On average, if 100 patients like this woman are treated with warfarin, the number of strokes is reduced by 3 (from 5.2 untreated to 3.2 treated). Therefore, if you treat 33.3 patients like this woman with warfarin, you reduce the number of strokes by 1: the NNT is 33.3.

An 86-year-old woman in whom nonvalvular atrial fibrillation has been detected. She has a CHADS2 score of 3 points. In the literature, similar patients on warfarin therapy have a stroke risk of 2.2% vs. 5.2% in patients without warfarin. What would be the number needed to treat (NNT) to prevent an emboligenic stroke with anticoagulation therapy:

Medical Costs of Oral Anticoagulants vs Warfarin for Atrial Fibrillation Patients with Different Stroke Risks.

The Apixaban for the Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE), Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY), and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trials demonstrated that the oral anticoagulants (OACs), apixaban, dabigatran, and rivaroxaban, respectively, are efficacious for stroke prevention among nonvalvular atrial fibrillation (NVAF) patients. Based on clinical trial results this study evaluated medical costs of clinical events associated with use of individual OACs relative to those of warfarin in NVAF patients with moderate and high stroke risk. Rates for primary and secondary efficacy and safety outcomes (i.e., clinical events) among NVAF patients with CHADS2 = 2 and ≥3 were determined from the three OAC trials. One-year incremental costs among patients with clinical events from a US payer perspective were obtained from the literature and inflation adjusted to 2010 costs. Medical costs for clinical events associated with each OAC vs. warfarin were estimated and compared. For NVAF patients with moderate stroke risk (CHADS2 = 2) differences in clinical event medical costs vs. warfarin were -$298, -$143, and +$117 per patient year for apixaban, dabigatran (150 mg), and rivaroxaban, respectively (negative numbers indicate cost reduction). For NVAF patients with high stroke risk (CHADS2 ≥ 3) differences in clinical event medical costs vs. warfarin were -$697, +$2, and -$100 for apixaban, dabigatran (150 mg), and rivaroxaban, respectively. Medical cost differences associated with OACs vs. warfarin vary according to stroke risk. Of the three OACs, apixaban demonstrated consistent medical cost reductions vs. warfarin for NVAF patients with moderate and high stroke risks.

Oral anticoagulation in atrial fibrillation.

Atrial fibrillation affects approximately 5 million patients in the United States. The rate of stroke in adults with atrial fibrillation depending on their risk factors varies between 1-20% annually. Anticoagulation with vitamin K antagonists such as warfarin has been the mainstay therapy but it is cumbersome and requires close follow-up. Since 2010, three new oral anticoagulants have received Food and Drug Administration approval for stroke prevention in atrial fibrillation. This review summarizes data from three landmark trials: RE-LY, ROCKET-AF, and ARISTOTLE. In addition, issues relating to cost, reversal, drug interactions, and perioperative discontinuation are discussed. Compared to Warfarin, Dabigatran 150 mg twice daily lowered the primary outcome of stroke/systemic embolism by 34% (number needed to treat/yr 169) and had similar incidence of major bleeding. Rivaroxaban demonstrated non inferiority compared to the warfarin group for the primary outcome of stroke and systemic embolism and major bleeding. Apixaban showed a relative risk reduction for the primary outcome of 21% (number needed to treat 300), and lowered major bleeding down by 31% (number needed to treat /yr 104). Apixaban also showed a mortality benefit compared to warfarin (3.52 vs. 3.94%/year, p 0.047). All 3 oral anticoagulants lowered rates of intracranial hemorrhage. The use of Rivaroxaban and Apixaban has been projected to reduce medical costs when compared to warfarin, and Dabigatran is projected to have similar costs. All the 3 oral anticoagulants have robust randomized controlled trials supporting their comparability to warfarin therapy for stroke prevention in non valvular atrial fibrillation, with Apixaban showing superiority in incidence of strokes, major bleeding and mortality.

Management of atrial fibrillation

Chronic anticoagulation Among patients with nonvalvular AF, anticoagulation with warfarin can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%. The combination of aspirin and clopidogrel reduced the risk of stroke by 25%, but increased the risk of major bleeding by 57%, which means that this combination is inferior to warfarin, and is not an alternative for patients who are judged to be at high risk of bleeding on warfarin therapy.

Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation.

Recent studies have investigated alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation (AF), but whether these alternatives are cost-effective is unknown. On the basis of the results from Randomized Evaluation of Long Term Anticoagulation Therapy (RE-LY) and other trials, we developed a decision-analysis model to compare the cost and quality-adjusted survival of various antithrombotic therapies. We ran our Markov model in a hypothetical cohort of 70-year-old patients with AF using a cost-effectiveness threshold of $50 000/quality-adjusted life-year. We estimated the cost of dabigatran as US $9 a day. For a patient with an average risk of major hemorrhage (≈3%/y), the most cost-effective therapy depended on stroke risk. For patients with the lowest stroke rate (CHADS2 stroke score of 0), only aspirin was cost-effective. For patients with a moderate stroke rate (CHADS2 score of 1 or 2), warfarin was cost-effective unless the risk of hemorrhage was high or quality of international normalized ratio control was poor (time in the therapeutic range <57.1%). For patients with a high stroke risk (CHADS(2) stroke score ≥3), dabigatran 150 mg (twice daily) was cost-effective unless international normalized ratio control was excellent (time in the therapeutic range >72.6%). Neither dabigatran 110 mg nor dual therapy (aspirin and clopidogrel) was cost-effective. Dabigatran 150 mg (twice daily) was cost-effective in AF populations at high risk of hemorrhage or high risk of stroke unless international normalized ratio control with warfarin was excellent. Warfarin was cost-effective in moderate-risk AF populations unless international normalized ratio control was poor.

