ACS in elderly

Author : Rina Ariani

Jumat, 08 Januari 2010 09:40:07

Dipresentasikan : Jum'at, 8 Januari 2010

Introduction
Elderly patients, often referred as patients aged > 75 years, represent approximately 30% of the total population
requiring medical care for acute coronary syndromes (ACS) and account for about 60% of overall mortality due to
ACS, and the incidence of ACS in the elderly is projected to increase due to advances in prior ACS treatment in an
aging population.(1) There are plenty of clinical trials published information regarding treatment of acute coronary
syndrome (ACS), but unfortunately there is a paucity of data to guide the evaluation and management of ACS in
the elderly, as only a minority of published clinical trials included elderly patients. Even when elderly patients are
enrolled in clinical trials, they typically account only for a disproportionately small number of the study population
and age-subset-specific results are often not reported. Indeed, patients above 75 years of age comprise only 9% of
clinical trial populations and only about 50% of trials enroll patients above the age of 75.(2) Data guiding coronary
reperfusion in elderly ACS patients are limited and comprise mostly of subset analyses from major trials and
retrospective studies. Thus, information is sparse to guide the care of this high risk ACS subset. The impact of age
alone for outcome of ACS based on GRACE risk model could be seen on table below.

Table.1 The impact of age alone for outcome of ACS based on GRACE risk model.(3)
The aim of this presentation is to review management of ACS in elderly, weighing the risk and benefit of
treatment, focused on revascularization and ancillary therapy selection.

Case Illustration
Mr. H, 84 years old, came to emergency department National Cardiovascular Center Harapan Kita Jakarta (NCCHK)
with chief complaint of chest pain since 3 hours before admission. The pain was felt like heaviness on the left side
of the chest, radiated to the back, with duration more > 30 minutes. The patient then took ISDN 5 mg sublingualy,
but it only improve nonsignificantly, He also felt diaphoresis, but with no dyspnea, nausea nor vomiting. He never
felt like this before, daily he could do his routine activity without limitation. He only took Blopress 1x 16 mg, daily
for his hypertension. History of dyslipidemia, diabetes, or family history was not known. He already stopped
smoking more than 20 years ago. There was no history of stroke before.
At admission, he still feel the pain. He was alert, his vital sign showed BP 142/64 mmHg, HR 89x/min, RR 22 x/min,
afebrile. His general examination was within normal limit. His ECG (Figure.1) showed sinus rhythm, HR 90 x/min,
axis 60, normal P wave, PR int 0,16, QRS duration 0,08, QS in II, III, aVF, V1-V6, ST elevation 1-5 mm at II, III,
AVF, V1-V6. Chest x ray (Figure.2) showed CTR of 60%, dilated aortic segment, normal cardiac waist, downward
apex, there was sign of congestion and infiltatre over both lung fields. His lab result was shown in table.2.
Figure.1 ECG of the patient on admission

