cardiovascular care of older adults: acute myocardial infarction

Cardiovascular Care of Older Adults:Acute Myocardial Infarction

Karen P. Alexander MD

Associate Professor Medicine

Duke Clinical Research Institute

Duke University Medical Center

Durham, NC

Outline• Understand the presentation of ACS in older adults• Safe and effective therapies for ACS in older adults.• Assess likely health outcomes among older adults with

ACS• Appreciate the role of discharge planning in optimizing

medication safety and return to independent functioning.• Needs for future research

Population Incidence of Heart Disease Cardiovascular Health Study

Rat

e/1,

000

Pers

on-Y

ears

Age (Yrs)

REF: Arnold AM, et al, JAGS 2005;53:211-218CHD = Fatal and Non-fatal MI, Angina, coronary revascularization

Caucasian Male: 10 year follow up

Risk Factors for First MIINTERHEART Case- Control Acute MI; 52 countries; >30,000

ptsYoung Old*

Smoking 3.33 (2.86 - 3.87) 2.44 (2.10 – 2.84)

HTN 2.24 (1.93 – 2.60) 1.72 (1.52 – 1.95)

Diabetes 2.96 (2.40 – 3.64) 2.05 (1.71 – 2.45)

Abdominal Obesity 1.79 ( 1.52 – 2.09) 1.50 (1.29 – 1.74)

Lipids: ApoB/ApoA1 4.35 ( 3.49 – 5.42) 2.50 (2.05 – 3.05)

Fruits and Vegetables 0.69 (0.58 – 0.81) 0.72 (0.61 – 0.85)

Exercise 0.95 (0.79 – 1.14) 0.79 ( 0.66 – 0.94)

Alcohol 1.00 (0.85 – 1.17) 0.85 (0.73 – 1.00)

Psychosocial Stress 2.87 ( 2.19 – 3.77) 2.43 (1.86 – 3.18)

93.9% 87.9%Pop. Attributable Risk

REF: Yusuf et al, Lancet 2004;364:937-52 * Old = Men >55 yrs; Women >65 yrs

Age ≥ 85 among the Myocardial Ischemia National Audit Project (MINAP) Registry

Rosengren EHJ 2012:33:562Year

% ≥

85

year

s

MINAP: Final MI Diagnosis

Gale, EHJ 2012;33:630-639

AGE AGE

1975/78 (REF) – 1993/95 Worcester Heart Attack Study

OR for In-hospital MortalityControlling for gender, med history, AMI type, complications

MI Type Age (yrs) QW NQWMI 55-64 65-74 75-84 ≥85

(REF)

1975/78 1.0 1.0 1.0 1.0 1.0 1.0Case Fatality = 21%Median Age = 66 yrs

1993/95 0.33* 0.89 0.23* 0.55* 0.48* 0.93Case Fatality = 11%Median Age = 74 yrs

REF: Goldberg, AJC 1998:82:1311-1317; Furman, J ACC 2001;37:1571-80*Significant

Time Trends2003 (REF) – 2011 (MINAP Registry)

OR In-Hospital Mortality By Age

Gale, EHJ 2012;33:630-639

NSTEMI <55 yrs >85 yrs

(2003) 1.9% 31.5%(2010) 0.9% 20.4%Mort. RR 0.89 (0.48-1.34) 0.56 (0.42-0.73)

STEMI <55 yrs >85 yrs

(2003) 2.0% 30.1%(2010) 1.5% 19.4%Mort. RR 0.72 (0.39-1.25) 0.56 (0.38-0.75)

MINAP: NSTEMI In-Hospital MortalityAdj. for Age, DM, HTN, CAD hx, HF, ward (REF: Age <55yr)

MEN

Years Years

Adj.

Odd

Rati

o (9

5% C

I)

Gale, EHJ 2012;33:630-639

050

100150200250300350400450

<50 50-64 65-74 75+0

5

10

15

20

25

3010%

25%

1 Yr mortality

Efficacy (RRR)

Efficacy (RRR)

Num

ber N

eede

d to

Tre

at1 year M

ortality*

Patient Age (Yrs)

Alter, AJM, 2004*Mortality Estimates based on AMI patients treated in Ontario from 1997-2000

Mortality and NNT Relationships

Age

Com

orbi

dity

Dise

ase

Seve

rity

62 69

Benefits Risks

Applying Guidelines Out of the Box

– Do they resemble patients in trials?– Is dosing and delivery of treatment similar?– Do conditions of aging dynamically alter treatment effect?– Do treatment risks outweigh benefits?– Do expected outcomes match desired outcomes?

