cardiovascular disease in the older adult · primary cv prevention in older adults: aspirin ascend...
TRANSCRIPT
Cardiovascular disease in
the older adult:
DEDE PIERCE PHARMD BCPS BCGP
UR MEDICINE THOMPSON HEALTH
Considerations in prevention, treatment,
and deprescription
DISCLOSURES
NOTHING TO DISCLOSE
2
Abbreviations
CVD: cardiovascular disease
CVA: cerebrovascular accident/ ischemic stroke
ICH: intracranial hemorrhage
GIB: gastrointestinal bleeding
MACE: major adverse cardiac event
MALE: major adverse limb event
MI: myocardial Infarction
USA: unstable angina
HTN: hypertension
PP: primary prevention
CrCl: creatinine clearance
3
Learning objectives
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1. Discuss medical evidence for use of pharmacotherapeutic strategies for
primary and secondary prevention of cardiovascular disease in the older
adult.
2. Describe considerations in treatment of heart failure, atrial fibrillation, stroke,
and hypertension in the older adult.
3. Demonstrate situations when deprescribing medications for cardiovascular
therapy may be appropriate.
Mind, Mobility, Medications, Multi-complexity, Matters Most
Geriatric Cardiology: two decades
1995-1999
2000-2004
2005-2009
2010-2014
2015-2019
5
2020+
8.1m
9.2m
10.7m
11.2m
12.1m 13.3m
# adults ≥ 80yo
1997 “Do we
practice geriatric
cardiology?
2007 “Society of
Geriatric Cardiology
merged into the ACC
2008: Hartford
Foundation Grants
Education in treating
older adults.
2008 NIH
Inclusion of age
in research
2017 ACC Implements
“Cardiosmart”
Multiple publications
CV Disease in the Older Adult: Challenges
Guidelines!!
Identify baseline benefit/risk:
Lack of tools/evidence for ASCVD risk in the very old
Diseases/multi-morbidities
ADR’s
Frailty
Polypharmacy
Cognitive dysfunction
6
7http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/
8https://www.easycalculation.com/medical/framingham.php
Framingham Risk Score Calculator
Framingham Risk Score is the estimation
of 10-year cvd (cardiovascular disease)
risk of a person. It was developed by the
Framingham Heart Study to assess the
hard coronary heart disease outcome. It
is used to estimate the risk of heart
attacks in adults older than 20.
In the below calculator enter your
gender, age, cholesterol level, BP and you
get the 'Framingham Risk Score' and the
risk of developing CHD. Higher the
score, higher is the percentage of
developing CHD
Primary CV prevention in older adults: Aspirin
ASCEND
Randomized, placebo-controlled, blinded
15,480 patients with DM and no established CV disease (7.4 year follow up)
Age 40 + (22-23% > age 70 years)
Aspirin 100mg po daily or placebo
Primary efficacy outcome: 1st serious CV event
MI, stroke, TIA, death from any vascular cause, except ICH
Primary safety outcome: 1st major bleeding event
ICH, sight-threatening bleed/eye, GIB
9ASCEND study group: A Study of Cardiovascular Events iN Diabetes. N Eng J Med. 2018 Oct 18;379(16) 1529-1529.
The ASCEND Study Collaborative Group. N Engl J Med 2018;379:1529-1539.
Primary CV prevention in older adults: Aspirin
Primary CV prevention in older adults: Aspirin
ASPREE: ASPirin in Reducing Events in the healthy Elderly
Randomized, blinded placebo-controlled, 4.7 year follow up
19,114 patients, ≥ 70 years or ≥ 65 years (African descent & Hispanic)
No CVD, dementia, disability, high-risk bleeding, anemia
100mg enteric-coated aspirin vs placebo
Primary endpoint: all cause mortality
Secondary endpoints:
Major bleeding,
CVD (fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure)
11ASPREE study group.. N Eng J Med 2018, Oct 18;379(16) 1509-1518 and1519-1528.
Primary CV prevention in older adults: Aspirin
Results:
All cause mortality:
Aspirin: 12.7 events per1000 patient-years (HR 1.14 95% CI 1.01-1.29)
Placebo: 11.1 events per 1000 patient-years
Cancer related deaths: 3.1% aspirin group vs 2.3% placebo
Cardiovascular disease
12
JJ McNeil et al. N Engl J Med 2018;379:1509-1518.
