43

For patients presenting to a PCI-capable hospital, PCI should be performed within

90 minutes after initial medical contact (also referred to as “door-to-balloon time”).

If a patient is at a non-PCI facility, immediate transfer to primary PCI is preferred

only if PCI can be performed within 120 minutes of first medical contact.

5 This

threshold is based on a multivariant analysis of patients undergoing PCI in which an

increased door-to-balloon time exceeding 120 minutes

p. 248

p. 249

was associated with a higher mortality rate.

44 Fibrinolytic therapy should be given

to patients when the 120-minute time goal cannot be met, unless a contraindication is

present.

5

The disadvantages of PCI include the longer amount of time needed to mobilize the

personnel needed to prepare the catheterization laboratory and its initial higher cost.

A potential advantage of PCI is the greater ability to achieve TIMI grade 3 flow in

the affected vessel compared to fibrinolytic therapy (90% vs. 50%–60%,

respectively).

5 PCI is associated with fewer major adverse cardiac events,

irrespective of patient presentation time. Additionally, rates of major bleeding and

intracranial hemorrhage are lower with PCI compared to fibrinolytic therapy.

Unfortunately, many hospitals do not have the facilities or skilled personnel to

complete this procedure in the necessary time frame.

5

For NSTE-ACS, coronary angiography aids in defining the extent and location of

coronary lesion and in directing the definitive care strategy (e.g., PCI with stent

placement, CABG, or medical management). However, because angiography is an

invasive procedure, there is a small risk of serious complications. Therefore,

coronary angiography should be used only in patients for whom the procedure’s

benefits outweigh its risks. With this principle in mind, two pathways of treatment for

NSTE-ACS patients have emerged: the early invasive strategy and the ischemiaguided strategy (Fig. 13-6). In the early invasive strategy, all patients without

contraindications undergo coronary angiography with the intent to perform

revascularization within 24 hours of hospital admission. The ischemia-guided

strategy consists of aggressive medical therapy for all patients and coronary

angiography only for those with certain risk factors or who fail medical therapy.

CLINICAL PRESENTATION OF ACS

CASE 13-1

QUESTION 1: P.H., a 68-year-old, 80-kg man, is being admitted to the ED after experiencing an episode of

sustained chest pain while mowing his yard. After waiting 6 hours, he called 911 and was transported to the ED

to a facility without the ability to conduct PCI. Physical examination reveals an anxious and diaphoretic man.

Heart rate and rhythm are regular, and no S3

or S4

sounds are present. Vital signs include BP 180/110 mm Hg,

heart rate 105 beats/minute, and respiratory rate 32 breaths/minute. P.H.’s chest pain radiates to his left arm

and jaw, and he describes the pain as “crushing” and “like an elephant sitting on my chest.” He rates it as a

“10/10” in intensity. Thus far, his pain has not responded to five SL NTG tablets at home and three more in the

ambulance. His ECG reveals a 3-mm ST segment elevation and Q waves in leads I andV2

to V4

. Based on his

history and physical examination, P.H. is diagnosed with an anterior infarction. Laboratory values include the

following:

Sodium (Na), 141 mEq/L

Potassium (K), 3.9 mEq/L

Chloride (Cl), 100 mEq/L

CO2

, 20 mEq/L

Blood urea nitrogen (BUN), 19 mg/dL

Serum creatinine (SCr), 1.2 mg/dL

Glucose, 149 mg/dL

Magnesium (Mg), 2 mEq/L

CK, 1,200 U/L, with a 12% CK-MB fraction (normal, 0%–5%)

Troponin I-Ultra, 60 ng/mL (normal, <0.02 ng/mL)

Cholesterol, 259 mg/dL

Triglycerides, 300 mg/dL

P.H. has a prior history of CAD. A previous cardiac catheterization 2 years ago revealed lesions in his

middle left anterior descending coronary artery (75% stenosis) and proximal left circumflex artery (30%

stenosis). His echocardiogram at the time showed an EF of 58%. These lesions were deemed suitable for

medical management. He also has a history of recurrent bouts of bronchitis associated with bronchospasm for

