guideline-based management of a patient with stemi · guideline-based management of a patient with...
TRANSCRIPT
Guideline-Based Management of a Patient With STEMI Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI
Patient History
KD, a 73-year-old woman, presented to the emergency department with burning pain in her chest. She arrived by
ambulance at 12:37 AM after calling 911 at 12:14 AM. While the ambulance was en route to the hospital, the crew gave her
sublingual nitroglycerin and had her chew an aspirin tablet. In her interview with the triage nurse, KD stated that the pain
woke her from sleep at about 11 PM. She tried some of her husband's over-the-counter antacid tablets but the pain
worsened and she decided to call 911. She has no history of heart disease or heartburn. She was placed on a cardiac
monitor, which found a heart rate of 110 beats/min.
What is the appropriate next action for this patient?
Take a detailed history and perform a physical examination
Take blood samples for troponin testing
Perform 12-lead electrocardiography (ECG)
Take a chest x-ray
Possible symptoms of STEMI include chest discomfort or pain, which may radiate to other locations; shortness of breath;
diaphoresis; nausea; light-headedness; and anginal equivalents.[1]
Chest discomfort or pain is particularly suggestive of STEMI, and the current American Heart Association/American College
of Cardiology (AHA/ACC) guidelines state that a 12-lead ECG should be obtained and examined within 10 minutes of arrival
at the emergency department for all patients who present with chest discomfort, anginal equivalents, or other symptoms
suggestive of STEMI. The 12-lead ECG is a core element in the diagnostic pathway for STEMI and is critical to early
diagnosis and identification of patients who require early effective therapy.[1] Medical history, blood tests, and x-rays are an
important part of the workup and are secondary to ECG for accurate and initial diagnosis.
By what percentage does a 30-minute delay in reperfusion increase 1-year mortality in patients with
STEMI?
1%
7.5%
15%
30%
Rapid reperfusion is a critical goal in treating patients who have had STEMI. Regardless of the method, the time between
symptom onset and reperfusion is a key factor in determining outcome. For instance, a study by De Luca and colleagues[2] in
patients who underwent primary percutaneous coronary intervention (PCI; n = 1791) found that a 30-minute delay in
reperfusion causes a 7.5% relative increase in 1-year mortality. Similarly, a study by McNamara and colleagues[3] using data
from the National Registry of Myocardial Infarction (NRMI) found that mortality increased with increasing door-to-balloon
time in 29,222 patients with STEMI. The mortality rate was 3.0%, 4.2%, 5.7%, and 7.4% for door-to-balloon times of ≤ 90
min, 91-120 min, 121-150 min, and > 150 min, respectively; P for trend: < .01).
Because of the close relationship between reperfusion time and outcomes, it is important to minimize the delay between
symptom onset and reperfusion. Much of this delay (ie, door-to-needle time for fibrinolytic therapy or door-to-balloon time for
PCI), occurs at the hospital and can be minimized by optimizing the hospital's protocols. However, the time between
symptom onset and arrival at the emergency department is also important. Several approaches have been used to try to
minimize this delay.
Patient education is a critical issue. Many patients do not recognize the symptoms of STEMI, particularly atypical symptoms.
Those who do not recognize their symptoms as indicating a possible heart attack are unlikely to call 911 right away, as
occurred in this case, or even at all. Patient education programs are ongoing at the national level. These include the
National Heart, Lung and Blood Institute's "Act in Time to Heart Attack Signs" program and the AHA's "Mission Lifeline."
Both programs are intended to teach patients to recognize heart attack signs, go to the hospital earlier, and be transported
via ambulance.[4,5]
Appropriately trained and equipped emergency response systems can also decrease the time to treatment by acquiring a
prehospital ECG or providing prehospital fibrinolysis. According to the STEMI guidelines put forth by the ACC and the AHA,
prehospital ECGs are an effective but underused strategy for improving care of patients with STEMI.[6] Unfortunately, the
barriers to implementation of prehospital ECG systems are substantial, and implementation is far from universal in the
United States.[7]
Prehospital fibrinolysis also appears to be effective. A meta-analysis found that prehospital fibrinolysis was associated with
significantly less mortality than in-hospital fibrinolysis.[1] In the CAPTIM (Comparison of Angioplasty and Prehospital
Thrombolysis in Acute Myocardial Infarction) trial, prehospital fibrinolysis was not inferior to PCI and appeared to be superior
to PCI for patients treated within 2 hours of symptom onset.[1,8,9]
Which statement correctly describes patients with STEMI who present with atypical or typical
symptoms?
Approximately 33% of STEMI patients present with atypical symptoms (ie, no chest pain or
discomfort)
Approximately 8% of STEMI patients present with atypical symptoms (ie, no chest pain or
discomfort)
Approximately 1% of STEMI patients present with atypical symptoms (ie, no chest pain or
discomfort)
Approximately 50% of STEMI patients present with typical symptoms (ie, no chest pain or
discomfort)
Although the symptoms of STEMI usually include chest pain, a considerable number of patients present without it. In a study
based on the GRACE (Global Registry of Acute Coronary Events) registry reported by Brieger and colleagues [10] in 2004,
atypical presentations occurred in 541 of 6926 patients (7.8%) ultimately diagnosed with STEMI. In the entire study sample,
which consisted of 20,881 patients with any acute coronary syndromes, 1763 patients presented without chest pain. Of
these, 23.8% were diagnosed incorrectly on presentation. In contrast, only 2.4% of patients who presented with chest pain
were diagnosed incorrectly.
Patients with STEMI who presented with atypical symptoms were less likely to receive fibrinolysis, PCI, aspirin, or beta-
blockers than those with typical symptoms (Table 1). This difference in care is reflected in mortality rates, which were almost
3-fold higher for patients with atypical symptoms than for those with typical symptoms.[10]
Table 1. Hospital Management and Outcomes of STEMI: Percentage of Patients With STEMI Who Received Each
Specified Therapy or Had Each Outcome, by Presence or Absence of Chest Pain
Variable Patients, %
P value No Chest Pain (n = 541) Chest Pain (n = 6385)
Intervention
Fibrinolysis 25.6 45.6 <.001
Primary PCI 11.0 21.0 <.001
Beta-blockers (within first 24 hours) 54.5 68.5 <.001
Aspirin (within first 24 hours) 86.3 92.8 <.001
Outcome
In-hospital mortality 18.7 6.3 <.001
PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction
Data from Brieger, et al.[10]
Delayed diagnosis and treatment are associated with adverse outcomes; as a result, it is critical to recognize the possibility
of STEMI in patients who present with atypical symptoms. Dominant presenting symptoms among patients who presented
without chest pain and were ultimately diagnosed with an acute coronary syndrome in the GRACE registry study include
dyspnea (49.3%), diaphoresis (26.2%), nausea and vomiting (24.3%), and syncope (19.1%).[10] Atypical presentations are
more common among older patients and patients with diabetes.[1,4] Atypical presentations may also be more common in
women than men. A heightened index of suspicion for STEMI is warranted for women, although evidence of higher
prevalence of atypical symptoms in this group is not entirely conclusive.[1]
Case Presentation, Continued
Nine minutes after KD's initial presentation, a 12-lead ECG showed 2- to 3-mm ST elevation in leads V3, V4, V5, and V6.
