Myocardial infarction warfarin

Warfarin has been the primary oral anticoagulant used in the United States for the past 60 years. Warfarin is the anticoagulant of choice when long-term or extended anticoagulation is required. Warfarin is FDA-approved for the prevention and treatment of VTE, as well as the prevention of thromboembolic complications in patients with myocardial infarction, atrial fibrillation, and heart valve replacement. While very effective, warfarin has a narrow therapeutic index, requiring frequent dose adjustments and careful patient monitoring.15,29... 

A 60- year-old male, following hospitalization for an acute myocardial infarction, is treated with warfarin. What is the mechanism of action of warfarin ... 

A 75 year old man was examined on a routine visit 1 month after discharge from hospital for a myocardial infarction. No communication had been received from the hospital on the patients stay and management. The patient seemed well but had a few purpuric 1 cm round lesions on his hands. The doctor assessed these as senile purpura. He then noticed that there were several more on both legs. He felt that these were both more extensive than with senile purpura and in an unusual site. He questioned the patient about injury, which the patient denied. On ringing the hospital it was learned that the patient had had a deep venous thrombosis and was treated with warfarin. They apologised for not informing the doctor earlier ... 

Herlitz J, Holm J, Peterson M, Karlson BW, Haglid Evan-der M, Erhardt L. Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction the LoWASA Study. Enr Heart J 2004 25 232-9. 

In present times, because of early mobilization and shorter stays in hospital, venous thrombosis in the legs and resulting pulmonary embolism has declined to a large degree. In persons with acute myocardial infarction, prophylactic low-dose heparin has reduced the incidence of venous thrombosis in the legs. It is considered as a reasonable alternative to warfarin in selected patients. Preventive anlicoagulalion may be indicated in some cases to prevent strokes due to left ventricular mitral thrombi embolizing in tire brain. 

The coumarin anticoagulants, which include warfarin [WAR far in] and dicumarol [dye KOO ma role] (formerly bishydroxycoumarin) owe their action to their ability to antagonize the cofactor functions of vitamin K. Initially used as a rodenticide, warfarin is now widely employed clinically as an oral anticoagulant. Conflicting opinions exist concerning the usefulness of these agents in clinical situations such as myocardial infarction and hip arthroplasty. The potential... 

At the time he noticed the episodes of slurred speech and left-sided weakness, he was taking no medications except for warfarin and clopi-dogrel. His diet consisted mainly of meats and fried potatoes, with very few fruits and vegetables. He admitted to drinking up to a 12-pack of beer on the weekends. His family history was negative for stroke or blood clots, but his father had suffered a fatal myocardial infarction (heart attack) at age 44. 

Patients in atrial fibrillation who have a TIA or stroke without other clear etiology should be given anticoagulation therapy if there are no contraindications (European Atrial Fibrillation Trial Study Group 1993, 1995). Recent studies have shown that warfarin is as safe as aspirin in elderly patients with atrial fibrillation (Rash et al. 2007 Mant et al. 2007). Patients with presumed cardioembolic TIA or stroke secondary to other causes should certainly receive antithrombotic therapy. Also they may benefit from anticoagulation in certain circumstances, such as intracardiac mural thrombosis after myocardial infarction, although there have been no randomized trials in situations other than non-valvular atrial fibrillation. 

In five of eight patients treated with fresh frozen plasma to achieve rapid correction of anticoagulation after warfarin-related intracranial hemorrhage, there were complications of fluid overload (10). In two of these patients congestive heart failure developed, resulting in myocardial infarction and renal insufficiency respectively. Two patients had supraventricular tachy-dysrhythmias and one developed pulmonary edema. 

Haug KB, Sharikabad MN, Kringen NK, et al. Warfarin dose and INR related to genotypes of CYP2C9 and VKORCl in patients with myocardial infarction. Thromb J 2008 6 7. 

Coumadin Aspirin Reinfarction Smdy (CARS) Investigators. Randomised, double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Lancet 1997 350 389-396. 

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. 

Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002 347 969-974. 

The most widely prescribed anticoagulant in North American is warfarin sodium (Coumadin). It was discovered serendipitously in the early 1940s at the University of Wisconsin after hemorrhagic deaths occurred in cattle eating spoiled sweet clover. Warfarin is approved by the FDA for the prevention and treatment of VTE as well as for the prevention of thromboembolic complications associated with atrial fibrillation, heart valve replacement, and myocardial infarction. Because of its narrow therapeutic index, predisposition to drug and food interactions, and propensity to cause hemorrhage, warfarin requires... 