10 years, diabetes mellitus treated with insulin for 18 years with a hemoglobin A1c of 6.8% obtained 6 months

prior to admission, and hypertension with BPs usually 140/85 mm Hg. His father died of an MI at age 70. His

mother and siblings are all alive and well. P.H. has smoked one pack of cigarettes a day for 30 years, and he

drinks approximately one six-pack of beer a week. He has no history of IV drug use. On admission, P.H.’s

medications include insulin glargine 40 units daily; albuterol inhaler as needed (PRN) for shortness of breath;

hydrochlorothiazide 25 mg daily; NTG patch 0.2 mg/hour; and NTG SL 0.4 mg PRN for chest pain.

What signs and symptoms does P.H. have that are consistent with the diagnosis of AMI?

P.H. described his pain as a pressure sensation, which is common with ischemic

heart disease. The chest discomfort associated with ACS often is described as

pressure or as a tight band around the chest rather than pain. Although P.H. was

involved in physical exertion when his chest discomfort began, this is not always the

case. It can begin at rest and, frequently, in the early morning hours. At least 20% of

patients with AMI have no pain or discomfort; these episodes are described as

“silent” MIs.

5 Presentations range from no symptoms to shortness of breath,

hypotension, HF, syncope, or ventricular arrhythmias. Silent or atypical infarctions

occur more commonly in people with diabetes and in the elderly. P.H. is diaphoretic,

a common finding, but other common symptoms such as nausea and anxiety are not

present. He also describes his pain as “10/10” in intensity, or perhaps “the worst

pain I’ve ever experienced,” which is typical of a STEMI. The diagnosis primarily

lies in the symptoms (e.g., the patient’s “story”), the ECG, and the laboratory

findings.

The history of diabetes, hypertension, smoking, and a positive family history in

P.H. are all risk factors for coronary disease. His admission BP is high, which could

indicate poor underlying control or anxiety and stress related to his ACS. The blood

sugar of 149 mg/dL is high, again indicating either poor control or a stress response.

Measurement of glycosylated hemoglobin is indicated during his hospitalization to

better assess his diabetes control.

Laboratory Abnormalities

CASE 13-1, QUESTION 2: What laboratory abnormalities can you expect to see in P.H.?

P.H. demonstrates several laboratory abnormalities commonly seen with both

STEMI and NSTEMI. Both his CK-MB and troponin are elevated, consistent with

myocardial necrosis. With UA, cardiac biomarkers are not elevated. Several other

nonspecific laboratory findings should be monitored in P.H. Hyperglycemia may

develop because P.H. has diabetes, but this can also occur in patients without

diabetes. ACS is also accompanied by an acute systemic inflammatory response

manifested by fever, leukocytosis, and elevation of the erythrocyte sedimentation rate

and C-reactive protein, as well as a drop in LDL, high-density lipoprotein, and total

cholesterol. Specifically, these lipoprotein changes may begin to decrease within 24

to 48 hours after an ACS event, reaching a nadir within 5 to 7 days and then gradually

recovering during the next 30 days.

45 Therefore, it is prudent to check serum lipid

profiles within the first 24 hours of the AMI to get an accurate determination of the

patient’s lipid values.

p. 249

p. 250

ST Segment Elevation Myocardial Infarction Versus

Non–ST Segment Elevation Myocardial Infarction

CASE 13-1, QUESTION 3: P.H. was noted to have ST segment elevation on the ECG. What are the

implications of an ST segment elevation versus non–ST segment elevation MI?

Perhaps the most important diagnostic test in someone suspected of having an AMI

is the ECG. The ECG is an important tool because it is noninvasive, can be

performed rapidly, is readily available in most settings, and helps determine where

the AMI is located (i.e., anterior, inferior, lateral). P.H. has classic ECG changes

(ST segment elevation), and presence in the anterior ECG leads (V2–V4

) points to the

coronary artery likely to be blocked. P.H.’s previous left anterior descending lesion

may have had a plaque rupture leading to thrombosis of the vessel.

