"resolved" atrial fibrillation and stroke risk; afib risk factors

A recent large data-mining study from the UK showed that those patients with “resolved” atrial fibrillation were still at substantial risk of TIA/stroke, suggesting continued anticoagulation is warranted (see afib resolved and subset stroke bmj2018​ in dropbox, or doi.org/10.1136/bmj.k1717).

Details:
--Patients were assessed within The Health Improvement Network (THIN) in the UK, a database of 14 million patients from 640 practices, from 2000 to 2016
--11,159 patients with “resolved” atrial fibrillation in their medical record were compared to 15,059 with atrial fibrillation and 22,266 controls without afib
--there was some variability in these risk factors in the different groups, but overall: mean age 72​, 59% men, 12% current smoker, 20% nondrinker/67% drinker/4% excessive drinker, BMI, 50% hypertension
--main outcome: incidence of TIA/stroke
--secondary outcome: all-cause mortality

Results:
--the % of patients with resolved afib has increased over time: 0.9% in 2000 to 10.5% in 2016.
--78.7% of those with resolved afib diagnosis were at moderate-to-high stroke risk, with CHA₂DS₂-VASc score  ≥​1, which increased from 54.5% in 2000 to 84.1% in 2016
--BUT: the proportion of those at moderate-to-high risk receiving anticoagulant therapy increased from 6.2% to 14.3% in 2016; far lower than those with unresolved afib where the treatment rates increased from 34.3%  to 71.8%
--stroke/TIA (adjusted incidence ratios, adjusting for age, sex, Townsend deprivation index of poverty/material deprivation, BMI, smoking, alcohol, Charlson comorbidity index, statins, anticoagulants), over median follow-up of 3 years:
    --resolved afib vs controls with afib: 24% less, HR 0.76 (0.67-0.85), p<0.001
    --resolved afib vs controls without afib: 63% more, HR 1.63 (1.46-1.83, p<0.001)
    ​--the crude (unadjusted) incidence rates were 30.0/1000 person-yrs in those with resolved afib, though was higher at 60.3/1000 person-yrs in those with ongoing afib but 24.4/1000 person-yrs in the non-afib controls
--all-cause mortality (adjusted incidence ratios, as above), over median follow-up of 3 years:
    --resolved afib vs controls with afib: 40% less, HR 0.60 (0.56-0.65), p<0.001
    --resolved afib vs controls without afib: 13% more, HR 1.13 (1.06-1.21, p<0.001)
    ​--the crude (unadjusted) incidence rates were 12.1/1000 person-yrs in those with resolved afib, though was higher at 16.7/1000 person-yrs in those with ongoing afib but 7.4/1000person-yrs​ in the non-afib controls
--22.8% of the patients with resolved afib had a subsequent record of recurrent afib
    --if the patient had documented recurrent afib, they were twice as likely to have a TIA/stroke, adjusted incidence rate ratio of 2.05 (1.69-2.50), p<0.001
    --if the patient had NO documentation of recurrent afib, their risk was still increased 45%, adjusted incidence rate ratio of 1.45 (1.26-1.67), p<0.001
    --no difference if the prior afib diagnosis were coded as paroxysmal afib or other types prior to having resolved afib
--a recent record of ablation was found in 131/11159 (1.2%) of the patients with resolved afib:
    -- no difference in stroke/TIA if patient had ablation or not
--17.4% of patients with resolved afib were on anticoagulants
    --the rate of TIA/stroke in those on anticoagulants was a non-significant 14% lower
           
