LMWH vs Warfarin for CVA
LMWH vs Warfarin for CVA
In an anticoagulation practice, I occasionally see patients discharged on low-molecular-weight heparin (LMWH) along with warfarin after cerebral vascular accident (CVA). Whether the CVA was cardioembolic or ischemic, is there any rationale/support for prescribing LMWH, rather than discharging on warfarin alone?
To address this question, we need to concentrate on 2 matters that are germane to the topic. The first is the early recurrence rate of ischemic stroke the other is the role of anticoagulants in the setting of stroke.
Some earlier data on the risk for early recurrent embolic stroke comes from the Cerebral Embolism Study Group, which estimated a 12% recurrence rate in untreated patients. More contemporary data suggest that these statistics may be an overestimation. In the International Stroke Study, there was a 5% recurrence rate for ischemic stroke over 14 days in the untreated group (approximately 0.4%/day). Other recent trials have reported similar recurrence rates, ranging anywhere from 0.2% to 0.5%/day. It seems that the risk for recurrent ischemic stroke is slightly lower in acute stroke patients without atrial fibrillation (AF) than in their counterparts who have AF.
The second issue germane to the question is the role of anticoagulants in the setting of stroke. This can be further divided into the use of emergent anticoagulation for acute stroke and oral anticoagulation for prevention of recurrences.
Emergent anticoagulation using unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), and heparinoids have not yielded any reduction in stroke mortality and morbidity or early stroke recurrence rates while increasing the risk for bleeding when compared with conventional therapy. In a joint statement by the American Academy of Neurology and the American Stroke Association, the use of UFH, LMWHs, and heparinoids early after stroke (within 48 hours) is discouraged, as there is no apparent benefit but risk for intracerebral and systemic bleeding is clearly increased.
While the role of oral anticoagulation with warfarin for prevention of stroke recurrence in patients with AF is well established, its value in noncardioembolic stroke is uncertain. A study comparing warfarin and aspirin in patients with transient ischemic attack (TIA) or minor noncardioembolic stroke was terminated early because the primary endpoint (nonfatal stroke, myocardial infarction, cardiovascular death or major bleeding) was 2-fold higher in the warfarin group than in the aspirin group. A recent Cochrane review comparing oral anticoagulants versus antiplatelets for prevention of stroke recurrence in patients with TIA or minor stroke did not find sufficient data to support the use of oral anticoagulants in this setting. Another well-designed, double-blind, randomized, prospective trial failed to show superiority of warfarin over aspirin in patients with noncardioembolic stroke. It is noteworthy that none of the warfarin studies mentioned above had a protocol that included overlap with UFH or LMWH.
In summary, considering the available data in total, overlap of any form of heparin with warfarin in this setting does not seem to be necessary or even justifiable. First, it should be emphasized that the only well-established role for warfarin in reduction of stroke recurrence at this point is in patients with AF. Second, considering the relatively low early recurrence rate and that early use of UFH or LMWH is associated with increased risk for bleeding with no added benefit, one cannot justify overlap of UFH or LMWH with warfarin. Finally, protocols for studies of warfarin in the setting of stroke have not used any heparin overlap. So to adhere to evidenced-based medicine, warfarin should be started at lower doses of 2-4 mg/day and adjusted to the desired international normalized ratio without an overlap with heparins. In fact, it is recommended that warfarin not be started in the first few days following ischemic stroke due to concerns of hemorrhagic transformation, although the exact timing for initiation of warfarin is still unclear and deserves further studies.
In an anticoagulation practice, I occasionally see patients discharged on low-molecular-weight heparin (LMWH) along with warfarin after cerebral vascular accident (CVA). Whether the CVA was cardioembolic or ischemic, is there any rationale/support for prescribing LMWH, rather than discharging on warfarin alone?
To address this question, we need to concentrate on 2 matters that are germane to the topic. The first is the early recurrence rate of ischemic stroke the other is the role of anticoagulants in the setting of stroke.
Some earlier data on the risk for early recurrent embolic stroke comes from the Cerebral Embolism Study Group, which estimated a 12% recurrence rate in untreated patients. More contemporary data suggest that these statistics may be an overestimation. In the International Stroke Study, there was a 5% recurrence rate for ischemic stroke over 14 days in the untreated group (approximately 0.4%/day). Other recent trials have reported similar recurrence rates, ranging anywhere from 0.2% to 0.5%/day. It seems that the risk for recurrent ischemic stroke is slightly lower in acute stroke patients without atrial fibrillation (AF) than in their counterparts who have AF.
The second issue germane to the question is the role of anticoagulants in the setting of stroke. This can be further divided into the use of emergent anticoagulation for acute stroke and oral anticoagulation for prevention of recurrences.
Emergent anticoagulation using unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), and heparinoids have not yielded any reduction in stroke mortality and morbidity or early stroke recurrence rates while increasing the risk for bleeding when compared with conventional therapy. In a joint statement by the American Academy of Neurology and the American Stroke Association, the use of UFH, LMWHs, and heparinoids early after stroke (within 48 hours) is discouraged, as there is no apparent benefit but risk for intracerebral and systemic bleeding is clearly increased.
While the role of oral anticoagulation with warfarin for prevention of stroke recurrence in patients with AF is well established, its value in noncardioembolic stroke is uncertain. A study comparing warfarin and aspirin in patients with transient ischemic attack (TIA) or minor noncardioembolic stroke was terminated early because the primary endpoint (nonfatal stroke, myocardial infarction, cardiovascular death or major bleeding) was 2-fold higher in the warfarin group than in the aspirin group. A recent Cochrane review comparing oral anticoagulants versus antiplatelets for prevention of stroke recurrence in patients with TIA or minor stroke did not find sufficient data to support the use of oral anticoagulants in this setting. Another well-designed, double-blind, randomized, prospective trial failed to show superiority of warfarin over aspirin in patients with noncardioembolic stroke. It is noteworthy that none of the warfarin studies mentioned above had a protocol that included overlap with UFH or LMWH.
In summary, considering the available data in total, overlap of any form of heparin with warfarin in this setting does not seem to be necessary or even justifiable. First, it should be emphasized that the only well-established role for warfarin in reduction of stroke recurrence at this point is in patients with AF. Second, considering the relatively low early recurrence rate and that early use of UFH or LMWH is associated with increased risk for bleeding with no added benefit, one cannot justify overlap of UFH or LMWH with warfarin. Finally, protocols for studies of warfarin in the setting of stroke have not used any heparin overlap. So to adhere to evidenced-based medicine, warfarin should be started at lower doses of 2-4 mg/day and adjusted to the desired international normalized ratio without an overlap with heparins. In fact, it is recommended that warfarin not be started in the first few days following ischemic stroke due to concerns of hemorrhagic transformation, although the exact timing for initiation of warfarin is still unclear and deserves further studies.
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