Primary CV prevention in older adults: Aspirin
JJ McNeil et al. N Engl J Med 2018;379:1509-1518.
Primary Prevention CV in Older adults: Aspirin
Primary CV prevention in older adults: Statins
JUPITER trial: 2008: Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin
Rosuvastatin 20 mg significantly reduced the primary end point
Composite of nonfatal MI, stroke, hospitalization w/USA, revascularization, and death from CV causes--by 44% vs placebo
HOPE: Heart Outcomes Prevention Evaluation-3
Rosuvastatin 10mg reduced the primary endpoint of composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke by 23% vs placebo
15
1.Ridker PM, ET AL. New Engl J Med 2008
Yusuf, S, et al. N Engl J Med. 2016 May 26;374(21):2021-31.
Primary CV prevention in older adults: Statins
Primary Prevention With Statin Therapy in the Elderly
Meta-analysis of JUPITER and HOPE-3
Subgroup analysis by age:
< ≥65 years
65 to < 70years
≥ 70 years
Composite end point of nonfatal MI, nonfatal stroke, or CV death
16Ridker PM, et al. Circulation. 2017;135:1979–1981
Primary
Prevention With
Statin Therapy
in the Elderly
17Ridker PM, et al. Circulation. 2017;135:1979–1981
Primary CV prevention in older adults: Statins
Conclusions
Starting point for discussions
Data supports using statins in among those ≥70 years
Still critical questions? Effect on:
Cognitive function, drug interactions, adherence, quality of life, and cost-
effectiveness.
The number of studied individuals age ≥80 years is modest.
With benefits for those > 70 and <70 years ….
Some benefit is likely, even among those ≥80 years of age.
18Ridker PM, et al. Circulation. 2017;135:1979–1981
Primary CV prevention in older adults: Statins
Efficacy and safety of statin therapy in older people: a meta-analysis of individual
participant data from 28 randomized-controlled trials.
Six age groups
≤ 55 years, 56–60 years, 61–65 years, 66–70 years
71–75 years, and > 75 years
Comparison of statin/intensive therapy with control/less intensive therapy
Composite of coronary events, stroke, revascularization
Results: Reduce # CV events in all age groups: HR 0.77 (CI 0.75-1.79)
Patients 75 and older: HR 0.82 ( CI 0.70-0.95)
19Lancet. 2019 Feb 2; 393(10170): 407–415.
Primary CV prevention in older adults: Statins
1mmol/L reduction in
LDL-C equivalent is
38 mg/dL
20
Primary CV prevention in older adults: Statins
Review: August 2019:
Large clinical trials and meta-analyses for primary prevention suggest:
Lowering the LDL-C with statins modestly reduces all-cause mortality
Decreases CV risk and rate of CV events
Statins:
Recommended in nearly all high-risk individuals (in women as well as men)
Use clinical judgment and an individualized approach (especially w/high
doses)
Should be used for primary prevention of ischemic stroke and TIA, in high risk
patients
Are cost-effective for primary prevention21
Hawley CE, et al. Drugs Aging. 2019 Aug;36(8):687-699.
Hypertension pearls in older adults
Lifestyle changes matter!!
Salt restriction (moderate)
Weight loss in overweight/obese
Isolated systolic hypertension is common
Increase in CV Risk: SBP
DBP < 60 mmHg mortality
Treatment should be considered in all older hypertensive patients
Even those ≥ 80 years
22
Chaudhry KN, et al. Cleve Clin J Med. 2012 Oct;79(10):694-704.
Appel LJ et al. Arch Intern Med. 2001;161(5):685.
Franklin SS, Hypertension. 2001;37(3):869. Somes GW, et al. Arch Intern Med. 1999;159(17):2004-2009.
Hypertension pearls in older adults
Initial goal <140/90 mm Hg is reasonable
SBP 140 to 145 mm Hg is acceptable in > 80 years old
Start w/low dosing
Titrate up slowly
Monitor closely for adverse effects.
Most antihypertensive drugs can be used 1st line
Consider patient factors
Compelling indications
Orthostatic hypotension
Frailty
Comorbidities
23Chaudhry KN, et al. Cleve Clin J Med. 2012 Oct;79(10):694-704.
