How To Adjust Warfarin Dose Based On Inr
Aust Prescr. 2015 Apr; 38(2): 44–48.
How to manage warfarin therapy
Philip A Tideman
1Australian Point of Intendance Practitioners Network
2Integrated Cardiovascular Clinical Network, Country Wellness Southward Australia, Adelaide
Rosy Tirimacco
1Australian Bespeak of Care Practitioners Network
2Integrated Cardiovascular Clinical Network, State Wellness South Australia, Adelaide
Andrew St John
iAustralian Betoken of Care Practitioners Network
Gregory Due west Roberts
iiiChemist's Section, Flinders Medical Eye, Adelaide
- Supplementary Materials
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This article has a Standing Professional Evolution activity for pharmacists.
GUID: 33ADD630-1E1F-4744-85D5-1EAE7970BF7D
Summary
Long-term treatment with warfarin is recommended for patients with atrial fibrillation at take a chance of stroke and those with recurrent venous thrombosis or prosthetic heart valves.
Patient didactics earlier commencing warfarin − regarding signs and symptoms of bleeding, the touch of nutrition, potential drug interactions and the actions to accept if a dose is missed − is pivotal to successful use.
Scoring systems such as the CHADS2 score are used to determine if patients with atrial fibrillation are suitable for warfarin treatment. To chop-chop achieve stable anticoagulation, employ an historic period-adapted protocol for starting warfarin.
Regular monitoring of the anticoagulant effect is required. Evidence suggests that patients who cocky-monitor using point-of-intendance testing have better outcomes than other patients.
Fundamental words: anticoagulants, INR, indicate-of-care services, warfarin
Introduction
Warfarin is recommended for the prevention of systemic embolism, stroke associated with atrial fibrillation, and venous thromboembolism (Table ane).one Its utilize is limited by several factors including a narrow therapeutic range, and drug–drug and drug–food interactions. Haemorrhage, particularly in the setting of over-anticoagulation, is a major concern.
Table 1
Indications, goals and duration of warfarin therapy1
The determination to get-go warfarin therapy requires an assessment of its harms and benefits for each patient. This assessment should take into account the patient'southward medical, social, dietary and drug history, level of education and adherence to previous therapy.ii While the risk of falls plays a office in the harm−benefit cess, published information indicate the propensity to fall is not an of import factor in this determination.3 Educating the patient is essential earlier they start warfarin. This includes informing them well-nigh 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 handling.
Stroke prevention
In patients with not-valvular atrial fibrillation, the conclusion to start warfarin should exist based on the CHADS2 score. This assigns one bespeak each for congestive middle failure, hypertension, historic period 75 years and older, and diabetes mellitus, and 2 points for previous ischaemic stroke or transient ischaemic attack.1
The CHADS2 score reliably identifies patients at intermediate and high take a chance of stroke, but less reliably identifies those truly at low risk.4 Anticoagulation with warfarin is recommended if the CHADS2 score is ≥ii and should be considered if the score is 1.
The CHA2DS2-VASc score (Table two),5 introduced by the European Society of Cardiology, provides a more comprehensive assessment of the hazard factors for stroke. Information technology is ameliorate at identifying 'truly low-risk' patients with atrial fibrillation, and is now preferred over CHADS2.
Table 2
Scorings system for assessing the chance of stroke (CHA2DStwo-VASc) and bleeding (HAS-BLED) in patients with atrial fibrillation5
The HAS-BLED score (Table two)5 has been developed to determine the chance of haemorrhage. Scores range from 0 to 9. Scores ≥3 betoken a high hazard of bleeding, the need for cautious direction and regular review of the patient. It is not the intention to use HAS-BLED scores to exclude warfarin, but to allow the clinician to identify take a chance factors for bleeding and to right those that are modifiable.six
Optimising warfarin direction
A patient's response to warfarin is driven primarily through genetic variance in the hepatic clearance, and vitamin Chiliad handling. Diet, age and dose as well influence the anticoagulant event. Assessing the response is complicated by a filibuster of 2–three days before the INR reflects any changes in warfarin dose.
Starting warfarin
When commencing warfarin information technology is important to measure the baseline INR. If this is 1.4 or above, without warfarin, liver function and nutrition status should exist assessed and specialist advice sought regarding the patient'south 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, only 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 historic period. 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.
Table 3
Historic period-adapted protocol for starting warfarin9
The age-adapted 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 ascension INRs.8 , ix
Warfarin can be safely started in the community setting, but a recognised initiation protocol should be used. Even purportedly 'safe' starting doses of five mg represent a big loading dose for a patient who requires a maintenance dose of only one−2 mg, and tin can lead to marked over-anticoagulation in a few days if INRs are not monitored. There is generally a meaning movement in INR on the third or fourth day subsequently starting warfarin, regardless of whether an initiation protocol is adhered to, or a 'prophylactic' dose of 5 mg is used.
When possible, a single strength warfarin tablet should preferably be prescribed so that doses are multiples of 1 tablet.x Patients should take their warfarin once a solar day at the same time in the evening, with INR testing in the forenoon. The INR should be measured daily for the first five days.
Maintenance therapy
One time the patient has had two consecutive INRs in the target range, the INR can exist measured at increasing intervals depending on its stability. One time the dose and INR are stable, patients tin can usually be well controlled with iv–6-weekly testing, but some patients will crave more frequent testing. Dose adjustment is not required for small-scale INR fluctuations, if the result remains inside the patient's target range.