Stroke

Previous stroke or TIA Keeping blood pressure below 140/90 mmHg is recommended. Anticoagulation can prevent recurrent ischemic strokes. Among people with nonvalvular atrial fibrillation, anticoagulation can reduce stroke by 60% while antiplatelet agents can reduce stroke by 20%. However, a recent meta-analysis suggests harm from anticoagulation started early after an embolic stroke. Stroke prevention treatment for atrial fibrillation is determined according to the CHA2DS2–VASc score. The most widely used anticoagulant to prevent thromboembolic stroke in people with nonvalvular atrial fibrillation is the oral agent warfarin while a number of newer agents including dabigatran are alternatives which do not require prothrombin time monitoring. Anticoagulants, when used following stroke, should not be stopped for dental procedures.

[A study on the evaluation of anticoagulation status comparing of CHADS2 versus CHA2DS2-VASc scores in patients with non valvular atrial fibrillation in Xinjiang area].

To evaluate the current status of anticoagulation therapy in patients with atrial fibrillation(AF)in Xinjiang, and compare the two scoring systems(CHADS2 and CHA2DS2-VASc scores) in determining the risk of strokes in AF patients in Xinjiang. Subjects with AF were collected by searching the electronic and paper medical records from 35 hospitals in Xinjiang area during October 2013 to October 2014, and followed up for the incident strokes after 10 to 12 months. Totally, 5 953 AF patients were enrolled in the study with the age of (67.9±12.0) years old, and men to women ratio of 1.44. Most patients were in age groups of 60-69 (23.92%) and 70-79 years (37.81%). Among patients with a CHADS2 score of 1 or less, the CHA2DS2-VASc scores of these subjects ranged from 0 to 3. After 10 to 12 months of follow-up, 22 patients developed new strokes. Only 30.79% patients ( n=1 460) received the anticoagulation treatment among those (n=4 742) who need to be treated with anticoagulation drugs. In patients receiving anticoagulant therapy, 1 162 patients were treated with warfarin, and 298 patients with new oral anticoagulant drugs.Totally 1 110 patients treated with warfarin were monitored with international normalized ratio (INR). The median INR was 1.14 with only 97 cases meeting the recommended INR ranging of 2.0-3.0 in the guidelines. The compliance rate was 8.74%. The current status of anticoagulation for AF in Xinjiang area is characterized by "low anticoagulation rate" and "low compliance rate". The CHA2DS2-VASc score is more suitable for predicting the risk of strokes in patients with non valvular atrial fibrillation in Xinjiang area.

Comparing mortality in patients with atrial fibrillation who are receiving a direct-acting oral anticoagulant or warfarin: a meta-analysis of randomized trials.

In patients with non-valvular atrial fibrillation (AF), direct-acting oral anticoagulants (DOACs) are at least non-inferior to warfarin for the prevention of stroke and systemic embolism. The main objective of this study was to obtain reliable and precise estimates for all-cause mortality, vascular mortality and bleeding mortality in patients with AF receiving a DOAC or warfarin for stroke prevention. A meta-analysis was performed on phase 3 randomized trials that compared a DOAC with warfarin for stroke prevention in AF. Published data were pooled by use of the DerSimonian random-effect model, with revman 5.2 and comprehensive meta analysis software version 2. The results were presented as risk ratios (RRs), absolute risk reduction (ARR), and number-needed-to-treat (NNT). A total of 71 683 patients were included in this meta-analysis from four randomized controlled trials (median patient follow-up: 1.8-2.8 years) that compared a DOAC with warfarin for stroke prevention in AF. As compared with warfarin, DOACs significantly reduced all-cause mortality (RR 0.89, 95% confidence interval [CI] 0.85-0.94; ARR 0.76%, 95% CI 0.39-1.13%; NNT = 132), vascular mortality (RR 0.88, 95% CI 0.82-0.94; ARR 0.53%, 95% CI 0.23-0.83%; NNT = 189), and bleeding mortality (RR 0.54, 95% CI 0.44-0.67; ARR 0.32%, 95% CI 0.21-0.43%; NNT = 313). As compared with warfarin therapy for stroke prevention in patients with AF, DOACs significantly reduce all-cause mortality, vascular mortality, and bleeding mortality. This mortality benefit appears to be driven by the reduction in vascular-related and bleeding-related mortality, which, in turn, may be related to the reduction in intracranial bleeding.

Secondary prevention of stroke in patients with nonvalvular atrial fibrillation: optimal intensity of anticoagulation.

