Thread by @MasriAhmadMD

A thread.
So the @US_FDA @SGottliebFDA issued a warning re: Fluoroquinolones (FLQ) and aortic dissection (AD) or aneurysm (AA). Do FLQs cause AD/AA? Not really. Is there an association? Maybe. Let’s go throw the evidence and you can decide for yourself.
#CardioTwitter #MedEd

1/ Why was this association even studied? FLQ are known to be associated with Achilles tendon rupture, tendinopathy, retinal detachment. How? 1)decrease collagen synthesis and increase MMP (especially 2, 9) activity (among others). Aorta is affected by these processes

2/First study was published in 2015 using a national database in Taiwan. 1477 cases (662 AD, 850 AA) matched to 147 700 controls. There was signal of the association of FLQ and AD; rate ratio ranging 1.37 - 2.11 with any FLQ use (tinyurl.com/ybhcpexz)

3/ Second study followed 1 month after, national data from Ontario. Of 1,744,360 patients, 38% used FLQ. AA occurred in 1.1% during follow up (0.35 in FLQ vs 0.13 in non-FLQ /100-person-years, p<0.001). tinyurl.com/ybxm8hqd

4/Third study from Sweden, 360 088 FLQ matched to 360 088 amoxicillin. Within 60 days, AD/AA rate was 1.2/1000 PY in FLQ vs 0.7/1000 PY in amoxicillin (HR 1.66 (95% CI 1.12 to 2.46) )tinyurl.com/yaex53o9

5/ cont'd. Per 1 million episode of FLQ treatment; 82 more episodes of AD/AA within 60 days. When broken down, AA HR 1.90 (1.22 - 2.96), for AD 0.93 (0.38 - 2.29).

6/ Forth study was an animal study where an AA mouse model should increased AD and rupture when given cirpo. Main mechanisms: decreased lysyl oxidase ( stabilizes elastin/collagen), increased MMP, aortic cell injury.
tinyurl.com/ydhb2syp

7/ 5th study, case-crossover design (2 periods to compare FLQ exposure within the same patient, one is 60 days pre AD/AA and the other is random referent period). 1213 AD/AA, risk during FLQ period was 1.6% vs. 0.6% for non-FLQ; OR 2.71 (1.14 - 6.46). tinyurl.com/y9xc2v56

8/ Sixth study, using WHO sponsored Vigibase, 172,588 FLQ (113 AD/AA) and 40,658 amoxicillin (8 AD/AA). FLQ had higher reporting OR for AD/AA 2.13 (1.03–4.37), seen on with Levoflox (2.79, 1.83-4.23).
tinyurl.com/y9urvp6y

9/ how commonly are FLQ used in a high risk population of Marfan or those with AD/AA (during hospitalization) ?
A recent study using admin data showed substantial use; 14% Marfan, 20% AD/AA
tinyurl.com/yb3tbx92

10/ How to reconcile all these data? No medication is free of risk. There appear to be a consistent pattern of adverse effects of FLQ on the connective tissue. Likely the best approach is to avoid any FLQ exposure in high risk patients (Marfan, LDS, EDS, BAV, any AA)

11/ It would have made more sense if the association was in AD only. How many believe that exposure to FLQ will lead to a finding of a clinically significant AA within a short period of time?
@IDPittStop

Please add any other study (or abstract) that you know of