More on atrial fibrillation & anticoagulation

Excellent review article on the newer anticoagulants for stroke and systemic embolism reduction in AF:

ACP Journal Club 18 Sept 2012

 

The CHA₂DS₂-VASc score identifies those patients with atrial fibrillation and a CHADS₂ score of 1 who are unlikely to benefit from oral anticoagulant therapy 

European Heart Journal Oct 2012

 

Various risk stratification schemes predict ischemic stroke and bleeding in atrial fibrillation

ACP Journal Club 16 Oct 2012

Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33:1500-10.

The CHA₂DS₂-VASc score had 100% sensitivity and 6% specificity for predicting stroke in patients with atrial fibrillation; CHADS₂ and Framingham scores had slightly lower sensitivities but higher specificities.

Commentary: In their analysis of 7 risk stratification schemes, Friberg and colleagues found that CHADS_2, CHA₂DS₂-VASc, and Framingham were the most accurate for predicting ischemic stroke, with c-statistics of 0.66 to 0.67. They also concluded that the 2 risk stratification schemes for bleeding had “similar predictive value,” but HEMORR₂HAGES had a higher c-statistic than the HAS-BLED scheme in 7 of 8 subgroups and the same value in 1 subgroup. A new risk stratification scheme, ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), was not evaluated (1).

Warfarin-associated major hemorrhage predicted by 7 risk stratification schemes in patients with atrial fibrillation
ACP Journal Club 15 Nov 2011

The ATRIA risk score has the potential to be a major clinical tool but needs further validation in other populations and comparisons with similar risk scores, such as HAS-BLED (2).

 ATRIA risk score had a similar c-statistic (0.69) to HEMORR2HAGES (0.67).

 

Patients at High Risk for Falls: A Reason Not to Anticoagulate?
(from Journal Watch)

Donzé J et al. Risk of falls and major bleeds in patients on oral anticoagulation therapy. Am J Med 2012 Aug; 125:773

Among patients taking anticoagulants, high risk for falls was not associated with elevated risk for major bleeding.
Despite the proven benefits of oral anticoagulants in preventing and treating certain cardiovascular and cerebrovascular diseases, they are underprescribed. Fear of falls is the most commonly cited reason. Prior studies suggest that high fall risk should not be a contraindication to oral anticoagulant use, but these studies were limited by retrospective design or exclusion of patients at high risk for falls.
Researchers evaluated whether fall risk is associated with risk for major bleeding in a prospective study of 515 patients (median age, 71) who were treated with vitamin K antagonists at a hospital in Switzerland. Patients were considered to be at high risk for falls if they answered yes to either of two validated questions: (1) Did you fall during the last year? (2) Did you notice any problem with gait, balance, or mobility? Sixty percent of patients were categorized as high risk and all others as low risk. Times to first major bleeding event (including fatal or intracranial) within the 12-month follow-up did not differ significantly between the groups. Polypharmacy was associated independently with risk for major bleeds, with a 12% increase in risk for each additional drug taken.
Comment: This study adds to evidence that patients should not be denied oral anticoagulation solely on the basis of high risk for falls. For patients with valid indications for anticoagulation, benefit generally outweighs risk. For example, an analytic model suggests that older patients (age, 65) who have a 5% annual risk for stroke (i.e., CHADS₂ score of 2–3) and are taking anticoagulants would need to fall approximately 295 times yearly for risks of fall-related subdural hemorrhages to outweigh benefits of stroke prevention (Arch Intern Med 1999; 159:677). In addition, providers should be aware of risks conferred by polypharmacy in patients taking anticoagulants and should discontinue unnecessary medications, monitor patients more closely, or both.

A 5-item score predicted risk for warfarin-associated major hemorrhage in patients with atrial fibrillation

ACPJC. 15 November 2011.
5-item ATRIA score (score range 0 to 10):
1. Anemia (3 points)
2. hyperTension (1 point)
3. severe Renal disease: GFR <30 ml/min or dialysis-dependent (3 points)
4. history of Incidental bleed, ie past hemorrhage (1 point)
5. Age ≥ 75 years (2 points)

ATRIA risk categories (annual risk):
1. low risk for hemorrhage, score ≤ 3 (0.8%)
2. intermediate risk, score = 4 (2.6%)
3. high risk, score ≥ 5 (5.8%)

Abstract

OBJECTIVES:

The purpose of this study was to develop a risk stratification score to predict warfarin-associated hemorrhage.

BACKGROUND:

Optimal decision making regarding warfarin use for atrial fibrillation requires estimation of hemorrhage risk.