Nonvalvular atrial fibrillation (NVAF) is frequently seen in elderly people and has become a main cause of cardioembolic stroke. The efficacy of anticoagulation for primary prevention of stroke or transient ischaemic attacks (TIAs) in patients with NVAF has been established by prospective, randomised and controlled trials. Warfarin decreased the frequency of all strokes by 68% and the rate of the combined outcome of stroke, systemic embolism or death by 48%. Anticoagulation with warfarin using international normalised ratios (INRs) ranging from 2.0 to 3.0 is recommended for patients with NVAF, who have any of the risk factors identified by the Atrial Fibrillation Investigators (AFI) [previous stroke or TIA, history of hypertension, diabetes mellitus, advanced age (> or = 65 years old), congestive heart failure and coronary artery disease], the American College of Chest Physicians (ACCP) [increased age (> 75 years old), prior stroke, hypertension and heart failure], or the Stroke Prevention in Atrial Fibrillation (SPAF) investigators [women > 75 years old, prior stroke, systolic blood pressure > 160mm Hg, recent heart failure, and fractional shortening < 25% on echocardiography]. For the secondary prevention of stroke, the efficacy of adjusted-dose warfarin therapy has been demonstrated by 2 major randomised trials. SPAF III (INR 2.0 to 3.0) demonstrated a lower incidence of ischaemic stroke or systemic embolism (3.4 %/year) compared with low fixed-dose warfarin plus aspirin (acetylsalicylic acid) [11.9%]. The European Atrial Fibrillation Trial [EAFT] (INR 2.5 to 4.0) showed a lower incidence of all stroke (4.0 %/year) with adjusted-dose warfarin compared with placebo (12.0 %/year). The incidence of major bleeding in the adjusted-dose warfarin group in SPAF III and EAFT was 2.4 and 2.8 %/year, respectively. EAFT incidence rates for the occurrence of a first ischaemic or haemorrhagic complication analysed by INR range indicated that the rate was lowest at INRs of 2.0 to 2.9, and higher with INRs of 3.0 to 3.9. Therefore, the optimal intensity of anticoagulation for prevention of recurrent stroke seems to be an INR of between 2.0 and 3.0, as for primary prevention. Retrospective and prospective studies from Japan reported that in the elderly, haemorrhagic complications occur frequently with INRs above 2.6 and major ischaemic events cannot be prevented at INRs below 1.6. Therefore, an INR target between 1.6 and 2.6 may be an alternative for secondary prevention of stroke in elderly patients with NVAF who have a potential risk of bleeding, to avoid both major ischaemic and haemorrhagic events. Antiplatelets may be administered in patients who are unable to manage taking warfarin properly or who have a high risk of falling and subsequently sustaining a head injury, although the efficacy of antiplatelets for secondary prevention of stroke in NVAF has not yet been established.

Management of atrial fibrillation

Latest ESC guidelines on atrial fibrillation recommend assessment of bleeding risk in AF using the HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile International Normalized Ratio, Elderly, Drugs/alcohol concomitantly) bleeding risk schema as a simple, easy calculation, whereby a score of ≥3 indicates "high risk" and some caution and regular review of the patient is needed. The HAS-BLED score has also been validated in an anticoagulated trial cohort of 7329 patients with AF – in this study, the HAS-BLED score offered some improvement in predictive capability for bleeding risk over previously published bleeding risk assessment schemas and was simpler to apply. With the likely availability of new oral anticoagulants that avoid the limitations of warfarin (and may even be safer), more widespread use of oral anticoagulation therapy for stroke prevention in AF is likely.

Nine-year trend of oral anticoagulant use in patients with embolic stroke due to nonvalvular atrial fibrillation.

Direct oral anticoagulants (DOACs) are increasingly used as an alternative to warfarin in patients with nonvalvular atrial fibrillation (NVAF). However, whether there is sufficient prescription of oral anticoagulants (OACs) to decrease the incidence of embolic stroke remains unclear. We conducted a retrospective observational study of patients hospitalized with ischemic stroke between January 1, 2010 and December 31, 2018. During the 8 years, the annual incidence ratio of embolic stroke to all ischemic strokes did not decrease over time (21-33%) except for that in 2018. The proportion of OAC users did not also change over time (from 23% to 45% [overall 31%], <iP</i = .78). Among the OAC users, 19% patients were warfarin users, and 12% patients were DOAC users. In 73% of warfarin users, prothrombin time was subtherapeutic, whereas in 60% of DOAC users, the dose was adequately prescribed. OACs were prescribed more often in patients with high CHADS2 score than in those with low score (<iP</i = .01). The number of patients who had no medical history of a doctor visit before admission increased significantly in the recent period of 2015-2018 (22% vs 8% in the previous period of 2010-2014) (<iP</i = .01). The incidence of embolic stroke patients without OACs did not decrease over time, and OACs in patients with NVAF have not been sufficient, even in DOAC era. In recent years, the incidence of undiagnosed AF has increased. To prevent embolic stroke, a correct AF diagnosis beforehand is important.

Guidelines for stroke prevention in patients with atrial fibrillation.

