Transcript Treatment of Hypertension in Patients over the age of 80

Treatment of
Hypertension in
Patients over the age
of 80
Debra Bynum, MD
Associate Professor
Division of Geriatric Medicine
The “Case”…

At grand rounds, a well respected geriatrician
presents an 84 year old who is functional and
independent, but having falls…

He has uncontrolled Systolic HTN

He is not orthostatic

He has evidence on scan of old cerebellar infarcts…

The recommendation for antihypertensive therapy
creates a stir in the audience…
Grand Rounds…

Audience remarks:
 We
should focus on making him
comfortable
 Everyone
 Is
has to die of something
there any evidence to support the
treatment of Hypertension in patients over
the age of 80?
Questions…

Is there ageism, even among well respected
physicians?

What is the average life expectancy of an otherwise
functional, independent 84 year old?

Is there evidence to support the treatment of
hypertension in patients over the age of 80?

What should the goals of treatment be in patients
over the age of 80?
Does ageism still exist?
What about current life
expectancy?
The Beat goes on…
Life expectancy… What we can
really expect

At birth, average life expectancy in US: 74 for
men, 79 for women

But…
 Average
65 y/o man will live to 82, woman to 85
 Average 75 y/o man will live to 85, woman to 88
 Average 85 y/o man will live to 91, woman to 92
 Average 90 y/o man will live to 94, woman to 95
 The
older you are, the older you are likely to be…
Take home..

The average 80 year old is likely to live
to 90

10 years… makes issues of treating or
not, screening or not very real (we are
not talking last year of life for most)
Is there evidence to support the
treatment of hypertension in patients
over the age of 80?
The controversy: Background

Systolic Hypertension in the Elderly so
common that once considered normal part
of aging

Previously : “Isolated Systolic
Hypertension”

1980: JNC on HTN defined ISH as SBP >160
with DBP <90
JNC 7 classification…
Classification
SBP
DBP
Normal
<120
And <80
PreHypertensio 120-139
n
Stage 1 HTN
140-159
Or 80-89
Stage 2 HTN
Or >100
>160
Or 90-99
Systolic Hypertension

Defined as SBP > 140 with DBP <90

No longer referred to as “Isolated”
How Common is Systolic
Hypertension?

Prevalence of HTN increases with age

67% over age 60 and ¾ of those over the age of 70
have HTN (National Health and Nutrition
Examination Survey: NHANES)

SH accounts for 75% of HTN in those over 65

Lifetime Risk Statistic:

Normotensive 65 year old adult who lives to age 85:
90% lifetime probability of developing stage 1 HTN
(140-159/90-99) and 40% risk of stage 2 HTN (>160/100)
PreHypertension

People over age 65: 26% four year risk of
HTN if BP 120-129/80-84

Those over age 65 with BP 130-139/85-89:
50% four year risk of HTN

Patients with BP 130-139/85-89 have twice
the risk of CVD events compared to those
with normal BP
Importance of the SBP

Continued increase in SBP with age (likely due to
increased arterial stiffness)

Level/decrease in DBP with age (after 50-60)

After age 50, SBP is much more important risk factor
for CV events than DBP

SBP more often poorly controlled than DBP
(difficulty in management plus physician attitudes);
Almost ALWAYS takes more than one medication…
SBP…

Framingham data from 1976 and meta-analysis of
60 observational studies: SH major risk factor for
stroke

Initial concern that SBP lowering would lead to
increased stroke in patients over age 80 NOT
SHOWN
Systolic Hypertension

JNC 7 clear in report: SH in patients over the age
of 60 much more important than DBP

SH assoicated with increased risk of CAD, LVH,
renal insufficiency, stroke, and CV mortality

SH more closely associated with CV risk than DBP
in older patients (even in older patients with
diastolic hypertension)
SH: Summary

SH more common in older patients

SH more closely correlated with CV and
stroke events

DBP drops with age

SH more difficult to control; If SH controlled,
DBP usually controlled
Why treat… the data

SHEP trial : 1991
 5000
patients, SBP 160-190, DBP <90, mean age
72
 Chlorthalidone
(thiazide) vs placebo
 Second
agents: atenolol, reserpine
 Primary
endpoint: stroke
 Significant
decrease in 5 year incidence of all
strokes (8% vs 5%, ARR 3%)
SHEP…

