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Research · Medication

Warfarin

Meta-analyses found adjusted-dose warfarin cut stroke by about 64% in atrial fibrillation against no treatment and by about 39% against antiplatelet drugs. Trials also found fewer repeat venous clots and valve clots. Major bleeding affected about 6% over trial follow-up, and its FDA boxed warning covers fatal bleeding. Many drugs, supplements and vitamin K intake shift its effect.

Add to Bio HackChecked 2026-11-13
Status
Prescription drug in the US, FDA-approved to prevent and treat venous thrombosis and pulmonary embolism, to prevent and treat clot complications of atrial fibrillation and heart valve replacement, and to reduce death, repeat heart attack and stroke after a heart attack. Its label carries an FDA boxed warning for major or fatal bleeding.
Also called
Coumadin, Jantoven, warfarin sodium, vitamin K antagonist, VKA, coumarin anticoagulant, blood thinner
Taken for
stroke prevention in atrial fibrillation, blood clots, deep vein thrombosis, pulmonary embolism, mechanical heart valves, after a heart attack, blood thinning

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help6

Reported risks16

What people take it for, and what was found

Shown to help6

StrongCommon

Stroke prevention in atrial fibrillation, against no treatment

Shown to cut stroke by about 64% against placebo or no treatment in adults with nonvalvular atrial fibrillation, with fewer deaths in one review.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Across six trials, adjusted-dose warfarin lowered stroke by 64% (95% CI 49 to 74) against control [1]. In five trials of people with no earlier stroke, warfarin lowered all stroke (OR 0.39, 95% CI 0.26 to 0.59), disabling or fatal stroke (OR 0.47, 95% CI 0.28 to 0.80) and death (OR 0.69, 95% CI 0.50 to 0.94) over a mean 1.5 years. The reviewers estimated about 25 strokes prevented each year for every 1,000 people treated [2].
Population
2,900 participants in six trials, within a meta-analysis of 29 trials and 28,044 participants, mean age 71 [1]; 2,313 participants without earlier stroke in five trials, mean age 69 [2].
Sources
[1], [2]
Caveats
The band above is the estimate of 25 strokes prevented a year per 1,000 treated. Follow-up was short, and bleeding estimates from these trials were imprecise [2].
Strong

Stroke prevention in atrial fibrillation, against aspirin

Shown to cut stroke by about 39% more than antiplatelet drugs in atrial fibrillation, and to halve stroke against aspirin in adults aged 75 or over.

The numbers and sources
Effect
Across 12 trials, adjusted-dose warfarin lowered stroke by 39% (95% CI 22 to 52) against antiplatelet therapy [1]. In people aged 75 or over, stroke, intracranial hemorrhage or systemic embolism occurred at 1.8% a year on warfarin against 3.8% on aspirin (RR 0.48, 95% CI 0.28 to 0.80). Extracranial hemorrhage occurred at 1.4% a year against 1.6% [3].
Population
12,963 participants in 12 trials [1]; 973 patients aged 75 or over, mean age 81.5, followed a mean 2.7 years [3].
Sources
[1], [3]
Caveats
Trial quality varied and was often incompletely reported [1].
Moderate

Treating and preventing venous clots

Shown to cut repeat venous clots by about 95% against placebo when continued after three months, in one trial of first unprovoked clots.

The numbers and sources
Effect
After three months of treatment for a first unprovoked venous thromboembolism, 17 of 83 people on placebo had a recurrence (27.4% per patient-year) against 1 of 79 who continued warfarin (1.3% per patient-year), a 95% reduction (95% CI 63 to 99). Three people on warfarin had nonfatal major bleeding against none on placebo [7]. Across six trials of acute venous thromboembolism, recurrence occurred in 2.2% on a vitamin K antagonist and 2.0% on a DOAC (RR 0.90, 95% CI 0.77 to 1.06), with more major bleeding on the vitamin K antagonist [8].
Population
162 patients followed an average 10 months [7]; 27,023 patients in six trials [8].
Sources
[7], [8]
Caveats
The placebo-controlled trial was small and stopped early for benefit [7].
Moderate

Mechanical heart valves

Linked to about 1 major embolism per 100 patient-years with coumarin treatment in people with mechanical valves, against 4 without antithrombotic treatment.