The presence of ST segment elevation in two contiguous leads indicates severe

ischemia and occlusion of the coronary artery. Every effort should be made to open

the infarct-related artery as soon as possible, which could consist of PCI or

fibrinolytic therapy. If the ECG showed ST segment depression (e.g., NSTE-ACS),

instead of elevation, P.H. would not be eligible for fibrinolytic therapy because the

risks of fibrinolytic therapy outweigh the benefits in NSTE-ACS.

Anterior Versus Inferior Infarction

CASE 13-1, QUESTION 4: What are the prognostic implications of an anterior versus an inferior MI?

Damage to the anterior section of the heart is more likely to be associated with

increased morbidity (e.g., LV dysfunction) and mortality. The patients at highest risk

of death are those with an anterior ACS, LV dysfunction, and complex ventricular

ectopy. P.H. is at an increased risk because he has sustained an anterior infarction.

Risk Stratification

CASE 13-1, QUESTION 5: What is P.H.’s initial risk of mortality based on his presenting signs and

symptoms?

Using the TIMI Risk Score for STEMI, P.H. has a score of 6 based on his age (2

points); history of angina, hypertension, and diabetes (1 point); heart rate (2 points);

and location of his MI (1 point) (Table 13-1). P.H. has a 30-day mortality rate of

16%, thereby highlighting the serious nature of this event. If P.H. had experienced an

NSTE-ACS with ST segment depression, he would have a TIMI risk score of 5

based on his age (1 point); at least three risk factors for CAD (1 point), prior CAD

history (1 point), ST segment deviation (1 point), and elevated cardiac biomarkers (1

point). Based on this TIMI risk score, P.H. would be at high risk for death, MI, or

need for urgent coronary artery revascularization within 30 days.

Therapeutic Objectives

CASE 13-1, QUESTION 6: What are the immediate and long-term therapeutic objectives in treating P.H.?

With both STEMI and NSTE-ACS, the immediate therapeutic objectives

particularly as they apply to P.H. are to restore blood flow to the infarct-related

artery, arrest infarct expansion, alleviate his symptoms, and prevent death. These

objectives are achieved primarily by restoring coronary blood flow (administering a

fibrinolytic or performing PCI for STEMI or performing PCI with NSTE-ACS) and

lowering myocardial oxygen demand with nitrates and β-blockers. Any lifethreatening ventricular arrhythmias that develop must be treated. The long-term

therapeutic objectives are to prevent or minimize recurrent ischemic symptoms,

reinfarction, HF, and sudden cardiac death. As P.H. is experiencing a STEMI, the

specific therapeutic regimens are discussed in the questions that follow.

TREATMENT FOR ST SEGMENT ELEVATION

MYOCARDIAL INFARCTION

Fibrinolytic Therapy

CASE 13-1, QUESTION 7: Is P.H. a candidate for fibrinolytic therapy? Is any one agent preferred?

STEMI is a medical emergency, and rapid administration of drug therapy is crucial

to save myocardial tissue. The results of several major trials have shown

unequivocally that if used appropriately, fibrinolytic agents can reduce the mortality

associated with an AMI. Because mortality benefit is greatest when fibrinolytic

therapy is administered within 2 hours of symptom onset, prehospital fibrinolytic

therapy, in which trained paramedics administer the fibrinolytic in the field, is an

attractive option to reduce total ischemic time.

46

If primary PCI cannot be performed

within 120 minutes, fibrinolytic therapy should be given if no contraindications are

present. For patients who present >12 hours after symptom onset, fibrinolytic therapy

should be administered only if there is ongoing ischemia, hemodynamic instability or

a large area of myocardium is involved. In the case of P.H., he is admitted to a

hospital that is not PCI capable and cannot be transferred to a PCI-capable hospital

within 120 minutes of first medical contact.

