cardiovascular medications in older adults
TRANSCRIPT
When one size doesn’t fit all: Managing cardiovascular
medications in older adults
Erin Yakiwchuk BSP, ACPR, MSc
Key Messages• Medication requirements often change with age
• Age is an important risk factor for both CV events and adverse drug reactions
• Chronological age vs physiological age
92 year old Harriette Thompson finishing the San Diego marathon – SMILING!
Public Health Agency of Canada
.
JAMA 2016;316:2115-25.
CV meds
= 58%
Challenges in Older Adults
• Multimorbidity
• Polypharmacy
• Pharmacokinetic/pharmacodynamic changes
• ↑adverse drug reactions and drug interactions
• Adherence issues
• Changing priorities
• Evidence-based medicine?
Pharmacokinetic Changes with Aging
PK Process Physiologic Change
Effect
Distribution ↓ body water
↑ body fat
↓Vd /↑effect of water-soluble drugs e.g. digoxin
↑ Vd / accumulation of lipid-soluble drugs e.g. amiodarone, propranolol
Metabolism ↓liver size, ↓hepatic blood flow,↓phase I
metabolism
↑effect / half-life (e.g. warfarin, propranolol, nitrates, diltiazem, verapamil)
Excretion ↓renal blood flow, ↓glomerular filtration,
↓tubular secretion
↑half life / accumulation (e.g. digoxin, ACEIs, atenolol, sotalol)
Nat Rev Cardiol 2011;8:13-28
Pharmacodynamic Changes with Aging
Physiologic Change Effect
↓baroreceptor response ↑incidence of orthostatic hypotension (nitrates, alpha-blockers, aggressive diuresis)
↑sensitivity to anticoagulants/antiplatelets
↑bleed risk
↑sensitivity to CNS effects of medications
↑drowsiness/dizziness with clonidine; ↑depression/memory changes from beta-blockers; ↑dizziness/confusion with digoxin
Nat Rev Cardiol 2011;8:13-28
Putting the issues into context…
Meet Mr. H.N.
Mr. H.N.• 93 year old man
• Referred for memory decline, dizziness, falls
• Medical History: MI in 1998 Atrial Fibrillation TIA in 2014 Hypertension Diabetes (A1c = 7.5%) Spinal Stenosis BPH/urinary urgency Several falls in last year
• BP (sitting) 95/51 mmHg
• ECG: Afib, HR 53 bpm
• CrCl = 33 ml/min
• Medications: Warfarin 1mg alt 1.5 mg daily Aspirin 81 mg daily Bisoprolol 5 mg daily Digoxin 0.125 mg daily Ramipril 5 mg daily Nitroglycerin 0.8 mg/h patch 12
h/d Nitroglyerin 0.4 mg spray prn Atorvastatin 20 mg daily Gabapentin 300 mg TID Tylenol Arthritis 650 mg prn Vitamin D 1000 units daily
(Cardiovascular)
Medication Issues for Mr. H.N.
• Anticoagulation/Antiplatelet Therapy• Warfarin + ASA needed?• Warfarin vs DOAC
• Rate control in atrial fibrillation Is digoxin needed?
• Hypertension• Too low?• Which medications to adjust?
• Dyslipidemia• At 93 – is a statin still worthwhile?
Atrial Fibrillation
The Dilemma of Age
• Incidence of atrial fibrillation ↑ with age 5% > 65 years 10% > 80 years
• Advanced age ↑ the risk for both stroke & major bleeds
Evidence for Anticoagulation• BAFTA
RCT of warfarin vs. ASA in patients > 75 y with AFib n=973, mean age 81 y
>70% had a CHADS2 score of 1 or 2
Exclusions: Recent major bleed, PUD, esophageal varices, SBP > 180,
physician discretion
Warfarin significantly ↓ strokes (HR 0.48, CI 0.28-0.80) NNT = 21 patients for 2.7 years
No significant difference in major bleed rates
Lancet 2007;370(9586):493.
Bleed Risk
• Cochrane meta-analysis of warfarin vs. aspirin trials
NNH = 250 for ICH with warfarin over aspirin NNH = 98 for major bleeds
Cochrane Database Syst Rev 2007;(3):CD006186
Considerations
• Is there an indication for anticoagulation?
• Is there a high risk of bleeding or a contraindication to warfarin?
• Will the patient be able to adhere to therapy and monitoring requirements?
• Patient/family preferences?
Is Anticoagulation Indicated?
.
CCS 2016 Focused Update of the Guidelines for Atrial Fibrillation
Is there a high risk of bleeding?• Determine HAS-BLED score
Risk Factor PointsHypertension (SBP > 160) 1
Abnormal renal/liver function 1 each
Stroke 1
Bleeding history or predisposition 1
Labile INRs 1
Elderly (age > 65) 1
Drugs (antiplatelets, NSAIDs, EtOH) 1 each
Caution if HAS-BLED > 3
What about fall risk?
