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Close on the heels of SAMSON, a series of randomized "n-of-1" trials showed no difference in muscle symptoms when people were put on a statin versus a placebo.

People who had previously reported statin myopathies ended up rating muscle symptoms similarly low during blinded atorvastatin (Lipitor) or placebo treatment (mean 1.68 vs 1.85 on a visual analog scale from 0 to 10, P=0.40), according to Liam Smeeth, MBChB, PhD, of the London School of Hygiene and Tropical Medicine, and colleagues in the group.

"Also, we found no differences for the effect of muscle symptoms on aspects of daily life (general activity, mood, ability to walk, normal work, relationships with other people, sleep, and enjoyment of life) between the statin and control periods," they reported in .

Thus, the study adds to the "incontrovertible" evidence from SAMSON and GAUSS-3 that a significant number of people who have problems with muscle pain associated with statins are experiencing a nocebo effect, according to GAUSS-3 lead author Steve Nissen, MD, of the Cleveland Clinic.

"My own view is that there are people that have muscle symptoms, that it's not correct that 90% of individuals are suffering from nocebo, but a significant percentage," Nissen said.

Paul Thompson, MD, of Hartford Hospital in Connecticut, told MedPage Today that he estimates one-third of people complaining of statin myopathy really have symptoms because of the statin.

He cited his group's , in which roughly 10% of people on atorvastatin met study criteria for myalgia compared with 5% of the placebo group. Additionally, a found only 36% of 120 patients with prior symptoms of statin myalgia actually got pain only on a statin.

"So out of 120 people from my practice that I thought had symptoms of statin myalgia, I was only right a third of the time," Thompson said.

The link between statins and muscle pain arose from observational reports, and has led to patients discontinuing treatment despite their risk of cardiovascular disease.

"I always say nothing cures statin muscle complaints like a heart attack. All those years, I've had a lot of patients who wouldn't take statins until they had a heart attack," Thompson said. Then "it's amazing" how many took them afterward, he added.

Smeeth and colleagues had 200 patients randomized to a sequence of six double-blinded treatment periods (2 months each) of atorvastatin 20 mg daily or placebo. The primary analysis included 151 participants who provided symptom scores for at least one statin period and one placebo period.

Notably, 86 out of the original 200 people did not complete the whole trial. Withdrawals from the trial due to intolerable muscle symptoms were observed in 9% of patients during statin treatment and 7% while on placebo.

"We found no evidence of a difference in withdrawals between the statin and placebo periods but StatinWISE was not powered to detect a difference in withdrawals between periods, and our estimates did not exclude a difference," the trialists acknowledged.

StatinWISE participants were enrolled at 50 primary care sites in the U.K.

The study cohort averaged age 69.1. Nearly 60% were men, and median total cholesterol was 5.3 mmol/L at baseline. Prior to enrollment, participants had recently stopped or were considering stopping statin treatment due to muscle symptoms.

Such recruitment could be an issue given that people considering stopping statins make "quite a different group" than people who tried two or three statins and had intolerable side effects, Nissen cautioned. He called the 9% and 7% withdrawals due to intolerable symptoms "a pretty low fraction for people who claim to be statin-intolerant."

Other limitations of StatinWISE include the lack of creatine kinase measurement and the assessment of only one statin.

Ultimately, two-thirds of the 113 patients completing the trial reported restarting long-term treatment with statins -- or the .

These are two different things because "unfortunately some of them will probably get symptoms when restarting the statins, even if the trial has shown them the symptoms were just as bad on placebo," cautioned SAMSON co-author James Howard, MB BChir, of Imperial College London, in an email to MedPage Today.

"These 'nocebo' symptoms are sometimes difficult to break, and whilst StatinWISE and SAMSON show that individualised patient discussions can make a huge difference to them, it appears some patients are still left suffering from [them]," Howard said.

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