Controversy still exists about which fibrinolytic should be used, the best dosing

regimen, the most appropriate adjunctive therapy, and whether the risk outweighs the

benefit in some subpopulations of patients (e.g., those with an inferior AMI). P.H.

has a history of hypertension, and at presentation his BP is 180/110 mm Hg. A BP

this high is a relative contraindication to fibrinolytic therapy because of an increased

risk of cerebral hemorrhage; however, P.H. has an anterior MI and is likely to benefit

from fibrinolytic therapy. In this case, he should receive IV NTG immediately

because the onset of BP control with this agent usually occurs within minutes. Once

his systolic BP is less than 180 mm Hg and the diastolic is less than 110 mm Hg, a

fibrinolytic can be administered. The NTG will also reduce the workload on his

heart and may provide pain relief.

Because P.H. has severe pain and ECG changes consistent with an anterior AMI,

he is at high risk for substantial morbidity or mortality. The argument for or against a

specific fibrinolytic is probably less important than the decision to use an agent and

to administer the medication as soon as possible after the onset of symptoms. P.H. is

fortunate because he has presented within 1 hour of the onset of chest pain. Options in

the United States include only fibrin-specific agents (Table 13-3).

Reteplase was compared with t-PA in the Global Utilization of Streptokinase and

t-PA for Occluded Arteries (GUSTO)-III trial.

47 Reteplase has a slower clearance

from the body, allowing the drug to be given as a bolus without the need for a

constant infusion. In the GUSTO-III trial, reteplase was administered in two bolus

doses of 10 million units, given 30 minutes apart. The mortality

p. 250

p. 251

rate and incidence of stroke were the same in the two groups of patients.

Tenecteplase (TNK) was compared with t-PA in the Second Assessment of Safety

and Efficacy of a New Fibrinolytic (ASSENT-2) trial.

48 Tenecteplase was

administered as a bolus of 30 to 50 mg for 5 to 10 seconds, based on body weight.

No difference existed between TNK and t-PA in 30-day mortality and stroke and

TNK had fewer bleeding complications. The 2013 guidelines do not explicitly

endorse one fibrinolytic versus another, and all are acceptable first-line agents.

Selection is usually based on clinician preference and hospital formulary.

ADJUNCT THERAPY

CASE 13-1, QUESTION 8: Orders are written for an infusion of t-PA along with UFH 4,000 units IV bolus,

followed by 960 units/hour by continuous infusion. Aspirin 325 mg is ordered stat. Are both UFH and aspirin

agents necessary?

The Second International Study of Infarct Survival (ISIS)-2 trial showed that the

combination of aspirin and streptokinase reduced mortality in patients with an AMI

by 42% compared to placebo.

49

In doses of 162 mg or more, aspirin generates a

prompt clinical antithrombotic effect as a result of its inhibition of thromboxane A2

production. Thus, immediate administration of 162 to 325 mg of aspirin in all

patients diagnosed with ACS is indicated. In the acute setting, aspirin should be

chewed because it is absorbed more quickly. All patients should receive low-dose

aspirin indefinitely after a diagnosis of ACS. If patients have a contraindication to

aspirin, clopidogrel can be substituted.

5

The use of UFH as adjunct therapy to prevent reocclusion has been evaluated in

many studies.

5 Because P.H. will receive t-PA, an IV UFH bolus followed by a

continuous infusion should be started before the end of the t-PA infusion. The

ACC/AHA guidelines recommend an initial UFH bolus of 60 units/kg (maximum of

4,000 units), followed by an initial infusion of 12 units/kg/hour (maximum of 1,000

units/hour) for 48 hours after fibrinolysis, with a targeted activated partial

thromboplastin time (aPTT) of 1.5 to 2 times the upper limit of normal. UFH should

always be considered in patients at high risk for systemic or venous embolism.

