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CARDIOLOGY - Treatment guidelines
Guidelines on anticoagulant therapy
DOSAGE REGIMEN FOR ORAL ANTICOAGULANTS

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Use of Oral Anticoagulants

Evidence from randomized trials continues to support the use of less-intense warfarin treatment for many indications. Within an INR range of 2.0 to 3.0, the lower level generally is safer and equally effective. Recommended therapeutic ranges for the various indications remain unchanged (Table 1). Recent studies do not support the use of fixed low-dose warfarin therapy in patients with acute myocardial infarction (AMI) or atrial fibrillation (AF).

Table 1 - Recommended therapeutic range for oral
anticoagulant therapy

INDICATION	INR RANGE
Prophylaxis of venous thrombosis (high-risk surgery) Treatment of venous thrombosis Treatment of PE Prevention of systemic embolism Tissue heart valves AMI (to prevent systemic embolism)* Valvular heart disease AF	2.0 to 3.0
Mechanical prosthetic valves (high risk)	2.5 to 3.5
Bileaflet mechanical valve in aortic position	2.0 to 3.0
Certain patients with thrombosis and the antiphospholipid syndrome	> 2.0 to 3.0

* If oral anticoagulant therapy is elected to prevent recurrent MI, an INR of 2.5 to 3.5 is
recommended, consistent with Food and Drug Administration recommendations.

Managing Oral Anticoagulant Therapy

It is recommended that warfarin therapy be started at an average maintenance dose of 5 mg compared with 10 mg, which usually is sufficient to lower the INR to 2.0 in 4 or 5 days. Lower starting doses may be appropriate in elderly patients, those with liver disease or inadequate nutrition, and those at high risk for bleeding. Larger starting doses e.g. 7.5 to 10 mg be selected if a rapid effects is urgently needed. A loading dose of warfarin is unnecessary for most patients.

Heparin can be given concurrently for ³ 4 days if a rapid effect is required. Heparin therapy is usually discontinued when the INR has been within therapeutic range in two measurements taken ³ 24 h apart.

Approaches for reducing an elevated INR are listed in Table 2.

Table 2 - Managing patients with high INR values

CLINICAL SITUATION	GUIDELINES
INR > therapeutic range but < 5.0; no significant bleeding	Lower the dose; or omit the next dose, and resume therapy at a lower dose when the INR is within therapeutic range; if the INR is only slightly above therapeutic range, dose reduction may not be necessary
INR > 5.0 but < 9.0; no significant bleeding	Omit the next dose or two, monitor INR more frequently, and resume therapy at a lower dose when the INR is within therapeutic range Alternatively, omit a dose and give vitamin K1 (1 to 2.5 mg orally), especially if the patient is at increased risk for bleeding Patients requiring more rapid reversal before urgent surgery : vitamin K1 (2 to 4 mg orally); if INR remains high at 24 h: an additional dose of vitamin K1 (1 to 2 mg orally)
INR > 9.0; no significant bleeding	Omit warfarin; give vitamin K1 (3 to 5 mg orally); closely monitor the INR; if the INR is not substantially reduced in 24 to 48 h, monitor the INR more often, giving additional vitamin K1 if necessary Resume therapy at a lower dose when the INR is within therapeutic range
INR > 20; serious bleeding	Omit warfarin; give vitamin K1 (10 mg slow I.V. infusion), supplemented with fresh plasma or prothrombin complex concentrate, depending on urgency; vitamin K1 injection can be repeated every 12 h
Life-threatening bleeding	Omit warfarin; give prothrombin complex concentrate with vitamin K1 (10 mg by slow I.V. infusion); repeat, if necessary, depending on the INR

If continuing warfarin therapy is indicated after high doses of vitamin K1, heparin can be given until the effects of vitamin K1 have been reversed and the patient becomes responsive to warfarin therapy.