The hospital has a 24-hour PCI facility, which is usually ready within 40 minutes of activation.
What is the appropriate next action for this patient?
Initiate fibrinolytic therapy
Take a history and perform a physical examination
Initiate laboratory tests to confirm a diagnosis of STEMI
Activate the PCI facility
An ECG showing ST-segment elevation is sufficient to identify patients who can benefit from reperfusion therapy. Several
laboratory tests and procedures in addition to the ECG are valuable for guiding therapeutic decisions. However, once ST-
segment elevation is identified, cardiac biomarker testing and other laboratory examinations should not delay
implementation of reperfusion therapy.[1]
The core goal of reperfusion is to minimize the total ischemic time by quickly providing reperfusion therapy.[1] The target time
is 90 minutes from first medical contact to balloon insertion for PCI or 30 minutes for fibrinolytics. PCI is preferred if the 90-
minute target is achievable.[6] Several situations also favor PCI over fibrinolytics[1]:
Cardiogenic shock;
Killip class III or IV;
Contraindications to fibrinolytics;
Presentation at more than 3 hours after symptom onset; and
STEMI diagnosis is uncertain.
In general, PCI is contraindicated only if it cannot be provided within the 90-minute target time. This could occur if, for
instance, PCI cannot be provided promptly at the hospital where the patient initially presented and transport to a PCI-
capable facility would take too long, or if vascular access is difficult.
In the case of KD, the anticipated first-contact-to-balloon time is 82 minutes: 23 minutes from the 911 call to arrival at the
emergency department, 9 minutes for diagnosis of the ECG, and 50 minutes to activate the PCI facility. This is well within
the 90-minute target.
Which conditions are considered absolute contraindications to fibrinolytic therapy?
History of intracranial hemorrhage (ICH) or recent internal bleeding
Pregnancy
History of hypertension or diabetes controlled by medication
History of recent acute cardiac syndrome
Although PCI is preferred over fibrinolytic therapy when PCI can be performed promptly, this preference should not obscure
the importance of time to reperfusion or the value of fibrinolytics in providing rapid reperfusion when PCI is not available
within 90 minutes. Hospitals that cannot provide prompt PCI should be able to initiate fibrinolytic therapy within 30 minutes of
presentation and should have written protocols in place for transferring patients to PCI-capable facilities when fibrinolytics
are contraindicated.[1,6]
Bleeding, especially ICH, is the primary risk of fibrinolytic therapy. Percutaneous coronary intervention should be
increasingly favored over fibrinolytics as the patient's risk for bleeding increases, and contraindications to fibrinolytics center
on patients with an increased risk for bleeding (Table 2).[1] Patients should be evaluated for bleeding risk factors as part of
their initial history and physical examination.[1]
Table 2. Contraindications for Fibrinolytic Therapy in Patients With STEMI*
Absolute Contraindications
Any prior intracranial hemorrhage
Known structural cerebrovascular lesion (eg, arteriovenous malformation)
Known malignant intracranial neoplasm (primary or metastatic)
Ischemic stroke within 3 months except acute ischemic stroke within 3 hours
Suspected aortic dissection
Active bleeding or bleeding diathesis (excluding menses)
Significant closed-head or facial trauma within 3 months
Relative Contraindications
History of chronic, severe, poorly controlled hypertension
Severe uncontrolled hypertension on presentation (systolic blood pressure > 180 mm Hg; diastolic > 110 mm Hg)†
History of prior ischemic stroke > 3 months, dementia, or known intracranial pathology not covered in contraindications
Traumatic or prolonged (> 10 minutes) cardiopulmonary resuscitation or major surgery (within 3 weeks)
Recent (within 2-4 weeks) internal bleeding
Noncompressible vascular punctures
Prior exposure (> 5 days ago) or prior allergic reaction to streptokinase or anistreplase
Pregnancy
Active peptic ulcer
Current use of anticoagulants: the higher the International Normalized Ratio, the higher the risk for bleeding
Data from Antman, et al.[1]
Which biomarker should be assessed after activation of the PCI facility?
Cardiac troponins
Creatine kinase (CK)
CK-MB
Myoglobin
Cardiac troponins are highly specific and sensitive for myocardial necrosis and are the preferred diagnostic marker for MI.
However, abnormal troponins may not appear in the blood for 3-6 hours after symptom onset. This is too late to be reliable
in making a timely diagnosis of STEMI, and patients with STEMI may present without elevated troponin levels. Because they
remain elevated for several days after STEMI, troponins are not reliable for detection of reinfarction.[1]
CK can be produced by injured skeletal muscle (eg, after an intramuscular injection) as well as by injured myocardium and is
therefore less specific than troponins. CK-MB is more specific than CK and responds faster than the troponins. Figure 1
shows changes in serum levels of cardiac troponin and CK-MB with and without reperfusion. It is the preferred biomarker for
monitoring reperfusion and detecting reinfarction. However, elevated CK-MB can result from cardiac stressors other than MI.
Myoglobins are nonspecific but respond quickly, sometimes within 2 hours of the infarction.[1,11]
Figure 1. Changes in levels of cardiac biomarkers with and without reperfusion.
Adapted from Antman, et al.[1]
Serum cardiac biomarkers are valuable diagnostic and prognostic tools in the management of patients with suspected MI.[1]
However, their utility for initial diagnosis of STEMI is limited because of the delay between the onset of STEMI and the
appearance of elevated serum biomarker levels, the limited specificity of some markers for cardiac damage, and the time
required to obtain laboratory values. Thus, 12-lead ECG is the primary tool for the initial diagnosis of STEMI, and cardiac
biomarkers are used primarily for confirmation, detection of small infarctions, and estimation of the size of the infarction. [1]
Reperfusion should not be delayed pending laboratory results in a patient with STEMI diagnosed by ECG.[1]
Bedside biomarker tests can provide qualitative results within a few minutes and are fast enough to be useful in confirming a
diagnosis of MI if elevated troponins are present, particularly if the ECG is ambiguous. However, bedside tests are less
sensitive and precise than quantitative laboratory assays and should be confirmed by a laboratory assay.[1]
Other biomarkers and laboratory evaluations are useful in managing patients with STEMI. Table 3 lists the laboratory
evaluations recommended in the ACC/AHA STEMI guidelines.