CASE 13-1, QUESTION 9: Would P.H. benefit from the addition of clopidogrel to his current drug regimen?

Two studies have evaluated the potential role of in-hospital clopidogrel as an

integral part of fibrinolytic therapy in patients with STEMI.

50,51 The Clopidogrel as

Adjunctive Reperfusion Therapy–Thrombolysis in Myocardial Infarction 28

(CLARITY-TIMI 28) evaluated patients with STEMI who received standard

fibrinolytic therapy, aspirin, and UFH, and were scheduled for angiography within 2

days.

51 Patients received either clopidogrel (300 mg loading dose, followed by 75

mg daily) or placebo within 10 minutes of fibrinolytic administration. Clopidogrel

was continued up to and including the day of angiography and then stopped. The

primary end point was the composite of an occluded infarct-related artery on

predischarge angiography or death or an MI up to the start of coronary angiography.

Compared with placebo, patients receiving clopidogrel demonstrated a 36%

reduction in the primary end point (p < 0.001). By 30 days, the clopidogrel treatment

group had a 20% reduction in cardiovascular death, recurrent MI, or recurrent

ischemia (p = 0.03). No difference in the rate of major bleeding was seen between

groups. In a substudy of patients proceeding to nonemergent PCI after fibrinolytic

therapy, patients receiving pretreatment with clopidogrel demonstrated a 66%

reduction in 30-day mortality compared with those receiving placebo (p = 0.034).

52

The Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT)

evaluated the effect of clopidogrel 75 mg daily (with no loading dose) or placebo in

45,852 patients presenting with STEMI.

50

In the trial population, 93% had ST

segment elevation or bundle branch block, 7% had ST segment depression, and 54%

were treated with fibrinolytic therapy. The initial clopidogrel dose was given within

24 hours of symptom onset and continued until hospital discharge or up to 4 weeks in

the hospital. Compared with placebo, clopidogrel was associated with a 9%

reduction in death, reinfarction, or stroke (p = 0.002), and a 7% reduction in allcause mortality (p = 0.03). No significant excess in bleeding was noted with

clopidogrel, either overall or in patients who received concomitant fibrinolytic

therapy or were older than 70 years. On the basis of these two studies, P.H. should

receive clopidogrel as an inpatient.

CASE 13-1, QUESTION 10: What dose of clopidogrelshould be considered?

According to the 2013 ACC/AHA guidelines, clopidogrel should be added to

aspirin in patients who undergo reperfusion with fibrinolytic therapy.

5 A loading

dose of clopidogrel 300 mg can be administered with fibrinolytic therapy followed

by 75 mg/day for maintenance. The maintenance dose should be continued for 14

days and up to 1 year. The 1-year duration is extrapolated from experience with

NSTE-ACS.

1 There are no studies evaluating a 600-mg loading dose in patients with

STEMI treated with fibrinolytics. Additionally, uncertainty exists about the safety of

giving a loading dose of clopidogrel in adults 75 years of age and older, particularly

when they receive a fibrinolytic. Therefore, in this population, a loading dose should

be avoided. A single loading dose of 300 mg of clopidogrel should be given to

patients less than 75 years of age who receive a fibrinolytic agent and are

subsequently proceeding to PCI within 24 hours.

5

If the patient received a fibrinolytic

and then proceeds to PCI after 24 hours has lapsed, then a loading dose of 600 mg is

preferred. For P.H., a loading dose of 300 mg of clopidogrel should be administered

at the time of fibrinolytic administration followed by 75 mg/day for 14 days to 1

year. Because P.H. has already received 325 mg of aspirin in the ED, he should

continue 81 mg of daily aspirin indefinitely.

CASE 13-1, QUESTION 11: What roles do the other anticoagulant and antiplatelet agents have in P.H.’s

management?

Data available with the newer P2Y12

inhibitors when used in the setting of

fibrinolytic therapy are lacking. It would be prudent to avoid giving prasugrel and

other potent P2Y12 antagonists no sooner than 24 hours after administration of a

fibrinolytic.

