Page 431 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 37: Myocardial Ischemia 301

Anticoagulants: Administration of full-dose heparin after thrombolytic TABLE 37-4 Doses for Antiplatelet/Anticoagulant Therapy in Acute
therapy with t-PA is essential to diminish reocclusion after successful Coronary Syndromes
reperfusion. 43,59 Dosing should be adjusted to weight, with a bolus of
60 U/kg up to a maximum of 4000 U and an initial infusion rate of Drug Initial Medical Treatment
12 U/kg/h up to a maximum of 1000 U/h, with adjustment to keep Antiplatelet Drugs
the partial thromboplastin time (PTT) between 50 and 70 seconds.
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Heparin should be continued for 24 to 48 hours. For patients undergo- 1. Aspirin 162-325 mg nonenteric formulation, orally or chewed
ing PCI who have already been treated with aspirin and a thienopyri- 2. Clopidogrel LD of 300-600 mg orally, MD of 75 mg orally per day
dine, both unfractionated heparin or bivalirudin (with or without prior 3. Prasugrel LD of 60 mg orally, MD of 10 mg orally per day
heparin administration) are acceptable anticoagulant regimens. 41 4. Ticlopidine LD of 500 mg orally, MD of 250 mg orally twice daily
Bivalirudin is 20-amino acid peptide based on the structure of hiru-
din, a natural anticoagulant isolated from the saliva of the medicinal Anticoagulants
leech, Hirudo medicinalis; bivalirudin is a direct thrombin inhibitor that 1. Unfractionated heparin LD of 60 U/kg (max 4000 U) as IV bolus
inhibits both clot-bound and circulating thrombin. It is administered MD of IV infusion of 12 U/kg/h (max 1000 U/h) to maintain
as an initial bolus of 0.75 mg/kg, followed by a continuous infusion at aPTT at 1.5-2.0 times control (approximately 50-70 seconds)
1.75 mg/kg/h for the duration of PCI, with adjustments for patients
with renal dysfunction. Bivalirudin is at least as good as heparin plus 2. Enoxaparin LD of 30 mg IV bolus may be given. MD = 1 mg/kg SC every
a glycoprotein IIb/IIIa inhibitor in reducing ischemic events associ- 12 hours. extend dosing interval to 1 mg/kg every 24 hours
ated with unstable angina and/or non-ST elevation myocardial infarc- if estimated Ccr <30 mL/min
tion with the added benefit of a reduction in bleeding. The potential 3. Fondaparinux 2.5 mg SC once daily. Avoid for Ccr <30 mL/min
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role of bivalirudin in STEMI was clarified by HORIZONS-AMI trial, 4. Eptifibatide LD of IV bolus of 180 µg/kg. MD of IV infusion of 2.0 µg/kg/
which randomized 3602 patients with STEMI undergoing primary PCI min; reduce infusion by 50% in patients with estimated
to unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor or to Ccr <50 mL/min
bivalirudin alone (with provisional glycoprotein IIb/IIIa in the cardiac
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catheterization lab). Major adverse cardiac event (MACE) rates were 5. Tirofiban LD of IV infusion of 0.4 µg/g/min for 30 minutes
equivalent, but use of bivalirudin alone was associated with a 40% reduc- MD of IV infusion of 0.1 µg/kg/min; reduce rate of infusion
tion in bleeding, and there was a suggestion that all-cause mortality at by 50% in patients with estimated Ccr <30 mL/min
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one year might be reduced (3.4% vs 4.8%, p = 0.03). Bivalirudin is also 6. Bivalirudin 0.1 mg/kg bolus, 0.25 mg/kg/h infusion
82
an excellent alternative to unfractionated or low-molecular weight hepa-
rin in patients with a history of heparin induced thrombocytopenia. Ccr, creatinine clearance; LD, loading dose; MD, maintenance dose.