Following a myocardial infarct, a patient is stabilized on warfarin, with the dose adjusted to give a prothrombin time of 22 seconds. Which one of the following statements regarding potential drug interactions in this patient is accurate ... 

Anticoagulant therapy, chiefly warfarin, and platelet inhibitors, such as aspirin, are used prophylactically to prevent thromboembolic disease while fibrinolytic drugs can be used to destroy thrombi already formed and can be life saving after a myocardial infarction or stroke. 

Warfarin (initially 10 to 15 mg p.o. for three days) is indicated as an anticoagnlant in pntmonary emboli, deep-vein thrombosis (DVT), myocardial infarction (Ml), rhenmatic heart disease with heart valve damage, and atrial arrhythmias. 

Whether there is a history of previous seizure, diabetes, warfarin or antithrombotic medication ( blood thinners ) use, prior stroke or hemorrhage, prior transient ischemic attack (TIA), prior myocardial infarction (MI), drug abuse, trauma, head or neck pain. 

In contrast, indobufen (Fig. 31.15), a reversible but very potent inhibitor of platelet COX-1 activity, was shown to have comparable clinical efficacy to that of aspirin in prevention of DVT after myocardial infarction and in blocking exercise-induced increase in platelet aggregation (99). In the secondary prevention of thromboembolic events, 100 or 200 mg of indobufen twice daily is as effective as warfarin or aspirin in patients with or without atrial fibrillation (100). Currently, indobufen is only available for routine clinical use in Europe. 

Secondary prevention. In a meta-analysis of randomised, controlled studies in patients following myocardial infarction or acute coronary syndrome, intensive warfarin (INR greater than 2) plus aspirin 80 to 325 mg daily was associated with 2.5-fold increased risk of major bleeding, when compared with aspirin alone, although the actual incidence was low (1.5% versus 0.6%). This analysis excluded studies of coronary stenting, see (b) above. In another similar meta-analysis, combined use of aspirin and warfarin (INR 2 to 3) was associated with a 2.3 odds ratio of a major bleed, when compared with aspirin alone.The number needed to treat to cause one major bleed was 100. This compared with a number needed to treat to avoid one major adverse event (death, myocardial infarction or stroke) of 33. 

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). ... 

Rothberg MB, Celestin C, Fiore LD, Lawler E, Cook JR. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome meta-analysis witii estimates of risk and benefit. Ann Intern Med (2005) 143,241-50. 

Buresly K, Eisenberg MJ, Zhang X, Pilote L. Bleeding complications associated witii combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction. Arch Intern Med (2005) 165,784-9. 

Walker FB. Myocardial infarction after diet-induced warfarin resistance. Arch Intern Med (1984) 144,2089-90. 

However, in 1998 the manufacturers of lansoprazole had on record two reports of possible interactions. An elderly patient taking warfarin developed an INR of 7 when lansoprazole was added. Despite a warfarin dosage adjustment he had a gastrointestinal haemorrhage, a myocardial infarction and died after 3 weeks. Another man taking warfarin (as well as amiodarone, furosemide and lisinopril) became confused, had hallucinations and developed an increased INR (value not known) when given lansoprazole. The lansoprazole was stopped after 4 days, and he then recovered. However, it is uncertain whether this was an interaction or whether he had taken an incorrect warfarin dosage because of his confusion. ... 

Tulloch JA, Marr TCK. Sulphinpyrazone and warfarin after myocardial infarction. BMJ (1979) ii, 133. 

Smith, R, Amesen, H., and Holme, I., for the WARIS Study Group (1990) The Effect of Warfarin on Mortality and Reinfarction After Myocardial Infarction, N. Engl. J. Med. 323,147-152. 

Haematologic In a study of rapid warfarin reversal for intracerebral haemorrhage using 3-factor prothrombin complex concentrate (PCC) and recombinant FVIIa, authors report that 2 of the 46 patients experienced thrombotic complications [124 J. Both patients experienced non-ST-elevated myocardial infarction. Notably, one of these occurred with a 2.4-mg dose of recombinant FVIIa and the study protocol was changed to all subsequent patients getting l.Omg of recombinant FVIIa. 

The comprehensive review by Douglas provides a recent discussion of the clinically useful anticoagulants. Recent studies have shown heparin to be clearly effective in clinical states In which disseminated Intravascular coagulation was Indicated to be a pathologic factor.75 xhe most commonly employed oral anticoagulants are of the coumarin type such as warfarin and nicoumalone. The oral anticoagulants appear to be of value in the prevention of thromboembolic complications after myocardial infarction.9 76 However, anticoagulation therapy has been found to have no effect on death-rate in these patients.77 Warfarin has been shown to be effective in the prevention of postoperative venous thrombosis. 

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