Reduction in Heart Failure
 2.3%
vs 4.4 %
 ARR 2%
 NNT 48
SHEP trial…

32 % Relative Risk Reduction and 5% Absolute
Reduction in total combined CV events (secondary
outcome)

NNT: need to treat 18 people over 5 years to
prevent 1 major cardiovascular or cerebrovascular
event

?underestimation: goal BP only reached in 70%
treatment group; 44% placebo group also treated
(intention to treat analysis)
Additional data…


Systolic Hypertension in Europe
Systolic Hypertension in China

All demonstrated decreased risk of stroke
and combined CV events in older patients
treated for SH

None powered to demonstrate difference in
all cause or cardiovascular mortality
Treatment of SH decreased
strokes…

SHEP data: both hemorrhagic and
ischemic strokes decreased

Immediate effect on bleeds seen

2 years needed to see full effect of
reduction in ischemic stroke
Treatment of ISH in the elderly:
Meta-analysis of outcome trials








SHEP
Syst-Eur
Syst-China
EWPHE (European Working Party on High Blood
Pressure in the Elderly)
HEP (HTN in Elderly Patients in Primary Care)
STOP (Swedish Trial in Old Patients with HTN)
MRC1 (Medical Research Council trials in mild HTN)
MRC2 (in older adults)

Lancet 2000
Meta-analysis

8 trials, over 15,000 patients with SH

Median follow up 3.8 years

Treatment decreased mortality by 13%,
stroke by 30%
NNT for 5 years to prevent one
major CV event….
Summary…

Treatment of SH in older patients with
SBP over 160 is beneficial

Largest benefit when treating patients
over age 70, men, and those with prior
cardiac events (higher risk=highest
benefit)
Will lowering the BP too much
cause harm?
1. Decreasing SBP
 2. Decreasing DBP
 3. Increasing PP (pulse pressure)

SBP

Longitudinal studies show elderly with the
lowest SBPs may have higher mortality (J
curve)

Problem: Patients with the lowest SBP
may be more likely to have more serious
underlying comorbidities
INVEST

International Verapamil SR Trandolapril
Study

Comparing beta blockers (atenolol) vs ca
channel blockers

Over 2000 of the 22,000 patients were
over the age of 80
INVEST

Overall greatest proportion of patients with
primary outcome (mortality/nonfatal MI/CVA)
found in those over 80 (23%)

J shaped relationship between BP and outcome

SBP <140 and DBP <70 associated with
increased HR
Will lowering the DBP cause
harm?
Population studies suggested lower DBP in
older patients associated with worse
outcomes
Low DBP…

Meta-analysis of 8 trials, over 15,000
patients from Lancet 2000

DBP inversely correlated with total
mortality (independent of SBP)
Pulse pressure…
Observation studies show patients with highest PP
(difference between SBP and DBP), especially when
over 50, have worse outcomes

Trials: those who had CV event on treatment were
more likely to have lower DBP and higher pulse
pressure (DBP < 68 and PP >50) than those without
CV event in tx group

SHEP: increase in CV events in treatment group if
DBP <60
Is “overtreatment” risky?

Patients with lower DBP and high PP who were in
placebo group also had higher rates of vascular
events

Risk of events in patients with lower DBP on
treatment still less than that in the placebo group!

Lower DBP and Higher PP likely more of a marker for
bad outcomes (stiffness of arteries)
Back to the question: Should we
treat those over the age of 80?

Observation that the very old with low BP have higher mortality

Fear of increased risk of side effects (orthostasis and falls)

JAGS 2007: retrospective cohort study of VA patients over age
80 found lower 5 year survival in patients with lower BPs

Concern that association between SH and stroke is not as
strong in those over 80 compared to those 65-80

INDANA subgroup meta-analysis (Lancet 1999): reduced stroke
and heart failure but 14% increase in all cause mortality; Used
high dose diuretics and beta blockers…
There is always a Big But…

But…This group has highest
ABSOLUTE risk of CV event, heart
failure and stroke -- leading to possible
greater ARR with treatment (risktreatment paradox)
HYVET: Hypertension in the Very
Elderly Trial

