cryptogenic stroke and atrial fibrillation

background: stroke is common, but 20-40% of strokes and 50% of TIAs have no evident cause after work-up (called "cryptogenic"). since afib is a common and treatable cause of stroke (and the treatment of afib with anticoagulants is different from that of other strokes with antiplatelet agents), and since those with untreated afib have higher likelihood of recurrent stroke, it seems reasonable to look hard for afib. 2 recent articles in NEJM tried to assess this --

the CRYSTAL AF trial (see stroke and cryptogenic afib1 nejm2014 in dropbox, or DOI: 10.1056/NEJMoa1313600) was an RCT of 441 patients >40yo (mean age 61.5) with cryptogenic stroke in prior 90 days (negative workup including 24-hr Holter) randomized to a long-term insertable cardiac monitor (ICM) vs conventional followup. primary endpoint was time to first detection of afib lasting >30 sec within 6 months. secondary endpt was time to first detection of afib within 12 months.  Mean baseline CHADS2 score of 3 points​. results:
    ​--by 6 months: afib detected in 19 patients in ICM group (8.9%) vs 3 pts (1.4%) of controls
    --by 12 months: afib in 29 ICM pts (12.4%) vs 4 control pts (2%), mean rate of detection of afib was 84 days after randomization. detection of afib in ICM group continued to increase after 36 months

the EMBRACE trial (see stroke and cryptogenic afib2 nejm2014 in dropbox, or DOI: 10.1056/NEJMoa1311376) was an RCT of 572 patients >55yo (mean age 72.5) who had cryptogenic ischemic stroke or TIA (63% had stroke) within past 6 months of undetermined cause (including negative 24-hr Holter as well as other standard tests), randomized to additional ambulatory EKG with either a 30-day event-triggered recorder (intervention group) or another 24-hr Holter (control group). Mean baseline CHADS2 score of 3 points. Primary outcome was newly detected afib lasting 30 seconds or longer within 90 days after randomization.  secondary outcome was episodes of afib lasting 2.5 minutes or longer and anticoagulation status at 90 days.  results:
    --atrial fib > 30 seconds in 45 of 280 pts (16.1%) in the intervention group and 9 of 277 (3.2%) in control group.
    --atrial fib > 2.5 min in 28 of 284 pts (9.9%) in intervention group vs 7 of 277 (2.5%) of controls; oral anticoag prescribed for 52 of 280 pts (18.6%) in intervention group vs 31 of 279 pts (11.5%) in controls

although these results are interesting (and made it into the popular press), i do not think they provide actionable conclusions. not exactly shocking that prolonged monitoring picked up more episodes of afib. but for me, the primary issue is not so much whether there were small episodes of atrial fibrillation only detectable with prolonged monitoring but whether these episodes had anything to do with the antecedent stroke, or even if the increased monitoring provides any utility in determining whether the patient is at risk for another stroke. these types of afib episodes are common, especially as people get older (estimates of 4% of those >60yo have paroxysmal afib, defined as at least 2 episodes of afib  >30 sec long in 7 day period. 90% are asymptomatic. episodes can vary greatly in length). so, it would have been useful to have a real control group (matched group without stroke) to see if the incidence of afib picked up on prolonged monitoring was higher in the group with stroke than in non-stroke controls. and, the real test: whether treating patients with afib found on prolonged monitoring (with warfarin, for example) actually decreased the incidence of subsequent strokes. these studies would help sort out such issues as well as: does a 30 second episode of afib matter? or a 2.5-minute one? what is the appropriate frequency and/or length of these afib episodes that confer a higher stroke risk?  also, as a matter of perspective, 25%+ of strokes (>3 million strokes) are cryptogenic and this aggressive monitoring still misses 85% of them (ie, the issue of cryptogenic strokes remains huge even if it turns out that by finding/treating rare afib events that benefits>risks -- esp since anticoag therapy is not exactly benign, both medically and socially)).

Comments

Post a Comment

if you would like to receive the near-daily emails regularly, please email me at gmodest@uphams.org

Popular posts from this blog

HDL a negative risk factor? or cholesterol efflux??

Although the data on HDL being protective of atherosclerotic disease is pretty consistent, there are negative studies, and the data on medications which dramatically improve HDL levels (eg, the cholesteryl ester transfer protein --CETP --inhibitors, such as torcetrapib) are clinically disappointing. there have been several explanations for this. for example, some HDL particles are "pro-inflammatory" and elicit an atherosclerotic response (which may be related to apolipoprotein C-III). a new article in NEJM highlights another angle -- that the issue is not the HDL number, but HDL's functionality in the reverse transport of cholesterol, as measured by the cholesterol efflux capacity (see  lipids HDL efflux capacity vs amt NEJM 2014 in dropbox, or  DOI: 10.1056/NEJMoa1409065). This article looks at the Dallas Heart Study, where they measured HDL levels, HDL particle concentrations, and cholesterol efflux capacity in 2924 adults free of cardiovascular disease and followed p
Read more

Drug company shenanigans: narcolepsy drug

I have not done a blog for a long time on drug company shenanigans. So it is my great pleasure to bring up a brand-new drug company approach to garner huge amounts of money (see  https://www.nytimes.com/2023/02/28/business/jazz-narcolepsy-avadel-patents.html?smid=nytcore-ios-share&referringSource=articleShare  ).  Based on an article by  Rebecca Robbins of the New York Times, who has written several articles on drug company excesses   As background, this will be my 42 nd  such blog: for the array, see  https://bucommunitymed.wpengine.com/page/4/?s=drug+company+shenanigans   Th e drug company  approach  this time  to extending  their  patents has a few “interesting” angles: -- this is a medication manufactured by Jazz Pharmaceuticals to treat narcolepsy: there are 2 versions: Xyrem and Xywav (Xywav has less sodium, so is marketed to those who should be on a low sodium diet). These meds are basically derivatives of gammahydroxybutyric acid (GHB)      -- the drug actually has a pretty
Read more

UPDATE: ASCVD risk factor critique

  I decided to do an extensive update of my prior ASCVD (atherosclerotic cardiovascular disease) risk analysis and critique of risk calculators, with much more information about the “non-traditional” risk factors. I felt that there should be more data/clarification, since I think we are really undertreating/not preventing the most common cause of death by relying on the ASCVD risk calculators   -- Cardiovascular risk models:      -- many of us rely on the various cardiovascular risk models to determine the appropriate approach to patients, and these are often integrated into the electronic medical records      -- these risk models have several very important limitations:          -- they are typically based on community data, eg from the Framingham study etc. But, in clinical practice, we are dealing with the individual and not the community:              -- there is very clear evidence that there are many individual risk factors that are associated with increased risk of a cardiovascu
Read more