The numbers and sources
Effect
Across 46 studies, the incidence of major embolism was 4 per 100 patient-years without antithrombotic treatment, 2.2 with antiplatelet treatment and 1 with coumarin treatment. Major bleeding on coumarins occurred at 1.4 per 100 patient-years [9]. In a randomized trial, stroke occurred in 5% on dabigatran and in none on warfarin [10]. The label gives a target INR of 2.5 or 3.0 by valve type and position [11].
Population
13,088 patients studied for 53,647 patient-years in 46 studies [9]; 252 patients with mechanical heart valves [10].
Sources
[9], [10], [11]
Caveats
The meta-analysis pooled mostly observational studies from 1970 to 1992, and embolism risk varied with valve type and position [9].
Limited

After a heart attack

One trial found death, repeat heart attack or stroke in 16.7% on warfarin against 20.0% on aspirin after a heart attack, with more major bleeding.

The numbers and sources
Effect
Death, nonfatal reinfarction or thromboembolic stroke occurred in 16.7% on warfarin against 20.0% on aspirin (rate ratio 0.81, 95% CI 0.69 to 0.95), and in 15.0% on warfarin plus aspirin (rate ratio 0.71, 95% CI 0.60 to 0.83). Major nonfatal bleeding occurred at 0.62% per treatment-year in both warfarin groups against 0.17% on aspirin [12].
Population
3,630 patients after acute myocardial infarction. Warfarin alone was dosed to an INR of 2.8 to 4.2 [12].
Sources
[12]
Caveats
One trial, published in 2002, at a higher INR target than the label gives for most uses.
Why limited
This rests on one trial, of 3,630 people. Strength counts independent studies that agree, so one trial is limited at any size.
Moderate

Self-testing and self-managing the INR

Shown to cut clotting events by about 42% when people tested or managed their own INR, with no change in major bleeding.

The numbers and sources
Effect
Across 18 trials, self-monitoring or self-management lowered thromboembolic events (RR 0.58, 95% CI 0.45 to 0.75). Self-management lowered death from any cause (RR 0.55, 95% CI 0.36 to 0.84) and self-monitoring did not (RR 0.94, 95% CI 0.78 to 1.15). Major hemorrhage did not change (RR 0.95, 95% CI 0.80 to 1.12) [15].
Population
8,950 participants in 28 randomized trials [15].
Sources
[15]
Caveats
Evidence quality was rated low to moderate. Trial participants were people able and willing to test themselves.

Mixed results2

Moderate

Time in the therapeutic INR range

Linked to fewer major bleeds and clots when more time was spent in the target INR range, in retrospective studies but not clearly in randomized trials.

The numbers and sources
Effect
Across 47 studies in atrial fibrillation, time in therapeutic range ran from 29% to 75%, and was higher in randomized trials than in retrospective studies (64.9% against 56.4%). Time in range correlated negatively with major hemorrhage (r -0.59) and thromboembolic rates (r -0.59). In retrospective studies, a 6.9% improvement in time in range lowered major hemorrhage by 1 event per 100 patient-years (95% CI 0.29 to 1.71). The correlations were not significant within randomized trials [13]. In the edoxaban trial the median time in range on warfarin was 68.4% [14]. The label states that keeping the INR in range does not eliminate the risk of bleeding [11].
Population
47 studies from 38 articles of people with atrial fibrillation on vitamin K antagonists [13]; 21,105 patients [14].
Sources
[13], [14], [11]
Caveats
Correlations across studies, not a trial of raising time in range.
Limited

Daily low-dose vitamin K to steady the INR

Small trials found mixed results: one found 150 micrograms of vitamin K a day improved unstable INR control, and a smaller one found no benefit.

The numbers and sources
Effect
In 70 people with unexplained unstable control, adding 150 micrograms of oral vitamin K a day improved anticoagulation control. In 30 people with highly variable INRs, 175 micrograms a day did not significantly improve stability against placebo. Neither study reported clots, bleeding or death from the added vitamin K [16].
Population
100 participants in two studies [16].
Sources
[16]
Caveats
Not an approved use. The second study was available as an abstract only, and the Cochrane reviewers judged the data insufficient to show an overall benefit [16].

Not shown to help1

Strong

Compared with DOACs in atrial fibrillation

Not shown to match DOACs in atrial fibrillation: stroke or systemic embolism occurred in 3.69% on warfarin against 3.01%, with about twice the brain bleeds.