REF: Tinetti, NEJM 2004; 351: 2870-2874

Trials

Community

0

5

10

15

20

25

30

35

40

45

50

<65 65-74 75-84 85+

CHFRenal InsuffStrokeFrailty*Cognitive Impairment

Older Adults: Comorbidity and Dysfunction

Patient Age

% o

f pop

ulat

ion

REFS: JACC 2005;46: 1479-87; CHS J Geront Biol Sci 2001; Canadian Health and Aging

* Frailty: Fatigue, Slow Gait, Weak Grip, Wt loss >10 lbs,

Low Activity

Older Adults: Disability

REF: Griffith L, et al. Age and Ageing 2010;39:738-745

Canadian Study of Health and Aging 9,008 Community Dwelling Seniors

Basic (physical) and Instrumental (functional) ADLs

Frailty

Frailty PhenotypeFeatures: Weakness, Muscle Wasting, Cognitive Impairment,

Depression, Nutrition, Isolation, Low Physical Function, Fatigue

Comorbidity(>2 conditions)

Disability(>1 ADL)25%66%

27%

Age (yrs)

Life Years Prevalence

>65 >25 ~8%

70 19.3 15%

75 11.7 28%

80 8.9 32%

85 6.6 38%

90 4.8 40%

Heterogeneity of Aging• Biological Phenotype

– Cumulative comorbidity counts– Cognitive Impairment– Disability – Functional Status– Visual and Hearing Impairments

• Physiologic Phenotype– ↓ Blood vessel integrity and response to injury– ↓ Vascular Compliance – D-dimer and inflammatory markers increase – Altered Clotting (low platelet turnover)– ↑ Thrombin, Fibrinogen, Factors IX, X

Jeanne Calment

(Photo Age 113)

Lived to 122 years, Arles France

REF: http://entomology.ucdavis.edu/courses/hde19/lecture3.html

Unmasking Narrow Reserves

• Less resilient to acute disease• Less resilient to drug effects

DECLINES OFFUNCTION

CHALLENGESTO HOMEOSTASIS

Fries, 1981

NSTEMI

CAD Limiting Reserves

• Cardiac disease was major health limitation• Treatment enables resumption of function


Fries, 1981

CAD Treatment

Non-CAD Limiting Reserves


Fries, 1981

• Underlying comorbidity impairs function• Non-cardiac disease limits survival

Unmasking Narrow Reserves

• Less resilient to acute disease• Less resilient to drug effects

DECLINES OFFUNCTION


Fries, 1981

NSTEMI

Presentation Atypical Yes

Under treated (Under studied)Yes

Independent risk Mortality YesIndependent risk Bleeding

YesMultiple Coexisting Conditions

Yes

Older Adults (≥75 y) = Special Population

REF: Anderson J, NSTEMI Guidelines. JACC 2007;50:652–726; Tinetti, NEJM 2004; 351: 2870

Presenting Signs by Age CRUSADE : Signs of CHF

NRMI 2-4 : EKG non-diagnostic (RBBB or other)

05

101520253035404550

<65 yrs 65-74 yrs 75-84 yrs >84 yrs

Signs of CHFEKG non-diagnostic

Patient Age

% P

opul

ation

0102030405060708090

100

Chest Pain Other* Hypoxia or Tachy Anemia

<75 Years>=75 Years

ED Presenting Signs and Symptoms Chart Review from CRUSADE (n=607)

*Other: Dizziness, Palpitations, Abdominal Pain, Headache, Altered Mentation

Nursing Home: 10 v. 2% (p<0.01)

All P<0.05

N=182

N=468

Krashnewski, AHA Outcomes Abs. Submitted

Heart Failure

Tachyarrhythmia

Procedures

Renal FailureAnemia

TYPE I

TYPE 2

Thrombus

Universal MI Definition

REF: Thygesen K, JACC 2007;27:2173-95

Type I: Spontaneous MIatherosclerotic plaque rupture with thrombus in one or more of the coronary arteries.Type 2: Secondary MIa condition other than CAD contributes to increased myocardial oxygen demand or decreased myocardial blood flow.

Type 3: Sudden Death MISudden cardiac death with or without ECG changes or biomarkers can be obtained. Type 4/5: Revasc MIPeri-procedural injury associated with instrumentation of the heart during revascularization, either PCI or CABG.

Older adults with UA/NSTEMI should be evaluated and treated for acute and discharge therapies in a similar manner as younger adults

IIIIII IIaIIaIIaIIaIIaIIa IIbIIbIIbIIbIIbIIb IIIIIIIIIIIIIIIIIIIIIIII IIaIIaIIaIIaIIaIIa IIbIIbIIbIIbIIbIIb IIIIIIIIIIIIIIIIIIIIIIII IIaIIaIIaIIaIIaIIa IIbIIbIIbIIbIIbIIb IIIIIIIIIIIIIIIIIIIIaIIaIIaIIaIIaIIa IIbIIbIIbIIbIIbIIb IIIIIIIIIIIIIIIIII

2011 UA/NSTEMI Guidelines : Special Population Section

REF: Circulation. 2011;123:000-000.