5 Coronary anatomy should be known to ensure the patient is not a

candidate for CABG.

The replacement of UFH with a LMWH, factor Xa inhibitor, or the addition of a

GP IIb/IIIa inhibitor to fibrinolytic therapy has been evaluated in patients with

STEMI.

In the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction

Study-25 (ExTRACT-TIMI 25), 20,506 patients with STEMI scheduled for

fibrinolytic therapy were randomized to receive either enoxaparin or continuous

infusion of UFH for 48 hours.

53 Enoxaparin was dosed according to age and renal

function. UFH was dosed according to weight and adjusted to achieve an aPTT 1.5 to

2.0 times control. The composite end point of death or nonfatal MI through 30 days

occurred in 12.0% in the UFH group and 9.9% in the enoxaparin group, representing

a 17% risk reduction (p < 0.001). No difference was noted in mortality between the

two groups. Major bleeding was higher in the enoxaparin group.

p. 251

p. 252

The Organization for the Assessment of Strategies for Ischemic Syndromes

(OASIS) 6 was a randomized double-blind trial of 12,092 patients with STEMI

assessing the effect of early initiation of fondaparinux with primary PCI and medical

therapy.

54 The study compared the effects of fondaparinux with two different control

arms. Patients with confirmed STEMI were assigned into one of the two following

strata. Stratum 1: no indication for UFH (patients receiving streptokinase or those not

receiving a thrombolytic agent) were assigned to this stratum. Stratum 2: indication

for UFH (patients receiving alteplase, reteplase, or tenecteplase, and those

undergoing primary PCI) were assigned to this stratum. Death or reinfarction at 30

days was significantly reduced in the fondaparinux group. However, fondaparinux

did not benefit patients who were managed with primary PCI. Although the rates of

death, MI, and severe bleeds did not differ in these patients, there was a higher rate

of catheter thrombosis with fondaparinux.

54

The TIMI-14 trial demonstrated enhanced reperfusion (TIMI 3 flow) using

reduced-dose t-PA combined with abciximab compared with full-dose t-PA alone.

55

The GUSTO-V trial compared standard-dose reteplase to half-dose reteplase plus

full-dose abciximab in STEMI patients.

56 The combination group had less

reinfarction and recurrent ischemia, but more episodes of moderate and severe

bleeding, especially in the elderly. Similar rates of enhanced reperfusion have also

been observed with the combination of double-bolus dose eptifibatide (180/90

mcg/kg, 10 minutes apart) with a 48-hour infusion (2 mcg/kg/minute) plus half-dose tPA (50 mg).

57 The ASSENT-3 trial assessed three regimens: (1) full-dose TNK plus

enoxaparin or (2) full-dose TNK plus UFH or (3) half-dose TNK plus UFH with a

12-hour infusion of abciximab. The addition of either abciximab or enoxaparin to

TNK reduced the composite end point of 30-day mortality, in-hospital reinfarction,

or ischemia compared with UFH. More major bleeding complications were seen

with abciximab compared with UFH.

58

In a meta-analysis of 11 trials involving

27,115 STEMI patients who received adjunctive abciximab in addition to either PCI

or fibrinolytic therapy, use of abciximab was associated with a significant reduction

in 30-day (p = 0.047) and 1- to 6-month mortality (p = 0.01) in patients undergoing

PCI but not in those receiving fibrinolytic therapy.

59 Despite an improvement in

patency rates, the combination of GP IIb/IIIa inhibitors with either full- or half-dose

fibrinolytic should be avoided if at all possible, especially in the elderly.

5

Based on data from ExTRACT-TIMI 25 and OASIS-6, the ACC/AHA guidelines

allow for substitution of UFH with either enoxaparin or fondaparinux.

5 However,

whereas fondaparinux appeared to be superior to control therapy in the OASIS-6

trial, relative benefit compared with placebo and UFH separately cannot be reliably

determined.

