treatment of hypertension in patients over the age of 80 debra bynum, md associate professor...
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Treatment of Hypertension in Patients over the age of 80Debra Bynum, MDAssociate 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 has to die of something
Is 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
PreHypertension
120-139 Or 80-89
Stage 1 HTN 140-159 Or 90-99
Stage 2 HTN >160 Or >100
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 (risk-treatment 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: resultsEndpoint 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…