Moderate-Intensity Exercise Possible For Patients With Statin Side Effects

Patients experiencing muscle symptoms from statin therapy can safely participate in moderate-intensity physical activity without fear it will exacerbate skeletal muscle injury or pain, according to the results of a new study.

In adults with documented statin-associated muscle symptoms (SAMS), moderate-intensity activity—in this case, participating in a 4-day walk covering anywhere from 30 to 50 km per day—did not increase any markers of injury or worsen muscle performance or statin-associated symptoms when compared with statin users who hadn’t reported these kinds of side effects, or with a healthy control group.

The findings, say researchers, should reassure symptomatic statin-treated patients that there are activities they can do.  

“It is really important to combine physical activity with statin therapy in patients at risk of cardiovascular disease,” lead investigator Neeltje A.E. Allard, MD (Radboud University Medical Center, Nijmegen, the Netherlands), told TCTMD. “Some patients might be a little hesitant to engage in exercise because they fear their muscle symptoms will get worse, but this study is quite reassuring. They can safely engage in moderate-intensity exercise. It’s safe in terms of muscle injury, but also in terms of muscle performance.”

While the benefits of statins are undisputed when it comes to reducing the risk of atherosclerotic cardiovascular disease (ASCVD), some patients report muscle pain and weakness and may fear that exercise could make their symptoms worse. The concern, say researchers, is that they’ll either stop their medication or drop their exercise routines, say researchers.  

Allard said there’s still not a lot known about SAMS, but there are plausible mechanisms through which the drugs could cause damage during increased physical activity. Statins decrease mevalonate production and downstream coenzyme Q10 (coQ10), which is essential in the mitochondrial electron transport chain. Lowering coQ10 could cause mitochondrial dysfunction. At high intensities, the increased energy demand can result in muscle fatigue and damage if energy production is compromised, she added.

“The mitochondria are necessary for energy metabolism,” said Allard. “You can imagine if [the mitochondria] are impacted by a statin and you start exercising and need more energy—where the mitochondria need to work harder—the impairment in the mitochondria can cause muscle damage.”

Past research has shown that vigorous physical activity or eccentric exercises may increase creatine kinase (CK) in statin users compared with those who are not taking statins, which suggests the drugs are contributing to exercise-induced muscle injury.

In the new study, published online ahead of the April 11, 2023, issue of the Journal of the American College of Cardiology, Allard said they wanted to assess the impact of moderate-intensity exercise on muscle injury or symptoms. The thinking was that even if there was some mitochondrial dysfunction, energy demands of moderate-intensity exercise could be met and no damage would result. Previous work by the group had shown that moderate-intensity endurance and resistance exercise training could improve muscle performance, capillarization, and mitochondrial content in symptomatic statin users, without increasing their muscle complaints.

Four Days of Walking

The study included 100 participants: 35 statin users who had SAMS, 34 taking statins who were asymptomatic, and 31 controls who were not taking statins. All individuals participated in the Nijmegen Four Day Marches, an annual event that draws thousands of people for the promotion of sport and physical activity. Each day, people walk either 30, 40, or 50 km, depending on their age and gender.

“It’s a real big event here in the Netherlands,” said Allard. “It’s very international. People come from all over the world to join, but this isn’t something they do every day. It’s a very special week and they train to do it.” 

Some patients might be a little hesitant to engage in exercise because they fear their muscle symptoms will get worse, but this study is quite reassuring. Neeltje A.E. Allard

Baseline measurements were taken 1 or 2 days before the walking event and postexercise measurements were performed either on the first, second, or third walking day. Patients were taking a range of statins, including simvastatin, atorvastatin, rosuvastatin, pravastatin, and fluvastatin, but in all, the statin dose potency was equivalent to atorvastatin. Overall, there was no significant difference in statin types, atorvastatin equivalence, and duration of statin therapy between the statin groups.

Exercise-induced muscle injury, assessed with lactate dehydrogenase, CK, cardiac troponin I, and N-terminal pro-brain natriuretic peptide, increased in all three groups after moderate-intensity exercise, but there was no significant difference between the groups. At baseline, muscle pain scores were higher in symptomatic patients, but increased to the same extent after the walk as it did in asymptomatic and control individuals. Similarly, fatigue scores were higher in those with SAMS before the walk but increased similarly in all three groups.

Researchers also checked muscle performance before and after exercise. Handgrip strength decreased after the walk in all three groups, with no between-group differences seen. Other measures of muscle performance, such as maximal voluntary contraction and muscle oxygen consumption, were no different at baseline and decreased similarly in the three groups after moderate-intensity exercise.

Allard said they also observed no correlation between coQ10 levels and muscle injury markers at baseline or after exercise but cautioned against making too much of these findings because they assessed coQ10 in leukocytes. “That’s not the gold standard,” she said. “You’d want to measure that with a muscle biopsy preferably, but you can imagine that you can’t take a biopsy from these people about to walk for 4 days.”

In an editorial, Robert Rosenson, MD (Mount Sinai Heart, New York, NY), agrees that patients with SAMS will sometimes avoid or limit physical activity because of concerns that it might make their muscle pain and weakness worse. However, exercise remains an essential component of restoring fitness for the maintenance of health in those with ASCVD, particularly among those who have had a disabling event, and those with ASCVD risk factors.

The new study, he writes, shows that “many patients who develop SAMS may engage in a moderately intensive walking program without concern for worsened muscle biomarkers or performance.”