SPRINT Research Group; Wright JT Jr, Williamson JD, et al. N Engl J Med 2015; 373:2103–2116
24
Treatment of hypertension: Compelling Indications
for Individual Drug Classes
Compelling Indication Initial Therapy Options Clinical Trial Support
High CAD risk THIAZIDE, ACEI, CCBALLHAT, HOPE, ANBP2, LIFE,
CONVINCE
Heart failureTHIAZIDE, BB, ACEI, ARB,
ALDOSTERONE ANTAGONIST
ACC/AHA Heart Failure
Guideline, MERIT-HF,
COPERNICUS, CIBIS, SOLVD,
AIRE, TRACE, ValHEFT, RALES
Post myocardial infarctionBB, ACEI, ALDOSTERONE
ANTAGONIST
ACC/AHA Post-MI Guideline,
BHAT, SAVE, Capricorn, EPHESUS
Recurrent stroke
prevention/stroke preventionTHIAZ, ACEI PROGRESS
https://edblogs.columbia.edu/pcore/hypertension-targets-for-treatment-of-essential-hypertension-for-adults/hypertension-evidence-
based-drugs-for-hypertensive-adults-with-specific-compelling-indications/
Heart Failure: pearls in older adults
Incidence increases with age
High mortality
Frailty/functional impairment
Co-morbidities (5 or more)
May affect HF treatment
Medications may exacerbate HF
May interact
Cognitive impairment reduces ability to manage
25Sakib S. Current Cardiology Reviews, 2016, 12, 180-185
Heart Failure: pearls in older adults
Anticholinergics
Overactive bladder
Antihistamines
Steroids (systemic)
NSAIDS
Dihydropyridine Calcium Channel
Blockers
Pioglitazone, rosiglitazone
Metformin
Pramipexole
Estrogens
26
Importance of medication review in HF patients
Heart Failure: pearls in older adults
Guideline directed management and therapy (GDMT)
Improve symptoms, prevent progression and mortality
Specific therapies and target doses
Older adults under-represented
HEFpEF vs HEFrEF ?
27
2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. Journal of the
American College of Cardiology. 2017 (70):6. 777-803.
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HEART FAILURE: PEARLS IN OLDER ADULTS
Medications to Treat HEFrEF
Class Mortality benefit Comments
ACEI Yes Cough/angioedema (ACEI)
Hypotension
Can worsen renal function
Hyperkalemia
ARB Yes
Neprolysin Inhibitor +
ARB
Yes
Aldosterone antagonists Yes Hyperkalemia
(Not used CrCl < 30ml.min)
Hypotension
Beta-blockers Yes Hypotension, Bradycardia
Ivabradine No Reduces hospitalizations in HEFrEF
Arrhythmias (bradycardia)
Hydralazine + Nitrate Yes Less benefit than ACEI and ARB
Diuretics No Reduce symptoms/volume overload
Hypokalemia
Can worsen renal function
2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure. Journal of the American
College of Cardiology. 2017 (70):6. 777-803
Atrial fibrillation/Stroke prevention: Pearls
Most common arrhythmia in older adults
Frailty and comorbidities complicate choices
Rate-control over rhythm-control for most
Beta-blockers, calcium channel blockers
Slow conduction through AV node
Digoxin
Vagal stimulations, effects on SA and AV node
29Cutis AB, et al. 2018 May 8;71(18):2041-2057
Atrial fibrillation/Stroke prevention: Pearls
Digoxin
Beer’s list
Narrow therapeutic index
Less effective than beta-blockers, calcium channel blockers
Significant toxicity: arrythmias
Increased mortality used for afib (levels ≥ 1.2 ng/ml)
When is it used:
Other therapy is ineffective/contraindicated?
30Van Gelder IC, et al.Lancet. 2016 Aug 20;388(10046):818-28.
Lopes RD, et al. J Am Coll Cardiol. 2018 Mar 13;71(10):1063-1074.
Atrial fibrillation/Stroke prevention: Pearls
Anticoagulation
Underutilized in the old and very old/frail
Absolute contraindications rare
33% strokes ≥ 80 years = atrial fibrillation
Validated tools for stroke risk and bleeding
Direct Acting Oral Anticoagulants (DOACS) are preferred over warfarin
Excluding mechanical valve replacement
31
Oqab Z1, et al. J Atr Fibrillation. 2018 Apr 30;10(6):1870.
