cardiovascular disease in the older adult · primary cv prevention in older adults: aspirin ascend...

Cardiovascular disease in

the older adult:

DEDE PIERCE PHARMD BCPS BCGP

UR MEDICINE THOMPSON HEALTH

[email protected] 1

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

4

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.



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.


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.


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 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



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.



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.


1mmol/L reduction in

LDL-C equivalent is

38 mg/dL

20


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


Anticholinergics

Overactive bladder

Antihistamines

Steroids (systemic)

NSAIDS

Dihydropyridine Calcium Channel

Blockers

Pioglitazone, rosiglitazone

Metformin

Pramipexole

Estrogens

26

Importance of medication review in HF patients


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.

28

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


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.


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.


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

38

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

cardiovascular disease in the older adult · primary cv prevention in older adults: aspirin ascend...

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