The headlines have taken our breath away:
“Statin Side-Effects Questioned”
“Statins do NOT have major side effects, claims study”
“Statins Have Virtually No Side-Effects, Study Finds”
“Side Effects Reported in Those Taking Statins Are Not Actually Attributable to the Drugs”
“Statins have ‘fewer side effects than placebo’, suggests UK study”
These headlines all resulted from an article published in The European Journal of Preventive Cardiology (March, 2014).
The authors concluded:
“At the doses tested in these 83,880 patients, only a small minority of symptoms reported on statins are genuinely due to the statins: almost all reported symptoms occurred just as frequently when patients were administered placebo. New-onset diabetes mellitus was the only potentially or actually symptomatic side effect whose rate was significantly higher on statins than placebo; nevertheless, only 1 in 5 of these new cases were actually caused by statins.”
So, what are we to make of this? Clearly, the media has announced to the world that statin-type drugs do not cause side effects. Reporters have gone so far as to suggest that sugar pills (placebos) cause more complications than statins. In other words, if you think your atorvastatin (Lipitor), lovastatin (Mevacor), rosuvastatin (Crestor) or simvastatin (Zocor) could be responsible for your muscle pain, weakness, mental confusion, nerve discomfort or cataracts, you are wrong. Such symptoms are all in your head. The only possible drug-induced complication of statins (according to these authors) is diabetes.
Pretty much ignored by the press has been a section in this article titled: “Comparison with real-live clinical experience.” The authors admit that:
“Many real-world patients report muscle-related symptoms with statins. This contrasts with the low placebo subtracted rate in blinded trials shown in this meta-analysis. Several explanations are possible. First, commercial sponsors of clinical trials may not be motivated to search exhaustively for potential side effects…Second, many trials do not state clearly how and how often adverse effects were assessed…”
This is a really important caveat. Other researchers have noted that “myopathy” (muscle pain, cramps and weakness) has been defined in all sorts of different ways in statin clinical trials. In some cases, it was restricted to enzyme elevation. In other words, a patient might suffer pain, but if their enzyme levels were within “reasonable” limits, this might not be counted as actual myopathy.
An article in BMJ (October 22, 2013) noted that “the prevalence of muscle pain in statin users is 50% greater than in non-users. In absolute terms, this increase in muscle pain is 100 times greater than that reported in clinical trials…”
Put another way, the gold-standard randomized controlled trials that were analyzed in the article making headlines this week may not have collected accurate data about muscle pain and weakness. The authors even admit that such studies may have underestimated the true incidence of new cases of diabetes attributable to statins (1 in 5 patients). As they point out, “This means that, of all new diabetes diagnoses on statins, 20% were directly pharmacologically attributable to statins…[though] new diagnosis of diabetes was only documented in three of the 29 trials.” Read between the lines and you will immediately realize that this serious complication of statin therapy was completely missed by the vast majority of clinical trials.
This has been pretty much ignored or glossed over by the media. One of the authors, Ben Goldacre, points out some of the caveats that should be taken into account on his blog.
People’s Pharmacy Analysis:
Randomized clinical trials, especially those designed to obtain FDA approval, are not set up for detecting adverse drug reactions and they don’t do it very well. They are really designed to demonstrate drug effectiveness rather than risk. A little-realized fact about such trials is that the way in which side effect information is collected may actually affect the study.
This was revealed in a landmark report by Jerry Avorn, MD, and his colleagues in a fascinating study titled: “Differences in Adverse Effect Reporting in Placebo Groups in SSRI and Tricyclic Antidepressant Trials: A Systematic Review and Meta-Analysis” (Drug Safety, Nov. 2009). Dr. Avorn and his co-authors concluded that:
“Conclusion: Adverse effect profiles reported in clinical trials are strongly influenced by expectations from investigators and patients. This difference cannot be attributed to ascertainment methods. Adverse effect patterns of the drug group are closely related to adverse effects of the placebo group. These results question the validity of the assumption that adverse effects in placebo groups reflect the ‘drug-unspecific effects’.”
In other words, the side effects reported in the placebo groups were seemingly affected by the kind of antidepressant being studied. If the drug itself caused dizziness, constipation and dry mouth in a high proportion of patients, the people getting the placebo in that trial magically had a high incidence of dizziness, constipation and dry mouth.
The conclusion doctors might make would be that since the symptoms were similar for both the placebo group and the drug group, there is no difference between them. But this is a trap. By comparing the side effects experienced only by people taking placebos in antidepressant trials the truth was revealed. You would imagine that people getting inactive placebos for the same condition (depression) would have similar side effects. But Dr. Avorn’s study shows that the placebo side effects vary enormously depending upon the type of antidepressant being studied.
We suspect that this may also be relevant for the current statin side effect analysis. If researchers influence side effect reports by the way they ask the questions or collect the data, it may be more difficult to determine the true incidence of adverse reactions to statins. We find it difficult to imagine that statins actually have no side effects. What do you think?
Here are some complications listed in the official prescribing information:
STATIN SIDE EFFECTS:
Muscle aches, muscle cramps, muscle pain, spasms:
(anywhere in the body, including legs, shoulders, back, arms or neck)
Arthritis, joint pain, joint stiffness
Abdominal pain, digestive upset, nausea, diarrhea, flatulence
Blood sugar elevation, diabetes
Sore throat, flu symptoms, sinusitis
Itching, rash, hives
Liver damage, liver failure, kidney damage
Insomnia, sleeping difficulties, nightmares
Forgetfulness, memory problems, amnesia, confusion, cognitive dysfunction
Peripheral neuropathy, nerve tingling, nerve burning
Sexual problems, erectile dysfunction, low libido
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