Aspirin with warfarin

Administration of zafirlukast and aspirin increases plasma levels of zafirlukast, When zafirlukast is administered with warfarin, there is an increased effect of the anti coagulant. Administration of zafirlukast and theophylline or erythromycin may result in a decreased level of zafirlukast. Administration of montelukast with other drugs has not revealed any adverse responses. Administration of montelukast with aspirin and NSAIDs is avoided in patients with known aspirin sensitivity. Administration of zileuton with propranolol increases the activity or the propranolol with theophylline increases serum theophylline levels and with warfarin may increase prothrombin time (PT). A prothrombin blood test should be done regularly in the event dosages of warfarin need to be decreased. 

Either UFH or LMWH should be administered to patients with NSTE ACS. Therapy should be continued for up to 48 hours or until the end of the angiography or PCI procedure. In patients initiating warfarin therapy, UFH or LMWHs should be continued until the International Normalized Ratio (INR) with warfarin is in the therapeutic range for 2 consecutive days. The addition of UFH to aspirin reduces the rate of death or MI in patients with NSTE ACS.47 Enoxaparin was mentioned as preferred over UFH in the 2002 ACC/AHA clinical practice guidelines, as two large clinical trials found a reduction in the combined endpoint of death, MI, or need for PCI in patients... 

Stroke Prevention All patients with paroxysmal, persistent, or permanent AF should receive therapy for stroke prevention, unless compelling contraindications exist. A decision strategy for stroke prevention in AF is presented in Fig. 6-9.27 In general, most patients require therapy with warfarin in some patients with no additional risk factors for stroke, aspirin may be acceptable. For some patients, serious consideration of the benefits of warfarin versus the risks of bleeding associated with warfarin therapy is warranted. The potential bleeding risks associated with warfarin may outweigh the benefits in... 

Warfarin has not been adequately studied in non-cardioembolic stroke, but it is often recommended in patients after antiplatelet agents fail. One small retrospective study suggests that warfarin is better than aspirin.30 More recent clinical trials have not found oral anticoagulation in those patients without atrial fibrillation or carotid stenosis to be better than antiplatelet therapy. In the majority of patients without atrial fibrillation, antiplatelet therapy is recommended over warfarin. In patients with atrial fibrillation, long-term anticoagulation with warfarin is recommended and is effective in both primary and secondary prevention of stroke.12 The goal International Normalized Ratio (INR) for this indication is 2 to 3. 

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 ... 

A contact dermatitis occurs infrequently. Because feverfew also inhibits human blood platelet aggregation, interactions are possible with antithrombotic medications such as aspirin or warfarin (Groenewegen and Heptinstall 1990). Abrupt discontinuation of feverfew by people taking it chronically for treatment of migraine can produce rebound withdrawal symptoms. These consist of migraines, anxiety, poor sleep patterns, and stiffness of the muscles and joints. 

Dipyridamole is a vasodilator that inhibits platelet function by inhibiting adenosine uptake and cGMP phosphodiesterase activity. Dipyridamole by itself has little or no beneficial effect. Therefore, therapeutic use of this agent is primarily in combination with aspirin to prevent cerebrovascular ischemia. It may also be used in combination with warfarin for primary prophylaxis of thromboemboli in patients with prosthetic heart valves. A combination of dipyridamole complexed with 25 mg of aspirin is now available for secondary prophylaxis of cerebrovascular disease. 

Adverse effects have been reported with a frequency comparable to that of placebo. These include nausea, headache, stomach upset, diarrhea, allergy, anxiety, and insomnia. A few case reports noted bleeding complications in patients using ginkgo. In a few of these cases, the patients were also using either aspirin or warfarin. 