The numbers and sources
Effect
Across four trials, DOACs lowered stroke or systemic embolism by 19% against warfarin (RR 0.81, 95% CI 0.73 to 0.91) and death by 10% (RR 0.90, 95% CI 0.85 to 0.95) [4]. In patient-level data, stroke or systemic embolism occurred in 3.69% on warfarin against 3.01% on a standard-dose DOAC, death in 8.42% against 7.76% and intracranial bleeding in 1.40% against 0.63% [5]. In rheumatic heart disease with atrial fibrillation, the result went the other way, with fewer cardiovascular events or deaths on a vitamin K antagonist than on rivaroxaban [6].
Population
71,683 participants in four trials, 29,272 of them on warfarin [4][5]; 4,531 patients with rheumatic heart disease and atrial fibrillation [6].
Sources
[4], [5], [6]
Caveats
The four trials were funded by DOAC manufacturers. The gap in major bleeding was larger at trial centers where warfarin control was poorer [4].

Doses studied

The label states that the starting dose is usually 2 to 5 mg once daily when genotype is not known, with typical maintenance doses of 2 to 10 mg once daily, adjusted to the INR. It gives a target INR of 2.5 (range 2.0 to 3.0) for venous clots and nonvalvular atrial fibrillation, and 3.0 (range 2.5 to 3.5) for mechanical valves in the mitral position. It states that an INR above 4.0 appears to add no benefit in most patients and carries a higher risk of bleeding [11].

The atrial fibrillation trials pooled in the Cochrane review reached mean INRs of 2.0 to 2.6 [2]. The trial in people aged 75 or over targeted an INR of 2 to 3 [3], and the trial after heart attack 2.8 to 4.2 [12].

Risks

Reported risks15

StrongCommon

FDA boxed warning: major or fatal bleeding

FDA states that warfarin can cause major or fatal bleeding. Major bleeding occurred in about 6% of people with atrial fibrillation over the pivotal trials.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
The boxed warning states that warfarin can cause major or fatal bleeding, and the label lists an INR above 4.0, age 65 or over, highly variable INRs, earlier gastrointestinal bleeding, kidney impairment and certain other drugs among risk factors. It states that bleeding is more likely in the first month [11]. In four atrial fibrillation trials, major bleeding occurred in 5.94% on warfarin against 5.05% on a standard-dose DOAC [5], and at a yearly rate of 3.43% on warfarin in the edoxaban trial [14]. Against control in older atrial fibrillation trials, the absolute increase in major extracranial hemorrhage was 0.3% a year or less [1]. After a heart attack, major nonfatal bleeding occurred at 0.62% per treatment-year on warfarin against 0.17% on aspirin [12]. Among people treated for venous clots, 13.4% of major bleeds were fatal (95% CI 9.4 to 17.4) [17].
Population
29,272 people on warfarin in four trials [5]; 28,044 participants in 29 trials [1]; 3,630 patients after heart attack [12]; 33 studies with 4,374 patient-years of treatment [17].
Sources
[11], [5], [14], [1], [12], [17]
Caveats
The band above is the share with major bleeding over the atrial fibrillation trials, whose comparator was a DOAC. Placebo-controlled trials were older and smaller.
StrongCommon

Bleeding in the brain

Shown to cause bleeding inside the skull in 1.40% of people with atrial fibrillation over the trials, about twice the 0.63% on DOACs.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In four atrial fibrillation trials, intracranial bleeding occurred in 1.40% on warfarin against 0.63% on a standard-dose DOAC (HR 0.45 for the DOAC, 95% CI 0.37 to 0.56) [5]. The trial-level meta-analysis gave a similar result (RR 0.48, 95% CI 0.39 to 0.59) [4]. Among people treated for venous clots, intracranial bleeding occurred at 1.15 per 100 patient-years [17]. In older placebo-controlled atrial fibrillation trials, intracranial hemorrhage was not significantly increased, with wide confidence intervals [2].
Population
29,272 people on warfarin in four trials [5][4]; 4,374 patient-years of treatment for venous clots [17].
Sources
[5], [4], [17], [2]
Caveats
The comparator in the large trials is a DOAC, not placebo.
ModerateCommon

