***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background It is not known whether patients on oral vitamin K antagonists who have unstable INRs achieve more stable INRs with daily vitamin K supplementation . We sought to determine whether vitamin K supplementation may decrease INR variability in patients with a history of unstable INRs , how soon the INR decreases after vitamin K therapy is initiated , the time to reach a therapeutic INR after vitamin K initiation , and how much of an increase in oral anticoagulant dose is needed to maintain the INR in the desired range . Methods This is a prospect i ve open label crossover study of patients on warfarin with a history of fluctuating INRs . A 9 week observation phase was followed by an 8 week period with patients receiving 500 μg of oral vitamin K daily . INRs were determined once weekly with a home point of care monitoring instrument . Results Vitamin K supplementation led to a decrease in INR variability in five of the nine patients studied ( 56 % ) . INR decrease occurred 2–7 days after initiation of vitamin K.  Therapeutic INRs were achieved 2–35 days after vitamin K therapy was initiated and an increase  in warfarin dose of 6–95 % was required to bring the INR back into the therapeutic range . Conclusions INR fluctuations may decrease in selected patients with unstable INRs who receive vitamin K supplementation .  A study with a larger sample size and longer follow-up period is needed . The results of the present study can help design such a study To determine the best way to reverse the excessive effect of regular anticoagulation in patients with INR > 5 and no bleeding complications , 23 patients with INR > 5 were r and omly subdivided into two groups : group A ( n = 12 ) discontinued warfarin for one day and group B ( n = 11 ) received 2 mg of vitamin K1 orally in addition to the usual warfarin dose .  INR was determined after 24 h ( day 1 ) , after which both groups continued with their usual dose of warfarin . After 48 h ( day 2 ) , warfarin dosage was changed according to the INR value . On day 9 , INR values were determined again . Five out of twelve patients in group A had INR values > 5 on day 1 . One patient in group A had an INR value < 5 both on days 1 and 2 . All eleven patients in group B had INR values < 5 on day 1 , and all but one on day 2 . On day 9 , INR values were acceptable ( INR 2.0 - 4.5 ) in ten group A patients and eight group B patients . These findings suggest that a low oral dose of vitamin K1 is a convenient treatment for excessive anticoagulation in patients with no bleeding complications Background and Purpose — Stroke risk increases with age in patients who have nonvalvular atrial fibrillation . It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age . The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants ( OAC ) and antiplatelet ( AP ) therapy ( including acetylsalicylic acid and triflusal ) on ischemic stroke , serious bleeding , and vascular events in patients with atrial fibrillation . Methods — This is an analysis of the Atrial Fibrillation Investigators data base , which contains patient level- data from r and omized trials of stroke prevention in atrial fibrillation . We used Cox regression models with age as a continuous variable that controlled for sex , year of r and omization , and history of cerebrovascular disease , diabetes , hypertension , and congestive heart failure . Outcomes included ischemic stroke , serious bleeding ( intracranial hemorrhage or systemic bleeding requiring hospitalization , transfusion , or surgery ) , and cardiovascular events ( ischemic stroke , myocardial infa rct ion , systemic embolism , or vascular death ) . Results — The analysis included 8932 patients and 17 685 years of observation from 12 trials . Patient age increased risk of ischemic stroke ( adjusted hazard ratio per decade increase 1.45 ; 95 % CI , 1.26 to 1.66 ) , serious bleeding ( 1.61 ; 1.47 to 1.77 ) , and cardiovascular events ( 1.43 ; 1.33 to 1.53 ) . Compared with placebo , OAC and AP significantly reduced the risk of ischemic stroke ( OAC , 0.36 ; 0.29 to 0.45 ; AP , 0.81 ; 0.72 to 0.90 ) and cardiovascular outcomes ( OAC , 0.59 ; 0.52 to 0.66 ; AP , 0.81 ; 0.75 to 0.88 ) , whereas OAC increased risk of serious bleeding ( 1.56 ; 1.03 to 2.37 ) . The relative