Beta vs. ACEI vs. CCB No difference in outcomes or BP lowering SHELL - 2003 1882 patients, >60 Diuretic vs CCB No difference in outcomes or BP lowering

Choice of Medications
NICS EH - 1999 414 patients, > 60 years CCB vs. diuretic No difference in outcomes or BP lowering SCOPE - 2003 4964 patients, 70-89 years Candesarten vs. placebo and usual care No difference in BP lowering Decrease in non-fatal stroke in ARB

Treatment of the Old Old

HYVET 2008 Nearly 4000 patients Over 80 years old Systolic BP at least 160 mm Hg Target BP was 150/80 Agents vs. placebo
Indapamide SR 1.5 mg +/ Perindopril 2 4 mg

Treatment of the Old Old

HYVET
Primary endpoint any stroke Secondary all cause mortality, CV mortality, cardiac death Beneficial effects seen within 1 year No increase in serious adverse events
Different from pilot study reported in 2006

Treatment of the Old Old

HYVET Total of 2.1 years of therapy
Lowered BP by 15/6 mm Hg 30% decrease in primary endpoint (p=0.06) 39% decrease in stroke deaths (p=0.046) 21% decrease in all cause deaths (p=0.02)

23% decrease in CV deaths (p=0.06)

64% decrease in rate of HF (p<0.001) Fewer adverse events in Rx group (p=0.001)

Treatment of the Old Old

HYVET Recommendations Screen for HTN in elderly like anyone else Begin treatment if SBP is >160 mm Hg
Indapamide +/- perinodopril

Questions
Indapamide = HCTZ or chlorthalidone? Perindopril = lisinopril or ramipril? Is there a better agent for old old? Are results due to BP lowering alone? What is the ideal BP for old old?

Follow up
After treatment begun
Monthly visits until control achieved More frequently as needed Check K+/Cr 1-2 times a year BP in control, F/U 3-6 months

Low dose ASA ONLY when in

control to avoid stroke

Choice of Medications
Quality of Life
Complex, multifactorial, hard to measure Treatment not associated with significant impairment in QOL and can improve No class is clearly superior ACEI and ARBs
Cognition dementia and memory, not learning or perceptual processing
Sexual activity

Special Consideration
Hypertension with heart failure
Diuretic - A Beta blocker - A ACE inhibitor A, NNT = 43 ARB - A Aldosterone antagonist A, NNT = 50
SOLVD/SAVE, CIBIS, CAPRICORN, COPERNICUS, RALES, EPHESUS, MERIT-HF, CHARM

Special Consideration
Hypertension post MI
Beta blocker Std of Care - A ACE inhibitor A, stable & normal LV fxn Aldosterone antagonist B

BHAT, Norwegian Multi Center Study, PEACE, TRACE, SMILE, HOPE, EUROPA

Special Consideration
Hypertension with high CAD risk
Diuretic - A

Beta blocker - A
ACE inhibitor - B

CCB - B

Special Consideration
Hypertension with diabetes
Diuretic thiazide induced DM is more benign

Beta blocker - B
ACE inhibitor - A CCB - B ARB - A

Special Consideration
Hypertension with chronic kidney disease
ACE inhibitor - A

ARB A
Combine ARB and ACEI

Special Consideration
Hypertension & recurrent CVA prevent
Diuretic - A ACE inhibitor - B

Perindopril + indapamide B, RRR 43%

PROGRESS

 Question 1

Improving Control
Atmosphere of trust in relationship Understanding cultural beliefs of patient

Agreement on BP goals
Overcome clinical inertia to achieve goals Consider cost and complexity of care

Improving Control
Increase knowledge In 2001, 41% of primary care providers were not familiar with JNC 7 Identify and treat Only 30-49 percent controlled in US Less than 10 percent in developing countries

Focus on widespread and cost-effective

HTN care, not what agent is best

Resistant HTN
Failure to reach goal on 3 drugs

including a diuretic
Exclude potential identifiable causes

Explore reasons why goal not met

May need higher doses of diuretics with

kidney disease
Consider referral to HTN specialist

Conclusions
Persons over 50, SBP is more important Thiazide diuretics are the mainstay of

treatment, tailor to medical conditions

Most patients will need 2 or more drugs
Patients and providers must be motivated

Lowering BP in patients and populations

is more important than agent

BPLTTC, STOP-2

Questions

Case #1
68 year Afri-Amer male Type 2 diabetes mellitus for 5 years No nephropathy No CV history On atorvastatin 80 mg and LDL is 80 BP is 148/98 last visit and now 150/98

Diagnosis?
Evaluation? Treatment

Case #1
Diagnosis Stage 1 HTN Evaluation Check for smoking other CV risks Exam normal Labs are normal (CBC, chem, UA, ECG) Treatment DASH HCTZ vs ACEI vs CCB

 Question #2

Case #2
75 year old Latino female Type 2 diabetes for 10 years, poor control LDL at 167, no treatment No CV history, non smoker On metformin 1000 bid BP is 165/88, then 163/80

Diagnosis?
Evaluation? Treatment?

Case #2
Diagnosis Stage 2 ISH Assessment Exam normal except obese Normal labs except UA + for protein and ECG with evidence of LVH Treatment DASH HCTZ vs ACEI vs ARB vs CCB

 Question 3

HTN and LVH

PRESERVE Enalapril = nifedipine gts LIVE Indapamide SR > enalapril LIFE Losarten > atenolol

In reversing hypertensive LVH

Case #3
69 year old white male No medical history BP 145/105, 147/102 No meds Diagnosis? Evaluation?

Treatment?

Case #3
Diagnsis Stage 2 HTN Evaluation No CV risk factors Exam normal Labs normal except K= 2.1, repeat =2.0 No diuretics Further work up

Case #3
Diagnosis Stage 2 HTN Secondary HTN Aldosteronism
Primary adrenal adenoma, hyperplasia Secondary high renin, accelerated HTN

Plasma renin Low Saline load high aldosterone CT scan no adenoma Hyperplasia

Case #3
Treatment Sodium restriction Antimineralocorticoids
Sprinonolactone 25-100 mg tid

If adenoma seen, surgery

BP normal for last two years