Figure.2 Chest x-ray on admission

Hb 14.3 gr/dL Ureum 38 Natrium 143 mmol/L
Leucocyte 13.100 /uL Creatinin 1.2 mg/dL Kalium 4,7 mmol/L
Hematocrit 41% GDS 303 Calsium 2,4 mmol/L
CKMB 110 Trop T 16, 8 Magnesium 1,8 mmol/L
Table. 2 Laboratory result on admission
He was first diagnosed as having acute extensive anterior and inferior STEMI, onset of 3 hours, with Killip I TIMI
risk score 5/14, stage I hypertension, and diabetes mellitus type 2 (differential diagnosed with reactive
hyperglycemia). at emergency department, he was given nasal oxygen 4 l/min, nitroglycerin iv starting from
5ug/min uptitrated, insulin iv starting from 2 UI/hour adjusted with glucose level, clopidogrel loading 300 mg
continued with maintenance dose 75 mg daily, aspirin loading 160 mg chewed continued with 80 mg daily,
simvastatin 1x20 mg, diazepam 5 mg daily, and laxative. The patient was planned for primary PCI, but the family
refused to do the intervention. Unfractionated heparin was started with loading dose of 3500 ui continued with
maintenance dose of 700 ui, adjusted with APTT level.
Patient was then transferred to CVC. At CVC he was no longer felt the pain, the hemodinamic was stable. At day 1
hospitalization the patient had hematemesis + 50 cc, and antother 200 cc after nasogastric tube was inserted.
Patient was given omeprazole 20 mg iv bid, sucralfat 15 cc tid, heparin iv, aspirin and clopidogrel were stopped.
Captopril 6,25 tid, ISDN 5 mg tid, and ceftriaxone iv 1 gr bid were added to therapy. Monitoring of hemoglobin
level was performed regularly, with result shown in table.3. During day -1 observation, the patient was stable
despite ongoing hematemesis-melena.
Day 1 2
Hb 14,7 15,3 14,7
Ht 44 48 45
Table.3 Follow up Hb and Ht level
Echocardiography was performed at that day, showing normal LV dimension (EDD 40 ESD 250), slightly reduced EF
(EF 40%, sipmson), there was akinetic on apical segment, and hypokinetic on septoapical. Other segmen
normokinetic. RV function was normal (TAPSE 1,7 cm), all valves were normal.
At day 3 hospitalization, the patient had decreased level of conciousness, and looks tachypneic. There was rhonki
heard at both lung fields. His BP was 110/70 mmHg, HR 98x/min, RR 40x/min temp 39.2 Blood gas analysis
showed partially compensated metabolic asidosis (pH 7,41/pO2 95/pCO2 20/HCO3 12,4/BE -9/Sat 95%, and
leucocyte increase to 16.300/ uL. He was diagnosed as having community acquired pneumonia, and suspected for
intracranial hemorrhage. The antibiotics was changed to Meropenem iv 1 gr bid and Netylmycin iv 300 mg od,
antipyretics, and correction for acidosis. and planned to have brain CT-scan to confirm the diagnosis, but the
condition was getting worse shortly after. The family decided to sign for DNR, and the patient died on day 3
hospitalization.
Discussion
Management for ACS in older persons present with a number of special and complex challenges. Elderly are more
likely to present with atypical symptoms, including dyspnea and confusion, rather than with the chest pain
typically experienced by younger patients with acute myocardial ischemia. Conversely, noncardiac comorbidities
such as chronic obstructive lung disease, gastroesophageal reflux disease, upper-body musculoskeletal symptoms,
pulmonary embolism, and pneumonia also are more frequent and may be associated with chest pain at rest that
can mimic classic symptoms ACS. Hence, successful recognition of true myocardial ischemia in the elderly is often
more difficult than in younger patients. They are also more likely to have abnormal cardiovascular anatomy and
physiology, such as diminished betasympathetic response, increased cardiac afterload due to decreased arterial
compliance and arterial hypertension, orthostatic hypotension, cardiac hypertrophy, and ventricular dysfunction.

Older patients also typically have concomitant cardiac comorbidities and risk factors, such as hypertension, prior
MI, HF, cardiac conduction abnormalities, prior CABG, peripheral and cerebrovascular disease, diabetes mellitus,
renal insufficiency, and stroke. And because of this larger burden of comorbid disease, these group of people tend
to be treated with a greater number of medications and are at higher risk for drug interactions and polypharmacy.
Hence, among an already high-risk population, older age is associated with higher disease severity and higher
disease and treatment risk at presentation.(1, 4)
Medication side effects are also more common in elderly patients due to differences in drug absorption,
metabolism, distribution, and excretion. Therefore, special attention must be directed to avoid adverse drug
interactions as well as ensuring appropriate medication dose adjustment according renal function. The
complication rates of PCI, thrombolysis, anticoagulation, and antiplatelet therapies exceed that observed in
younger patients. However, elderly ACS patients are also more likely to benefit from appropriate therapies, owing
to their higher risk status.(5-6)
Revascularization strategy in elderly
Many elderly STEMI patients also do not meet ideal criteria for reperfusion therapy for either PCI or fibrinolysis,
due to their delayed and ECG changes that are abnormal at baseline or of unclear duration. In addition, many
elderly present without ongoing chest pain, and up to 9% have absolute contraindications to fibrinolytic
therapy.(5)
From ACC/AHA guideline in 2004, it is stated that primary PCI is reasonable for selected patients 75 years or older
with ST elevation or LBBB or who develop shock within 36 hours of MI and are suitable for revascularization that
can be performed within 18 hours of shock. Patients with good prior functional status who are suitable for
revascularization and agree to invasive care may be selected for such an invasive strategy (Class IIa, Level of
Evidence: B).(7) Data from the GUSTO IIb substudy l showed that primary PCI was superior to thrombolysis in all
age subgroups, with elderly patients deriving the most benefit.(8) A metaanalysis that included 10 trials comparing
thrombolysis with PCI showed that 30-day mortality in patients over 70 years was halved in the PCI group
compared to thrombolysis.(9) Again, elderly patients derived the greatest benefit compared to their younger
counterparts. In two retrospective analyses of Medicare STEMI in patients aged > 65 years, primary PCI was
superior to both thrombolysis and medical therapy in reducing both, 30-day mortality and 1- year mortality.(10)
The risk of major bleeding, including intracerebral hemorrhage, is increased with thrombolytic use compared to
PCI. How ever, based on small randomized trials, meta-analyses, and observational studies, it seems that risk
benefit ratio favors PCI over fibrinolytic therapy in the elderly. The major benefit from PCI is a reduction in
reinfarction and need for target-vessel revascularization. Mortality reductions trend in the same direction but are
less robust.(5)
Thrombolytics, though less preferable to PCI, improve outcomes in elderly STEMI patients compared to lack of
revascularization. Subgroup comparisons from trials have shown that fibrinolytic therapy, as compared with
placebo, reduces mortality rates in the elderly.(2, 5) A pooled analysis of 28 896 patients from the GISSI-1 and ISIS2 trials showed that thrombolytics were associated with a survival benefit in elderly STEMI patients, with
combined absolute benefit of 39/1000 patients treated with streptokinase compared to placebo (p=0.02).(11) The
Fibrinolytic Therapy Trialists (FTT) Collaborative Group demonstrated a greater absolute reduction in death in
elderly subjects (>75 years of age) treated with fibrinolytic therapy. Subgroup analysis that limited the original
population to those meeting contemporary eligibility criteria for fibrinolytic therapy (presentation within 12 hours
and ST-segment elevation or bundle-branch block) demonstrated a significant relative reduction in mortality rate
of 15% (P=0.03) in patients >75 years of age. Although the relative reduction was less in the elderly than in
younger patients (<55 years of age), the absolute benefit in terms of lives saved was 3-fold higher (34 lives per
1000 treated versus 11 lives per 1000 treated) and extended to age 85 years.(12) The consensus, as described in
the ACC/AHA guidelines, is that thrombolytics should be used for elderly STEMI patients in the absence of
contraindications if PCI is not promptly available.(7)
Meanwhile, for rescue PCI after failed thrombolytics ACC/AHA had updated the guideline in 2007, and gave
different class of recommendation between high risk patients aged less than 75 years (Class I indication), and
elderly patients (Class IIa Indication), showing that consideration for such management should be done selected
patient after weighing the risk and benefit of intervention.(13)