Table 3. Laboratory Evaluations Recommended for the Management of STEMI in the ACC/AHA STEMI Guidelines
Serum biomarkers for cardiac damage (do not wait for results before implementing reperfusion strategy)
Complete blood count, including platelet count
International Normalized Ratio
aPTT
Electrolytes and magnesium
Blood urea nitrogen
Creatinine
Glucose
Serum lipids
aPTT = activated partial thromboplastin time; STEMI = ST-segment elevation myocardial infarction
Data from Antman, et al.[1]
Case Presentation, Continued
The emergency department physician activated the PCI facility. The interventional cardiologist on call confirmed that the
facility would be ready within 40-50 minutes. While the PCI facility personnel were in transit and setting up the facility, the
emergency team continued their evaluation. During this evaluation, KD reported mild nausea and dyspnea in addition to
chest pain. She had no radiated pain. Her medical history included diagnoses of hypertension and hypercholesterolemia at
least a decade ago. She has been treated with hydrochlorothiazide 25 mg/day and simvastatin 20 mg/day since then.
Physical examination found that KD is mildly obese, with a body mass index of 32 kg/m2. Her vital signs were heart rate 110
beats/min, blood pressure 150/70 mm Hg, and respiratory rate 12 breaths/min. She was afebrile, and her lungs were clear.
Heart rhythm was regular with normal S1 and S2, positive S4, and intact peripheral pulses. No peripheral edema was
apparent. A bedside troponin test was positive. Chest x-ray found no evidence of aortic dissection.
A blood sample was drawn for CK-MB and routine laboratory analyses, including creatinine, complete blood count, blood
urea nitrogen, electrolytes, baseline lipids, prothrombin time, and partial thromboplastin time, were done.
The PCI facility was ready 47 minutes after the call. The procedure went smoothly; reperfusion and stent placement were
successful. The total contact-to-balloon time was 70 minutes.
On the basis of clinical evidence, which statement correctly describes anticoagulant therapy in PCI
patients?
Anticoagulant therapy is not appropriate for a patient like KD
A combination of 2 or more anticoagulation agents is appropriate
Patients taking enoxaparin (vs unfractionated heparin [UFH]) are more likely to reach
anticoagulation levels
Similar results can be expected when fondaparinux is used alone or with heparin
Montalescot and colleagues[12] compared enoxaparin with UFH in 3528 patients who underwent elective PCI. Non-CAGB-
related bleeding rates were 8.5% with UFH, 5.9% with enoxaparin 0.5 mg/kg, and 6.5% with enoxaparin 0.75 mg/kg. The
difference was highly significant (P = .01) for enoxaparin 0.5 mg/kg vs UFH and almost significant (P=0.51) for enoxaparin
0.75 mg/kg vs UFH. With both enoxaparin doses, rates of major bleeding were significantly lower than with UFH, and
patients were significantly more likely to reach target anticoagulation levels.
The 2008 update of the ACC/AHA guidelines includes a discussion of UFH, enoxaparin (low-molecular-weight heparin), and
fondaparinux as anticoagulant therapies for patients with STEMI.[6] Data on use of any of these agents in patients
undergoing primary PCI are limited. The guidelines state that patients undergoing primary PCI should receive UFH in a
weight-adjusted bolus of 70-100 U/kg.[1]
The core analysis of EXTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction
Treatment [ExTRACT]- Thrombolysis in Myocardial Infarction [TIMI]) compared UFH with enoxaparin in 20,479 STEMI
patients.[13] Of these, 4676 patients underwent PCI within 30 days of the initial event, and these patients were evaluated in a
subgroup analysis. In the analysis, patients who received enoxaparin were less likely to require PCI than those who received
UFH (22.8% vs 24.2%, P = .0027). Major events occurred in 11.5% of patients receiving enoxaparin vs 14.8% of patients
receiving UFH (Figure 2) (relative risk, 0.78; 95% confidence interval [CI], 0.67-0.90; P < .001). The difference emerged
before PCI and persisted for up to 30 days.[14]
Figure 2. Rates of death or MI among patients undergoing PCI in EXTRACT-TIMI 25.
Adapted from Gibson, et al.[14]
For fondaparinux, the OASIS-6 trial compared fondaparinux vs usual care (placebo or UFH depending on whether the
investigator felt that UFH was indicated) in 12,092 patients with STEMI. Of these, 3788 patients underwent primary PCI, and
rates of death and MI were similar between controls and patients receiving fondaparinux. However, catheter thrombosis and
coronary complications were more common among patients receiving fondaparinux.[15] Thus, if fondaparinux is used, it
should be used with an agent having anti-IIa activity for PCI to minimize the risk for catheter thrombosis.[6]
Stone and coworkers[16] reported on a comparison of the direct thrombin inhibitor bivalirudin vs heparin plus glycoprotein
IIb/IIIa inhibitors in STEMI patients from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial
Infarction (HORIZONS-AMI) study. A total of 3602 patients with STEMI presented within 12 hours after the onset of
symptoms and were scheduled for primary PCI. These patients were treated with either bivalirudin vs heparin plus
glycoprotein IIb/IIIa inhibitors (either abciximab or eptifibatide). Treatment with bivalirudin resulted in a reduced rate of net
adverse clinical events at 30 days (9.2% vs 12.1%; relative risk, 0.76; 95% CI, 0.63-0.92; P = .005) due to a lower rate of
major bleeding (4.9% vs 8.3%; relative risk, 0.60; 95% CI, 0.46-0.77; P < .001).
Which antiplatelet therapy would be appropriate for KD?