benefit of OAC versus placebo or AP did not vary by patient age for any outcome . Compared with placebo , the relative benefit of AP  for preventing ischemic stroke decreased significantly as patients aged ( P=0.01 ) . Conclusions — As patients with atrial fibrillation age , the relative efficacy of AP to prevent ischemic stroke appears to decrease , whereas it does not change for OAC . Because stroke risk increases with age , the absolute benefit of OAC increases as patients get older PURPOSE The potential association between vitamin K intake and  coagulation instability has been explored primarily in case reports and small , retrospective , uncontrolled studies . We prospect ively evaluated the effects of dietary vitamin K intake on anticoagulation parameters . METHODS In an observational protocol , clinical characteristics and vitamin K intake , assessed semiquantitatively , were evaluated in 39 out patients who made 230 visits to our anticoagulation clinic . In a r and omized crossover protocol , 12 patients with stable anticoagulation underwent 4-day in-hospital dietary interventions , 1 to 2 weeks apart , providing a 500 % increase and an 80 % decrease in vitamin K intake relative to the baseline level . RESULTS Univariate analysis of the observational data demonstrated a progressive , statistically significant inverse association between the vitamin K intake score and different levels of anticoagulation . Multivariate logistic regression analysis showed that vitamin K intake was independently associated with both overcoagulation and undercoagulation . In the r and omized protocol , the international normalized ratio increased from 2.6 + /- 0.5 at baseline to 3.3 + /- 0.9 at day 7 ( P = 0.005 ) in subjects on the vitamin K-depleted diet and decreased from 3.1 + /- 0.8 at baseline to 2.8 + /- 0.6 at day 4 ( P = 0.04 ) in those on the vitamin K-enriched diet . CONCLUSION Our prospect i ve data strengthen the concept that the interaction between vitamin K and coumarin is a clinical ly relevant , major independent factor that interferes with anticoagulation stability Various methods have been described to evaluate efficacy of anticoagulant therapy  using the international normalized ratio ( INR ) . We compared the following approaches : ( 1 ) total INR 's or the most recent measurement ; ( 2 ) percent time within therapeutic range , with INR changing directly or halfway between visits ; and ( 3 ) total observation time assuming INR changing linearly . The study population comprised 1700 post myocardial infa rct ion patients . Treatment comprised 3725 patient-years . There were 61,471 INR assessment s with target therapeutic level of 2.8 - 4.8 . Acenocoumarol as well as phenprocoumon were employed . Therapeutic achievement in the first months of treatment was low : less than 60 % of INR 's were in range . Treatment stabilized after 6 months . Patients on acenocoumarol were within range 70 % of the time compared to 80 % for phenprocoumon . Method 3 is preferred because it incorporates time and is capable of calculating incidence rates at different INR levels . Our findings call for an urgent improvement of st and ard of anticoagulant control in the first months following commencement of treatment BACKGROUND Dietary vitamin K intake has been considered a major factor that influences stability of oral anticoagulation ( OA ) with coumarins . Few studies have evaluated the relationship between amounts of dietary vitamin K intake and stability of anticoagulation . OBJECTIVE To assess whether high dietary vitamin K intake is associated to stability of International Normalized Ratio ( INR ) of the prothrombin time . METHODS We performed a sub- analysis of a r and omized clinical trial involving out patients from the anticoagulation clinic of a university hospital .  