Atrial fibrillation (AF) is a major independent risk factor for stroke. AF is most commonly associated with nonvalvular cardiovascular disease and is especially frequent among the elderly. The annual risk for stroke in patients with AF is approximately 5% with a wide range depending on the presence of additional risk factors. For patients who cannot successfully be converted and maintained in normal sinus rhythm (NSR), antithrombotic therapy is an effective method for preventing stroke. The 2 drugs which are indicated for stroke prophylaxis in patients with AF are warfarin and aspirin. For primary prevention, warfarin reduces the risk of stroke approximately 68%. Aspirin therapy is less effective, resulting in a 20 to 30% risk reduction. Combination therapy with aspirin and low intensity warfarin adjusted to an International Normalised Ratio (INR) of 1.2 to 1.5 has not been shown to be superior to standard intensity warfarin with a target INR of 2.0 to 3.0. In patients with AF and a prior history of stroke or transient ischaemic attack (TIA), the absolute risk reduction with warfarin is even greater because of the high risk of stroke in this population. In contrast, aspirin has not been shown to significantly reduce the risk of stroke in patients with AF when used for secondary prevention. When appropriately managed, warfarin is associated with a low risk of major bleeding. In controlled trials of highly selected patients, the annual rate of intracranial haemorrhage (ICH) with warfarin was approximately 0.3%. Studies have shown that specialty anticoagulation clinics can achieve similar low rates of major bleeding. However, these results cannot be extrapolated to the general population. Factors which have been identified as predictors of bleeding include advanced age, number of medications and most importantly, the intensity of anticoagulation. INR values above 4.0 have been associated with an increased risk of major bleeding while values below 2.0 have been associated with thrombosis. Slow careful dosage titration, regular laboratory monitoring and patient education can substantially reduce the risk of complications. In patients with AF, antithrombotic therapy has been shown to be cost effective. For high risk patients, warfarin is the most cost-effective therapy, provided the risks for bleeding are minimised. In contrast, aspirin is the most cost-effective agent for low risk patients. Current practice guidelines for stroke prophylaxis recommend warfarin (target INR 2.5: range 2.0 to 3.0) for AF patients at high risk for stroke including those over 75 years of age or younger patients with additional risk factors. Aspirin should be reserved for low risk patients or those unable to take warfarin. Although these recommendations are strongly supported by the clinical trial evidence, studies show that many patients are not receiving appropriate antithrombotic therapy. In particular, warfarin is underutilised in high risk elderly patients. Additional studies are needed to identify barriers that prevent implementation of the clinical trial findings into clinical practice.

HAS-BLED

2020 ESC guidelines on atrial fibrillation recommend assessment of bleeding risk in AF using the HAS-BLED bleeding risk schema as a simple, easy calculation, whereby a score of ≥3 indicates "high risk" and some caution and regular review of the patient is needed. The HAS-BLED score has also been validated in an anticoagulated trial cohort of 7329 people with AF - in this study, the HAS-BLED score offered some improvement in predictive capability for bleeding risk over previously published bleeding risk assessment schemas and was simpler to apply. With the likely availability of new oral anticoagulants that avoid the limitations of warfarin (and may even be safer), more widespread use of oral anticoagulation therapy for stroke prevention in AF is likely.

SAMe-TT2R2 score

The SAMe-TT2R2 score is a clinical prediction rule to predict the quality of vitamin K antagonist anticoagulation therapy as measured by time in therapeutic INR range (TTR) (VKA e.g. warfarin). It has been suggested that it can aid in the medical decision making between VKAs and new oral anticoagulant/non-VKA oral anticoagulant (NOAC e.g. dabigatran, rivaroxaban, apixaban or edoxaban) in patients with atrial fibrillation (AF). This score can be used with patients with ≥1 additional stroke risk factors using the CHA2DS2-VASc score, where oral anticoagulation is recommended or should be considered. This score reflects the need to offer an improved patient care pathway when using oral anticoagulants. While NOACs avoid the need for drug monitoring (e.g. INR monitoring), they have an unstable bioavailability and are not indicated for patients with chronic kidney failure or in patients with valvular replacement surgery.

Cost-Effectiveness of High-Dose Edoxaban Compared with Adjusted-Dose Warfarin for Stroke Prevention in Non-Valvular Atrial Fibrillation Patients.

To estimate the quality-adjusted life-years (QALYs), costs, and cost-effectiveness of high-dose edoxaban compared with adjusted-dose warfarin in patients at risk for stroke who have nonvalvular atrial fibrillation (NVAF) and a creatinine clearance (Clcr ) of 15-95 ml/minute. A Markov model was created to compare the cost-effectiveness of high-dose edoxaban and adjusted-dose warfarin in patients with a Clcr of 15-95 ml/minute. The model was performed from a U.S. societal perspective and assumed patients initiated therapy at 70 years of age, had a mean CHADS2 (congestive heart failure, hypertension, age 75 or older, diabetes, stroke) score of 3, and no contraindications to anticoagulation. The model assumed a cycle length of 1 month and a lifetime horizon (maximum of 30 years/360 cycles). Data sources included renal subgroup analysis of the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation (ENGAGE-AF) trial and other published studies. Outcomes included lifetime costs (2014 US$), QALYs, and incremental cost-effectiveness ratios. The robustness of the model's conclusions was tested using one-way and 10,000-iteration probabilistic sensitivity analysis (PSA). Patients treated with high-dose edoxaban lived an average of 10.50 QALYs at a lifetime treatment cost of $99,833 compared with 10.11 QALYs and $123,516 for those treated with adjusted-dose warfarin. The model's conclusions were found to be robust upon one-way sensitivity analyses. PSA suggested high-dose edoxaban was economically dominant compared with adjusted-dose warfarin in more than 99% of the 10,000 iterations run. High-dose edoxaban appears to be an economically dominant strategy when compared with adjusted-dose warfarin for the prevention of stroke in NVAF patients with a Clcr of 15-95 ml/minute and an appreciable risk of stroke.

