Clopidogrel with warfarin

Clopidogrel may be substituted for aspirin when aspirin is absolutely contraindicated Long-acting nondihydropyridine calcium antagonists instead of /3-blockers as initial therapy ACEIs are recommended in patients with CAD or other vascular disease Low-intensity anticoagulation with warfarin, in addition to aspirin, is recommended but bleeding would be increased Therapies to be avoided include ... 

When given in combination with warfarin or thienopyri-dine class of antiplatelet agents the ASA dose is usually lowered to 80 to 100 mg based on a post hoc analysis of data from the clopidogrel in unstable angina to prevent recurrent events (CURE), which showed similar efficacy but less major bleeding with the low dose (< 100 mg) of ASA (38). 

The addition of ticlopidine to aspirin has been shown to have a synergistic effect on the inhibition of platelet aggregation after stent insertion (6), and this combination has also been found to be superior in terms of prevention of in-stent thrombosis to both aspirin alone and aspirin combined with warfarin (7). However, due to the rare but serious side effect of agranulocytosis associated with ticlopidine (8), and its slow onset of action, ticlopidine is no longer used in most countries. The combination of clopidogrel and aspirin has been proved to be as effective as aspirin and ticlopidine in the prevention of intrastent thrombosis (9). 

In two of the five spontaneous bleeding episodes described in Heading 4, medications that can affect platelet function or prothrombin time (PT) (i.e., aspirin and warfarin) were involved. Because GB is known to be an inhibitor of PAF (41), in theory GB could interact with antiplatelet drugs (e.g., aspirin, nonsteroidal anti-inflammatory drugs, clopidogrel, ticlopidine, dipyridamole) or anticoagulants (e.g., warfarin, heparin). EGb 761 was shown to potentiate the antiplatelet effect of ticlopidine in rats (42). However, in two studies in humans, the coadministration of GB with warfarin had no effect on either international normalized ratio or warfarin metabolism (43,44). 

Orford JL, Fasseas P, Melby S, Burger K, Steinhubl SR, Holmes DR, Berger PB. Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation. Am Heart J (2004) 147, 463-7. 

He was diagnosed with moderate hyperhomocysteinemia and treated with 2.0 mg folic acid daily. He continued to take warfarin and clopidogrel. After 1 month, his plasma total homocysteine level had decreased to 9 pmol/L. He had no further episodes of weakness or other neurological symptoms during the ensuing 12 months. 

Medications known to increase the risk of bleeding in cirrhotic patients include aspirin, clopidogrel, dipyridamole, corticosteroids, NSAIDs, heparin and warfarin. Mrs MW would need to be counselled about the risks associated with these medications and advised to always check with the pharmacist before buying any medications over the counter. 

Anticoagulant (warfarin) and antiplatelet agents (ticlopidine, clopidogrel) reduced platelet adhesiveness and G1 tract damage by NSAIDs increase risk of alimentary bleeding (notably with azapropazone). Phenylbutazone, and probably azapropazone, inhibit the metabolism of warfarin, increasing its effect. 

Clinically important, potentially hazardous interactions with amiodarone, atazanavir, azithromycin, bosentan, ciprofibrate, clarithromycin, clopidogrel, cyclosporine, darunavir, delavirdine, diltiazem, erythromycin, fosamprenavir, fusidic acid, gemfibrozil, grapefruit juice, imatinib, itraconazole, lopinavir, rabeprazole, ranolazine, red rice yeast, ritonavir, roxithromycin, selenium, St John s wort, tacrolimus, telithromycin, tipranavir, verapamil, warfarin... 

Nevertheless, as with other antiplatelet drugs, eombined use might in-erease the risk or intensity of bleeding. Therefore, in the UK, the manufacturers of clopidogrel state that the concurrent use of warfarin is not recommended, whereas the US manufacturers recommend caution. This caution would be prudent with clopidogrel and any coumarin or indane-dione. 

Similarly, in an observational cohort study of elderly survivors of acute myocardial infarction, the rate of bleeding was higher in patients receiving warfarin with aspirin (0.08 per patient year), or the triple drug combination of warfarin and aspirin with either clopidogrel or ticlopidine (0.09 per patient-year), than in patients receiving aspirin alone (0.03 per patient-year). ... 

Many physicians prescribe anticoagulants and antiplatelet medications to prevent thromboembolic events and access thrombosis in dialysis patients despite limited evidence of their efficacy in this population. Chan et al. [54] concluded that warfarin, aspirin, or clopidogrel prescription is associated with higher mortality among hemodialysis patients [54]. 

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