60

If enoxaparin or fondaparinux are selected, anticoagulation should be

continued for the duration of the hospitalization, up to 8 days or until

revascularization. For P.H., enoxaparin would be the more appropriate choice;

however, he will have a higher risk for bleeding and need to be monitored closely.

Because P.H. is not undergoing PCI, the bleeding risks outweigh any benefit from the

addition of a GP IIb/IIIa at this time.

5

DETERMINATION OF REPERFUSION

CASE 13-1, QUESTION 12: How can you monitor for successful reperfusion in P.H. after he has received

fibrinolytic therapy?

It is important to determine whether thrombolysis has been successful because the

prognosis of the patient is related to the presence or absence of an open infarctrelated artery. If fibrinolytic therapy fails to open the infarct-related artery, then the

patient may benefit from PCI or a CABG. Although coronary angiography has been

the standard for determining the success of reperfusion, this procedure is expensive

and may be misleading, as some studies have suggested that microvascular perfusion

may be impaired even when TIMI grade 3 flow has been achieved. A simple and

readily available technique is evaluation of ECG ST segment resolution. A resolution

of more than 50% of the ST segment elevation at 60 to 90 minutes after the initiation

of fibrinolytic therapy is a good indicator of improved myocardial perfusion.

5 Relief

of symptoms, maintenance or restoration of hemodynamic or electrical stability or

both, and a reduction of >70% in the initial ST segment elevation are all suggestive

of adequate reperfusion. P.H. should undergo a 12-lead ECG to evaluate

reperfusion.

5

CASE 13-1, QUESTION 13: P.H. continues to have chest pain, should the thrombolytic be readministered?

READMINISTRATION OF THROMBOLYTIC AGENTS

Reocclusion of the infarct-related artery after initial successful thrombolysis is a

major setback. If reocclusion occurs, mechanical intervention (e.g., PCI) is often

attempted. Several studies have evaluated whether to readminister the fibrinolytic or

refer the patient for PCI. In a meta-analysis of eight trials of patients with STEMI

who failed fibrinolytic therapy, those receiving rescue PCI showed no significant

reduction in all-cause mortality, but had a 27% risk reduction in HF (p = 0.05) and

42% reduction in reinfarction (p = 0.04) when compared with standard medical

therapy. Repeat fibrinolytic therapy was not associated with significant

improvements in all-cause mortality or reinfarction. Both treatment strategies

demonstrated a significant increase in minor bleeding, but PCI was associated with

an increase in stroke.

61 The Rapid Early Action for Coronary Treatment (REACT)

study found that patients who received rescue PCI compared to repeat fibrinolytic or

conservative care had a significantly lower composite of death, reinfarction, stroke,

or severe HF at 6 months (event-free survival rate: 84.6% vs. 70.1% vs. 68.7%,

respectively, p = 0.004).

62 The ACC/AHA guidelines recommend that patients who

have failed fibrinolytic therapy undergo catheterization with appropriate

antithrombotic therapy if possible.

5 Patients best suited for catheterization consist of

those with high-risk features such as cardiogenic shock, significant hypotension,

severe HF, or ECG evidence of an extensive area of myocardial jeopardy.

In the case of P.H., a repeat infusion with t-PA would probably be safe, but it may

not be effective. If a PCI-capable institution exists, P.H. should be transferred for an

invasive strategy at this time.

USE IN THE ELDERLY

CASE 13-1, QUESTION 14: If P.H. had been 85 years of age, should he have still received fibrinolytic

therapy?

Some of the early trials with fibrinolytic therapy excluded the elderly. Although

the elderly may have a higher prevalence of relative contraindications such as severe

hypertension or history of stroke at presentation, they also have a higher incidence of

mortality after an AMI. The 30-day mortality rate after an AMI is 19.6% for patients

between 75 and 84 years of age and 30.3% for those who are 85 years of age and

older.