Attention should be given to adjusting anti-platelet and anticoagulant doses based on weight and renal function (eg. estimated creatinine clearance) in older adults.

Decisions on management of older adults should not be based solely on chronologic age but should be patient-centered, with consideration given to general health, functional and cognitive status, comorbidities, life expectancy, and patient preferences


NSTEMI – Case55yo ♀ 85yo ♀

Presents with SOB, CP no prior cardiac hx

BP: 130/89 mmHgWeight: 238 lbsEKG: Sinus 95, TWI laterallyCreat 1.0, HCT 33%

BP: 165/75 mmHgWeight: 108 lbsEKG: Sinus 95, LVH, TWI laterallyCreat 1.0, HCT 33%

Comorbidities: HTN GERD Obesity Smoking

Comorbidities: HTN Prior stroke HF NEF OA

ASA, 2L O2 NC, Nitro, Beta Blocker Troponin +

Older Adults: Conservative v. Invasive

Older patients face increased early procedural risks with revascularization relative to younger patients, yet the overall benefits from invasive strategies are equal to or perhaps greater in older adults.

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

REF: Anderson J. J Am Coll Cardiol 2007;50:652-726

Older Adults: Benefit of Invasive Care (TACTICS TIMI 18)

Source: Bach AIM 2004; 141:186-195

DEATH or MI at 6 mo

Age Group (n)

≤55 y (716)

56-65 y (614)

66-75 y (612)

≥75 y (278)

1 2.01.50.50

Conservative BetterInvasive Better

Event Rate (%) OR

Cons. Inv. (Inv v. Cons)

4.8 5.0 1.07

9.1 7.6 0.82

10.3 7.8 0.73

21.6 10.8 0.44** P <0.016

NNT = 9

NNT = 67


IV heparin: 5000 U then 1000 U/hr Cath Lab: LCX 95% hazy

IV Integrelin, Drug-eluting stent

Appropriate HeparinAppropriate Integrilin CrCl=98 ml/min

Excess Heparin (3000 U/ 600 U/hr) Excess Integrelin CrCl = 30 ml/min

*Based on Heparin 60 U/kg bolus and 12 U/kg infusion, cap 4000/1000 and Integrilin reduced infusion dose if CrCl <50ml/min

Creatinine 1.0 mg/dl Creatinine 1.0 mg/dl

Weight 238 lbs Weight 108 lbs



Attention should be given to adjusting anti-platelet and anticoagulant doses based on weight and renal function (eg. estimated creatinine clearance) in older adults.


Excess Antithrombotic Dosing

12.5

28.7

8.512.8

3733.1

16.5

38.5

64.5

0

10

20

30

40

50

60

70

LMW Heparin UF Heparin GP IIb/IIIa

% E

xces

sive

Dos

e

< 65 yrs 65-75 yrs >75 yrs

REF: Alexander KA, JAMA 2005

Avoidable Risk


Mortality = 0.8%Bleeding = 6.5%Low Crusade Bleeding Risk

Mortality = 3.9%Bleeding = 18.2%Very High Crusade Bleeding Risk

D/C home day 3 Major Bleed, transfusion, volume overload, HFNEF, bouts of afib, hemodynamic instability, Confusion, ↑ LOS

*Based on Heparin 60 U/kg bolus and 12 U/kg infusion, cap 4000/1000 and Integrilin reduced infusion dose if CrCl <50ml/min

CRUSADE Bleeding Score

REF: Subherwal S. The Crusade Bleeding Score. Circulation 2009;119: Epub

HCT (%)CrCl (mL/min)

DM

FemaleSigns of CHFPVDHeart rate

SBP

REF: Subherwal S. The Crusade Bleeding Score. Circulation 2009;119: Epub

Major Bleeding with Antithrombotic therapy

≥2 Antithrombotics (anti-platelet [aspirin or clopidogrel], anti-coagulant, or GP IIb/IIIa; n=50,969; c-index 0.72)<2 Antithrombotics (anti-platelet, anti-coagulant, or GP IIb/IIIa; n=5,931; c-index 0.73)

REF: Subherwhal, Circ 2009;119: 1872-1882

Unavoidable Risk

Therapeutics in ACS Among Patients >90 Years Old

In-hospital Mortality by Number of Therapies

0

5

10

15

20

25

30

None One Two Three Four FiveNumber of Recommended Therapies*

(p<0.001 for trend)

% m

orta

lity

Age 75-89Age 90 and older

Major Bleeding by Number of Therapies

0

2

4

6

8

1012

14

16

18

20

None One Two Three Four FiveNumber of Recommended Therapies*

(p<0.01 for trend) (CABG Pts and contraindications excluded)