Aspirin alone
Clopidogrel
Ticlopidine
Aspirin and clopidogrel in combination
Antiplatelet therapy is not appropriate
The updated ACC/AHA guidelines recommend both aspirin and clopidogrel for all patients with STEMI regardless of the
reperfusion strategy used.[6] Patients with a suspected STEMI should receive aspirin as early as possible at an initial dose of
162-325 mg, and therapy should continue indefinitely at a maintenance dose of 75-162 mg. Aspirin is contraindicated only
for patients with a true aspirin allergy.[1] The benefits of aspirin in the setting of STEMI have been known since at least 1988,
when the ISIS-2 (Second International Study of Infarction Survival) study found that aspirin significantly reduced nonfatal
reinfarction (1.0% vs 2.0%).[17]
Patients with STEMI should receive clopidogrel 75 mg/day in addition to aspirin for at least 14 days; longer durations are
recommended for patients who receive a stent. The recommended duration depends on the type of stent: For a bare-metal
stent, clopidogrel should continue for at least 1 month and ideally 12 months; patients who receive a drug-eluting stent
should receive clopidogrel for at least 12 months. The duration of therapy should be reduced for patients at high risk for
bleeding.[8]
Several studies, including PCI-CURE (The PCI-Clopidogrel in Unstable angina to prevent Recurrent ischaemic Events),[18]
PCI-CLARITY (The PCI-Clopidogrel as Adjunctive Reperfusion Therapy),[19] and CREDO (Clopidogrel for the Reduction of
Events During Observation),[20] have demonstrated that clopidogrel in combination with aspirin is more effective than aspirin
alone.
The PCI-CURE study, reported by Mehta and colleagues[18] in 2001, compared clopidogrel plus aspirin to placebo plus
aspirin in 2658 patients with non-ST-elevation MI or unstable angina who had PCI a median of 10 days after symptom onset.
Patients who received clopidogrel were significantly less likely to experience MI or cardiovascular death than those who
received placebo, with rates of MI or death at 8.8% for clopidogrel vs 12.6% for placebo (relative risk 0.69; 95% CI, 0.54-
0.87; P = .002).
PCI-CLARITY, reported by Sabatine and colleagues[19] in 2005, was a subgroup analysis of CLARITY-TIMI 28. The parent
trial compared clopidogrel plus aspirin with placebo plus aspirin in 3491 STEMI patients who were treated with fibrinolysis.
Approximately half of these patients (1863, 53.4%) went on to undergo PCI during the index hospitalization, at a median of 3
days after the initiation of the study drug. Among these patients, pretreatment with clopidogrel significantly reduced rates of
the combined endpoints of cardiovascular death, recurrent MI, or stroke within 30 days for the overall sample, regardless of
the patient's age, sex, diabetes status, or infarct location. Table 4 summarizes the post-PCI outcomes.
Table 4. Summary of 30-Day Outcomes After PCI in PCI-CLARITY
Outcome Patients, n (%)
Adjusted Odds Ratio (95% CI) P Value Clopidogrel (n = 933) Placebo (n = 930)
Cardiovascular death, MI, or stroke 34 (3.6) 58 (6.2) 0.54 (0.35-0.85) .008
Cardiovascular death or MI 31 (3.3) 50 (5.4) 0.58 (0.36-0.94) .03
Cardiovascular death 13 (1.4) 24 (2.6) 0.49 (0.24-1.03) NR
MI 18 (1.9) 29 (3.1) 0.60 (0.33-1.11) NR
Stroke 4 (0.4) 11 (1.2) 0.35 (0.11-1.11) NR
MI = myocardial infarction; NR = not reported; PCI = percutaneous coronary intervention
Data from Sabatine, et al.[19]
CREDO compared early, sustained clopidogrel therapy (a 300-mg loading dose followed by 75 mg/day for 1 year) with
standard clopidogrel therapy (75 mg/day for 1 month) in 2116 patients who had evidence of coronary ischemia, were
undergoing elective PCI, or had a high likelihood of requiring PCI.[20] The results were analyzed at 28 days to assess the
loading dose and at 1 year to assess sustained therapy. The loading dose did not significantly reduce 28-day rates of the
combined endpoint (6.8% with loading dose vs 8.3% without; relative risk reduction, 18.5%; 95% CI, -14.2 to 41.8%; P =
.23). Patients who received early, sustained therapy had significantly lower risk for the combined endpoint (death, MI, or
stroke) at 1 year than those who received conventional therapy, with rates of 8.5% and 11.5% in the sustained- and
conventional-therapy groups, respectively (relative risk reduction, 26.9%; 95% CI, 3.9-44.4%; P = .02). Figure 3 shows
results for the combined endpoint at 1 year.
Figure 3. Occurrence of death, MI, stroke, for clopidogrel 75 mg vs placebo in CREDO.
Adapted from Steinhubl, et al[20]
Clopidogrel was also evaluated as a preventive therapy among 15,603 patients with multiple risk factors for cardiovascular
disease or clinically evident stable disease. Clopidogrel did not provide a significant benefit in the overall sample or in the
subgroup of patients with risk factors but no documented vascular disease, but it did provide a marginally significant
reduction in the risk for cardiovascular death, MI, or stroke among patients with documented cardiovascular disease.
However, clopidogrel increased the risk for bleeding.[21] Table 5 summarizes the results.
Table 5. Effect of Clopidogrel for Prevention of Cardiovascular Events and Bleeding by Patient Group
Endpoint Patients With Event, %
P Value Clopidogrel Placebo
Cardiovascular death, MI, or stroke
All patients 6.8 7.3 .22
No documented CVD (n = 3284) 6.6 5.5 .2
Documented CVD (n = 12,153) 6.9 7.9 .046
Bleeding
Severe, all patients 1.7 1.3 .09
Moderate, all patients 2.1 1.3 < .001
CVD = cardiovascular disease; MI = myocardial infarction
Data from Bhatt, et al.[21]
Clopidogrel is currently the only thienopyridine approved for the treatment of STEMI. Ticlopidine, an early thienopyridine, is
no longer used because the safety profile was worse than that of clopidogrel with no better efficacy.[22]
Two novel adenosine diphosphate-receptor antagonists, prasugrel and ticagrelor, recently completed clinical trials.