Atrial fibrillation

For those with non-valvular atrial fibrillation, DOACs are at least as effective as warfarin for preventing strokes and blood clots embolizing to the systemic circulation (if not more so) and are generally preferred over warfarin. DOACs carry a lower risk of bleeding in the brain compared to warfarin, although dabigatran is associated with a higher risk of intestinal bleeding. Dual antiplatelet therapy with aspirin and clopidogrel is inferior to warfarin for preventing strokes and has comparable bleeding risk in people with atrial fibrillation. In those who are also on aspirin, however, DOACs appear to be better than warfarin.

Transient ischemic attack

Anticoagulants may be started if the TIA is thought to be attributable to atrial fibrillation. Atrial fibrillation is an abnormal heart rhythm that may cause the formation of blood clots that can travel to the brain, resulting in TIAs or ischemic strokes. Atrial fibrillation increases stroke risk by five times, and is thought to cause 10-12% of all ischemic strokes in the US. Anticoagulant therapy can decrease the relative risk of ischemic stroke in those with atrial fibrillation by 67% Warfarin is a common anticoagulant used, but direct acting oral anticoagulants (DOACs), such as apixaban, have been shown to be equally effective while also conferring a lower risk of bleeding. Generally, anticoagulants and antiplatelets are not used in combination, as they result in increased bleeding risk without a decrease in stroke risk. However, combined antiplatelet and anticoagulant therapy may be warranted if the patient has symptomatic coronary artery disease in addition to atrial

Stroke

Those with atrial fibrillation have a 5% a year risk of stroke, and this risk is higher in those with valvular atrial fibrillation. Depending on the stroke risk, anticoagulation with medications such as warfarin or aspirin is useful for prevention. Except in people with atrial fibrillation, oral anticoagulants are not advised for stroke prevention—any benefit is offset by bleeding risk. In primary prevention, however, antiplatelet drugs did not reduce the risk of ischemic stroke but increased the risk of major bleeding. Further studies are needed to investigate a possible protective effect of aspirin against ischemic stroke in women.

Stroke in atrial fibrillation: Review of risk stratification and preventive therapy.

Atrial fibrillation (AF) is a leading preventable cause of ischemic stroke for which early detection and treatment are critical. The risk of stroke in people with AF can be stratified by the use of such validated prediction instruments such as CHADS<sub2</sub or CHA<sub2</sub DS<sub2</sub-VASc. The CHA<sub2</sub DS<sub2</sub-VASc adds to the evaluation of the risk of stroke by reliably identifying patients at very low risk. Additional points are assigned for an additional age category of 65-74 years (1 point), female sex (1 point), and vascular disease other than cerebrovascular disease (1 point). Two points are awarded for age ≥75 years. The risk of stroke increases according to point score: 0.5% per year (0 points), 1.5% per year (1 point), 2.5% per year (2 points), 5% per year (3 points), 6% per year (4 points), and 7% per year (5-6 points). For decades, Vitamin K antagonists were the only class of oral anticoagulants available to clinicians for the prevention of stroke in AF. However, new oral anticoagulants (NOACs), such as apixaban, dabigatran, and rivaroxaban, are currently available and have proved to be safe and effective in preventing stroke in patients with nonvalvular AF. In addition, a nonpharmacologic procedure like left atrial appendage occlusion is a possible option in selected patients. In this article, we have reviewed the stratification of stroke risk in AF, prevention of stroke in nonvalvular AF, warfarin versus NOACs, weighting risk of bleeding versus stroke risk when deciding on the anticoagulation protocol in patients with AF, and the use of nonpharmacologic therapy for stroke prevention.

Systematic review and network meta-analysis of the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants among patients with nonvalvular atrial fibrillation and CHADS2 score ⩾ 2.

