No clear evidence statin use in athletes harms exercise performance
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Although statins increase exercise muscle injury and may reduce exercise training response, they appear to be safe in athletes, a presenter said.
The evidence suggesting that statins may affect exercise performance were anecdotal or were from uncontrolled studies, Paul D. Thompson, MD, chief of cardiology – emeritus at Hartford Hospital in Connecticut, said during his presentation at the virtual American Society for Preventive Cardiology Congress on CVD Prevention.
“We think overall that careful clinical studies show no evidence [of harming exercise performance] in humans,” Thompson said during the presentation. “Now, I said humans because there’s a ton of basic science work that suggests statins have deleterious effects on mitochondria, etc. I point that out because the customer, or the athlete, is always right. If somebody thinks that statins are interfering with their exercise performance despite my attempts to convince them that they don’t, I often have to accept the patient’s conclusion.”
Evidence base
The question of whether statins might be problematic in athletes stemmed from findings from a study published in the British Journal of Clinical Pharmacology in 2004, Thompson said. The study assessed data from 22 professional athletes with LDL receptor defects and found that only six could tolerate statins despite multiple attempts with other statins.
In addition, the PRIMO study published in Cardiovascular Drugs and Therapy in 2005 found that 10.5% of patients on statin therapy reported muscular symptoms. When assessed by physical activity, 14.7% of those in the study who practiced an intense form of sport reported symptoms compared with 10.8% of those who only participated in leisure-time activities.
Weakness is a common complaint in patients taking statin therapy, although complaints regarding decreased exercise tolerance are uncommon. There are very few controlled studies that assess the effect of statin therapy on exercise performance or muscle strength.
Thompson said exercise alone can lead to significant creatinine kinase increases.
“Many of the [creatinine kinase] increases that clinicians like ourselves attribute to statins are really due to or at least exacerbated by physical exercise,” Thompson said during the presentation.
A study published by Thompson and colleagues in Metabolism: Clinical and Experimental in 1997 compared creatinine kinase elevations the day after downhill walking in patients assigned lovastatin or placebo. Patients assigned lovastatin had almost a doubling of the creatinine kinase response related to downhill exercise compared with those assigned placebo.
“Downhill exercise like running the downhill Boston Marathon course causes more muscle injury,” Thompson said during the presentation.
This increase in creatinine kinase was also observed in a study published in The American Journal of Cardiology in 2012, which found that patients taking statins had significantly higher levels compared with controls the day after running the Boston Marathon.
In a study published in the Journal of the American College of Cardiology in 2013, researchers analyzed the effects of a 12-week exercise program in patients with overweight and two metabolic risk factors. Patients were assigned exercise training with or without simvastatin. After exercise training, oxygen uptake increased by 10% in patients assigned no statin therapy compared with 1.5% in those assigned statins. Citrate synthase, a measure of mitochondrial activity, in patients not taking statins increased by 13% compared with a decrease of 4.5% in those assigned statins.
“This study suggests that exercise training response in terms of increased oxygen update is really almost eliminated by statin treatment, and it seems to be related to mitochondrial function,” Thompson said during the presentation.
Some studies do not show this effect, including a study published in the Journal of the American College of Cardiology in 2014. In this paper, researchers found that increases in peak oxygen uptake were similar in patients taking statins and those who were not.
Evidence of reduced response to aerobic training has not been confirmed, Thompson said.
Clinical studies have not shown evidence of consistent problems related to exercise performance and statin therapy. The STOMP study published in Circulation in 2012 assessed data from 440 patients with no prior statin use who were assigned 80 mg of atorvastatin or placebo for 6 months. Several factors were analyzed, including muscle function, aerobic performance, physical activity and muscle symptoms. The average creatinine kinase increased by 20.8 U/L in patients assigned atorvastatin with no change in patients assigned placebo. Myalgia was observed in 19 patients assigned atorvastatin compared with 10 patients assigned placebo, which was statistically significant (P = .05). There were no consistent reductions in muscle strength or aerobic performance in this study.
Thompson and colleagues also assessed the effect of statin cessation on exercise performance in active patients and determined that short-term statin cessation of 1 month did not affect peak oxygen consumption.
Low doses may be optimal
Thompson concluded that the approach for athletes requiring lipid-lowering therapy should include low doses of long-acting statins twice per week such as rosuvastatin, atorvastatin or pitavastatin in addition to ezetimibe twice per week. Other drugs like PCSK9 inhibitors can be considered if patients still have muscle complaints with this approach, he said.
“A lot of us don’t realize it, but you get the biggest reduction per milligram of drug at very low drug doses, but you also get the fewest side effects at very low drug doses,” Thompson said during his presentation.
References:
- Bruckert E, et al. Cardiovasc Drugs Ther. 2005;doi:10.1007/s10557-005-5686-z.
- Mikus CR, et al. J Am Coll Cardiol. 2013;doi:10.1016/j.jacc.2013.02.074.
- Parker BA, et al. Am J Cardiol. 2012;doi:10.1016/j.amjcard.2011.08.045.
- Parker BA, et al. Circulation. 2012;doi:10.1161/circulationaha.112.136101.
- Rengo JL, et al. J Am Coll Cardiol. 2014;doi:10.1016/j.jacc.2014.02.554.
- Sinziger H, et al. Br J Clin Pharmacol. 2004;doi:10.1111/j.1365-2125.2003.02044.x.
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Thompson PD. Statin Usage in Athletes – Problematic or Problem Free? Presented at: American Society for Preventive Cardiology Congress on CVD Prevention; July 25-26, 2020 (virtual).
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