Lopes RD, et al. J Am Coll Cardiol. 2018 Mar 13;71(10):1063-1074.
Steinberg, BA, et al. Cardiovasc Ther. 2015 Aug;33(4):177-83.
AFIB CHA2DS2-VASc
Characteristic Score
Congestive HF 1
Hypertension 1
Age ≥75 years 2
Diabetes mellitus 1
Stroke/TIA 2
Vascular disease 1
Age 65 to 74 years 1
Female 1
Maximum score 9
CHA2DS2-VASc
Score
Stroke Rate (%/y)
0 0.2
1 0.6
2 2.2
3 3.2
4 4.8
5 7.2
6 9.7
7 11.2
8 10.8
9 12.2Friberg L, Eur Heart J 2012; 33:1500
Has-bled Score
Characteristic Points
H Hypertension 1
AAbnormal renal or liver function (one point for each)
1 or 2
S Stroke 1
B Bleeding tendency or predisposition 1
L Labile INR (for warfarin patients) 1
E Elderly > 65 years 1
DDrugs (aspirin, NSAIDS) or excessive alcohol used (one point for each)
1 or 2
9
ScoreBleeds per 100
patient years
0 1.13
1 1.02
2 1.88
3 3.74
4 8.70
5-9 Insufficient data
Pisters R. Chest 2010; 138:1093. Lip GY, et al. J Am Coll Cardiol. 2011 Jan 11;57(2):173-80.
Efficacy/Safety (RCT DOAC vs warfarin)
Outcome HR (p value)
Rivaroxaban
20/15 mg
Apixaban
5/2.5 mg
Stroke/SSE* ↔ 0.88 (.12) ↓0.79 (.01)
Ischemic stroke ↔ 0.94 (.58) ↔ 0.92 (.42)
Hemorrhagic stroke ↓0.59 (.02) ↓0.51 (< .001)
Bleeding Major ↔ 1.04 (.58) ↓0.69 (< .001)
Bleeding ICH ↓0.67 (.02) ↓0.42 (< .001)
Bleeding GI ↑1.66 (< .001) ↔ 0.89 (.37)
• SSE = systemic embolismPatel, MR, et al. N Engl J Med. 2011 Sep 8;365(10):883-91.
Granger, CB, et al. N Engl J Med. 2011 Sep 15;365(11):981-92.
Atrial fibrillation/Stroke prevention: Pearls
Nonvalvular Atrial FibrillationCrCl (ml/min) Dose
Rivaroxaban
36% renal
elimination
>50 20mg daily (evening meal)
15-50 15mg daily (evening meal)
<15 Not recommended
Apixaban
27% renal
elimination
Usual dose
CrCl undefined
5mg 2x day
At least 2 of 3:
Age ≥80, Scr≥1.5
Wt≤ 60kg
2.5mg 2x day
Deprescription in older CV patients
Guideline-based management in CVD:
Prescription of multiple medications
Contributes to polypharmacy
Risk for adverse drug events
Consider deprescribing to mitigate risks (without clear benefit)
Goals:
Withdraw or reduce dose:
Correct/prevent medication-related complications
Improve outcomes and reduce costs
36Krishnaswami, A, et al. J Am Coll Cardiol. 2019 May 28; 73(20): 2584–2595.
37Krishnaswami, A, et al. J Am Coll Cardiol. 2019 May 28; 73(20): 2584–2595.
Deprescription General Tools
Apply to the CV patient
Implicit tools
ARMOR
GPGP
Explicit tools
Beer’s Criteria
STOPP
STOPPFrail
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Potentially Inappropriate CV Medications (R vs B)
Central alpha agonists (e.g., clonidine) Central nervous system effects, orthostatic hypotension,
bradycardia
Dronedarone Heart failure
Digoxin More effective alternatives exist (avoid as 1st line)
Aspirin for primary prevention of cardiac events Risk may exceed benefits for adults ≥70 yrs when used for primary
prevention.
Dabigatran Increased risk of GIB in older adults
Prasugrel Increased risk of fatal and intracranial bleeding
Vasodilators Syncope
Peripheral alpha-1 blockers (e.g., doxazosin,
prazosin, terazosin)
Orthostatic hypotension
39Krishnaswami, A, et al. J Am Coll Cardiol. 2019 May 28; 73(20): 2584–2595
AGS Beer‘s Criteria Expert Panel. J Am Geriatr Soc 2019;67:674–94.
