Warfarin Indications (5)
Warfarin Contraindications (4 + 3)
Target INR
Warfarin & Diet
Initiating Warfarin
Educating the patient is essential before they start warfarin. This includes informing them about the signs and symptoms of bleeding, the impact of diet, potential drug interactions and actions to take if a dose is missed.
The safety and efficacy of warfarin is critically dependent on maintaining the INR within the target range. Patients must agree to undergo regular blood tests during treatment.
(In patients with non-valvular atrial fibrillation, the decision to start warfarin should be based on the CHADS2 score. This assigns 1 point each for congestive heart failure, hypertension, age 75 years and older, and diabetes mellitus, and 2 points for previous ischaemic stroke or transient ischaemic attack)
Indications, goals and duration of warfarin therapy
Indication
Target INR (range)
Duration of therapy
2.5 (2.0–3.0)
3 weeks before scheduled cardioversion and for 4 weeks after successful cardioconversion
2.5 (2.0–3.0)
Bare-metal stent (1 month) and drug-eluting stent (3–6 months) as triple therapy with clopidogrel and aspirin
After initial triple therapy, continue warfarin and a single antiplatelet drug until 12 months after stent placement
After 12 months, use warfarin alone
Bileaflet or tilting-disk valves: 2.5(2.0–3.0) in the aortic position and3.0 (2.5–3.5) in the mitral position
Long termRecommended to use aspirin in addition, 50–100 mg daily, if low bleeding risk
Starting warfarin
When commencing warfarin it is important to measure the baseline INR. If this is 1.4 or above, without warfarin, liver function and nutrition status should be assessed and specialist advice sought regarding the patient’s suitability for anticoagulation with warfarin.
Warfarin is usually started with loading doses. The Fennerty warfarin loading protocol published in 1984 was efficient in the relatively young population tested, but it was subsequently shown to cause significant over-anticoagulation in the elderly.7,8 Another protocol, based on the Fennerty protocol, decreased the loading dose with increasing age. This age-adjusted protocol (Table 3)9 recommends a 10 mg starting dose for patients aged 50 years and under, decreasing to 6 mg for patients over 80 years old.
The age-adjusted protocol was superior to the Fennerty protocol and to empirical prescribing.8 Patients more rapidly achieved a stable INR, had fewer results above 4.0 during the initiation phase and fewer doses withheld due to rapidly rising INRs
Warfarin can be safely started in the community setting, but a recognised initiation protocol should be used. Even purportedly ‘safe’ starting doses of 5 mg represent a large loading dose for a patient who requires a maintenance dose of only 1–2 mg, and can lead to marked over-anticoagulation in a few days if INRs are not monitored. There is generally a significant movement in INR on the third or fourth day after starting warfarin, regardless of whether an initiation protocol is adhered to, or a ‘safe’ dose of 5 mg is used.
When possible, a single strength warfarin tablet should preferably be prescribed so that doses are multiples of one tablet. Patients should take their warfarin once a day at the same time in the evening, with INR testing in the morning. The INR should be measured daily for the first five days.
Maintenance therapy
Once the patient has had two consecutive INRs in the target range, the INR can be measured at increasing intervals depending on its stability. Once the dose and INR are stable, patients can usually be well controlled with 4–6-weekly testing, but some patients will require more frequent testing. Dose adjustment is not required for minor INR fluctuations, if the result remains within the patient’s target range.
When adjusting maintenance doses for high or low INR values, it is important to think in terms of adjusting the dose as a percentage-based change. There is a reasonable linear relationship between dose and INR response during maintenance dosing, so a 10% dose increase will result in an increase of approximately 10% in the INR. 1 mg increment is a major adjustment for a patient normally receiving 2 mg daily (50% adjustment), and would result in a major INR change, but not for a patient receiving 10 mg daily (10% adjustment). Table 4 gives an example of the dose changes that may be needed to maintain the INR within a target range of 2–3.
For INR ≥5 follow the Australian consensus guidelines. In all cases of out-of-range INRs, possible causes for altered INR should be considered to determine if they are reversible. For example, if the INR has been elevated by antibiotics it can be expected to fall when the course is finished. This can be factored into the dosing and monitoring requirements.
Warfarin is subject to multiple interactions including:
- diet – for example beetroot, liver, green leafy vegetables (decreased INR)
- drugs that may increase INR – macrolide antibiotics, imidazole antifungals, sulfamethoxazole/trimethoprim, amiodarone, statins, some non-steroidal anti-inflammatory drugs.
- weight loss or weight gain
- excess alcohol.
The risk of bleeding is minimised by regularly monitoring the INR, and ensuring the patient understands the action of warfarin and how to recognise the signs of bleeding. Patients should have their INR checked after any dose changes, the addition of any potentially interacting drugs, or dietary changes.
To prevent INRs outside of target range:
- consider potential warfarin–drug interactions
- wait at least 48 hours before testing INR after any change of dose, as earlier testing will not reflect the full response to the dose adjustment
- if INR drifts below the target, avoid excessive increases in dose
- provide ongoing patient education.
Although bleeding can occur in the target range, the risk increases with a rising INR. Elevated INRs between 4.5 and 10, and not associated with bleeding or a high risk of bleeding, can be safely managed by withholding warfarin and carefully monitoring the INR. Vitamin K1 can be given orally or intravenously to reverse the effect of warfarin in patients with INRs above 10 or those with bleeding or a high risk of bleeding. In patients who are not actively bleeding, it is important to avoid overtreatment as this will make it difficult to re-establish control of the INR. The initial intravenous dose of vitamin K should probably not exceed 0.5–1 mg. If immediate reversal is required, prothrombin complex is preferred to fresh frozen plasma.