In this case, with patient aged of 85 years old, fortunately came with typical symptom of acute coronary
syndrome, and his ECG showing ST elevation in extensive anterior and inferior segment, and ongoing chest pain.
He met the criteria suitable for revascularization (ST elevation MI onset within 12 hours, with good prior functional
status), so primary PCI seems the best method for reperfusion. Unfortunately, the family refused to do so.
Meanwhile, the risk-benefit ratio to do thrombolytic for this patient is somehow contradictory. Most trials
studying the benefit of fibrinolytics limit their conclusion to patient aged below 85 years old. In GUSTO trial, which
include 415 subjects aged > 85 years showed the greatest mortality risk and stroke events, and revealed wide
variety of outcome.
Ancillary therapy
Aspirin should be given to all STEMI patients as soon as diagnosis is deemed probable.(14). Guideline for
antiplatelet therapy could be seen on table.2. In elderly STEMI patients who receive thrombolytics, a loading dose
of clopidogrel is not recommended due to increased risk of intracerebral hemorrhage A loading dose of
clopidogrel is recommended in elderly STEMI patients only if primary PCI is performed. The recommended dose is
600 mg orally, before or at the time of PCI, which produces rapid antiplatelet activity.(15) No data are available to
guide decision making regarding an oral loading dose of clopidogrel in patients 75 years of age or older who
receive fibrinolytic treatment or who do not received reperfusion therapy.(13)
Intracranial hemorrhage (ICH) and nonhemorrhagic stroke are devastating complications of fibrinolysis that
increase with age. However, these complications are rare in trial populations (1.5% overall and 2.9% of those > 85
years of age) The interaction between age and reduced dosing of adjunctive heparin minimizes risks of bleeding
without compromising efficacy. Although unfractionated heparin appears preferable in some studies, lowmolecular-weight heparin, when delivered in an adjusted dose, has been shown to result in superior outcomes.(5)
Based on ESC guideline for persistent ST elevation MI in 2008 , and ACC/AHA focused update for management of
STEMI patients in 2007, it was mentioned that there was no need to give loading dose of enoxaparin for elderly
patients, and maintenance dose should be reduced on first administration. With fibrinolytic treatment, the dosage
of enoxaparin in should be reduced to 0,75 mg/kg for the first two doses, with maximum total two doses of 75
mg.(13-14). ESC guideline 2008 also stated information regarding the use of antithrombotic agent in patient who
did not received reperfusion therapy, as seen on table.4
Based on the data above, there is no evidence benefit to give oral loading dose of clopidogrel in this patient,
considering patient did not received reperfusion therapy and older age. Oral maintenance dose of clopidogrel 75
mg daily might be the best treatment option.
Table.4 Left : Doses from antiplatelet co-therapies. Right : Antithrombotic treatment without reperfusion
therapy(14)
Regarding the selection of antithrombotic agent in this patient, considering age and CCT level, this patient could
received either unfractionated heparin or low molecular weight heparin, with consideration of not giving loading
dose if we choose to had enoxaparin. In SYNERGY trial, it is stated that although higher rates of adverse events are
seen in the oldest subgroup (age >75 years) treated with enoxaparin, statistical comparisons confirm similar
efficacy and safety of enoxaparin and UFH across age subgroups.(16)
Summary
Elderly, which donate for 30% patient requiring medical care for acute coronary syndromes still ended with high
mortality. Clinical trials held for acute coronary syndrome management seems still unrepresentative for this group
age. A case presentation of male, 84 years old, came to hospital with typical infarction angina, ECG consistent for
acute extensive anterior and inferior MCI and clinical condition suitable for revasculatization, planned for primary
PCI but canceled due to family refusal. The patient then had conservative management, but during hospitalization
the condition got worse and finally died due to pulmonary infection and suspicion for intracranial hemorrhage.