When adjusting maintenance doses for high or low INR values, information technology is of import to retrieve in terms of adjusting the dose as a percentage-based change. There is a reasonable linear human 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.11 A 1 mg increment is a major aligning for a patient normally receiving 2 mg daily (50% aligning), and would event in a major INR alter, simply 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.
Tabular array 4
Suggested dose changes for maintaining INR within a target range of 2–iii
For INR ≥five follow the Australian consensus guidelines.12 In all cases of out-of-range INRs, possible causes for contradistinct INR should be considered to determine if they are reversible. For example, if the INR has been elevated past antibiotics it tin can be expected to fall when the course is finished. This can exist factored into the dosing and monitoring requirements.
Warfarin is subject to multiple interactions including:
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nutrition – for example beetroot, liver, green leafy vegetables (decreased INR)
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drugs that may increase INR – macrolide antibiotics, imidazole antifungals, sulfamethoxazole/trimethoprim, amiodarone, statins, some not-steroidal anti-inflammatory drugs
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weight loss or weight gain
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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 later any dose changes, the addition of any potentially interacting drugs, or dietary changes.
To forestall INRs outside of target range:
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consider potential warfarin–drug interactions
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expect at least 48 hours earlier testing INR later any change of dose, as earlier testing will non reflect the full response to the dose adjustment
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if INR drifts beneath the target, avoid excessive increases in dose
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provide ongoing patient didactics.
Although haemorrhage can occur in the target range, the run a risk increases with a rising INR. Elevated INRs between 4.v and x, and not associated with haemorrhage or a high run a risk of haemorrhage, tin be safely managed by withholding warfarin and carefully monitoring the INR. Vitamin K1 tin can be given orally or intravenously to contrary the issue of warfarin in patients with INRs above ten or those with bleeding or a loftier take chances of bleeding. In patients who are not actively bleeding, information technology is important to avoid overtreatment equally this will make it difficult to re-plant command of the INR. The initial intravenous dose of vitamin K should probably not exceed 0.5–i mg. If immediate reversal is required, prothrombin complex is preferred to fresh frozen plasma.12
Warfarin management strategies
Approaches for managing patients taking warfarin include:
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usual care by the GP
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patient cocky-monitoring
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laboratory care program.
Anticoagulation clinics coordinate and optimise the commitment of anticoagulant therapy by providing specialised monitoring and management. Patients treated in anticoagulation clinics spend more than time in the therapeutic range (fifty.4% vs 35%). They also experience less pregnant bleeding (8.1% vs 35%), major or fatal bleeding (1.half dozen% vs three.9%) or thromboembolic events (3.3% vs eleven.8%).13 In general do information technology should be possible to have patients within the therapeutic range 60% of the time.
Some centres use calculator-assisted warfarin dosing.fourteen This assists in achieving a stable state of anticoagulation faster, and increases the overall percentage of fourth dimension in the target range, potentially reducing the frequency of testing. It as well reduces the risk of bleeding and thromboembolic events and is more cost-effective than manual dosing using clinical assessment.15
Betoken-of-care testing
Point-of-care testing of the INR can be done in full general practice, in other locations such as pharmacies, or by the patients themselves (known as cocky-monitoring). These approaches are more than convenient for patients than visits to an anticoagulation dispensary in a pathology do or in a hospital.
The convenience of self-monitoring tin can be extended farther to a model of cocky-management. Patients employ algorithms to make up one's mind any necessary dose adjustments post-obit INR measurement.sixteen Testify supports the practice of self-monitoring, with or without self-direction, but an essential prerequisite is the power of the patient to correctly, competently and safely use the testing devices.17
A number of randomised controlled trials of both self-monitoring and self-management have been included in systematic reviews and meta-analyses.xvi , 18 - twenty In iii systematic reviews, self-monitoring and self-direction had like results to routine care in a hospital clinic. Patients undertaking cocky-monitoring had pregnant reductions in thromboembolic events and death, with more than time in the target range, compared to those who did not self-monitor.18 - 20 A farther systematic review of 22 randomised controlled trials showed like results including a 26% reduction in death.21 A contempo meta-analysis also found that patients who cocky-monitored had a reduced risk of thromboembolic events.16
Few studies accept compared INR betoken-of-care testing by GPs with laboratory testing. A systematic review included iii studies, but none showed improvements in the proportion of patients within the target range.22
An Australian trial of point-of-intendance testing in general practice included INR testing likewise every bit other tests. While information technology showed improvements in glycated haemoglobin (HbA1c) and some lipid profiles, at that place was no such comeback for anticoagulated patients.23
There is evidence of a poor understanding of INR testing, including therapeutic guidelines, among physicians and GPs in several countries, including Commonwealth of australia.24 The possibility remains that the improved outcomes achieved by self-management may be because patients more consistently follow therapeutic guidelines, especially if they manage their doses using software algorithms.
Conclusion
Warfarin can be a challenging drug to manage, only if used appropriately it tin exist effective for the prevention of systemic embolism, stroke associated with atrial fibrillation, and venous thromboembolism. Regular monitoring and good patient didactics are of import for successful treatment.
CPD for pharmacists
This article has a Standing Professional Development activity for pharmacists.
Footnotes
Conflict of involvement: none alleged
References
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653986/
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