Page 2408 - Hematology_ Basic Principles and Practice ( PDFDrive )

2150 Part XII Hemostasis and Thrombosis

GP IIb/IIIa inhibitor was associated with similar rates of the primary Strategies Aimed at Minimizing the Risk of Bleeding
outcome, MI, target vessel revascularization, stroke, or death (5.4% TABLE in Patients Treated With Triple Therapy (Dual
vs. 5.5%) at 30 days, but bivalirudin significantly reduced major 146.7 Antiplatelet Therapy and an Oral Anticoagulant)
bleeding (4.9% vs. 8.3%; p < .0001).
The EUROMAX (European Ambulance Acute Coronary Syn- Proposed Approach Rationale
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drome Angiography) trial evaluated the use of prehospital bivaliru- Aspirin maintenance dose Higher aspirin maintenance doses
din in 2218 participants treated with aspirin and a P2Y12 receptor ≤100 mg/day increase bleeding, and there is no
antagonist (more than 50% received ticagrelor or prasugrel) being evidence that they improve efficacy
transported for primary PCI. Compared with heparin (unfraction-
ated or low-molecular-weight) plus optional GP IIb/IIIa inhibitor, PPI with a preference for Much of the excess bleeding is from the
bivalirudin reduced the risk of death or non-CABG major bleeding agents that interfere less GI tract. The use of acid-suppressive
(5.1% vs. 8.5%; p = .001), a difference that was primarily driven by with CYP 2C19 (e.g., agents that interfere less with CYP
a reduction in major bleeding (2.6% vs. 6.0%; p < .001). Bivalirudin pantoprazole) 2C19 minimizes the potential for a
was associated with an increase in stent thrombosis within 24 hours negative interaction with clopidogrel
(1.1% vs. 0.2%; p = .007). Preference for a non– Dabigatran 110 mg twice daily and
The single-center, open-label HEAT-PPCI (unfractionated heparin vitamin K antagonist apixaban 2.5 or 5.0 mg twice daily
versus bivalirudin in primary percutaneous coronary intervention) oral anticoagulant are associated with lower rates of
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trial evaluated the use of bivalirudin in 1829 participants treated bleeding than warfarin
with aspirin and a P2Y12 receptor antagonist (almost 90% received For warfarin, use a target Some evidence that a restricted target
ticagrelor or prasugrel) undergoing emergency angiography. Compared INR of 2–2.5 INR range reduces the risk of
with heparin (13% also received a GP IIb/IIIa inhibitor), bivalirudin bleeding
(15% also received a GP IIb/IIIa inhibitor) was associated with an
increase in the composite of death, stroke, reinfarction, or unplanned Manage warfarin in a Compared with usual care, specialist
target lesion revascularization (8.7% vs. 5.7%; p = .01). The rates of specialized clinics achieve a higher TTR of the
major bleeding were similar (3.5% vs. 3.1%; p = .59), but there was anticoagulation clinic INR
more stent thrombosis with bivalirudin (3.4% vs. 0.9%; p = .001) Minimize duration of triple The risk of bleeding is highest during
The BRIGHT (Bivalirudin vs Heparin With or Without Tirofiban) therapy the first 30 days but remains elevated
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trial evaluated the use of bivalirudin continued for 30 minutes to 4 with long-term treatment
hours after PCI in 2194 participants with acute MI. Compared with Avoid NSAIDs NSAIDs are a common cause of upper
heparin alone or heparin plus a GP IIb/IIIa inhibitor, bivalirudin GI bleeding
reduced the risk of death, reinfarction, stroke, ischemia-driven target
vessel revascularization or any bleeding (8.8% vs. 13.2%; p = .008, and Avoid prasugrel and Prasugrel and ticagrelor cannot be
8.8% vs. 17%; p < .001), primarily driven by a reduction in bleeding ticagrelor recommended because they are more
(4.1% vs. 7.5% vs. 12.3%; p < .001) with similar rates of major adverse potent than clopidogrel and cause
cardiac or cerebral events (5.0% vs. 5.8% vs. 4.9%; p = .74) and stent more bleeding
thrombosis (0.6% vs. 0.9% vs. 0.7%; p < .77). Prolonged bivalirudin CYP, Cytochrome P450; GI, gastrointestinal; INR, international normalized ratio;
therapy following PCI might explain the lack of excess stent thrombosis NSAID, nonsteroidal antiinflammatory drug; PPI, proton pump inhibitor;
TTR, time in therapeutic range.
that was seen in most of the earlier bivalirudin trials.