Prasugrel was evaluated in TRITON-TIMI 38, which compared prasugrel with clopidogrel in 13,608 patients scheduled to
undergo PCI to treat a moderate-to-severe acute coronary syndrome.[23] The results of a substudy involving only the 3534
patients with STEMI were published by Montalescot and colleagues[24] in 2009. They concluded from the STEMI subgroup
that rates of ischemic events (cardiovascular death, MI, or stroke) were lower with prasugrel than with clopidogrel, with rates
of 10.0% and 12.4%, respectively (hazard ratio, 0.79; 95% CI, 0.65-0.97; P = .0221). Rates of major bleeding in the STEMI
subgroup were similar for the 2 agents, at 2.1% for prasugrel and 2.4% for clopidogrel (P = .6451), although in the overall
trial major bleeding was significantly increased with prasugrel.[24]
Ticagrelor, also known as AZD 6140, has been investigated in the DISPERSE (Dose confIrmation Study assessing anti-
Platelet Effects of AZD6140 vs clopidogRel in non-ST-segment Elevation myocardial infarction) trial. It provided greater
inhibition of platelet aggregation than clopidogrel in patients with acute coronary syndromes not related to STEMI, but it did
not cause significantly greater rates of major bleeding. The study was not designed to determine the efficacy of ticagrelor,
but there appeared to be a trend toward lower rates of cardiovascular death, MI, and stroke with that drug than with
clopidogrel.[25,26] PLATO, a large phase 3 study comparing ticagrelor to clopidogrel in acute coronary syndromes, has recently
been completed and the full results are to be reported soon.[27]
Which intervention would be appropriate if the PCI facility were already in use to treat another patient
and would not be available for another hour? (Assume that the nearest other PCI facility is
approximately 70 minutes away and can be ready within that time.)
Initiate fibrinolytics
Wait for the PCI facility to become available
Transport to the nearest PCI facility
Administer fibrinolytics and then transport for PCI
The timing of reperfusion plays a critical role in treatment decisions. In this situation, fibrinolysis is preferred because the
first- contact-to-balloon time would exceed 90 minutes. Transport to another PCI-equipped facility is a reasonable option to
consider. However, the 70-minute transfer time is also too long in this case.[1]
Almost one fourth of physicians who responded to a survey conducted by Peacock and colleagues[28] were no more than
"somewhat familiar" with the guidelines. About one fifth of the respondents indicated that fibrinolytics were underused -- that
is, that patients who could not receive PCI within 90 minutes and were appropriate candidates for fibrinolysis would rarely if
ever receive fibrinolytic therapy.
The updated ACC/AHA guidelines state that facilitated PCI using full-dose fibrinolytic therapy followed immediately by PCI
may be harmful and is not recommended. Facilitated PCI with lower fibrinolytic dosages might be considered for high-risk
patients (those with large MI or hemodynamic or electrical instability) and for patients at low risk for bleeding when PCI is not
available within 90 minutes.[6]
Facilitated PCI has been investigated in multiple trials, most recently the FINESSE (Facilitated Intervention with Enhanced
Reperfusion Speed to Stop Events) trial reported by Ellis and colleagues[29] in 2008 and in a meta-analysis by Keeley and
colleagues[30] in 2006.
The FINESSE trial evaluated 3 regimens for facilitated PCI: half-dose reteplase in combination with abciximab, abciximab
alone, and primary PCI. The primary endpoint was a composite of death, ventricular fibrillation, cardiogenic shock, and
congestive heart failure.[29] Among the 2452 patients randomized, the primary endpoint occurred within 90 days in 9.8% of
patients in the reteplase plus abciximab group, 10.5% of patients in the abciximab monotherapy group, and 10.7% in the
primary PCI group. These differences were not significant. The hazard ratio for the reteplase plus abciximab group vs the
primary PCI group was 0.81 (95% CI, 0.67-1.23). Bleeding was more significantly common in the reteplase plus abciximab
group than in the primary PCI group. The study authors concluded that the results of the trial did not support facilitated PCI
with the regimens used in the study.
The meta-analysis included 17 trials of 4504 patients who received either facilitated (n = 2237) or primary (n = 2267) PCI. Of
these, 9 trials involved glycoprotein IIb/IIIa inhibitors, 7 involved fibrinolytics, and 2 involved both in combination. Differences
between facilitated and primary PCI in the percentage of patients with final TIMI (Thrombolysis in Myocardial Infarction)
grade 3 flow were not significant (89% with facilitated PCI vs 88% with primary PCI; P = .3).[30] The incidences of mortality,
nonfatal recurrent MI, urgent target-vessel revascularization, and major bleeding were all significantly higher with facilitated
PCI than with primary PCI (Table 6). Most of the increased risk with facilitated PCI was attributed to an increased adverse
event rate in regimens that used thrombolytic therapy rather than glycoprotein IIb/IIIa inhibitors. The study authors
concluded that facilitated PCI offers no benefit over primary PCI and that facilitated PCI with thrombolytic therapy was
associated with increased rates of adverse events and should be avoided.
Table 6. Summary of Outcomes in a Meta-analysis of 17 Trials of Facilitated PCI
Outcome Patients, %
P Value Facilitated PCI Primary PCI
Final TIMI grade 3 flow 89 88 .3
Mortality 5 3 .04
Nonfatal recurrent MI 3 2 .006
Urgent target-vessel revascularization 4 1 .01
Major bleeding 7 5 .01
MI = myocardial infarction; PCI = percutaneous coronary intervention; TIMI = Thrombolysis in Myocardial Infarction
Data from Keeley, et al[30]
The FINESSE trial evaluated 3 regimens for facilitated PCI: half-dose reteplase in combination with abciximab, abciximab
alone, and primary PCI. The primary endpoint was a composite of death, ventricular fibrillation, cardiogenic shock, and
congestive heart failure.[29]Among the 2452 patients randomized, the primary endpoint occurred within 90 days in 9.8% of
patients in the reteplase plus abciximab group, 10.5% of patients in the abciximab monotherapy group, and 10.7% in the
primary PCI group. These differences were not significant. The hazard ratio for the reteplase plus abciximab group vs the
primary PCI group was 0.81 (95% CI, 0.67-1.23). Bleeding was more significantly common in the reteplase plus abciximab
group than in the primary PCI group. The study authors concluded that the results of the trial did not support facilitated PCI
with the regimens used in the study.
Which anticoagulant therapy would have been appropriate if KD had undergone fibrinolytic therapy
instead of PCI?
Enoxaparin
UFH
Fondaparinux
UFH, enoxaparin, or fondaparinux
UFH, enoxaparin, and fondaparinux have all been demonstrated to be effective among patients undergoing reperfusion by
fibrinolysis. Therapy should continue for at least 48 hours and preferably be continued for the duration of the index
hospitalization, with a maximum duration of 8 days. Prolonged therapy with UFH may cause heparin-induced
thrombocytopenia, so other agents should be used if anticoagulant therapy is continued for more than 48 hours. [6] The
recommended dosages are summarized in Table 7.
