Statin-Associated Muscle Symptoms: Real or ‘Artificial,’ Physicians Should Take Time to Manage Patients

INNSBRUCK, Austria—Recent controversy over statin intolerance and patient-reported muscle symptoms has researchers and clinicians struggling to make sense of why the vast literature supporting the safety and efficacy of these drugs increasingly does not seem to match up with real-world experience, notably as newer, more expensive drugs are entering the market.

A session at the 2016 European Atherosclerosis Society Congress featured perspectives from both a trialist and a practicing clinician. Moderator Chris Packard, PhD (University of Glasgow, Scotland), told TCTMD that the session’s theme stemmed from the frustration of the original researchers “who did the big trials and generated an evidence base second to none—statins are used by millions of people. All of the sudden we’re fighting the battle again to get them used and complied with.”

In his presentation, Ulrich Laufs, MD (Universitätskliniken des Saarlandes, Homburg, Germany), said “there are very few experiences like this in clinical medicine” where the data conflict with real life. Asking attendees if they encounter patients who report muscle symptoms after being treated with statins, he was met with a room full of raised hands. Yet this hasn’t always been the case.

Looking back on the research, it could be argued that statin-associated muscle symptoms are “artificial,” he observed, but noted that does not erase the fact that patients are experiencing real problems. While it’s easy to dismiss these symptoms as delusions, Laufs said, clinicians need to put themselves in the patient’s shoes.

“We know that one-third of the statins we prescribe are not taken,” he said. “This is the greatest opportunity we are missing in terms of LDL lowering. I see myopathy as one of the several barriers to adherence. If a patient is unconformable, he will not take it.”

The optimal way for physicians to approach these patients, Laufs explained, is to first take the time needed to treat them, “even if it’s not reimbursed.” Research shows that the majority of patients can eventually be treated with a statin, but it takes effort to find the right one, he said, adding that new options exist including PCSK9 inhibitors and ezetimibe.

Personal experience has taught Laufs that the majority of patients can be treated with a statin, he reported, although some can only tolerate them in small doses. Using alternating day dosing is an option, but only for those who have no other adherence difficulties, he suggested. “We have to find a way for the patients to become friends with the statin again,” he said adding that it is only the very rare patient who cannot tolerate them at all.

As for the possibility that much of the criticism that has arisen recently over statin-associated muscle symptoms stems from pharmaceutical companies attempting to introduce newer, and more expensive, drugs to market, Laufs told TCTMD it’s possible but hard to prove. These symptoms are “a bag of highly diverse problems,” he said. “There is no simple explanation.”

Proper Counseling Needed

For her presentation, Jane Armitage (University of Oxford, England), gave the trialist’s perspective.

Looking at the early cholesterol trials from the 1990s, she points out that there were not yet any patient preconceptions with regard to side effects from statins. The first randomized clinical trial she participated in as a junior researcher—the Oxford Cholesterol Study—involved her asking countless patients about several symptoms, including muscle pain. “At 3 years, there was absolutely no suggestion of a muscle pain association” with simvastatin doses of either 40 mg or 20 mg compared with placebo, she said. “It was very reassuring.”

But in the wake of randomized trials, Armitage said that observational data have “bombarded” the literature with much higher reports of side effects, introducing substantial bias.

While patients are “undoubtedly” having genuine symptoms, the data show that it’s rare for them to have a true myopathy, according to Armitage. Some trials show a slight excess of this outcome with statins, “but even if it’s there, it’s only in the order of 1% or less. So [myopathy is] much rarer than other people have suggested based on observational data,” she said.

Proper counseling is the key, but physicians must remain cognizant going forward, Armitage continued. “We need to be reassuring our patients, the general public, and our colleagues, because there is a huge amount of misinformation out there,” she concluded.

Clinicians, Patients Must Be Persistent

Echoing both presenters sentiments, Packard told TCTMD that it is fundamentally wrong for physicians to tell a patient their muscle symptoms do not exist and are all in his or her mind. “One of the things that you have to do is work with the patient to help them understand the benefits of statin therapy, and that they mustn’t stop,” he said, adding that many options exist to manage treatment including adding ezetimibe and PCSK9 inhibitors.

With regard to whether statin-associated muscle symptoms are a problem for clinicians or rather are occurring as a result of their actions, Packard said it’s both. Clinicians obviously have to deal with this on an almost daily basis, he said, but the problem with clinicians is that they are not being patient enough. “If [physicians] give it time, then I think the message from Ulrich Laufs was the majority of your patients will get onto something that enables them to control their cholesterol level. But I think we shouldn’t just take the easy option and just give up.”

Packard called upon the medical press to retract “some of the more inflammatory papers that were published recently,” calling out the BMJ in particular. The journal, in 2014, elected to redact “erroneous statements about the side-effects of statins” in a paper and viewpoint it had published. They never fully retracted the respective paper and viewpoint, however. “They should know better,” Packard said. “So let’s have a robust literature developed on the need to dampen this down.”

He also called upon the scientific media to own up to its mistakes in communicating information about statins. “Like any celebrity, the media like to build you up, so statins were built up as the magic bullet. And then, they like to knock you down,” he said, explaining that the media once touted the benefits of statins and have switched to hype their side effects, especially with regard to primary prevention.

Lastly, Packard advocated for the creation of new tools that will enable a patient to understand what muscle symptoms actually mean to them and display their options in terms of changing doses, shifting drugs, or adding additional medications. “They don’t just have to give up” on their medications, he said, adding that patient advocacy groups also have an important role in explaining the risks/benefits of lipid-lowering drugs.