Page 433 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 37: Myocardial Ischemia 303

STEMI Evidence of cardiogenic
shock or conduction disturbance

Aspirin 325 mg chewed,
O , NTG
2
UFH or enoxaparin
MSO IV for pain LD of clopidogrel or prasugrel No
4
Determine strategy for reperfusion in -blocker
shortest time possible

Suspect mechanical complication
No Yes
(ie, papillary muscle rupture, VSD)
Cardiogenic shock, symptom onset > 3 h Diagnostic cardiac cath and
contraindication to fibrinolytics, failed
fibrinolytics, or door to balloon time < 90 min emergent operative repair as indicated

Yes No Fibrinolytic therapy No

Cardiac cath and C P free, ST segment by 50%,
PCI as clinically indicated hemodynamically/electrically stable Cardiac cath

FIGURE 37-2. Treatment algorithm for ST-elevation myocardial infarction. C P, chest pain; LD, loading dose; MSO , morphine; NTG, nitroglycerin; O , oxygen; UFH, unfractionated
4
2
heparin; VSD, ventricular septal defect.

angina or NQMI. Aspirin also reduces events after resolution of an acute vascular disease (prior stroke, myocardial infarction or peripheral vascular
coronary syndrome, and should be continued indefinitely. disease), randomized patients to either 75 mg/d of clopidogrel or 325 mg
As in patients with STEMI, patients with NSTEMI have been shown aspirin. After an average follow-up of 1.6 years, patients treated with
110
to benefit from the use of a thienopyridine in addition to aspirin. In the clopidogrel had significantly fewer cardiovascular events than patients
CURE trial, 12,562 patients were randomized to receive clopidogrel or treated with aspirin (5.8% vs 5.3%, a relative risk reduction of 8.7%). 110
placebo in addition to standard therapy with aspirin, within 24 hours of The TRITON TIMI-38 trial comparing prasugrel to clopidogrel
unstable angina symptoms. Clopidogrel significantly reduced the risk included 10,074 UA/NSTEMI patients as well as 3534 STEMI patients.
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69
of myocardial infarction, stroke or cardiovascular death from 11.4% to The primary end point, cardiovascular death, nonfatal MI, and nonfa-
9.3% (p < 0.001). It should be noted that this benefit came with a 1% tal stroke, was significantly lower in the prasugrel group at the cost of
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absolute increase in major, non-life-threatening bleeds (p = 0.001) as increased bleeding in the prasugrel-treated patients. The dosing regi-
69
well as a 2.8% absolute increase in major/life-threatening bleeds asso- men of prasugrel for patients with UA/NSTEMI is identical to the dose
ciated with CABG within 5 days (p = 0.07). Because percutaneous used in STEMI patients (60 mg load and 10 mg maintenance); it should
107
revascularization was performed on only 23% of patients in the CURE not be used in patients with a history of stroke or TIA and it should be
trial during the initial hospitalization, the study provides convincing used with caution in patients over the age of 75 or with a weight less
evidence that clopidogrel is beneficial in patients who are managed than 60 kg. 41
medically in addition to those undergoing PCI. Ticagrelor, a nonthienopyridine platelet inhibitor that binds revers-
The PCI-CURE report examined the subset of patients (n = 2658) ibly to the P2Y12 platelet receptor, exhibited greater efficacy than
with UA/NSTEMI who underwent PCI, and showed a 31% reduction clopidogrel in the PLATO trial. Major bleeding events did not differ
111
in cardiovascular death or MI with no difference in major bleeding between the groups, although bleeding not related to coronary-artery
(p < 0002). PCI-CURE suggests that in patients with UA/NSTEMI bypass grafting occurred more often with ticagrelor. Both prasugrel and
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who undergo PCI, pretreatment with clopidogrel followed by up to ticagrelor may have a quicker onset of action than clopidogrel and may
1 year of clopidogrel therapy is beneficial in reducing major cardiovas- prove to be very useful in patients who are clopidogrel-resistant or have
cular events, but the trial did not adequately address the question of dose recurrent cardiovascular events while on clopidogrel.
or timing of clopidogrel in relationship to PCI. The subsequent CREDO The current guidelines recommend a loading dose of 300 to 600 mg
trial randomized 2116 patients to a 300-mg loading dose of clopidogrel of clopidogrel in patients with UA/NSTEMI followed by 75 mg daily.
or placebo (3-24 hours before PCI), and all patients were treated with Prasugrel should be administered as a 60-mg loading dose followed by
325 mg of aspirin and 75 mg of clopidogrel daily for 1 year. Although a 10-mg a day maintenance dose. The duration of clopidogrel may
41
there was no difference between groups in the 28-day composite end depend on whether or not the patient has received a stent. Typically
point of death, MI, or urgent target-vessel revascularization, treatment patients who received bare metal stents (BMS) should remain on
with clopidogrel was associated with a 26.9% relative risk reduction in clopidogrel for at least 4 weeks, and those with drug eluting stents (DES)
the 1-year composite end point of death, MI, or stroke. 109 should remain on clopidogrel for at least 12 months. 41,112 For DES, how-
Clopidogrel has also been tested for secondary prevention of events. ever, adequate long-term data have not been sufficient to formulate a
The CAPRIE trial, a multicenter trial of 19,185 patients with known definite recommendation on the duration of therapy.

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