40
A. May Exacerbate Heart Failure B. May Increase Blood Pressure
Antiarrhythmic medications
• flecainide, disopyramide
• sotalol
• dronedarone
Antihypertensive medications
• Dihydropyridine (DHP) calcium channel
blockers: nifedipine, amlodipine
• Non DHP: diltiazem, verapamil
Calcineurin inhibitors
• cyclosporine
• Tacrolimus
NSAIDs
Amphetamines
Alcohol
Caffeine
Herbal supplements
C. May increase risk of syncope, falls and/ or
fractures
D. May Increase Risk of Gastrointestinal
Bleeding
Peripheral alpha-1 blockers (doxazosin,
prazosin, terazosin)
• Aspirin (>325 mg/day)
Krishnaswami, A, et al. J Am Coll Cardiol. 2019 May 28; 73(20): 2584–2595
AGS Beer‘s Criteria Expert Panel. J Am Geriatr Soc 2019;67:674–94.
Deprescribing example
Medical condition/multimorbidity overview:
84-year-old woman presents for routine cardiology clinic follow-up She has history
of poorly controlled hypertension requiring 4 medications, CAD with a stent placed
2 years ago.
Non-CV comorbidities: diet controlled diabetes mellitus, mild chronic obstructive
pulmonary disease.
Mobility/physical domain: walks around her yard daily. Normal activities of daily living.
Mind/cognitive domain: normal. Social domain: retired, lives with husband at home.
Matters most/goals of care: her primary concern is to avoid cardiovascular events
(heart attack, stroke).
41Krishnaswami, A, et al. J Am Coll Cardiol. 2019 May 28; 73(20): 2584–2595
Deprescribing example: Medications
losartan 100mg daily
atenolol 100 mg daily
hydrochlorothiazide 25mg daily
amlodipine 5mg daily
alendronate 70 mg weekly
vitamin E 400 units daily
Multivitamin daily
co-enzyme Q 10 daily
aspirin 81 mg daily
clopidogrel 75 mg daily
atorvastatin 40 mg daily
nitroglycerin 0.4mg SL q5minprn chest pain
42
Deprescribing example: Process
Step 1: All medications were reviewed and reconciled.
Step 2: Individual medication risk of adverse effects were assessed.
She was on 4 HTN medications with systolic BP <120 mm Hg. Concern was regarding future adverse drug reactions. Also, the use of amlodipine and HCTZ can possibly be considered a prescribing cascade.
Step 3: Assess candidacy for individual medication discontinuation or dose reduction
All 4 anti-HTN medications were candidates for removal or dose reduction. along with clopidogrel and supplements.
Step 4: Prioritize drug discontinuation or dose reduction.
Based on her concomitant conditions, it was decided to attempt to discontinue hydrochlorothiazide and amlodipine with dose reduction of atenolol and losartan. Vitamins and supplements discontinuation were discussed.
43
Deprescribing example: Process
Step 5: Discontinue and implement monitoring protocol.
After a discussion regarding balancing the benefits of intensive BP treatment with
associated risks and setting a systolic BP goal of 120–125 mm Hg, the
deprescribing process was implemented over a period of 6 months.
Hydrochlorothiazide and amlodipine were safely removed with dose reduction of the
beta-blocker and angiotensin receptor blocker.
Follow up: at the end of 5 months with BP checks every 2–3 weeks, the systolic BP
range was between 120 mm Hg and 125 mm Hg. Her BP regimen at the end of 6
months was losartan 50 mg daily, atenolol 25mg daily.
She agreed to discontinue vitamin E, and co-enzyme Q10, but wished to stay on
the single daily multivitamin tablet44
Key Takeaways
Most older adults will not benefit enough from using aspirin as primary prevention in
CVD to offset the risks
Data supports the benefit of using statins in older adults for primary prevention of
CVD
Guideline based therapy drives decision making for treatment of hypertension, heart
failure, and afib/stroke. When making treatment decisions, there are additional
considerations in older adults.
When risks of therapy exceed benefit, even in CVD treatment, careful consideration
fro deprescription will reduce medication-related complications, and reduce costs.
45