RCT of nearly 4000 patients from Europe, China,
Australia, Tunisia


Age over 80
SBP > 160

Indapamide vs placebo

ACE inhibitor (perindopril) or placebo added as
second agent when needed

Primary endpoint: stroke
HYVET…

Mean age : 83

Mean standing BP: 173/90

12% had hx of CV disease

1.8 year follow up

Treatment group: 15/6 lower BP
HYVET: results
Endpoint
Treatment (rate per
1000 patient-year/#
events)
Placebo
Stroke
12.4 (51)
17.7 (69)
Death from stroke
6.5 (27)
10.7 (42)
Mortality
47.2 (196)
59.6 (235)
Death from CV cause
23.9 (99)
30.7 (121)
Any MI
2.2 (9)
3.1 (12) p=.45
Any heart failure
5.3 (22)
14.8 (57)
Any CV event
33.7 (138)
50.6 (193)
Any CV event:
Death from CV cause,
stroke, MI, CHF
HYVET results…

30% decrease in rate of fatal or nonfatal stroke

39% decrease in rate of death from stroke

21 % decrease in all cause mortality

23% decrease in CV death

64% decrease in heart failure

Fewer adverse events in treatment group
HYVET… additional points

Target SBP of <150

Only 50% treatment group reached target SBP

Excluded patients with SBP over 200

Followed standing BP to keep over 140

7.9% in treatment group vs 8.8% in placebo group
had orthostatic hypotension
HYVET: Take Home points

Overall number of events small (healthy population
of elderly)

Stroke: ARR of almost 1% (NNT near 100 over 2
years to prevent one stroke)

Older patients more likely to die from stroke

All cause mortality (secondary outcome): ARR 1.2 %
(NNT about 80): Some concern about this finding
based upon results of other studies…
Recent Meta-analysis of Treatment
of patients over the age 80

Primary outcome: total mortality

Secondary outcomes: coronary events, CV
events, CVA, CHF, cause specific mortality

Over 6000 patients in 7 studies

Journal of HTN 2010
Meta-analysis of patients over 80…

Biggest differences:
 Decrease
in CVA (35% RRR)
 Decrease in CV events (27% RRR)
 50% decrease in CHF

ARR 3 % over 5 years for stroke prevention

Did not show improvement in mortality, but also
did NOT show worse mortality….
Treating over 80: summary

There is evidence that those over 80 have
similar reductions in bad outcomes as in
those 60-80 (and may have greater
absolute reductions)

Although mortality may or may not be
improved, there is a consistent theme of
decreased risk of stroke, CHF, and CV
events
What should the target BP in
those over 80?

JNC 7: recommends overall similar treatment
guidelines for the elderly (goal SBP under 140)

But, NO study has looked at patients with
baseline BP of <160

Average SBP achieved in large RCTS: 143

No trial achieved average SBP of <140
Valsartan in Elderly Isolated Systolic
Hypertension Study (VALISH)

Compared CV mortality and morbidity in eldelry
patients with SH with strict control (SBP<140) vs
moderate control (140-150) goals

3000 patients (70-85), 2.8 year follow up

SBP 136 in tight control, 142 in moderate control
group achieved

No difference in outcomes…
Target BP

HYVET: Target SBP of 150

INVEST: increased risk seen with SBP <140
(not compared to placebo….)

VALISH: no difference in outcomes with
stricter control

Reasonable goal of SBP 150
Summary

Systolic hypertension in older patients is common
and difficult to treat

There is strong evidence that treatment of SH in
patients over 65 reduces risk of CVA and CHF

There is now strong evidence that treating SH in
patients over the age of 80 also reduces the risk of
stroke and heart failure

Although the evidence is not strong that treating
decreases mortality, there is no evidence that
treatment increases mortality in those over 80
Summary…

The association between stroke and SH may not as
strong in older patients as those in midlife, but the
higher absolute risk of stroke and heart failure push
toward treating

Balance risk of orthostasis and falls – but patients in
the HYVET study who were not orthostatic benefited
with SBP in the 140 - 150 range!

Stroke reduction is not insignificant in a patient who
on average may live another 10 years, reducing the
potential for disability and placement in addition to
mortality
Summary:

Patients with the highest risk (those over 70,
men, those with prior CV events, and those
with a high PP) actually may stand to gain
the most from treatment…

Even modest treatment goals may have
significant benefit
Recommendations…

Check and follow BP while standing

Remember diet/lifestyle changes

Treat patients with SBP >160 with medications (start
with thiazide or ACE or Ca channel blockers)

Target BP in those over 80: 150

Recognize that patients with DBP <60 or PP >50 have
a higher risk of CV events, but not clear if this can be
modified
Questions and Discussion…