Wednesday, 10 June 2015

ClinicSpeak: fingolimod affects heart function

Does the effect that fingolimod has on the heart function affect exercise? #ClinicSpeak #MSBlog #MSResearch 

"The following study shows that fingolimod affects the function of the heart in MSers. In essence fingolimod reduces the amount of blood ejected from the heart with each heart beat; we call this the ejection fraction. In comparison, natalizumab had no effect on heart function in MSers. However, when MSers were switched from natalizumab to fingolimod there was a reduction in ejection fraction. The drop in ejection fraction is small and is probably not clinically significant unless there is an underlying cardiac disease or the MSers' concerned participate in elite or endurance sports. This finding is clearly worrying and further studies are required to reproduce these findings and  to ascertain the long-term effects of fingolimod on heart function. I would be interested to know if any of you who are on fingolimod have noticed a change in your exercise tolerance or endurance?"



Epub: Racca et al. Fingolimod effects on left ventricular function in multiple sclerosis. Mult Scler. 2015 Jun 3. pii: 1352458515587753.

BACKGROUND: Cardiovascular side effects such as bradycardia and atrioventricular block were observed during the early clinical trials of fingolimod in multiple sclerosis, and one cardiovascular- linked death has been reported in the post-marketing period.

OBJECTIVE: To investigate the medium-term effects of fingolimod on heart function in order to obtain further insights into its cardiac safety profile.

METHODS: The study involved 53 patients starting treatment with fingolimod 0.5 mg daily and 25 MSers treated with natalizumab 300 mg monthly. Cardiac function was assessed by means of echocardiography at baseline (T0), and after one (T1), six (T6), and (in the case of the fingolimod group) 12 months (T12).

RESULTS: Mean left ventricular ejection fraction significantly decreased and end-systolic volume increased from T0 to T1 (p=0.005) and T6 (p=0.0001) in the fingolimod but not the natalizumab group, although a slight increase was observed at T12. A similar decrease in ejection fraction was also observed after six months in nine patients switched from natalizumab to fingolimod.

CONCLUSION: Fingolimod significantly reduces left ventricular systolic function in MS patients. This effect has no clinical consequences in subjects without previous cardiac disorders, but suggests that more caution is required in patients with current or previous heart failure.

CoI: multiple

6 comments:

  1. The most important question is , is this a permanent or reversible effect , I would not be as concerned if it was reversible ..

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    1. Re: "..is this a permanent or reversible effect..."

      This was not studied. You may find the following sobering:

      By month 6 left ventricular ejection fraction (LVEF) was lower than the normal lower limit of 0.55 in 7 MSers (13.2%) and lower than 0.50 in 4 MSers (7,69%). 23 MSers (43.4%) had a decrease in LVEF of more than 5%, and a significant percentage of MSers (30%) showed a decrease of more than 10%.

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  2. MSers are addicted to a non-existent cure.

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  3. Gavin, this study has a very small n number and any effect size will be large. The authors do not provide the clinical details of the subjects which dropped below EF of 0.55 or even 0.50 - this would be important and again no info on conmeds.

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  4. Was this study properly blinded? The pressure to publish in cardiology is such that a cardiologist who knows which drug the patient is on could easily "produce" the effect - measuring things on an echo screen is not exact science.

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