Enoxaparin is a low molecular weight heparin with established effi- Adapted with permission from Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 Guidelines for the
cacy as an anticoagulant in patients with STEMI who have received Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction: A Report of the
fibrinolytics or are undergoing PCI. 83,84 The standard dose of enoxaparin American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol.
is a 30-mg intravenous bolus, followed 15 minutes later by subcutaneous August 14, 2007;116(7):e148-e304.
injections of 1.0 mg/kg every 12 hours. Patients with decreased creati- β-Blockers: β-Blockers are beneficial both in the early management of
nine clearance or those older than 75 are at higher risk of bleeding with
standard dose enoxaparin and should not receive a bolus but can receive myocardial infarction and as long-term therapy. In the prethrombolytic
era, early intravenous atenolol was shown to significantly reduce rein-
a reduced dose of 0.75 mg/kg every 12 hours. Patient undergoing PCI 89
should have an additional bolus if the last dose was given 8 to 12 hours farction, cardiac arrest, cardiac rupture, and death. In conjunction with
thrombolytic therapy with t-PA, immediate β-blockade with metoprolol
prior. Maintenance dosing of enoxaparin should be given during the
hospitalization (up to 8 days). resulted in a significant reduction in recurrent ischemia and reinfarction,
although mortality was not decreased.
90
Fondaparinux, a synthetic pentasaccharide factor Xa inhibitor, can
The COMMIT-CCS 2 trial of 45,852 patients with acute MI had a
be dosed daily in patients receiving fibrinolytics for STEMI (initial dose factorial arm (the clopidogrel arm was discussed above) and random-
of 2.5 mg intravenously followed by subcutaneous injections of 2.5 mg
once daily). The OASIS-6 trial randomized over 12,000 patients with ized patients, 93% of whom had STEMI and 54% of whom were treated
with lytics, to treatment with metoprolol (three intravenous injections
STEMI to 2.5 mg of fondaparinux or placebo, and showed a reduction 91
in the combined end point of death or reinfarction at both 30 days and of 5 mg each followed by oral 200 mg/d for up to 4 weeks) or placebo.
Surprisingly, there was no difference in the primary end point of death,
6 months, accompanied by a reduction in severe bleeds. In patients
85
undergoing PCI for STEMI, however, fondaparinux administration was reinfarction, or cardiac arrest by treatment group (9.4% for metoprolol
vs 9.9% for placebo, p = NS) or in the coprimary end point of all-cause
associated with an increased rate of catheter related thrombosis, and so
85
when PCI is performed, unfractionated heparin should be administered mortality by hospital discharge (7.7% vs 7.8%, p = NS). Although rein-
farction was lower in the metoprolol group, there was an increase in the
with fondaparinux in the catheterization laboratory. See Table 37-4
86
regarding doses of antiplatelet and anticoagulant therapy. risk of developing heart failure and cardiogenic shock (5.0% vs 3.9%,
p < 0.0001), and death due to shock occurred more frequently in the
Nitrates: Nitrates have a number of beneficial effects in acute myocar- metoprolol group (2.2% vs 1.7%). Based on these findings, routine use
91
dial infarction. They reduce myocardial oxygen demand by decreas- of intravenous β-blockers in the absence of systemic hypertension is no
ing preload and afterload, and may also improve myocardial oxygen longer recommended. 79
supply by increasing subendocardial perfusion and collateral blood In contrast to the use of early, aggressive β-blocker therapy, the
flow to the ischemic region. Occasional patients with ST elevation long term use of β-blockers post-MI has favorable outcomes on
25
due to occlusive coronary artery spasm may have dramatic resolution mortality. 92,93 The CArvedilol Post-infaRct survIval COntRolled
of ischemia with nitrates. In addition to their hemodynamic effects, evaluatioN (CAPRICORN) trial randomized patients with systolic
nitrates also reduce platelet aggregation. Despite these benefits, dysfunction already treated with ACE inhibitors after MI to carvedilol
the GISSI-3 and ISIS-4 trials failed to show a significant reduction or placebo, and showed decreased cardiovascular mortality as well as
in mortality from routine acute and chronic nitrate therapy. 87,88 a decrease in the composite outcome of all-cause mortality or non-
Nonetheless, nitrates are still first-line agents for the symptomatic fatal MI. This study supports the claim that β-blocker therapy after
94
relief of angina pectoris and when myocardial infarction is compli- acute MI reduces mortality irrespective of reperfusion therapy or ace-
cated by congestive heart failure. inhibitor use. Relative contraindications to oral β-blockers include heart

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