Harm to the fetus in pregnancy

The label states that first trimester exposure caused a pattern of birth defects in about 5% of exposed babies. It lists pregnancy as a contraindication except with mechanical valves.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
The label states that warfarin crosses the placenta, that exposure in the first trimester caused a pattern of congenital malformations in about 5% of exposed offspring, and that brain and eye abnormalities have followed later exposure. It lists pregnancy as a contraindication except in women with mechanical heart valves at high risk of clots [11]. In pregnant women with mechanical valves, treatment with a vitamin K antagonist throughout was associated with maternal clot complications in 2.7%, live births in 64.5% and anticoagulant-related fetal or neonatal harm in 2.0%, against 8.7%, 92.0% and 0% with low molecular weight heparin. Fetal anomalies occurred in 2.3% at first trimester warfarin doses of 5 mg a day or less and 12.4% at higher doses [26].
Population
Reports summarized in labeling [11]; 46 articles on pregnant women with mechanical heart valves [26].
Sources
[11], [26]
Caveats
The label notes its 5% figure did not come from controlled studies. The included studies had moderate or high risk of bias [26].
LimitedRare

Skin and tissue death

The label warns of necrosis or gangrene of skin and other tissues in fewer than 0.1% of people, usually within days of starting.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
The label describes necrosis or gangrene of skin and other tissues as an uncommon but serious risk (under 0.1%), usually appearing within a few days of starting warfarin, with debridement or amputation reported in severe cases. It also warns of limb ischemia, necrosis and gangrene when warfarin was started in people with heparin-induced thrombocytopenia [11].
Population
Reports summarized in labeling [11].
Sources
[11]
Caveats
The label gives the frequency without the underlying counts.
LimitedHow often is not known

Emergency hospital admissions in older adults

Linked to a third of emergency hospital admissions for adverse drug events among US adults aged 65 or over, in national surveillance data from 2007 to 2009.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Of an estimated 99,628 emergency hospitalizations a year for adverse drug events in US adults aged 65 or over, warfarin was implicated in 33.3%, ahead of insulins (13.9%), oral antiplatelet agents (13.3%) and oral hypoglycemic agents (10.7%). Nearly two thirds of hospitalizations were due to unintentional overdoses [18].
Population
5,077 cases in a national surveillance sample, 2007 to 2009 [18].
Sources
[18]
Caveats
A share of admissions, not a rate among people taking warfarin. The data predate wide use of DOACs.
ModerateHow often is not known

Antibiotics and antifungals

Linked to about twice the odds of a bleeding admission within 15 days of an antibiotic in older warfarin users, and over four times with azole antifungals.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Among older continuous warfarin users, exposure to any antibiotic within 15 days was associated with bleeding requiring hospitalization (adjusted OR 2.01, 95% CI 1.62 to 2.50). The association held for azole antifungals (4.57), cotrimoxazole (2.70), cephalosporins (2.45), penicillins (1.92), macrolides (1.86) and quinolones (1.69) [20]. A systematic overview found consistent reports of interaction with azoles, macrolides and quinolones [21]. The label reports INR changes with antibiotics and antifungals, while pharmacokinetic studies have not shown consistent effects on warfarin blood levels [11].
Population
A case-control study within 38,762 continuous warfarin users aged 65 or older [20]; 181 articles on 120 drugs or foods [21].
Sources
[20], [21], [11]
Caveats
Observational. The infection being treated may itself affect bleeding risk.
ModerateHow often is not known

NSAIDs

Linked to about twice the odds of stomach and gut bleeding when an NSAID was taken with warfarin, compared with warfarin alone.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Across 11 studies, gastrointestinal bleeding was more frequent with warfarin plus an NSAID than with warfarin alone (OR 1.98, 95% CI 1.55 to 2.53), and with warfarin plus a COX-2 inhibitor (OR 1.90, 95% CI 1.46 to 2.46). Any bleeding was more frequent with warfarin plus an NSAID (OR 1.58, 95% CI 1.18 to 2.12) [22]. The label lists NSAIDs, including celecoxib, ibuprofen and naproxen, among drugs that can increase the risk of bleeding [11].
Population
11 studies comparing warfarin with an NSAID against warfarin alone [22].
Sources
[22], [11]
Caveats
Mostly observational studies. The abstract gives odds ratios, not the share of people who bled.
LimitedHow often is not known

Aspirin, clopidogrel and other blood thinners

The label lists aspirin, clopidogrel and other antiplatelet and anticoagulant drugs as raising bleeding risk with warfarin. Studies of anticoagulants with aspirin found about 1.7 times the bleeding.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label lists anticoagulants such as heparin and dabigatran and antiplatelet agents such as aspirin, clopidogrel, dipyridamole and prasugrel among drugs that can increase the risk of bleeding [11]. Among people on anticoagulants for venous clots, clinically relevant bleeding occurred at 36.6 per 100 patient-years during aspirin use against 16.9 without (HR 1.70, 95% CI 1.38 to 2.11) [23]. In people with mechanical valves, bleeding became significantly more frequent when antiplatelet therapy was added to a coumarin [9].
Population
8,246 patients on rivaroxaban or enoxaparin with a vitamin K antagonist [23]; 46 studies of mechanical valves [9].
Sources
[11], [23], [9]
Caveats
In one trial after heart attack, major bleeding was 0.62% per treatment-year on warfarin with or without aspirin [12]. Rates are per patient-years.
ModerateHow often is not known