• Retrospective study of 1245 patients at high fall risk1 Warfarin ↓ deaths and hospitalizations
NNT = 81/y
• Meta-analysis of anticoagulation in patients at risk of falls2 Patient with a CHADS2 score of 2-3 would need to have 300
falls/y for bleed risk to outweigh stroke prevention benefit
1Am J Med. 2005;118(6):6122Arch Intern Med. 1999;159(7):677
Warfarin + Aspirin
• Combination appropriate for AFib + post-MI for 1 year1
Thereafter warfarin alone
• Warfarin + Aspirin for Afib + stable coronary artery disease is on the STOPP criteria ↑ bleed risk without ↑ benefit
12016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation
DOACs vs. Warfarin
Advantages Disadvantages
> Efficacy Cost
Less ICH (NNT 96-250/2y) More GI bleeds (NNH ~100/y)(rivaroxaban and dabigatran)
No INR monitoring No long-term safety data
Fewer drug and food interactions Caution in renal impairment Contraindicated in CrCl < 30
No antidote*
Dabigatran (Pradaxa), Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban
*Praxbind recently released – antidote to dabigatran
Rate Control in Atrial Fibrillation• Generally preferred (vs rhythm control) in older
adults
• Medications: Beta-blockers
Preferred when concurrent CAD, HF
Non-Dihydropyridine calcium channel blockers May be preferred in severe or poorly controlled asthma/COPD
Digoxin
• Target HR < 100 bpm at rest RACE II: No benefit of target HR < 80 bpm vs < 110 bpm^
^N Engl J Med 2010; 362:1363-137
Digoxin in Older Adults • Add-on if HR not at target OR for heart failure
symptomatic despite optimized medical therapy AFFIRM trial - ↑ mortality when digoxin used for Afib+
• 0.0625 – 0.125 mg daily
• Signs of toxicity: anorexia, nausea, vomiting, weakness, dizziness, cognitive changes, vision changes
• Blood levels are not a target but a tool to avoid toxicity! Toxicity may occur with levels > 1nmol/L in elderly SHR reports levels within range if 1.3-2.6 nmol/L
Caution in renal impairment!+Eur Heart J 2012;34:1481-88Geri-RxFilesRxFiles.ca
Hypertension in Older Adults
Hypertension in Older Adults• Primarily Isolated Systolic Hypertension (ISH)
Increased stiffness of large arteries with age
• Physiological changes ↓ Baroreceptor response Impaired cerebral autoregulation
• Avoid overly-aggressive SBP reductions Risk of tissue hypoperfusion and ischemia
Start low, go slow!
Target BP in Older Adults• 2016 CHEP Guidelines
Target BP < 150/90 in patients > 80y Caution with ↓ diastolic BP < 65 if CAD
• ACCF/AHA 2011 Consensus Document on Hypertension in the Elderly Avoid SBP < 130 and DBP < 60 mmHg if > 80y
But then…• SPRINT Elders
• Randomized, open-label study of 2636 patients > 75 y • Excluded diabetes, HF, history of stroke, or BP < 110 after 1min
standing
• SBP target < 140 (standard) vs. < 120 mmHg (intensive)• Achieved 135 vs 123 mmHg
• NNT 27 over 3 years to prevent one CV death, MI/ACS, stroke, or acute decompensated HF
• NNT 42 for 3 years to prevent one death
• Non-significant increase in hypotension, syncope, and acute kidney injury in intensive group• NNH = 27 over 3 years to cause one patient to have > 30% decrease
in GFR
JAMA 2016;315:2673-82
.
.
Practical Considerations – SPRINT Elders
• Ideal BP measurement in SPRINT
• Numerous exclusions
• ~ One more drug/person
• Diastolic BP 62 mmHg (intensive) vs 67 (standard)
To SPRINT or not to SPRINT?
Medication Considerations - Hypertension
• Treatment of ISH (CHEP) Thiazide diuretic, dihydropyridine CCB (e.g.
amlodipine) +/or ARB
• Consider comorbiditiesComorbidity Agent(s) of Choice
Previous MI Beta-blocker, ACEI or ARB
HF Beta-blocker, ACEI or ARB, aldosterone antagonist
DM + albuminuria ACEI or ARB
Previous stroke/TIA ACEI, thiazide diuretic
CHEP 2016
Evaluating Antihypertensive Therapy
.
AvoidBeta-blockers as first-line antihypertensives
Central alpha agonists - clonidine, methyldopa
Alpha-1 antagonists
- doxazosin, prazosin, terazosin
Vasodilators- hydralazine, minoxidil
Orthostatic Hypotension
• >20/10 mmHg ↓ BP within 3 minutes of standing
• Risk factor for falls, hospitalizations, CV events
May limit ability to achieve BP targets!
Orthostatic Hypotension
• Up to 70% of patients in long-term care
• Associated with: ↑ age - Parkinson’s disease Hypertension - Cognitive impairment Diabetes - Drugs
Freeman et al. Auton Neurosc 2011:161;46-8
SPRINT Elders excluded patients with SBP < 110 mmHg after 1 min of standing
Cholesterol Medications in Older Adults
Statins in the Elderly• Limited evidence for primary prevention > 80y
Older adults more susceptible to statin adverse effects
• Meta-analysis of secondary prevention studies in patients 65-82y† 9 trials, > 19,000 patients, 4.9 y of follow-up NNT (95% CI):
To save one life: 28 (15-56) To prevent one non-fatal MI: 38 (16-118) To prevent one stroke: 58 (27-177)
• Time to benefit ~ 2 years
†J Am Coll Cardiol 2008;51:37-45
Other Cholesterol Medications?