Table 7. Recommended Dosages for Antithrombotic Agents in STEMI Patients Undergoing Reperfusion by
Fibrinolysis*
UFH
Initial IV bolus 60 U/kg (maximum 4000 U) followed by IV infusion of 12 U/kg/hr (maximum 1000 U/hr)
Adjust to maintain aPTT from 1.5 to 2.0 times control
No benefit to prolonging therapy beyond 48 hours in the absence of ongoing indications
No benefit to prolonging therapy beyond 48 hours in the absence of ongoing indications
Enoxaparin*
For patients with serum creatinine < 2.5 mg/dL (males) or < 2.0 mg/dL (females)
< 75 years of age: Initial IV bolus: 30 mg followed by SC injections of 1.0 mg/kg every 12 hours
Continued for the duration of the index hospitalization with a maximum duration of 8 days
Fondaparinux
For patients with serum creatinine < 3.0 mg/dL
Initial IV dose: 2.5 mg followed by SC injections: 2.5 mg daily
Continued for the duration of the index hospitalization with a maximum duration of 8 days
aPTT = activated partial thromboplastin time; IV = intravenous; SC = subcutaneous; UFH = unfractionated heparin
*For patients of any age, if creatinine clearance using the Cockroft-Gault formula is < 30 mL/min, the SC dose is
1.0 mg/kg every 24 hours.
Data from Antman, et al.[6]
UFH has been used as an antithrombotic for decades and is generally the standard to which newer antithrombotic agents
are compared. Several trials have compared enoxaparin and fondaparinux with UFH.
The EXTRACT-TIMI 28, reported by Antman and colleagues[13] in 2006, is a key comparison of enoxaparin with UFH.
EXTRACT-TIMI 28 randomized 20,506 patients with STEMI to receive either enoxaparin throughout the index hospitalization
or UFH for at least 48 hours. Rates of the primary endpoint (death or nonfatal MI at 30 days) were significantly lower among
patients receiving enoxaparin (9.9%) than among patients receiving UFH (12.0%), with a hazard ratio of 0.83 (95% CI, 0.77-
0.90; P < .001). Rates of the primary endpoint at 8 days and urgent revascularization at 8 days and 30 days were lower with
enoxaparin. Rates of major bleeding were significantly worse among patients receiving enoxaparin than among those
receiving UFH (2.1% vs 1.4%, respectively; P < .001). However, rates of ICH were similar between the groups (0.8% vs
0.7%, respectively; P = .14). In patients who underwent PCI within 30 days after randomization, there was a 23% reduction
in relative risk The study authors concluded that enoxaparin throughout the index hospitalization is superior to UFH for 48
hours as an adjunct to fibrinolytic therapy for STEMI.
The OASIS-6 (Organization for the Assessment of Strategies for Ischemic Syndromes) trial evaluated fondaparinux vs usual
care in 12,092 patients with STEMI.[15] Patients were stratified by whether the investigator judged UFH to be indicated.
Patients for whom UFH was not indicated (stratum 1) were randomized to receive fondaparinux or placebo, while patients for
whom UFH was indicated (stratum 2) received either fondaparinux or UFH. The combined analysis found that fondaparinux
significantly reduced rates of the primary endpoint (death or nonfatal MI at 30 days) compared with usual care (relative risk
reduction, 12%; P = .008). The benefit of fondaparinux was apparent at 9 days after randomization. Fondaparinux was
superior to usual care in both strata but was equivalent to UFH among patients who underwent PCI. Table 8 summarizes the
results for the primary endpoint by strata and timepoint. Rates of bleeding were similar for fondaparinux and UFH in stratum
2. The authors concluded that fondaparinux provides early and persistent reduction in mortality and reinfarction vs usual
care.
Table 8. Efficacy of Fondaparinux vs Usual Care in OASIS-6
Timepoint Stratum Events, n (%)
Hazard Ratio (95% CI) P Value for Interaction †
Usual Care* Fondaparinux
9 days 1 314 (11.1) 239 (8.5) 0.76 (0.64-0.89)
.13 2 223 (6.9) 205 (6.4) 0.92 (0.76-1.11)
30 days 1 396 (14.0) 317 (11.2) 0.79 (0.68-0.92)
.10 2 281 (8.7) 268 (8.3) 0.96 (0.81-1.13)
Study end 1 469 (17.3) 413 (15.9) 0.87 (0.76-0.99)
.88 2 388 (12.7) 343 (11.2) 0.88 (0.76-1.02)
*Usual care was placebo in stratum 1 and unfractionated heparin in stratum 2. † P ≤ .01 required for significance.
Data from Yusuf, et al.[15]
Which duration of clopidogrel therapy would be appropriate if KD had undergone fibrinolytic therapy
instead of PCI?
7 days
14 days to 1 year
Duration of hospital stay
None; clopidogrel should not be administered
The updated ACC/AHA guidelines recommend clopidogrel 75 mg/day in addition to aspirin for patients with STEMI, whether
they receive reperfusion with PCI or fibrinolytics or no reperfusion. For patients receiving fibrinolytics who are younger than
75 years of age, a 300-mg loading dose is reasonable but not specifically recommended. With fibrinolytics, long-term
maintenance therapy with clopidogrel 75 mg/day is also reasonable, although there are no specific recommendations for the
duration of therapy.[6] The recommendations for clopidogrel are based primarily on 2 studies: CLARITY (Clopidogrel as
Adjunctive Reperfusion Therapy)[31] and COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial).[32]
CLARITY compared clopidogrel with placebo in 3491 STEMI patients 75 years of age or younger who received reperfusion
with fibrinolysis. Patients were randomized to receive clopidogrel (300-mg loading dose followed by 75 mg/day) or placebo
and underwent angiography from 48 to 192 hours after starting study medication. The primary endpoint was an occluded
infarct-related artery on angiography or death or MI prior to angiography.[31] Rates of the primary endpoint were 15.0% in the
clopidogrel group and 21.7% in the placebo (relative risk reduction, 36%; 95% CI, 24-47; P < .001). Outcomes were better in
terms of the primary endpoint with clopidogrel for all subgroups (Figure 4). Patients in the clopidogrel group had significantly
better improvement in angiographic measures and lower rates of recurrent MI than patients in the placebo group (P < .001
and P = .02, respectively). Bleeding rates were not significantly different between groups (1.3% clopidogrel vs 1.1% placebo;
P = .64). The study authors recommended clopidogrel to improve rates of infarct artery patency and reduce rates of
ischemic complications.
Figure 4. Efficacy outcomes for clopidogrel vs placebo in the entire patient sample and selected predefined
subgroups in CLARITY.