SSRI and SNRI antidepressants

Linked to about 35% more major bleeding when an SSRI was taken alongside an oral anticoagulant, in a meta-analysis of eight observational studies.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Across eight cohort and case-control studies, major bleeding was more frequent with an SSRI plus an oral anticoagulant than with the anticoagulant alone (HR 1.35, 95% CI 1.14 to 1.58) [24]. The label lists serotonin reuptake inhibitors, including citalopram, sertraline, fluoxetine, paroxetine, duloxetine and venlafaxine, among drugs that can increase the risk of bleeding with warfarin [11].
Population
98,070 patients in eight studies [24].
Sources
[24], [11]
Caveats
Observational. The pooled studies covered warfarin and DOACs together.
LimitedHow often is not known

Medicines that raise or lower warfarin levels

The label lists dozens of drugs that change warfarin's effect through liver enzymes, including amiodarone, fluconazole, metronidazole, some statins, oral contraceptives, rifampin, carbamazepine and phenytoin.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that inhibitors of CYP2C9, 1A2 or 3A4 can raise the INR and inducers can lower it. Its examples of inhibitors include amiodarone, cotrimoxazole, fluconazole, metronidazole, fluvastatin, atorvastatin, fluoxetine, fluvoxamine, clarithromycin, ciprofloxacin, diltiazem, verapamil, cimetidine and oral contraceptives. Its examples of inducers include rifampin, carbamazepine, phenobarbital, phenytoin, bosentan and cigarette smoking [11]. A systematic overview found consistent reports of interaction for azole antifungals, macrolides, quinolones, omeprazole, lipid-lowering agents, amiodarone and fluorouracil. It rated 84% of all reports as poor quality, most of them single case reports [21].
Population
Enzyme interaction lists in labeling [11]; 181 articles on 120 drugs or foods [21].
Sources
[11], [21]
Caveats
The label states its list is not complete. Most published reports were single cases.
LimitedHow often is not known

Herbal products and supplements

The label warns that garlic and ginkgo may add to bleeding, and that coenzyme Q10, St. John's wort and ginseng may weaken warfarin. Few controlled studies exist.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that some botanicals may cause bleeding when taken alone, naming garlic and Ginkgo biloba, and that these effects would be expected to add to warfarin's. It names coenzyme Q10, St. John's wort and ginseng as possibly decreasing warfarin's effect, and echinacea, grapefruit juice, ginkgo, goldenseal and St. John's wort as interacting through liver enzymes. It states that few adequate, well-controlled studies exist and that product contents vary [11]. A systematic overview added reports for green tea and danshen [21].
Population
Statements in labeling [11]; case reports and small studies in 181 articles [21].
Sources
[11], [21]
Caveats
Mostly case reports and expected effects, with no rates.
ModerateHow often is not known

Acetaminophen

Shown to raise the INR by a mean 0.62 against placebo in people on vitamin K antagonists, more at higher daily doses. No major bleeding was reported.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Across seven randomized trials, acetaminophen raised the INR by a mean 0.62 (95% CI 0.46 to 0.78) against placebo in people on vitamin K antagonists, with a mean rise of 0.17 for each daily gram (95% CI 0.004 to 0.33). The studies did not report any major bleeding event [25].
Population
225 patients in seven randomized trials [25].
Sources
[25]
Caveats
Small trials measuring a lab value, not bleeding.
LimitedHow often is not known

Calciphylaxis and cholesterol microemboli

The label warns of fatal and serious calciphylaxis, and of cholesterol microemboli that can cause purple toes syndrome. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that warfarin can cause fatal and serious calciphylaxis in people with and without end-stage kidney disease. It states that anticoagulation may enhance the release of atheromatous plaque emboli, most often to the kidneys, and describes microemboli to the feet as purple toes syndrome, with some cases progressing to necrosis or death [11].
Population
Reports summarized in labeling [11].
Sources
[11]
Caveats
No denominator is given.
LimitedHow often is not known