Commentary:
--overall, afib increases stroke risk 5-fold, and treatment with anticoagulants reduces that risk by 2/3
--this study did not have detailed information about the decision to call the afib “resolved”, which makes it a little difficult to interpret. But the large numbers of patients makes it more likely to reflect true clinical practice reasonably accurately.
--though other studies do suggest that even with catheter ablation, long-term success rates in sustained normal sinus rhythm can be as low as 20%. And the many older studies on anti-arrhythmics also showed that there was a sufficiently high risk of afib recurrence and embolic events that continued anticoagulation was warranted and advised
--as with the older med studies on afib (back in the days we tried hard to restore sinus rhythm), meds like amiodarone worked really well, but still half the patients or so did have bouts of afib despite their predominant normal sinus rhythm.  So, it is not surprising that those with continued diagnosis of afib had higher stroke/TIA risk than those with resolved afib, since probably a sizable proportion with resolved afib probably did have sustained normal sinus rhythm.  But those with resolved afib, as a group, still had a higher stroke/TIA risk than those without afib
--this article is a large data-mining one and not an RCT assessing how outcomes differ with anticoagulation, with strict criteria governing the definition of "resolved" afib.  but, the concern addressed in this article is that there really are no good data available. the UK NICE guidelines on afib do not comment at all.  the authors do comment "that common clinical practice is to continue to treat patients in accordance with their pre-ablation stroke risk score". the US, Canadian and European guidelines also do not comment on resolved atrial fibrillation 

so, 
--it is clear from the above study that:
    --there was a remarkably strong tendency for patients labeled as "resolved afib" to not be on anticoagulation therapy despite their high CHA₂DS₂-VASc score.
    --their residual risk for TIA/stroke remains significantly higher than the background population (and having a stroke can be a really outcome....)
    --though the numbers were small, there does not seem to be adequate stroke protection in those having ablation
    --and we clinicians do not have the data to risk-stratify which patients are at high risk of a stroke off anti-coagulation

--given the lack of good prospective data, this large-scale evaluation of patients with resolved afib suggest:
    ​--those with resolved afib, including those having had ablation therapy, should still be considered to be at increased risk of stroke, and this is likely to be more so in those with CHA₂DS₂-VASc scor​e  ≥​1
   --at this time, the imperative, it seems to me, is to discuss with patients their continued risk of stroke if their inclination is to stop anticoagulation therapy (though this risk may be less so than those with continued afib)

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and, another article just came out from the Framingham Heart Study (see afib risk factors bmj2018 in dropbox, or doi.org/10.1136/bmj.k1453).

Details:
--5338 patients at age 55; 4805 at age 65; 3199 at age 75, all free of afib at index age
--approx 35% nonsmoker/45% former smoker/17% current smoker (there were fewer smokers in the older age groups); 82% men drank ≤14 units alcohol/week, women ≤7 units; BMI<25 in 33%/25-29 in 41%/>30 in 25%; BP <120/80 in 16% (decreased with age),120-39/80-89 in 25%, >140/90 in 50% (increased with age); blood sugar normal in 70%/borderline 22%/elevated 8%; no history of MI or heart failure in 90%
--patients were classified as follows:
    --optimal: based on these 5 criteria: never smoker; men drinking ≤14 units of alcohol/week and women ≤7; BMI <25; SBP<120 and DBP<80, fasting blood sugar <100 or nonfasting<140 if fasting not available; no history of heart failure or MI
    --borderline: former smoker; BMI 25-29; SBP 120-39 or DBP 80-89; fasting BS 100-125 or nonfasting 140-199
    --elevated: current smoker; men drinking >14 units of alcohol/week, women >7; BMI>30; SBP>140 or DBP>90; fasting BS >126 or nonfasting >200; history of MI or heart failure

Results:
--age 55:
    --4.6% had optimal risk profile, 26.5% had borderline risk profile, 68.9% elevated risk profile
    --lifetime risk of afib 37.0% (34.3-39.6%)
        --optimal risk group: 23.4% (12.8-34.5%)
        --borderline risk group: 33.4% (27.9-38.8%)
        --elevated risk group: 38.4% (35.5-41.4%)
        ​--people with at least one elevated risk factor: 37.8% had lifetime risk of afib
    ​--median follow-up time til developed afib: 14 years
--age 65:
    --2.1% had optimal risk profile

