Lancet Study Highlights "Nocebo" Effect of Statins – AJMC.com Managed Markets Network
The debate over statins has gone on for years. These inexpensive lipid-lowering drugs can markedly trim the risk of heart attacks or strokes, but some patients report muscle aches and refuse to take them. The uproar grew louder in late 2013, when the American Heart Association and the American College of Cardiology released guidelines that most experts said would greatly expand the pool of people advised to take statins.
Since then, the arrival of the PCSK9 inhibitors, a class of drugs that promises to reduce low-density lipoprotein (LDL) cholesterol even further, has added to the debate: are complaints about statins real, or are they all in patients’ heads?
A study published Tuesday in The Lancet adds a new wrinkle: after examining data on 26 side effects from 10,000 patients, researchers concluded that patients were more likely to report side effects when they knew they were taking statins. When they had no idea, there was no increase in muscle-related effects.1
This “nocebo” effect may explain the difference between patient reports in clinical trials, which have found little to no increase in side effects, and those in observational studies, where up to one-fifth of the patients report side effects.
“Just as the placebo effect can be very strong, so too can the nocebo effect,” Professor Peter Sever, senior author from the National Heart and Lung Institute, Imperial College London, United Kingdom, said in a statement. “This is not a case of people making up symptoms, or that the symptoms are ‘all in their heads.’”
Data were collected from 1998 to 2002 from 10,180 patients aged 40-79 who had hypertension and at least 3 other cardiovascular risk factors. Patients were from the United Kingdom, Ireland, and Scandinavia. They were randomly assigned to take 10 mg of atorvastatin or 10 mg or placebo and were followed for 3 years. This phase was a blinded randomized trial: neither the doctors nor the participants knew whether they were receiving the drug or a placebo.
At the end of the 3 years, the drug was shown to be effective and the same patients were offered the choice of taking a statin or not. During this unblinded phase of the trial, 9899 of the original participants were followed for another 2 years, and 65% stayed on a statin.
During the blinded phase, the rate of muscle-related symptoms was nearly identical whether patients took a statin (2.03%) or placebo (2%). But once patients knew they were taking a statin, muscle-related symptoms were 41% more likely among those taking statins compared with those who weren’t (1.26% vs 1%).
“Patients can experience very real pain as a result of the nocebo effect and the expectation that drugs will cause harm,” Sever said. “What our study shows is that it’s precisely the expectation of harm that is likely causing the increase in muscle pain and weakness, rather than the drugs themselves causing them.”