Does Serious Exercise Harm Muscles in Statin Users?

Dutch authors have published a nifty study on exercise and statin use

Before I start, I want to congratulate our medical-student writer Dave the Knave for his critical appraisal of the recent NEJM publication of the RSV vaccine in pregnant mothers. While we at Sensible Medicine laud the use of randomized controlled trials to inform practice, it is vitally important to appraise these studies in a neutral manner. The author did this exceedingly well. This is the sort of content that we aim to provide in this newsletter. And we appreciate your support.

---

This week I will show you that not all trials have to include huge numbers of subjects.

The study setting is unique, yet the topic pertains to everyday use of one of cardiology’s most common drugs—statins.

I was on a group ride recently when a similar-aged rider asked me if all this exercising increased the chance of muscle damage, given that he took a statin drug. He had read that statins may harm muscles, and he wondered whether cycling as much as we do made him more susceptible to muscle damage.

The Journal of the American College of Cardiology published this inquiry into muscle injury from prolonged exercise in statin users.

Dutch authors took advantage of an event called the 4Days Marches in Nijmegen Netherlands.

The event began as a military march in 1909. It has grown into a massive participatory event with up to 45,000 walkers. Get this: people walk 30, 40, or 50 kilometers per day—for four days.

You might wonder why people would walk that far. Well, of course, finishers win a cross:

(I don’t know if you have ever walked that far. I have done maybe 20 miles in a day, and it was super-hard.)

The investigators’ idea was to compare markers of muscle injury in three groups—statin users with no symptoms, statin users who had muscle complaints, and controls.

Before I tell you the results, let’s do some background. I will keep it short.

• Statin drugs reduce future adverse cardiac outcomes. By about 25%. As I have said many times, these are heart-attack-reducing drugs.

• But statins can cause statin-associated muscle symptoms. (We can argue about the cause, drug effect or nocebo) but there is no denying that people on statins have SAMS.

• This can affect physical activity. People with muscle symptoms may not exercise or they may stop statins. Both are not ideal.

• Previous studies have suggested that vigorous or eccentric exercise may increase muscle damage markers –like CK—more in statin users compared to statin nonusers.

• There are less data on moderate exercise. There are also questions regarding mechanism of SAMS or statin-induced muscle injury.

Now to the study

They enrolled symptomatic (n = 35; age 62 ± 7 years) and asymptomatic statin users (n = 34; age 66 ± 7 years) and control subjects (n = 31; age 66 ± 5 years).

The authors made baseline measurements and then studied as a primary endpoint muscle damage markers, such as CK, myoglobin, LDH, troponin and bnp levels.

Secondary measures were muscle pain, strength, fatigue and CoQ10 levels.

Results

• All muscle injury markers were comparable at baseline and increased following exercise, with no differences in the magnitude of exercise-induced elevations among groups

• Muscle pain scores were higher at baseline in symptomatic statin users and increased similarly in all groups following exercise.

• CoQ10 levels also did not differ in the groups.

The Authors’ Conclusions

Statin use and the presence of statin-associated muscle symptoms does not exacerbate exercise-induced muscle injury after moderate exercise. Muscle injury markers were not related to leukocyte CoQ10 levels

Comments

I like this study. It provides useful data – the authors state clearly that moderate level exercise may not translate to more vigorous types, but I think they undersell the degree of exercise in the 4Days Marches.

It’s a lot. Walking may not be as intense as weight lifting or sprinting, but it is still hard to walk that much.

These observations contrast with previous studies of more intense level exercise in that walking for many hours does not cause any demonstrable negative effects on muscle injury markers.

---

I think we can use this paper to add to our education of patients with statin muscle complaints.

First, of course, we can discuss the SAMSON trial data showing that statins exert their negative effects mostly through a nocebo effect. (I need to write specifically about this important trial.)

Next in our discussion with patients, we can add this paper, which shows, that if there are mild to moderate SAMS, exercising at moderate levels—even for hours on end--will not harm muscles.

What I love about papers like this is that we can help people with education. Education is such an under-rated therapeutic.

Here we encourage our patients to stay on a drug that reduces outcomes, and, more importantly, to continue exercising.

---

Final caveat: The decision to take a medicine is preference-sensitive.

I want patients to have all available statin information but, in the end, it is up to them to decide if the risk reduction is enough to take a pill every day.