Dipyridamole (Persantine) is a vasodilator that, in combination with warfarin, inhibits embolization from prosthetic heart valves and, in combination with aspirin, reduces thrombosis in patients with thrombotic diseases. Dipyridamole by itself has little or no benefit in fact, in trials where a regimen of dipyridamole plus aspirin was compared with aspirin alone, dipyridamole provided no additional beneficial effect. Dipyridamole interferes with platelet function by increasing the cellular concentration of adenosine 3, 5 -monophosphate (cyclic AMP). This effect is mediated by inhibition of cyclic nucleotide phosphodiesterase and by blockade of uptake of adenosine, which acts at A2 receptors for adenosine to stimulate platelet adenylyl cyclase. The only current recommended use of dipyridamole is for primary prophylaxis of thromboemboli in patients with prosthetic heart valves the drug is given in combination with warfarin. 

When the classic anticoagulants are described in some recent publications, they are often labeled as bad drugs with many adverse effects. In fact, the classical anticoagulants may not have any more adverse effects than the newer drugs. Needless to say, all pharmacologic agents have their limitations. Heparin, aspirin, and warfarin certainly have drawbacks, some of which have already been addressed, although improvements have been made. 

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 this case the patient is 61-years-old with additional risk factors for stroke (hypertension and smoking). He is at moderate risk and could be offered either aspirin or warfarin. 

Long-term treatment with warfarin is almost mandatory to reduce embolic complications. The efficacy of aspirin as an antiembohc agent is probably less in this group, but has been shown to be of value in patients where warfarin is considered inappropriate. 

Patients with accumulation of uremic toxins have increased sensitivity to certain drugs. There may be an enhanced response to CNS depressants (such as barbiturates and benzodiazepines), hemorrhagic effects from aspirin or warfarin, and other bleeding effects from antibiotics that inhibit platelet aggregation, such as carbenicillin, ticarcillin, and piperacillin. 

Meade TW, Brennan PJ, Wilkes HC, Znhrie SR. Thrombosis prevention trial randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The Medical Research Council s General Practice Research Framework. Lancet 1998 351(9098) 233-41. 

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). 

Following Ml, all patients, in the absence of contraindications, should receive indefinite therapy with aspirin, a 8-blocker and an angiotensin-converting enzyme (ACE) inhibitor for secondary prevention of death, stroke, and recurrent infarction. Most patients will receive a statin to reduce low-density lipoprotein cholesterol to less than 70 to 100 mg/dL. Anticoagulation with warfarin should be considered for patients at high risk of death, reinfarction, or stroke. 

Fiore LD, Ezekowitz MD, Brophy MT, et al. Department of Veterans Affairs Cooperative Smdies Program Qinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction Primary results of the CHAMP smdy. Circulation 2002 105 557-563. 

As mentioned earlier, the presence of antiphospholipid antibodies may result in several clinical manifestations, including thrombosis. There is no agreement on prophylaxis of patients with antiphospholipid antibodies without a history of thromboembolism. In such patients, low-dose aspirin (100-325 mg/day) may be used prophylactically, although efficacy has not been established. Patients with an acute thrombotic event should receive standard treatment with anticoagulants (e.g., heparin). Follow-up treatment with warfarin to prevent recurrence may require an international normahzed ratio (INR) of 3 or greater in patients with antiphosphohpid syndrome. However, currently, there is no consensus on the intensity of anticoagulation or duration of secondary prophylaxis, but since recurrence is common, patients usually are treated with oral anticoagulants indefinitely. ... 

Drugs can compete for the same protein binding sites and this is a form of drug interaction. A well-known and important example is that of warfarin and aspirin. Warfarin is an anticoagulant, which binds extensively to plasma proteins, and this is taken into account when dosages are worked out. Aspirin taken with warfarin competes for the same... 

Dipyridamole was briefly mentioned in Chapter 10. In addition to vasodilator effects, the drug inhibits phosphodiesterase, thereby increasing intraplatelet c-AMP. Although these events do lead to decreased platelet aggregation, the drug s effectiveness clinically seems poor unless synergistically combined with either aspirin or warfarin. 

---