INR and vitamin K intake were prospect ively collected at baseline , 15 , 30 , 60 and 90 days after r and omization . Patients were considered with a stable anticoagulation when their INR coefficient of variation was less than 10 % . Dietary vitamin K intake was assessed by a food frequency question nair and a score of intake was derived . RESULTS We studied 132 patients on chronic OA ( 57 ± 13 years ; 55 % males ) ; 23 patients ( 17 % ) were achieved stable anticoagulation . Stable and unstable patients had no significant differences in baseline characteristics . The dietary vitamin K score over the entire follow-up for stable patients was significantly lower than that for unstable patients ( p = 0.012 ) . DISCUSSION Our findings suggest that INR stability could be achieved with relatively low amounts of dietary vitamin Patients receiving warfarin who have unstable control of anticoagulation have a significantly lower intake of dietary vitamin K compared with their stable counterparts . We hypothesized that supplementation with oral vitamin K would improve stability in patients with previously unstable control of anticoagulation . Seventy warfarin-treated patients with unstable anticoagulation control were r and omly assigned in a double-blinded fashion to receive a daily amount of 150 mug oral vitamin K or placebo orally for 6 months . Measures of stability of anticoagulation control in the 6-month study period were compared with those in the 6 months immediately prior to it . Vitamin K supplementation result ed in a significantly greater decrease in st and ard deviation of international normalized ratio ( INR ) compared with placebo ( -0.24 + /- 0.14 vs -0.11 + /- 0.18 ; P < .001 ) and a significantly greater increase in percentage time within target INR range ( 28 % + /- 20 % vs 15 % + /- 20 % ; P < .01 ) . Anticoagulation control improved in 33 of 35 patients receiving vitamin K supplementation ; of these , 19 fulfilled our criteria for having stable control of anticoagulation . However , only 24 of 33 patients receiving placebo demonstrated some degree of improvement , with only 7 patients fulfilling the criteria for having stable control . Concomitant supplementation of vitamin K , perhaps through reducing the relative day-to-day variability in dietary vitamin K intake , can significantly improve anticoagulation control in patients with unexplained instability of response to warfarin Evidence for the selectivity of S-warfarin metabolism by CYP2C9 is substantial , suggesting that warfarin may be a potential CYP2C9 phenotyping probe . It is , however , limited by its ability to elevate the international normalized ratio ( INR ) and potentially cause bleeding . The effect of vitamin K to attenuate the elevation of INR may enable the safe use of warfarin as a probe . The objective of this study was to investigate the pharmacokinetics and pharmacodynamics of S- and R-warfarin in plasma following the administration of warfarin alone versus warfarin and vitamin K in CYP2C9 * 1 homozygotes . Healthy adults received , in a r and omized crossover fashion in a fasted state , warfarin 10 mg orally or warfarin 10 mg plus vitamin K 10 mg orally . Blood sample s were obtained over 5 days during each phase . INR measurements were obtained at baseline and day 2 in each phase . INR , AUC0-infinity , and t1/2 of plasma S- and R-warfarin were examined . Eleven CYP2C9 * 1 homozygotes ( 3 men , 8 women ) were enrolled .  INR at day 2 following warfarin 10 mg was 1.18 + /- 0.19 , which differed significantly from baseline ( INR = 1.00 + /- 0.05 ) and warfarin with vitamin K ( INR = 1.06 + /- 0.07 ) . INR at baseline was not significantly different from warfarin with vitamin K.  t1/2 and AUC0-infinity of both enantiomers did not significantly differ between the phases . It was concluded that INR is apparently attenuated by concomitant administration of a single dose of vitamin K without affecting the pharmacokinetics of either warfarin stereoisomer . Warfarin 10 mg may be safely used as a CYP2C9 probe in * 1 homozygotes when given concomitantly with 10 mg of oral vitamin The Canadian Atrial Fibrillation Anticoagulation Study was a r and omized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage . As a result of the publication of two other " positive " studies of similar design and objective , this study was stopped early before completion of its planned recruitment of 630 patients . There were 
    Output:
    
The study concluded that vitamin K supplementation did not significantly improve the stability of anticoagulation for participants on chronic anticoagulation therapy .
AUTHORS ' CONCLUSIONS Two included studies in this review compared whether the addition of a low dose ( 150 to 175 mcg ) of  vitamin K  given to participants with a high-variability response to warfarin  improved their INR control .