• Ezetimibe (Ezetrol), fenofibrate, gemfibrozil, niacin
Stable Coronary Artery Disease
• Stable angina, prior acute coronary syndrome, previous PCI or CABG
• Consider: Time since event Symptom stability Activity level Patient goals and preferences
• As activity ↓, medication requirements might ↓ as well! • E.g. nitroglycerin
Back to Mr. H.N..
Mr. H.N.• 93 year old man
• Referred for memory decline, dizziness, falls
• Medical History: MI in 1998 Atrial Fibrillation TIA in 2014 Hypertension Diabetes (A1c = 7.5%) Spinal Stenosis BPH/urinary urgency Several falls in last year
• BP (sitting) 95/51 mmHg
• ECG: Afib, HR 53 bpm
• CrCl = 33 ml/min
• Medications: Warfarin 1mg alt 1.5 mg daily Aspirin 81 mg daily Bisoprolol 5 mg daily Digoxin 0.125 mg daily Ramipril 5 mg daily Nitroglycerin 0.8 mg/h patch 12
h/d Nitroglyerin 0.4 mg spray prn Atorvastatin 20 mg daily Gabapentin 300 mg TID Tylenol Arthritis 650 mg prn Vitamin D 1000 units daily
(Cardiovascular)
Medication Issues for Mr. H.N.
• Anticoagulation/Antiplatelet Therapy• Should he be on warfarin for atrial fibrillation, ASA
for CAD, or both?• Would a direct oral anticoagulant (DOAC) be a better
choice?
• Rate control in atrial fibrillation Are both bisoprolol and digoxin necessary?
• Hypertension• Too low?• Which medications to adjust?
• Dyslipidemia• At 93 – is a statin still beneficial?
Resources• Geri-RxFiles, www.rxfiles.ca
• www.cadth.ca/longtermcare
• McMaster Optimal Aging Portal https://www.mcmasteroptimalaging.org
Resources• Stroke Prevention in Atrial Fibrillation Risk Tool
(SPARC) http://www.sparctool.com/
• 2015 American Geriatrics Society Beers Criteria– Available at: http://geriatricscareonline.org/toc/american-
geriatrics-society-updated-beers-criteria-for-potentially-inappropriate-medication-use-in-older-adults/CL001
• STOPP criteria (version 2)• Available at:
http://ageing.oxfordjournals.org/content/44/2/213.full.pdf+html
• Medstopper.com
References• Shehab et al. US emergency department visits for outpatient
adverse drug events, 2013-14. JAMA 2016;316:2115-25.
• http://www.phac-aspc.gc.ca/publicat/2009/cvd-avc/pdf/cvd-avs-2009-eng.pdf. Accessed 1 April 2017.
• Fleg JL, Aronow WS, Frishman WH. Cardiovascular drug therapy in the elderly: benefits and challenges. Nat Rev Cardiol 2011; 8:13–28
• Aguilar MI et al. Cochrane Database Syst Rev 2007;Jul 18(3):CD006186
• Macle et al. 2016 Focused update of the CCS Guidelines for the management of atrial fibrillation. Can J Cardiol 2016;32:1170-85.
• Man-Son-Hing M et al. Anticoagulant-related bleeding in older persons with atrial fibrillation. Arch Int Med 2003;163:1580-6
References• Mant J et al. The Birmingham Atrial Fibrillation in the
Aged (BAFTA) Study. Lancet 2007;370:493-503.
• Aguilar M et al. Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with nonvalvular atrial fibrillation. Cochrane Database Syst Rev 2007;(3):CD006186
• Gage BF et al. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med. 2005;118(6):612
• Man-Son-Hing et al. Choosing antithrombotic therapy for elderly patients with atrial fibrillation who are prone to falls. Arch Intern Med. 1999;159(7):677
• Rxfiles.ca. Accessed 1 April 2017
References• Van Gelder IC et al. Lenient vs strict rate control in patients
with atrial fibrillation. N Eng J Med 2010;362:1363-73.
• Geri-RxFiles 2nd Edition
• Whitbeck MG et al. Increased mortality among patients taking digoxin – analysis from the AFFIRM study. Eur Heart J 2012;34:1481-88
• 2016 CHEP Guidelines available at: http://guidelines.hypertension.ca/chep-resources/. Accessed 13 September 2016.
• Aronrow WS. ACCF/AHA Expert consensus document on hypertension in the elderly. Circulation 2011;123:2434-506.
• Williamson JD et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults > 75 years. JAMA 2016;315:2673-82
References• Freeman R et al. Consensus statement on the definition
of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Auton Neurosc 2011:161;46-8
• Afilalo et al. Statins for secondary prevention in elderly patients. J Am Coll Cardiol 2008;51:37-45