Adapted from Sabatine, et al.[31]
The larger COMMIT trial compared clopidogrel 75 mg/day with placebo in 45,852 patients with suspected acute MI. No
loading dose was used. STEMI or bundle branch block was present in 93% of the patients enrolled. Clopidogrel significantly
reduced the composite endpoint of death, reinfarction, or stroke (9.2% clopidogrel vs 10.1% placebo; P = .002) and death
from any cause (7.5% clopidogrel vs 8.% placebo; P = .03). Clopidogrel increased the incidence of serious bleeding (fatal,
cerebral, or requiring transfusion) (0.58% clopidogrel vs 0.55% placebo; P = .59). The study authors concluded that
clopidogrel reduces mortality and major vascular event rates without increasing bleeding.
In STEMI patients who are receiving enoxaparin anticoagulant therapy concomitantly with fibrinolytics,
which level of renal impairment requires adjustment of the initial enoxaparin IV bolus dose?
No dose adjustment is needed for renal impairment
Mild (creatinine clearance 50-80 mL/min)
Moderate (creatinine clearance 30-50 mL/min)
Severe (creatinine clearance < 30 mL/min)
The STEEPLE (SafeTy and Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation) trial
investigated the use of IV bolus doses of enoxaparin (0.5 mg/kg or 1.0 mg/kg enoxaparin vs UFH; N = 3528) in patients
undergoing elective PCI. A subanalysis of this trial, reported by White and colleagues[33] in 2009, compared bleeding rates,
achievement of target anticoagulation levels, and rates of a composite of death, nonfatal MI, and urgent target-vessel
revascularization for the 3 treatment regimens and for patients with and without renal impairment (creatinine clearance ≤ 60
mL/min).
Patients without renal impairment were less likely to have major bleeding and were more likely to achieve target
anticoagulation levels than were those with renal impairment. Differences in rates of minor bleeding and the composite
endpoint were not significant.
Among patients with renal impairment, rates of major bleeding were similar for all 3 treatment groups, but significantly more
patients achieved target anticoagulation levels with either dose of enoxaparin than with UFH (Figure 5). Rates of the
composite endpoint of death, nonfatal MI, and urgent target-vessel revascularization were similar for all 3 groups, at 6.2%
for enoxaparin 0.5 mg/kg, 5.3% for enoxaparin 0.75 mg/kg, and 5.6% for UFH (P = .76 and .90 for enoxaparin 0.5 mg/kg and
0.75 mg/kg, respectively, vs UFH).
Figure 5. Rates of major bleeding and achievement of target anticoagulation levels among patients with impaired
renal function.
Adapted from White, et al.[33]
The investigators concluded that enoxaparin provided a more predictable therapeutic response than UFH without increasing
rates of major bleeding.[33] They also concluded that anticoagulant therapy needs to balance the therapy's efficacy in terms of
prevention of ischemic events with the risk for bleeding, and point out that bleeding risk varies across the spectrum of renal
dysfunction.[34]
Case Presentation, Conclusion
KD recovered and was discharged home with a referral to a cardiac rehabilitation program and instructions to continue
clopidogrel for 1 year and aspirin indefinitely, along with her current statin and antihypertensive regimen.
This article is a CME certified activity. To earn credit for this activity visit:
http://cme.medscape.com/viewarticle/706518
References
1. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation
myocardial infarction -- executive summary. A report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the
management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004;44:671-719. Abstract
2. De Luca G, Suryapranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in primary
angioplasty for acute myocardial infarction: every minute of delay counts. Circulation. 2004;109:1223-1225. Abstract
3. McNamara RL, Wang Y, Herrin J, et al. Effect of door-to-balloon time on mortality in patients with ST-segment
elevation myocardial infarction. J Am Coll Cardiol. 2006;47:2180-2186. Abstract
4. AHA. Mission: Lifeline. 2007. Available at: http://www.americanheart.org/presenter.jhtml?identifier=3048034
Accessed July 21, 2009.
5. NHLBI. Act in time to heart attack signs. 2001. Available at: http://www.nhlbi.nih.gov/actintime/index.htm Accessed
July 21, 2009.
6. Antman EM, Hand M, Armstrong PW, 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;117:296-329.
Abstract
7. Frendl DM, Palmeri ST, Clapp JR Jr, et al. Overcoming barriers to developing seamless ST-segment elevation
myocardial infarction care systems in the United States: recommendations from a comprehensive Prehospital 12-
lead Electrocardiogram Working Group. J Electrocardiol. 2009. May 14. [Epub ahead of print]
8. Bonnefoy E, Lapostolle F, Leizorovicz A, et al. Primary angioplasty versus prehospital fibrinolysis in acute
myocardial infarction: a randomised study. Lancet. 2002;360:825-829. Abstract
9. Bonnefoy E, Steg PG, Boutitie F, et al. Comparison of primary angioplasty and pre-hospital fibrinolysis in acute
myocardial infarction (CAPTIM) trial: a 5-year follow-up. Eur Heart J. 2009. 30:1598-1606. Abstract
10. Brieger D, Eagle KA, Goodman SG, et al. Acute coronary syndromes without chest pain, an underdiagnosed and
undertreated high-risk group: insights from the Global Registry of Acute Coronary Events. Chest. 2004;126:461-
469. Abstract
11. Antman EM, Braunwald E. ST-Segment-Elevation Myocardial Infarction. In: Kaspar DL, Fauci AS, Longo DL, et al,
eds. Harrison's Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005:1448-1459.
12. Montalescot G, White HD, Gallo R, et al. Enoxaparin versus unfractionated heparin in elective percutaneous
coronary intervention. N Engl J Med. 2006;355:1006-1017. Abstract
13. Antman EM, Morrow DA, McCabe CH, et al. Enoxaparin versus unfractionated heparin with fibrinolysis for ST-
elevation myocardial infarction. N Engl J Med. 2006;354:1477-1488. Abstract
14. Gibson CM, Murphy SA, Montalescot G, et al. Percutaneous coronary intervention in patients receiving enoxaparin
or unfractionated heparin after fibrinolytic therapy for ST-segment elevation myocardial infarction in the ExTRACT-
TIMI 25 trial. J Am Coll Cardiol. 2007;49:2238-2246. Abstract
15. Yusuf S, Mehta SR, Chrolavicius S, et al. Effects of fondaparinux on mortality and reinfarction in patients with acute
ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA. 2006;295:1519-1530. Abstract
16. Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl
J Med. 2008;358:2218-2230. Abstract
17. ISIS-2. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of
suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative
Group. Lancet. 1988;2:349-360. Abstract
18. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term
therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001;358:527-
533. Abstract
19. Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreatment before percutaneous coronary
intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study.
