Improving the CHADS2 Score

Motivation: Recently, I met a man with CHADS2 score of one.  We shook hands, and he had atrial fibrillation.  Slowing his heart down was relatively easy, but what about anti-coagulation, aspirin or warfarin?  A CHADS2 score of one is a grey "intermediate risk" zone without clear indications for using warfarin or aspirin.  About two years ago, a group from England and Netherland proposed a further refinement to the CHADS2 score (called CHA2DS2-VASc) to help decide on anti-coagulation in these intermediate risk cases.

Paper: Lip, G.Y.H., Nieuwlaat, R., Pisters, R., et. al. "Refining Clinical Risk Stratification for Predicting Stroke and Thromboembolism in Atrial Fibrillation Using a Novel Risk Factor-Based Approach: The Euro Heart Survey on Atrial Fibrillation." Chest (2010); 137: 263-272.

Methods: The authors proposed a revised point scoring system with the following components:

Congestive Heart Failure or LV dysfunction: 1
Hypertension: 1
Age 75 or over: 2
Age 65 or over: 1
Diabetes: 1
Stroke, TIA, or other embolic disease: 2
Vascular disease (MI, PAD, or known aortic plaque): 1
Female gender: 1


To validate the predictive value of this scoring system, the authors analyzed data from 1,084 patients without mitral stenosis or heart valve surgery who did not use warfarin.  The authors tracked survival status and risk of thromboembolic disease.  The patients were derived from Euro Heart Survey cohort, which tracked patients among 182 hospitals in 35 countries.

Results:
Cohort Characteristics: The patients in the tracked cohort were on average 66 years of age and 40.8% were women.  The most common risk factor was hypertension (67.3%) followed by CAD (38.4%).  Overall, 34.9% of the cohort had CHADS2 score of one, 20.4% with score of zero, and rest with higher scores.  74% took anti-platelet agents.

Thromboembolic Risk: The annual risk of thromboembolic events by risk factor is shown below (only the low risk rates are shown).  Adjusted rate for aspirin use assumes a 22% risk reduction by aspirin use.

Score: 0 (103 patients, no risk factors) - Event rate: 0, annual rate adjusted for ASA use: 0
Score: 1 (162 patients) - Event rate: 0.6%, annual rate adjusted for ASA use: 0.7%
Score: 2 (184 patients) - Event rate: 1.6%, annual rate adjusted for ASA use: 1.9%
Score: 3 (203 patients) - Event rate: 3.9%, annual rate adjusted for ASA use: 4.7%

One of the novel risk factors that this scoring system adds is female gender.  In univariate analysis, female gender is associated with event rate odds ratio of 2.53 (1.08-5.92).

Discussion: This paper provides help in further distinguishing patients really at low risk not requiring further treatment.  I was pretty impressed with the zero annual event rate in patients with no risk factors.  On the other hand, for patients with score of 2, treatment with warfarin is likely indicated since the risk of symptomatic embolic complication  (1.9%) balances the risk of major bleeding (about the same risk).  Especially in an older population, aspirin carries a major bleeding risk (estimated to be about the same in elderly population) but provides substantially decreased protection against embolic disease.

The study, while helpful, has some limitations.  First, the analysis was done retrospectively in a cohort.  It is unclear why these patients were not anti-coagulated.  It is possible that factors which led to decision not to anti-coagulate also substantially modified the subsequent risk of embolic events (high risk behaviors such as IV drug use).  Nonetheless, I think that this study adds to the identification of the truly low risk group.    

The Flutter-Fibrillation Spectrum

Motivation: Every time I encounter a patient with atrial flutter and hard to control ventricular rates, I wonder why the patient is on the floor and not in an electrophysiology suite. I mean, why should we spend time titrating diltiazem when the ablation procedure (ablation of cavo-tricuspid isthmus) has more than 90% success rate.  In fact, general guidelines state that in contrast to a-fib, for patients with recurrent atrial flutter, ablation should be the first-line approach rather than rate control.  Ablation, however, is not a good long-term fix if patients with atrial flutter also develop atrial fibrillation, which does not respond well to ablation.  I have at times heard of the "flutter fibrillation spectrum." But, how often do patients with atrial flutter actually develop atrial fibrillation in the future?

Paper: "Risk of Stroke in Patients with Atrial Flutter", Biblo, L.A. et. al. Am. J. of Card. (2001) 87: 346-349.  http://www.ncbi.nlm.nih.gov/pubmed?term=11165976%20

Methods: In this large retrospective study, the authors scanned Medicare inpatient files in 1984 for patients older than 65 who were diagnosed with atrial flutter or atrial fibrillation without stroke.  For control, a 5% random sample of other hospitalized patients were chosen without atrial flutter or fibrillation.  Patients were followed for 8 years.  The primary endpoints assessed were incidence of stroke and incidence of atrial fibrillation in patients with atrial flutter.

Results:
Subjects: The study followed 17,413 patients with atrial flutter, 337,428 with atrial fibrillation, and 395,147 controls.

Atrial Flutter to Fibrillation Incidence: Patients with atrial flutter developed atrial fibrillation in an almost linear fashion over the 8 year follow-up period.  By about 6.5 years of follow-up, half of the initial group of patients with atrial flutter had developed an episode of atrial fibrillation.  The top three factors which predicted which patients would develop fibrillation were rheumatic heart disease (Risk Ratio: 1.464, CI: 1.250-1.715)., systemic hypertension (RR: 1.333, CI: 1.267-1.402), and congestive heart failure (RR: 1.243, CI: 1.174-1.316).

Stroke Risk: After adjusting for known risk factors like hypertension, CHF, rheumatic heart disease, DM, and MI, the stroke risk in patients with atrial flutter was greater than controls (RR: 1.406, p < 0.0001).  The adjusted stroke risk in patients with atrial fibrillation (RR: 1.642, p < 0.0001) was greater than those with atrial flutter.  Importantly, the stroke risk for patients initially with atrial flutter with new onset atrial fibrillation was not significantly different from the stroke risk in patients with atrial fibrillation.

Discussion: I think that this paper nicely illustrates why it is hard to manage atrial flutter.  Patients with atrial flutter are at significant risk for atrial fibrillation (about half have atrial fibrillation by about 6.5 years of follow-up).  In these patients, going through ablation is questionable since a-fib requires rate-control and anti-coagulation regardless.  On the other hand, for the half of patients who do not develop a-fib by seven years, conversion to sinus rhythm through ablation would save them many years of hazards of warfarin anti-coagulation.  I think that it is still unclear exactly which subgroup benefits most from ablation.  Likely as suggested by the paper, patients with additional risk factors like HTN, CHF, and rheumatic heart disease are likely to go on to develop a-fib.  Another point underscored by the paper is that while both atrial flutter and fibrillation have elevated stroke risk, patients with atrial fibrillation are at higher risk than those with flutter.   Finally, while the paper is impressive in the large number of subjects tracked, the paper is retrospective in nature and only examines patients older than 65.   Also, I have some doubts about how accurately atrial flutter/fibrillation is coded during hospitalizations (!).