Warfarin Clopidogrel

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 ... 

Clopidogrel [NP] Decreased warfarin metabolism and inhibits platelet function. 

The study design included three comparisons ACTIVE W ACTIVE A, and ACTIVE I in 14,000 patients, (Maximum follow-up was for 48 months), The primary endpoint was the time to first vascular event (stroke, Ml, vascular death, systemic emboli). ACTIVE W arm was halted when 6600 patients were enrolled because there a clear benefit from warfarin treatment compared to clopidogrel + aspirin 3.63% of vascular events versus 5,64% (P = 0,0002). Subgroup analysis showed that these disappointing results were observed in patients on warfarin prior to study (HR = 1.5, P = 0.0006), but there was no difference between the two strategies—when the patients were not on warfarin prior to study (HR = 1.32, P = 0,17), Nevertheless, further results are awaited from the ACTIVE-A arm (ASA or ASA + clopidogrel) in patients who cannot or would not take OAC. 

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). 

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. 

A randomised blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 348 1329-1339 Chimowitz MI, Kokkinos J, Strong J et al. (1995). The Warfarin-Aspirin Symptomatic Intracranial Disease Study. Neurology 45 1488-1493... 

NSAIDs Aspirin Clopidogrel Dipyridamole Warfarin Heparin SSRIs... 

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. 

Garlic ASA, NSAIDs Clopidogrel, ticlopidine Warfarin Additive antiplatelet effects Additive antiplatelet effects Increased risk of bleeding... 

Ginseng ASA, NSAIDs Antidiabetic agents Clopidogrel, ticlopidine CNS stimulants, caffeine Corticosteroids Digoxin MAO inhibitors Warfarin Additive antiplatelet effects Additive hypoglycemia Additive antiplatelet effects Additive CNS toxicity Additive CNS toxicity Falsely elevated levels Increased toxicity Increased risk of bleeding... 

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). 

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... 

Ischemic stroke TPA, heparin, ASA, clopidogrel, ticlopidine, dipyridamole and aspirin, warfarin, surgery Neurological worsening, bieeding, PT/APTT, INR, CBC... 

There are no documented drug interactions, but garlic s antiplatelet effect might be dangerous in patients taking warfarin or antiplatelet agents such as aspirin, clopidogrel, ticlopidine, or dipyridamole. 

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