Do statins actually cause muscle pain?

Important Takeaways

• Patients typically report muscle soreness as a rationale for discontinuing statin medication.
• According to research, these drugs do not cause discomfort in more than 90% of instances.
• To better navigate reports of statin-associated muscular discomfort in patients, prescribing doctors can become acquainted with the most recent research.

Patients frequently discontinue statin medication due to muscular soreness and cramping. Is the statin, however, to blame for the pain?

A 2022 Lancet meta-analysis suggests that more than 90% of the time, statins are not the root of the issue.

Moreover, the evidence of cardiovascular benefit with statins far surpasses the risks of muscular complaints, experts noted.

Within the research

Studies having more than 1,000 participants and a mean follow-up of at least 2 years was required to be included in the meta-analysis. The trials had to be double-blind and placebo-controlled, or they had to compare more intense and less intensive statin regimens.

The analysis comprised 19 double-blind studies comparing statins versus placebo (a total of 123,940 participants), as well as four double-blind trials comparing statin medication regimes (30,724 patients).

The study approach distinguished this meta-analysis from earlier research, which comprised non-randomized observational studies comparing patients who received and did not take statins. Including such trials would have added “moderate biases (particularly if participants are aware of which medicines they are taking),” an issue that statistical correction cannot eliminate, according to the researchers.

The results

Throughout the study’s 34,533 participants’ follow-up period, 27.1% of those who took statins reported muscular soreness or weakness, whereas 26.6% of those who received placebos reported the same.

The data also offered information on the length of statin therapy. Approximately 7% of patients, for example, had a “relative increase in muscular discomfort or weakening” over the first year of treatment.

This equated to around 11 complaints of symptoms per 1,000 person-years. According to the researchers, this suggests that one out of every 15 reports of muscular discomfort or weakness was caused by statins.

After the first year of statin medication, there was no rise in complaints of muscular discomfort or weakness, as could be predicted if statins were to blame. The answer to the question of dosage dependence was less certain—but only marginally so.

Patients who got larger dosages of statins showed a higher incidence of symptoms than those who received less rigorous regimens (108 [104-113] vs 103 [00-105]). Furthermore, higher doses tended to cause “a slight excess” of adverse events after the first year (105 [099-112]).

However, the information was ambiguous as to whether the rate ratio changed amongst statins or in various clinical settings, according to the researchers.

Overall, the researchers determined that statins only caused minor muscular soreness in a small percentage of instances.

“Most (> 90%) of all reports of muscle symptoms by participants allocated statin therapy were not due to the statin. The small risks of muscle symptoms are much lower than the known cardiovascular benefits.”

— Reith, et al., The Lancet

The overall image

The findings of this meta-analysis are likely to be welcomed news for any prescriber of statins, the effectiveness of which has been well established. This effectiveness was demonstrated in a 2016 Lancet research.

The research included 10,000 participants with high LDL cholesterol. If these patients had pre-existing occlusive vascular disease, using 40 mg of atorvastatin daily to decrease their LDL by 2 mmol/L would avert cardiovascular events in about 1,000 patients over the course of 5 years. Statins might be expected to prevent vascular events in 500 people among those who have never had one.

This study emphasized a concern that many physicians may have: that statin side-effect rates may be exaggerated, driving patients away from the medications’ life-saving advantages.

“Whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.”

— Collins, et al., The Lancet

In addition to the estimated 3%-5% of people who develop statin-associated muscular complaints, the researchers discovered that certain patients may experience unusual occurrences of rhabdomyolysis.

However, according to a position document published in 2022 by the International Lipid Expert Panel, many of the symptoms are caused by musculoskeletal damage or inflammation.

Symptoms may be influenced by patient expectations and the nocebo/drucebo effect.

All of this appears to be consistent with the findings of the 2022 Lancet meta-analysis.

“For patients who report mild muscle symptoms when taking a statin, our findings suggest that it is most likely that the symptoms are not due to the statin, and statin therapy should continue until other potential causes have been explored.”

— Reith, et al., The Lancet

Physicians may want to get acquainted with information indicating statins do not cause muscular soreness in patients. These findings may be useful in talks with patients who are considering stopping their statin regimen because they believe the medicine is causing their pain.

What does this imply for you?

According to the research, the majority of muscular soreness related to statin usage is most likely due to other causes. This study might increase patient adherence to statin regimens, perhaps saving lives. You should educate yourself on such research so that you can explain the data to patients who feel their statins are causing them discomfort.