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 ISIS-2 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, low-molecular-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
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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.
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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
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