The ACUITY (Acute Catheterization and Urgent Intervention
Triage Strategy) trial evaluated the use of bivalirudin in 13,819
patients with NSTE ACS undergoing PCI who were treated with the 15,526 ACS patients, the majority of whom were also treated with
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combination of aspirin plus clopidogrel as well as a GP IIb/IIIa the combination of aspirin and clopidogrel. Treatment was started
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inhibitor. Bivalirudin was noninferior to heparin or enoxaparin plus a median of 4.7 days after onset of symptoms and was continued for
a GP IIb/IIIa inhibitor for the prevention of MI, unplanned revas- a mean of 13 months. Rivaroxaban significantly reduced the risk of
cularization, or death at 30 days (7.8% vs. 7.3%) but was associated MI, stroke, or cardiovascular death (8.9% vs. 10.7%; p =.008) at the
with a lower rate of major bleeding (3.0% vs. 5.7%; p < .001). cost of an increase in non-CABG major bleeding (2.1% vs. 0.6%;
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A metaanalysis of 16 trials involving 33,958 participants showed p < .001) and intracranial bleeding (0.6% vs. 0.2%; p = .009). Based
that compared with heparin-based treatment regimens, bivalirudin on these results, rivaroxaban (2.5 mg twice daily) has been approved
was associated with increased major adverse cardiac events and stent in Europe for post ACS patients.
thrombosis and a reduction in major bleeding, with no different in The APPRAISE trial compared apixaban (5 mg twice a day;
death. 2.5 mg twice a day in selected patients) with placebo in patients with
ACS. The trial was stopped early because of an excess of bleeding
with no significant reduction in ischemic events. 27
Oral Anticoagulation The oral direct thrombin inhibitor dabigatran etexilate has been
tested in a phase II trial but has not undergone evaluation in a phase
Warfarin is an oral vitamin K antagonist that has been evaluated in III trial in ACS patients (see Table 146.7 and box on Case 4: Triple
the long-term management of patients with ACS who are treated Therapy).
with aspirin but has not been rigorously tested on a background of
dual antiplatelet therapy. Furthermore, the efficacy and safety of the
combination of aspirin plus warfarin have not been compared with CONCLUSIONS AND FUTURE DIRECTIONS
those of dual antiplatelet therapy.
The results from a metaanalysis of 14 trials involving 25,307 Antiplatelet and anticoagulant drugs are effective for the prevention
patients demonstrated that compared with placebo or no warfarin, of MI and death across the spectrum of patients presenting with ACS,
long-term warfarin (target INR, 2.0–3.0) reduced the risk of MI, including STEMI patients treated with fibrinolytic therapy and those
ischemic stroke or death (9.4% vs. 12.3%; p < .0001) at the cost of undergoing mechanical reperfusion. Aggressive antithrombotic treat-
a twofold increase in major bleeding (2.6% vs. 1.1%; p < .00001). 44 ment regimens involving multiple antiplatelet drugs given in combi-
Rivaroxaban and apixaban are orally active direct factor Xa inhibi- nation with an anticoagulant during the acute phase have substantially
tors that have undergone evaluation in phase III trials for the long- reduced the risk of early and late recurrent ischemic events and stent
term management of patients with ACS. The ATLAS TIMI-51 trial thrombosis in ACS patients but at the cost of an increased risk of
compared rivaroxaban (2.5 or 5 mg twice a day) with placebo in bleeding. Clinicians require detailed knowledge of the pharmacology