The nonvitamin K antagonist oral anticoagulants pivotal clinical trials for stroke prevention in atrial fibrillation have important differences in trial designs and baseline patient characteristics. We sought to evaluate the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants in the management of stroke prevention in atrial fibrillation by adjusting for differences in baseline stroke risk and the length of follow-up among the four phase 3 randomized controlled trials. We conducted a systematic literature review of randomized controlled trials evaluating the nonvitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation and performed a network meta-analysis using data from ENGAGE AF-TIMI 48, RE-LY, ROCKET-AF, and ARISTOTLE, with warfarin as a common comparator. To adjust for between-trial differences in CHADS2 score and length of follow-up, annualized event rates among patients with CHADS2 score ⩾ 2 were analyzed using a mixed Poisson's regression model. Once-daily high-dose edoxaban was associated with significant lower major bleeding episodes compared with once-daily rivaroxaban (risk ratio, 0.76; 95% confidence interval, 0.66-0.89), twice-daily dabigatran 150 mg (risk ratio, 0.78; 95% confidence interval, 0.61-0.84), and twice-daily dabigatran 110 mg (risk ratio, 0.83; 95% confidence interval, 0.71-0.98) and similar bleeding risk compared with twice-daily apixaban (risk ratio, 1.08; 95% confidence interval, 0.91-1.28). Risk of stroke and systemic embolism was similar for the high-dose edoxaban and other nonvitamin K antagonist oral anticoagulant regimens. The low-dose edoxaban regimen was associated with a significant lower risk of major bleeding than other nonvitamin K antagonist oral anticoagulants and a significant higher risk of stroke and systemic embolism compared with apixaban and dabigatran 150 mg. Among patients with atrial fibrillation and CHADS2 score ⩾ 2, the high-dose edoxaban regimen may offer similar efficacy to the other nonvitamin K antagonist oral anticoagulants but with a significant major bleeding benefit over rivaroxaban and dabigatran.

VKORC1

Warfarin is a commonly prescribed oral anticoagulant, or blood thinner used to treat blood clots such as deep vein thrombosis and pulmonary embolism and to prevent stroke in people who have atrial fibrillation, valvular heart disease or artificial heart valves. Warfarin causes inhibition on VKORC1 activities and leads to a reduced amount of vitamin K available to serve as a cofactor for clotting proteins. Inappropriate dosing of warfarin has been associated with a substantial risk of both major and minor hemorrhage. As the pharmacological target of warfarin, VKORC1 is considered a candidate gene for the variability in warfarin response. Previous researches have shown that the CYP2C9 genotype of patients also played a role in warfarin metabolism and response. Gene The human gene is located on chromosome 16. Two pseudogenes have been identified on chromosome 1 and the X chromosome. Clinical relevance

CHA2DS2–VASc score

{{DISPLAYTITLE:CHA2DS2–VASc score}} The CHADS2 score and its updated version, the CHA2DS2-VASc score, are clinical prediction rules for estimating the risk of stroke in people with non-rheumatic atrial fibrillation (AF), a common and serious heart arrhythmia associated with thromboembolic stroke. Such a score is used to determine whether or not treatment is required with anticoagulation therapy or antiplatelet therapy, since AF can cause stasis of blood in the upper heart chambers, leading to the formation of a mural thrombus that can dislodge into the blood flow, reach the brain, cut off supply to the brain, and cause a stroke. A high score corresponds to a greater risk of stroke, while a low score corresponds to a lower risk of stroke. The CHADS2 score is simple and has been validated by many studies. In clinical use, the CHADS2 score (pronounced "chads two") has been superseded by the CHA2DS2-VASc score ("chads vasc"), which gives a better stratification of low-risk patients.

Management of atrial fibrillation

in those who are allergic to aspirin). In contrast, those with a high risk of stroke derive most benefit from anticoagulant treatment with warfarin or similar drugs. A new class of anticoagulant drugs, the direct thrombin inhibitors (Dabigatran), has recently arrived on the scene and shown efficacy in treating complications of nonvalvular chronic AF.

Atrial fibrillation

Anticoagulants Anticoagulation can be used to reduce the risk of stroke from AF. Anticoagulation is recommended in most people other than those at low risk of stroke or those at high risk of bleeding. The risk of falls and consequent bleeding in frail elderly people should not be considered a barrier to initiating or continuing anticoagulation since the risk of fall-related brain bleeding is low and the benefit of stroke prevention often outweighs the risk of bleeding. Similarly, the presence or absence of AF symptoms does not determine whether a person warrants anticoagulation and is not an indicator of stroke risk. Oral anticoagulation is underused in atrial fibrillation, while aspirin is overused in many who should be treated with a direct oral anticoagulant (DOAC) or warfarin. In 2019, DOACs were often recommended over warfarin by the American Heart Association.

Edoxaban

Compared with warfarin it has fewer drug interactions. It was developed by Daiichi Sankyo and approved in July 2011, in Japan for prevention of venous thromboembolisms following lower-limb orthopedic surgery. It was also approved in the United States by the Food and Drug Administration (FDA) in January 2015, for the prevention of stroke and non–central-nervous-system systemic embolism. It was approved for use in the European Union in June 2015. It is on the World Health Organization's List of Essential Medicines. Medical uses In the United States, edoxaban is approved for treating deep vein thrombosis and pulmonary embolism following five to ten days of initial therapy with a parenteral anticoagulant. It is also approved for reducing the risk of blood clots in people with nonvalvular atrial fibrillation.

Management of atrial fibrillation

To compensate for the increased risk of stroke, anticoagulants may be required. However, in the case of warfarin, if someone with AF has a yearly risk of stroke that is less than 2%, then the risks associated with taking warfarin outweigh the risk of getting a stroke from AF. However, since these older data, there is now greater recognition of the importance of good anticoagulation control (as reflected by time in therapeutic range) as well as greater awareness of bleeding risk factors as well as data from recent trials that aspirin carries a similar rate of major bleeding to warfarin, especially in the elderly.