Kidney injury

The label warns that acute kidney injury may occur in people with kidney disease, possibly related to episodes of excessive anticoagulation and blood in the urine.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that in people with altered glomerular integrity or a history of kidney disease, acute kidney injury may occur with warfarin, possibly in relation to episodes of excessive anticoagulation and hematuria [11].
Population
A warning in labeling, with no study counts [11].
Sources
[11]
Caveats
The label gives no rate.
LimitedHow often is not known

Liver, skin and stomach reactions on the label

The label lists hepatitis and raised liver enzymes, allergic reactions, rash, hair loss, nausea and diarrhea among other adverse reactions. It gives no rates.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Other adverse reactions on the label include hypersensitivity reactions including hives and anaphylaxis, vasculitis, hepatitis and elevated liver enzymes, nausea, vomiting, diarrhea, abdominal pain, rash, itching, hair loss and calcification of the windpipe [11].
Population
Reports summarized in labeling [11].
Sources
[11]
Caveats
The label gives no frequencies or comparator rates for these reactions.

Mixed results1

LimitedHow often is not known

Vitamin K in food

Mixed results: studies conflict on whether vitamin K in food changes the INR, with an effect seen only at intakes above about 150 micrograms a day.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
A systematic review of two dietary trials and nine observational studies found conflicting evidence. Some studies found a negative correlation between vitamin K intake and INR changes, and others suggested a minimum intake is needed for stable anticoagulation. An effect on coagulation was detectable only at high intakes, above 150 micrograms a day. The reviewers concluded that the evidence did not support restricting dietary vitamin K [19]. The label states that the amount of vitamin K in food may affect therapy and describes a consistent intake, with no drastic changes such as large amounts of green leafy vegetables [11].
Population
11 studies of people on vitamin K antagonists for varied reasons [19].
Sources
[19], [11]
Caveats
Mostly observational, with varied INR targets and measures of stability [19].

Claims tested and not found

  1. That dosing warfarin by genotype improves control. Across 9 trials with 2,812 patients, genotype-guided dosing did not raise time in the therapeutic range (standardized difference 0.14, 95% CI -0.10 to 0.39) or lower major bleeding (RR 0.60, 95% CI 0.29 to 1.22) or clots (RR 0.97, 95% CI 0.46 to 2.05) [27].
  2. That cutting green vegetables out of the diet steadies the INR. A systematic review found conflicting evidence and concluded that restricting dietary vitamin K did not improve anticoagulation quality [19].
  3. That self-testing the INR lowers major bleeding. Across 20 trials with 8,018 participants, major hemorrhage did not change (RR 0.95, 95% CI 0.80 to 1.12) [15].
  4. That aspirin causes less bleeding than warfarin in older people with atrial fibrillation. In 973 people aged 75 or over, extracranial hemorrhage occurred at 1.4% a year on warfarin and 1.6% on aspirin (RR 0.87, 95% CI 0.43 to 1.73) [3].
  5. That DOACs outperform warfarin in every group. With mechanical heart valves, strokes occurred in 5% on dabigatran and none on warfarin [10], and in rheumatic heart disease with atrial fibrillation, outcomes were better on a vitamin K antagonist than on rivaroxaban [6].

Sources

  1. Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Annals of Internal Medicine. 2007. https://doi.org/10.7326/0003-4819-146-12-200706190-00007
  2. Aguilar MI, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database of Systematic Reviews. 2005. https://doi.org/10.1002/14651858.CD001927.pub2
  3. Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. The Lancet. 2007. https://doi.org/10.1016/S0140-6736(07)61233-1
  4. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. The Lancet. 2014. https://doi.org/10.1016/S0140-6736(13)62343-0
  5. Carnicelli AP, Hong H, Connolly SJ, et al. Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex. Circulation. 2022. https://doi.org/10.1161/CIRCULATIONAHA.121.056355
  6. Connolly SJ, Karthikeyan G, Ntsekhe M, et al. Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation. New England Journal of Medicine. 2022. https://doi.org/10.1056/NEJMoa2209051
  7. Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. New England Journal of Medicine. 1999. https://doi.org/10.1056/NEJM199903253401201
  8. van Es N, Coppens M, Schulman S, Middeldorp S, Büller HR. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood. 2014. https://doi.org/10.1182/blood-2014-04-571232
  9. Cannegieter SC, Rosendaal FR, Briët E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation. 1994. https://doi.org/10.1161/01.CIR.89.2.635
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