% m

ajor

ble

edin

g**

Age 75-89Age 90 and older

Mortality Major Bleeding

Even among oldest old – better outcomes with better adherence to ACC/AHA Guidelines

Optimal

- Skolnick et al, JACC 2007

(1) Acute Aspirin, (2) Acute Beta-blockers, (3) Acute Heparin, (4) GP IIb/IIIa inhibitors with PCI, (5) Cardiac Catheterization <48 hours

ACUITY: Major Bleeding in PCI CohortStrategy Matters

0%

2%

4%

6%

8%10%

12%

14%

16%

18%

<55 55-64 65-74 >=75

Hep + GPI Biv + GPI Biv alone

4.3 4.2

1.7

5.76.6

3.0

6.75.5

4.2

12.3

16.5

6.1

Patient AgeN=1376N=2121N=2240N=2052

P=0.006

P=0.001 P=NS

P<0.001

P=0.007

P=0.010 P=0.033

P=0.001

Excluding CABG-related bleeding REF: Lopes JACC 2009

NNT to prevent one major bleedAge <55 – NNT 38

Age >75 – NNT 16

% M

ajor

Ble

edin

g E

vent

s

Quality of Care for Hospitalized Elders and Post-Discharge Mortality

6,392 Vulnerable Elderly Patients identified a using VES-13 Survey

One year mortality based on adherence to Geriatric ACOVE Measures

REF: Aurora JAGS 2010;58: 1642-1648

ACOVE Quality of Care above Median = 18% reduction in 1 year death

Discharge PlanningAssess NutritionAssess CognitionAssess Mobility

Mobility interventionDelerium Management

Pressure Ulcer Management

Quality of Care for Hospitalized Elders and Post-Discharge Mortality

6,392 Vulnerable Elderly Patients identified a using VES-13 Survey

One year mortality based on adherence to ACOVE Measures

REF: Aurora JAGS 2010;58: 1642-1648

ACOVE Quality of Care above Median = 18% reduction in 1 year

death

MI – Discharge55yo ♀ 85yo ♀

ASA, Plavix, BB, Statin ASA, Plavix, BB, ACEi, Statin+

6 other medications

5 days returned to workFollow up appointment 1 weekEnrolled in Cardiac Rehab

At home alone during the dayNo follow up appointmentSedentary, weak

Discharge: Take-off and Landing• Successful Outpatient visit plan

– Early Follow up Appointment (Cardiology or Medicine)– Successful communication

• Return to Independent Function– Consider caregiver support, home safety

• Avoid Complications, Rehospitalization– Medication Review, Education, Simplification– Symptom Education– Clear Contact Information

Cardiac Rehab and Survival In Older Cardiac Patients

REF: Suaya JA et al, JACC 2009;54:25-33

>600,000 Medicare Beneficiaries (ICD-9: AMI, ACS, Stable CAD, CABG, PCI)

70,040 Propensity Matched Pairs; Regression Modeling; Instrumental Variable Analysis

Cardiac Rehab Participation = 21% to 34% lower Mortality



Consideration should be given to patient and family preferences, quality-of-life issues, end-of-life preferences, and sociocultural differences in older patients with UA/NSTEMI.


“What are the most important goals from the treatment of your heart disease?”

0

10

20

30

40

50

60

70

80

45-59 60-69 70-79 80+

Lengthen LifeMaintain Mental AbilityMaintain Independence

REF: Alexander ACC Abstract

Patient Age

% R

epor

ting

in T

op 3 N=626

STEMI Reperfusion

REF: Bueno, EHJ 2010;54:25-33

Conclusions Chronologic age ≠ biologic age

– Age 75 is cut point for altered paradigm of care– Comorbidities, altered physiology, function alter risk/benefit

Treatment recommendations similar….– Avoid errors of omission and commission– Dosing and delivery matter…perhaps more– Avoid hazards of hospitalization, transitions of care

Extending EBM to personalized care …– More representative trials– Best practice recommendations– Explicit discussions of patient goals for treatment– Transitions of Care, Goals of Care

Corinth Canal: Isthmus 5 miles long between Greece and Peloponnesus

Older Adult

Cardiologist

OUTCOMES

COMORBIDITYCOMPLICATIONS

http://ferrelljenkins.files.wordpress.com/2008/03/corinth_canal_t.jpg

Future Directions– Advance Science

• Adding Key data elements to large registry work• Comorbidity: non-cardiac issues that alter cardiac management• Physiology (Vascular Stiffness, HF NEF, Sinus node

dysfunction)• Genetics (Telomere length, genetic aging)

– Advance “Best Practice” and systems research• Drug Safety• Care models, collaboration• Transitions of care

– Broaden perspectives on goals of care• Functional Status and recurrent procedures

cardiovascular care of older adults: acute myocardial infarction

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