[Anticoagulation in permanent atrial fibrillation after 75 years of age].

More than 10% of the population over 75 years old is concerned by non valvular permanent atrial fibrillation which is responsible for at least 30% of ischemic strokes. The indication of an anticoagulant therapy is discussed in two different situations: primary or secondary prevention of stroke and acute phase of stroke. Patients over 75 years old have a high risk of stroke (> 8% year). All the studies have demonstrated the benefit of a primary or secondary prevention by antivitamin K with an INR between 2 and 3 (reduction of the relative risk of about 68%). Conversely, the efficacy of aspirin has not been proven in this population of elderly patients. Once stroke has occurred, it is not recommended to initiate an anticoagulation (unfractioned or low molecular weight heparin) within the first hours. Prevention of venous thrombosis remains necessary. Currently, less than 30% of the patients older than 75 years are given anticoagulation, the risk of the treatment being probably overestimated. The risk benefit ratio should be evaluated more properly for a given patient.

CHA2DS2–VASc score

Use The CHA2DS2-VASc score is a widely used medical tool used to guide physicians on blood thinning treatment to prevent stroke in people with non-valvular atrial fibrillation (AF). CHADS2 The CHADS2 score does not include some common stroke risk factors, and its various pros/cons have been carefully discussed. Adding together the points that correspond to the conditions that are present results in the CHADS2 score, that is used to estimate stroke risk. CHA2DS2-VASc To complement the CHADS2 score, by the inclusion of additional 'stroke risk modifier' risk factors, the CHA2DS2-VASc-score has been proposed. In clinical use, the CHADS2 score has been superseded by the CHA2DS2-VASc score, which gives a better stratification of low-risk patients. The CHADS2 score has been outperformed by the CHA2DS2-VASc in multiple patient groups including patients with AF who are receiving outpatient elective electrical cardioversion.

A review of anticoagulation with warfarin in patients with nonvalvular atrial fibrillation.

Warfarin therapy has proved safe and effective in a number of randomized controlled trials of stroke prophylaxis in patients with nonvalvular atrial fibrillation (NVAF), reducing the risk of stroke in these patients by two thirds. However, participants in the clinical trials were carefully selected and younger than patients in actual clinical practice. This analysis sought to determine whether the results of clinical trials in patients with NV can be extrapolated to the general population seen in clinical practice. A MEDLINE search from 1966 to the present was used to identify observational trials of anticoagulation in patients with NVAF that addressed warfarin use, anticoagulation control, efficacy, and complications. The search terms used were atrial fibrillation and anticoagulation. Although warfarin prophylaxis against stroke in patients with NVAF appeared to be as well tolerated and effective in clinical practice as in clinical trials, it was generally underused, particularly in the elderly. Anticoagulation control was not as good in clinical practice as in clinical trials, although the rates of stroke and major bleeding were comparable. Judicious use of warfarin, tailored to individual stroke risk, seems to be a reasonable policy. Warfarin therapy increases quality-adjusted survival in patients at high risk for stroke, and it is recommended for medium-risk patients unless their risk of bleeding is high or their quality of life while taking warfarin would be poor. Patients at a low risk for stroke will have equivalent health outcomes and incur lower costs if treated with aspirin. Despite the increased risk of hemorrhage in elderly patients, the net benefit of warfarin therapy is greater in this age group because of the higher risk of stroke. Active involvement of patients and their caregivers in an anticoagulation service setting may improve outcomes of anticoagulation therapy.

Comparison of Aspirin and Naoxintong Capsule () with Adjusted-Dose Warfarin in Elderly Patients with High-Risk of Non-Valvular Atrial Fibrillation and Genetic Variants of Vitamin K Epoxide Reductase.

To compared the therapeutic effect of a Chinese patent medicine Naoxintong Capsule (, NXT) and aspirin with adjusted-dose warfarin in Chinese elderly patients (over 65 years) with nonvalvular atrial fibrillation (NVAF) and genetic variants of vitamin K epoxide reductase (VKORC1), who are at high-risk of thromboembolism. A total of 151 patients, with NVAF and AA genotype of VKORC1-1639 (a sensitive genotype to warfarin) and a CHA<sub2</subDS<sub2</sub-VASc clinical risk score of 2 or above, were chosen for this study. Patients were randomized into two groups and orally treated with a combination of aspirin (100 mg/day) and NXT (1.6 g thrice a day) or adjusted-dose warfarin [international normalized ratio 2.0-3.0). The primary end points including ischemic stroke and death as well as the secondary end points including hemorrhage events were followed up for at least 1 year. Baseline clinical data and the rates of primary end points were similar between groups. However, the rate of serious bleeding (secondary event) in the combination therapy group was lower than that in the adjusted-dose warfarin group (0% vs. 7.9%, odds ratio: 0.921, 95% confidence interval: 0.862-0.984, P=0.028). Aspirin combined with NXT and warfarin displayed comparable rates of primary end point including ischemic stroke and all-cause death during the 1-year follow-up. However, as compared with warfarin, the combination therapy reduced the rate of serious bleeding. Therefore, aspirin combined with NXT might provide an alternative pharmacotherapy in preventing ischemic stroke for elderly patients with NAVF who cannot tolerate warfarin. (No. ChiCTR-TRC-13003596).