METHODS:

We followed up 9,186 patients with atrial fibrillation contributing 32,888 person-years of follow-up on warfarin, obtaining data from clinical databases and validating hemorrhage events using medical record review. We used Cox regression models to develop a hemorrhage risk stratification score, selecting candidate variables using bootstrapping approaches. The final model was internally validated by split-sample testing and compared with 6 published hemorrhage risk schemes.

RESULTS:

We observed 461 first major hemorrhages during follow-up (1.4% annually). Five independent variables were included in the final model and weighted by regression coefficients: anemia (3 points), severe renal disease (e.g., glomerular filtration rate <30 ml/min or dialysis-dependent, 3 points), age ≥75 years (2 points), prior bleeding (1 point), and hypertension (1 point). Major hemorrhage rates ranged from 0.4% (0 points) to 17.3% per year (10 points). Collapsed into a 3-category risk score, major hemorrhage rates were 0.8% for low risk (0 to 3 points), 2.6% for intermediate risk (4 points), and 5.8% for high risk (5 to 10 points). The c-index for the continuous risk score was 0.74 and 0.69 for the 3-category score, higher than in the other risk schemes. There was net reclassification improvement versus all 6 comparators (from 27% to 56%).

CONCLUSIONS:

A simple 5-variable risk score was effective in quantifying the risk of warfarin-associated hemorrhage in a large community-based cohort of patients with atrial fibrillation.

Atrial Fibrillation and Anticoagulation Articles

Dronedarone in High-Risk Permanent Atrial Fibrillation (PALLAS Trial)

http://www.nejm.org/doi/full/10.1056/NEJMoa1109867

Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients.

Dronedarone in Atrial Fibrillation — Jekyll and Hyde? (Editorial)

http://www.nejm.org/doi/full/10.1056/NEJMe1111997

Has a nice comparison of the ATHENA, PALLAS, and ANDROMEDA studies.

Take home messages:

1)      Patients with permanent atrial fibrillation have no reason to receive antiarrhythmic drugs, and on the basis of the PALLAS findings, they should certainly not receive dronedarone;

2)      Dronedarone will also need to be avoided in high-risk patients with nonpermanent atrial fibrillation, particularly those with heart failure;

3)      Dose adjustment of digoxin is clearly essential in patients taking dronedarone;

4)      Reserve dronedarone for selected low-risk patients with persistent or paroxysmal atrial fibrillation, possibly those in whom other antiarrhythmic drugs have failed.

(UPDATE) FDA puts new warnings on Dronedarone
December 19, 2011 (Silver Spring, Maryland) — The FDA is requiring new safety warnings to be included on the labeling for the antiarrythmic drug dronedarone (Multaq, Sanofi-Aventis) in light of clinical data showing the drug increases the risk of serious cardiovascular events, including death, in patients with permanent atrial fibrillation (AF).
The agency is adding the following revisions and recommendations to the drug's label: Healthcare professionals should prescribe the drug only to patients who can be converted into normal sinus rhythm, and the drug should be discontinued in patients in AF. Healthcare professionals should monitor the heart rhythm of patients taking dronedarone by ECG at least once every three months.
Dronedarone is indicated to reduce hospitalization for AF in patients in sinus rhythm with a history of paroxysmal or persistent AF. Patients on dronedarone should also be on appropriate antithrombotic therapy, the FDA insists.

Risks for Stroke, Bleeding, and Death in Patients With Atrial Fibrillation Receiving Dabigatran or Warfarin in Relation to the CHADS₂ Score: A Subgroup Analysis of the RE-LY Trial

http://www.annals.org/content/155/10/660.full

Higher CHADS₂ scores were associated with increased risks for stroke or systemic embolism, bleeding, and death in patients with atrial fibrillation receiving oral anticoagulants.

Learning the Respective Roles of Warfarin and Dabigatran to Prevent Stroke in Patients With Nonvalvular Atrial Fibrillation (Editorial)

http://www.annals.org/content/155/10/714.full

1)    Dabigatran is more effective and safer for many patients with nonvalvular atrial fibrillation, especially younger patients, patients with CHADS₂ scores of 0 or 1, and those in whom the INR is not maintained within the therapeutic range at least 60% of the time;

2)    If less frequent INR monitoring can also safely keep patients within the therapeutic range of warfarin at least 70% of the time, warfarin may remain the preferred anticoagulant therapy, especially in patients aged 75 years or older or with CHADS₂ scores of 3 or higher.

FDA Approves Rivaroxaban for Stroke Prevention in AF Patients

http://www.medscape.com/viewarticle/752961?src=ptalk