Reference
1. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE, Jr., et al. ACC/AHA 2007 guidelines for the
management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American
College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise
the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial
Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for
Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American
Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine.
Circulation. 2007 Aug 14;116(7):e148-304.
2. Jokhadar M, Wenger NK. Review of the treatment of acute coronary syndrome in elderly patients. Clin Interv
Aging. 2009;4:435-44.
3. Avezum A, Makdisse M, Spencer F, Gore JM, Fox KA, Montalescot G, et al. Impact of age on management and
outcome of acute coronary syndrome: observations from the Global Registry of Acute Coronary Events (GRACE).
Am Heart J. 2005 Jan;149(1):67-73.
4. Nadelmann J, Frishman WH, Ooi WL, Tepper D, Greenberg S, Guzik H, et al. Prevalence, incidence and prognosis
of recognized and unrecognized myocardial infarction in persons aged 75 years or older: The Bronx Aging Study.
Am J Cardiol. 1990 Sep 1;66(5):533-7.
5. Alexander KP, Newby LK, Armstrong PW, Cannon CP, Gibler WB, Rich MW, et al. Acute coronary care in the
elderly, part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals
from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric
Cardiology. Circulation. 2007 May 15;115(19):2570-89.
6. Alexander KP, Newby LK, Cannon CP, Armstrong PW, Gibler WB, Rich MW, et al. Acute coronary care in the
elderly, part I: Non-ST-segment-elevation acute coronary syndromes: a scientific statement for healthcare
professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society
of Geriatric Cardiology. Circulation. 2007 May 15;115(19):2549-69.
7. Eagle KA, Guyton RA, Davidoff R, Edwards FH, Ewy GA, Gardner TJ, et al. ACC/AHA 2004 guideline update for
coronary artery bypass graft surgery: summary article: a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary
Artery Bypass Graft Surgery). Circulation. 2004 Aug 31;110(9):1168-76.
8. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial
infarction. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO
IIb) Angioplasty Substudy Investigators. N Engl J Med. 1997 Jun 5;336(23):1621-8.
9. Zijlstra F, Patel A, Jones M, Grines CL, Ellis S, Garcia E, et al. Clinical characteristics and outcome of patients with
early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary coronary angioplasty or
thrombolytic therapy for acute myocardial infarction. Eur Heart J. 2002 Apr;23(7):550-7.
10. Berger AK, Schulman KA, Gersh BJ, Pirzada S, Breall JA, Johnson AE, et al. Primary coronary angioplasty vs
thrombolysis for the management of acute myocardial infarction in elderly patients. JAMA. 1999 Jul
28;282(4):341-8.
11. Berger AK, Radford MJ, Wang Y, Krumholz HM. Thrombolytic therapy in older patients. J Am Coll Cardiol. 2000
Aug;36(2):366-74.
12. White HD. Thrombolytic therapy in the elderly. Lancet. 2000 Dec 16;356(9247):2028-30.
13. Antman EM, Hand M, Armstrong PW, Bates ER, Green LA, Halasyamani LK, et al. 2007 Focused Update of the
ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction: a report of
the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in
collaboration With the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians:
2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of
Patients With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing Committee. Circulation.
2008 Jan 15;117(2):296-329.
14. Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, et al. Management of acute myocardial
infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-

Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2008
Dec;29(23):2909-45.
15. Kushner FG, Hand M, Smith SC, Jr., King SB, 3rd, Anderson JL, Antman EM, et al. 2009 Focused Updates:
ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004
Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention
(updating the 2005 Guideline and 2007 Focused Update): a report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2009 Dec 1;120(22):2271306.
16. Lopes RD, Alexander KP, Marcucci G, White HD, Spinler S, Col J, et al. Outcomes in elderly patients with acute
coronary syndromes randomized to enoxaparin vs. unfractionated heparin: results from the SYNERGY trial. Eur
Heart J. 2008 Aug;29(15):1827-33.
4/10/09
Hb 14.7 Chol 187
Ht 44 HDL 50
Uric Acid 7,0 LDL 135
RBG 193 Trig 61
HbA1c 6,7
CKMB 110
Trop T 16,89