Relationship between CHADS2 score and ischemic stroke during rhythm control therapy for paroxysmal atrial fibrillation.

The CHADS2 score has been proposed for stratifying patients with nonvalvular atrial fibrillation (NVAF) according to the risk of thromboembolism in the AHA/ACC/ESC guidelines. However, there is little information about its usefulness for predicting the long-term risk of ischemic stroke in Japanese patients with paroxysmal AF. We retrospectively evaluated the incidence of ischemic stroke and the efficacy of anticoagulant therapy in paroxysmal AF patients on rhythm control therapy who were stratified by their CHADS2 score. The subjects were 334 NVAF atients (229 men and 105 women, mean age, 68 +/- 12 years, mean follow-up period, 60 +/- 35 months) who were categorized into low risk (score 0), moderate risk (1 or 2), and high risk (3 or more) groups for thromboembolism. The low, moderate, and high risk groups accounted for 34%, 50%, and 16% of the patients, respectively. Among 257 patients without warfarin therapy, the annual rate of symptomatic ischemic stroke was 0.6% in the score 0 group, 0.5% in the score 1 group, 3.1% in the score 2 group, and 9.6% in the score 3 or more group. Among 77 patients treated with warfarin (target PT-INR: 1.6-3.0), the stroke rate was 0% in the score 0 group, 0% in the score 1 group, 1.4% in the score 2 group, and 6.6% in the score 3 or more group. The annual rate of ischemic stroke was 0.88% in patients treated with warfarin versus 2.67% in those without warfarin, or a decrease in risk of 68% with warfarin (P < 0.01). In Japanese patients with paroxysmal AF, the CHADS2 score is useful for predicting the risk of ischemic stroke. Anticoagulant therapy is needed to prevent ischemic stroke in patients with paroxysmal AF, especially those who have a CHADS2 score of 2 or more.

Cost-effectiveness of apixaban vs warfarin for secondary stroke prevention in atrial fibrillation.

To compare the cost-effectiveness of apixaban vs warfarin for secondary stroke prevention in patients with atrial fibrillation (AF). Using standard methods, we created a Markov decision model based on the estimated cost of apixaban and data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and other trials of warfarin therapy for AF. We quantified the cost and quality-adjusted life expectancy resulting from apixaban 5 mg twice daily compared with those from warfarin therapy targeted to an international normalized ratio of 2-3. Our base case population was a cohort of 70-year-old patients with no contraindication to anticoagulation and a history of stroke or TIA from nonvalvular AF. Warfarin therapy resulted in a quality-adjusted life expectancy of 3.91 years at a cost of $378,500. In comparison, treatment with apixaban led to a quality-adjusted life expectancy of 4.19 years at a cost of $381,700. Therefore, apixaban provided a gain of 0.28 quality-adjusted life-years (QALYs) at an additional cost of $3,200, resulting in an incremental cost-effectiveness ratio of $11,400 per QALY. Our findings were robust in univariate sensitivity analyses varying model inputs across plausible ranges. In Monte Carlo analysis, apixaban was cost-effective in 62% of simulations using a threshold of $50,000 per QALY and 81% of simulations using a threshold of $100,000 per QALY. Apixaban appears to be cost-effective relative to warfarin for secondary stroke prevention in patients with AF, assuming that it is introduced at a price similar to that of dabigatran.

[Atrial fibrillation and apoplexy--risks and prevention].

The annual incidence of ischemic stroke among patients with chronic non-valvular atrial fibrillation is about 4.5 percent. In five controlled trials, oral anticoagulant therapy with warfarin reduced the annual incidence of stroke by 68 percent to 1.4 percent. The effect of aspirin has not been unequivocally determined. Aspirin reduced the annual risk of stroke by 18 percent (n.s.) in one trial, and by 44 percent in another, though the two trials differed both in mean age of the patients and in aspirin doses. Direct comparison of warfarin and aspirin revealed no difference in efficacy. Advanced age, previous stroke or transient ischemic attack (TIA), hypertension and diabetes were all found to be risk factors for stroke in patients with atrial fibrillation. In patients under 65 years of age without risk factors, the annual risk of stroke was 1 percent. After TIA or minor stroke, warfarin reduced the annual risk of a second stroke from 12 percent to 4 percent. Aspirin had no such effect. The annual incidence of major bleeding episodes was 0.2-2.0 percent in the warfarin-treated subgroup, 0.2-1.5 percent in the aspirin subgroup and 0-1.6 percent in the placebo subgroup. Based on findings in the above mentioned trials, warfarin (INR 2.0-3.0) is recommended for stroke prevention in patients over 60 years of age with non-valvular atrial fibrillation. Trials are under way to ascertain whether conventional warfarin treatment can be replaced by less complicated and safer treatments in patients with chronic atrial fibrillation.