Transcript The Risk of Hip Fracture after Initiating Antihypertensive Drugs in the

“THE RISK OF HIP FRACTURE
AFTER INITIATING
ANTIHYPERTENSIVE DRUGS IN
THE ELDERLY”
Journal Club
Mallory McClester, PGY-4
August 16, 2013
Objectives
 Review the article contents
 Discussion of article critically
 Feedback from the group
 Final conclusions
Background
 More than 50% of all adults >65 have
hypertension.
 Likelihood of developing htn during the
average lifespan is >90%.
 Hypertension, antihypertensive drugs, and
fall injury form a complicated triad.
Background
 Hypothesis: Initiating antihypertensive
agents in the elderly has been associated with
an increased risk of falls, and therefore
increased risk of hip fracture.
Methods
 Population based, self-controlled case series
 Prescription Drug Database used to identify
all Ontario residents aged 66+, initiating antihypertensive
 All patients with other conditions for which
an anti-hypertensive drug may be used were
excluded
Methods
 Cases: First occurrence of hip fx from
4/1/2000-3/31/2009
 Linked to: Cohort of newly treated
hypertensive elderly patients
 To clarify, first patients over the age of 66
starting an antihypertensive were identified.
From that, cases of hip fractures were studied
specifically.
Methods
 High risk period
 45 days immediately following antihypertensive
initiation, observe closely for orthostatic
hypotension
 Control period (low risk, unexposed)
 3 consecutive 45 day periods in preexposure and
postexposure
 Total observation period was 450 days
From: The Risk of Hip Fracture After Initiating Antihypertensive Drugs in the Elderly
Arch Intern Med. 2012;172(22):1739-1744. doi:10.1001/2013.jamainternmed.469
Figure Legend:
Figure 1. Antihypertensive drug use and hip fracture risk: self-controlled case series design. Time division for each patient is
included to assess incidence of first acute hip fracture in relation to antihypertensive prescription. All patients in the analysis had at
least 1 prescription for an antihypertensive drug and a single incident hip fracture.
Date of download: 8/14/2013
Copyright © 2012 American Medical
Association. All rights reserved.
Results
 301,591 newly treated Ontario hypertensive
elderly pts identified
 Mean age (SD): 81 (7.3)
 Gender: Females (80.7%)
Results
 Hypertensive Elderly patients with hip fx:
 Most exposed to ACE inhibitors (30.1%)
 Least exposed to ARBs (4.4%)
 This study shows that patients starting
treatment had a 43% increased risk of hip
fracture during the first 45 days of treatment.
From: The Risk of Hip Fracture After Initiating Antihypertensive Drugs in the Elderly
Arch Intern Med. 2012;172(22):1739-1744. doi:10.1001/2013.jamainternmed.469
Figure Legend:
Date of download: 8/14/2013
Copyright © 2012 American Medical
Association. All rights reserved.
Results
 Incident Rate Ratio consistent among the 5
different classes of antihypertensive drugs
 Only ACE-I and Beta-blockers were statistically
significant
From: The Risk of Hip Fracture After Initiating Antihypertensive Drugs in the Elderly
Arch Intern Med. 2012;172(22):1739-1744. doi:10.1001/2013.jamainternmed.469
Figure Legend:
Figure 2. Forest plot of antihypertensive drugs and hip fracture risk using incidence rate ratios with 95% CIs. Each data point and
95% CI (error bars) represent results from the conditional Poisson regression analysis. The line at 1.0 represents no association;
estimates to the right of the line represent an increased risk of hip fracture. ACE indicates angiotensin II converting–enzyme; ARB,
angiotensin II receptor antagonist/blocker; BB, β-adrenergic blocker; and CCB, calcium channel blocker.
Date of download: 8/14/2013
Copyright © 2012 American Medical
Association. All rights reserved.
From: The Risk of Hip Fracture After Initiating Antihypertensive Drugs in the Elderly
Arch Intern Med. 2012;172(22):1739-1744. doi:10.1001/2013.jamainternmed.469
Figure Legend:
Date of download: 8/14/2013
Copyright © 2012 American Medical
Association. All rights reserved.
From: The Risk of Hip Fracture After Initiating Antihypertensive Drugs in the Elderly
Arch Intern Med. 2012;172(22):1739-1744. doi:10.1001/2013.jamainternmed.469
Figure Legend:
Figure 1. Antihypertensive drug use and hip fracture risk: self-controlled case series design. Time division for each patient is
included to assess incidence of first acute hip fracture in relation to antihypertensive prescription. All patients in the analysis had at
least 1 prescription for an antihypertensive drug and a single incident hip fracture.
Date of download: 8/14/2013
Copyright © 2012 American Medical
Association. All rights reserved.
Discussion
 Demonstrates immediate increased risk of
hip fracture on initiation of antihypertensive
tx in community dwelling hypertensive
elderly patients.
 Main mechanism supported is orthostatic
hypotension leading to falls.
Discussion
 Thiazide diuretics:
 No statistical difference
 ACE inhibitors
 First dose hypotension? related to venodilation
 Beta blockers
 Likely Less effective in controlling hypertension in
elderly
Discussion
 Identified Strengths of Study
 Large population based study (301,591)
 10 year period
 Self controlled case series allowed for study of this
association
 Selection bias avoided (only used cases)
 Removed fixed covariates
 Identified Limitations
 Patients may have been exposed to antihypertensives
before age 65
 Drug Samples?
 No investigation of specific subclasses of medications
Critically Speaking
 Why is this relevant?
 Using these medications is beneficial long term
even if short term risk may be increased
Relevance:
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 (140-159/9099) and 40% risk of stage 2 HTN (>160/100)
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….
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
 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)
Discussion
 So looking more closely at the study data and
applying this information:
 Roughly 300,000 patients
 1436 have hip fractures
 143 occurred during “risk period”
 104 occurred during washout period
 Therefore, of 300,000 patients, it seems that
the risk of antihypertensive agents may have
contributed to 39 more hip fractures.
Any thoughts from the audience?
Conclusions
 This study supports that there is atleast to some
degree an increased risk of hip fracture after patients
initiate anti-hypertensive agents, most likely
secondary to orthostatic hypotension.
 No data to support that the risk actually outweighs
the benefit of these medications
 Use caution when beginning anti-hypertensive
agents and warn your patients of side effects.
 May be beneficial to actually check all of our
patient’s blood pressures while they are standing.
References

Butt D, Muhammad M et al. The Risk of Hip Fracture After Initiating Antihypertensive Drugs in the
Elderly. JAMA Internal Medicine. 2012; 172(22): 1739-1744.

Hemmelgarn BR, Chen G, Walker R, et al. Trends in antihypertensive drug prescriptions and
physician visits in Canada between 1996 and 2006. Can J Cardiol. 2008;24(6):507-512.

Wolf-Maier K, Cooper RS, Banegas JR, et al. Hypertension prevalence and blood pressure levels in
6 European countries, Canada, and the United States. JAMA. 2003;289(18):2363-2369.

Beckett N, Peters R, et al. Treatment of Hypertension in Patients 80 Years of Age and Older. New
England Journal of Medicine. 2008; 358(18): 1887-1898.

Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes
on falls in elderly persons. Arch Intern Med. 2009;169(21):1952-1960.

Tinetti ME, Williams CS. Falls, injuries due to falls, and the risk of admission to a nursing home. N
Engl J Med. 1997;337(18):1279-1284