biased by lack of testing to exclude patients with mild cognitive impairment at baseline . However , while bleeding and vascular events were higher in patients with lower MMSE , the risk lost significanceafter adjusting for time in therapeutic range .
What about the non-vitamin K oral anticoagulants ( NOACs )? Dr . Bunch and colleagues just reported the results of a retrospective populationbased study of 5,254 patients managed with either warfarin or a NOAC ( n = 2,627 per group ). 10
Rivaroxaban was the most commonly used NOAC ( 55.3 %), followed by apixaban ( 22.5 %) and dabigatran ( 22.2 %). Dementia occurred more frequently in patients taking warfarin ; however , while statistically significant , the clinical impact of the difference is unclear ( 0.7 % vs . 0.3 % of the patients on a NOAC ; p = 0.03 ). Also , they found no difference in rates between the different NOACs . After multivariable adjustment , patients taking NOACs had a 51 % decreased risk of dementia incidence or subsequent stroke or transient ischemic attack ( TIA ) compared with those taking warfarin ( HR : 0.49 ; p < 0.0001 ).
Dr . Bunch admits there a number of problems with that analysis because of its retrospective nature and the differences in patient characteristics among those who could pay for or had coverage that would cover the NOACs versus those who could only afford warfarin . Consequently , the Utah team has initiated a prospective trial that will randomize people to clinic-managed warfarin therapy versus dabigatran . The study patients will be followed for 2 years with batteries of cognitive function as well as volumetric brain scans so that they can start to see where these events are occurring , the number of such events , and their cumulative impact .
Obviously , the brain is not the only organ along the peripheral pathway , so the Intermountain team looked at long-term renal function and possible correlation to efficacy of warfarin therapy in their AF patients chronically managed in their anticoagulation service . Again , in an almost linear manner , the worse the patient ’ s warfarin levels , the lower their glomerular filtration rate , the higher their creatinine levels , and the more rapid the progression to renal failure .
“ No matter which metric we looked at ,” Dr . Bunch said , “ whether they started with normal renal function , mild or moderate dysfunction , if their anticoagulation control was poor , they progressed — in a similar analogy to the brain study but looking at a different organ : the kidneys .”
Patient X The initial patient who prompted the Intermountain group ’ s study into the association of dementia and AF would speak coherently while in sinus rhythm . However , when his rhythm would change to AF , he would abruptly lose his thought process and look to his wife to complete his sentence . While the patient would refer to these as “ senior moments ,” Dr . Bunch could see the heart monitor behind the patient and the effect was clear every time he slipped into AF or back into sinus rhythm . “ I started asking other doctors and they would say , ‘ I ’ ve had patients like that ,’ and that began the whole idea of research into cognitive function and AF .”
That ’ s not explainable by clots or bleeds , so what might the mechanism be ? An autopsy study of 84 Alzheimer ’ s patients showed the most common form of cerebral vascular atherosclerosis in these patients was in the Circle of Willis , which is critical for cerebral perfusion . It creates a means of redundancies and collaterals that will provide generalized blood flow throughout the brain , even if more proximal atherosclerosis develops . Thus , it is likely that people with Circle of Willis atherosclerosis , when exposed to beat-by-beat alterations in blood flow , would not retain the same ability to distribute cerebral blood flow globally as those without atherosclerosis . This might explain a patient with abrupt cognitive dysfunction upon onset of AF .
This whole issue brings us around to a controversy that seemed to have ended years ago in terms of which is better : a rate- or a rhythm-control strategy . The issue seemed to be settled by the AF- FIRM ( Atrial Fibrillation Follow-up Investigation of Rhythm Management ) study , which suggested rhythm control offers no survival advantage over
rate-control strategy , plus there may be a lower risk of adverse drug effects with a rate-control strategy . 11 However , mean age of study participants was almost 70 ( mean : 69.7 years ) and mean follow-up was 3.5 years . More recent data suggest that patients treated with rhythm control had reduced mortality when follow-up was extended beyond 4 years . 12
But even 4 years is a drop in the bucket compared to a decade or more with AF . Eric N . Prystowsky , MD , is a pioneer in electrophysiology and heads up the cardiovascular disease program at St . Vincent Hospital in Indianapolis . At an AHA meeting , he noted that there are no safety data related to allowing patients to stay in AF for 20 , 30 , or 40 years . Given evidence of potential deleterious effects of longstanding AF , such as cognitive effects , dementia , and even Alzheimer ’ s , Dr . Prystowsky said , “ I am not telling you what to do . What I am asking people to do is to rethink this issue with your patients . There are new data suggesting that leaving patients in A-fib is not as safe as you think .” According to Dr . Prystowsky , the “ prime directive of AF management ” is to preserve the brain . He has written about this in JACC , 13 emphasizing that stroke is clearly not the only neurological consequence of AF . He mentioned the data pointing to cognitive impairment and silent cerebral infarcts
AF Patients on Long-term Warfarin at Increased Risk for Dementia , Renal Dysfunction
To watch an interview with T . Jared Bunch , MD , director of heart rhythm research at Intermountain Medical Center Heart Institute and medical director for heart rhythm services for the Intermountain Healthcare System , please see the JACC Grand Rounds program featuring highlights of the recent 2016 Heart Rhythm Society meeting in San Francisco , CA . http :// jaccgrandrounds . org
in patients with AF . In what appeared to be the first study to investigate the relationship between AF and cognitive decline based on cerebral MRI , investigators reported that patients with either paroxysmal or persistent AF have a higher prevalence of silent cerebral ischemia and worse cognitive performance compared with controls . 2 “ This is a passion of mine ,” said Dr . Prystowsky , “ and I think it is , unfortunately , not something we always think about as much as we should .”
CSWN asked Gregory YH Lip , MD , director of the haemostasis thrombosis and vascular biology unit at the University of Birminham in the U . K ., for his opinion . Given the growing evidence of decreased cognitive function and even dementia , even deleterious effects on renal function , especially when AF is poorly controlled , is it time to go beyond stroke and consider other peripheral effects of AF when choosing therapy ? He agreed , adding “ We forget that AF independently increases all-cause mortality — even in the historical placebo-controlled trials , warfarin reduced stroke by 64 % and all-cause mortality by 26 %.” Optimal AF management leads to reduced risk across the board , but studies show that too many patients aren ’ t receiving anything close to optimal care , with some clinicians still mistakingly using aspirin as some sort of “ safer alternative ” when , in fact , Dr . Lip noted aspirin has no impact on mortality . None . Even worse : it ’ s not just that aspirin is no substitute for antithrombotic therapy . He pointed to a paper form his group that is online before print demonstrating that there is no net clinical benefit for antiplatelet therapy compared to no antithrombotic therapy at all . 14
Risk Aversion If you ’ re trying to reduce cognitive risks , one answer is certainly NOT to avoid anticoagulation in patients who qualify for such therapy . Remember that UK study of 4.3 million people cited above ? For each of the nine vascular events analyzed , the investigators evaluated risk with and without antithrombotic therapy . Baseline AF was associated with a 57 % higher risk of vascular dementia ( HR : 1.57 ; 95 % CI : 1.14 – 2.17 ) with no antithrombotic therapy ; for those who were on antithrombotic therapy , the risk was only 29 % higher ( HR : 1.29 ; 95 % CI : 1.08 – 1.54 ). Considering only fatal events , the comparable risk was 4.91 ( 95 % CI : 1.46 – 16.48 ) and 2.88 ( 95 % CI : 1.44 – 5.78 ), respectively .
ACC . org / CSWN CardioSource WorldNews
27