    --lifetime risk of afib 33.7% (34.3-39.6%)

        --optimal risk group: 18.1% (6.7-29.4%)

        --borderline risk group: 26.1% (22.0-30.1%)

        --elevated risk group: 35.8% (33.8-37.9%)

        ​--people with at least one elevated risk factor 35.7% had lifetime risk of afib

    ​--median follow-up time til developed afib: 11 years

--age 75:
    --1.0% had optimal risk profile

 --lifetime risk of afib 30.8% (34.3-39.6%)

        --optimal risk group: 15.4% (1.3-29.5%)

        --borderline risk group: 23.6% (19.1-28.2%)

        --elevated risk group: 32.2% (30.0-34.3%)

        ​--people with at least one elevated risk factor: 29.2% had lifetime risk of afib

    ​--median follow-up time til developed afib: 8 years​

--the lifetime risk was consistently higher in men than women for both the different index ages as well as whether they had optimal, borderline or elevated risk factors

Commentary:
--interestingly, there was not much difference in lifetime afib risk for each index age group if they had 1 vs >1 elevated risk factors. This seems to be in contradistinction to atherosclerotic disease, where the more risk factors, the risk of disease increases dramatically
--also, the relative lifetime risk of afib in patients with optimal lifestyles noted above is higher than anticipated for the risk of clinical atherosclerotic cardiovascular disease. This reinforces the importance of afib itself, since the estimated death rates are 20% and 50% at 1 and 5 years after diagnosis. So, preventing afib seems like a good idea.
--the Framingham Heart Study, though one of the most rigorous databases for cardiac epidemiology, is limited by its lack of ethnic diversity, diminishing the generalizability of its findings. However, the more ethnically-diverse ARIC study (Atherosclerosis Risk in Communities) did find similar results by similar categorizations of risk
--of the modifiable risk factors in the Framingham Study, obesity was the most significant one associated with increased afib risk, and diabetes itself was not significantly associated with afib. smoking actually had a negative association with afib.  ??why.  perhaps related to increased death rate (and smoking is the most profound modifiable risk factor for atherosclerotic cardiovascular disease)

so, this study, though an observational one, does reinforce the importance of risk factors in the development of atrial fibrillation, and highlights that we clinicians really should focus on prevention.  And the fact that even one elevated risk factor is associated with more afib may be very important (clinicians and patients may not attach as much significance to only one isolated elevated risk factor).

The modifiable lifestyle risk factors associated with afib are pretty much the same ones associated with atherosclerotic disease, cancer, dementia, diabetes……. but the current study adds to our imperative to help patients address their risk factors, as well as all of us addressing the broader social issues which make it so difficult to have a healthy lifestyle in the US (food access, food quality, advertising, lack of regular venues to exercise/ride bikes, etc etc.

Here are some older blogs looking at afib risk factors and some studies showing benefit of modifying them:

http://gmodestmedblogs.blogspot.com/2016/03/atrial-fibrillation-and-lower-bp.html  documents the relationship between blood pressure and afib in patients in the LIFE study, finding lower likelihood with lower achieved systolic BP
http://gmodestmedblogs.blogspot.com/2015/10/atrial-fibrillation-and-dementia.html comments on the relationship between afib and dementia in the Rotterdam Study
http://gmodestmedblogs.blogspot.com/2015/07/atrial-fibrillation-and-weight-loss.html found that weight loss in those with afib was associated with more resolved afib
http://gmodestmedblogs.blogspot.com/2014/08/alcohol-consumption-and-atrial.html is a Swedish study noting the dose response curve of alcohol consumption and afib
http://gmodestmedblogs.blogspot.com/2014/04/nsaids-and-atrial-fibrillation.html is an observational study suggesting that NSAID use was associate with afib
http://gmodestmedblogs.blogspot.com/2014/05/olive-oil-and-atrial-fibrillation.html ​ suggested that extra-virgin olive oil might decrease afib risk