JAMA. 2005;294:1224-1232. Abstract
20. Steinhubl SR, Berger PB, Mann JT III, et al. Early and sustained dual oral antiplatelet therapy following
percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288:2411-2420. Abstract
21. Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of
atherothrombotic events. N Engl J Med. 2006;354:1706-1717. Abstract
22. Bertrand ME, Rupprecht HJ, Urban P, Gershlick AH. Double-blind study of the safety of clopidogrel with and without
a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary
stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation. 2000;102:624-629.
Abstract
23. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary
syndromes. N Engl J Med. 2007;357:2001-2015. Abstract
24. Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing
percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind,
randomised controlled trial. Lancet. 2009;373:723-731. Abstract
25. Storey RF, Husted S, Harrington RA, et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12
receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol.
2007;50:1852-1856. Abstract
26. Cannon CP, Husted S, Harrington RA, et al. Safety, tolerability, and initial efficacy of AZD6140, the first reversible
oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment
elevation acute coronary syndrome: primary results of the DISPERSE-2 trial. J Am Coll Cardiol. 2007;50:1844-
1851. Abstract
27. James S, Akerblom A, Cannon CP, et al. Comparison of ticagrelor, the first reversible oral P2Y(12) receptor
antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline
characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2009;157:599-605.
Abstract
28. Peacock WF, Bhatt DL, Diercks D, et al. Cardiologists' and emergency physicians' perspectives on and knowledge
of reperfusion guidelines pertaining to ST-segment-elevation myocardial infarction. Tex Heart Inst J. 2008;35:152-
161. Abstract
29. Ellis SG, Tendera M, de Belder MA, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl
J Med. 2008;358:2205-2217. Abstract
30. Keeley EC, Boura JA, Grines CL. Comparison of primary and facilitated percutaneous coronary interventions for
ST-elevation myocardial infarction: quantitative review of randomised trials. Lancet. 2006;367:579-588. Abstract
31. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial
infarction with ST-segment elevation. N Engl J Med. 2005a;352:1179-1189.
32. Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial
infarction: randomised placebo-controlled trial. Lancet. 2005;366:1607-1621. Abstract
33. White HD, Gallo R, Cohen M, et al. The use of intravenous enoxaparin in elective percutaneous coronary
intervention in patients with renal impairment: results from the SafeTy and Efficacy of Enoxaparin in PCI patients,
an internationaL randomized Evaluation (STEEPLE) trial. Am Heart J. 2009;157:125-131. Abstract
34. Fox KA, Bassand JP, Mehta SR, et al. Influence of renal function on the efficacy and safety of fondaparinux relative
to enoxaparin in non ST-segment elevation acute coronary syndromes. Ann Intern Med. 2007;147:304-310.
Abstract
RESPUESTAS CORRECTAS
What is the appropriate next action for this patient?
Perform 12-lead electrocardiography (ECG)
KD's chest pain is suggestive of a possible ST-segment elevation myocardial infarction (STEMI). Thus, a 12-lead ECG should be obtained within 10 minutes of the patient's arrival at the emergency department. The other actions listed, while important for diagnosis and management, should not delay the ECG.
By what percentage does a 30-minute delay in reperfusion increase 1-year mortality in patients with
STEMI?
7.5%
Current therapies for reperfusion of patients with STEMI need to be instituted rapidly after the onset of symptoms to be optimally efficacious. Every minute of delay increases mortality; a 30-minute delay increases mortality by 7.5%.
Which statement correctly describes patients with STEMI who present with atypical or typical
symptoms?
Approximately 8% of STEMI patients present with atypical symptoms (ie, no chest pain or
discomfort)
Approximately 8% (1 in 13) of patients with STEMI present without chest pain or discomfort. These patients are less likely to be initially diagnosed as having STEMI and have a worse prognosis than those who present with typical symptoms.
What is the appropriate next action for this patient?
Activate the PCI facility
The ECG is sufficient for a diagnosis of STEMI. Thus, reperfusion is the next step and confirmatory testing should not delay reperfusion. The updated ACC/AHA STEMI guidelines recommend reperfusion with PCI for patients with STEMI if it can be provided within 90 minutes of presentation.
Which conditions are considered absolute contraindications to fibrinolytic therapy?
History of intracranial hemorrhage (ICH) or recent internal bleeding
Any history of ICH or a recent history of ischemic stroke is an absolute contraindication to fibrinolytics because this indicates increased risk for ICH, a serious risk of fibrinolytic therapy. Recent internal bleeding and uncontrolled hypertension are relative contraindications.
Which biomarker should be assessed after activation of the PCI facility?
Cardiac troponins
Troponins are the preferred biomarker for diagnosing MI because of their high specificity and sensitivity for myocardial necrosis.
On the basis of clinical evidence, which statement correctly describes anticoagulant therapy in PCI
patients?
Patients taking enoxaparin (vs unfractionated heparin [UFH]) are more likely to reach
anticoagulation levels
The ACC/AHA STEMI guidelines recommend UFH for patients undergoing PCI or surgical revascularization.
Which antiplatelet therapy would be appropriate for KD?
Aspirin and clopidogrel in combination
All patients with STEMI should receive the combination of aspirin and clopidogrel unless contraindications are present.
Which intervention would be appropriate if the PCI facility were already in use to treat another patient
and would not be available for another hour? (Assume that the nearest other PCI facility is
approximately 70 minutes away and can be ready within that time.)
Initiate fibrinolytics
Which anticoagulant therapy would have been appropriate if KD had undergone fibrinolytic therapy
instead of PCI?
UFH, enoxaparin, or fondaparinux
UFH, enoxaparin, and fondaparinux all have established efficacy in STEMI patients undergoing reperfusion with fibrinolysis. The ACC/AHA guidelines do not express a preference for any of these agents, aside from stating that UFH is not recommended if treatment duration will exceed 48 hours.
Which duration of clopidogrel therapy would be appropriate if KD had undergone fibrinolytic therapy
instead of PCI?
14 days to 1 year
The ACC/AHA guidelines recommend continuing aspirin indefinitely and clopidogrel for at least 14 days.
In STEMI patients who are receiving enoxaparin anticoagulant therapy concomitantly with fibrinolytics,
which level of renal impairment requires adjustment of the initial enoxaparin IV bolus dose?
No dose adjustment is needed for renal impairment
The ACC/AHA guidelines do not recommend any change in the IV bolus dose of enoxaparin based on renal impairment, although they do recommend reducing the subcutaneous doses that follow to 1 mg/kg/day for patients with severe renal impairment (creatinine clearance < 30 mL/min).