Statin enthusiasts are hell bent on convincing the world that these cholesterol-lowering drugs don’t cause side effects. Last week we told you that the United States Preventive Services Task Force (USPSTF) had just published its latest statin guidelines in JAMA (Aug. 23/30, 2022). These experts concluded that statins are unlikely to cause serious side effects such as diabetes or muscle pain. This week, the Cholesterol Treatment Trialists’ Collaboration published its assessment of statin side effects in The Lancet (Aug. 29, 2022). The bottom line seems to be that statin side effects are imaginary. In particular, the researchers insist that people who complain about muscle pain, muscle weakness or other musculoskeletal side effects are anticipating such adverse drug reactions. According to these statin enthusiasts, reports of muscle pain after taking drugs like atorvastatin, rosuvastatin or simvastatin are “not due to the statin.” Is that true?
The Lancet Study:
The authors of the new Lancet study were specifically interested in muscle symptoms. They analyzed 19 placebo-controlled trials involving nearly 124,000 patients plus 4 additional clinical trials comparing intensive statin therapy to more moderate dosing. The conclusion:
“Statin therapy caused a small excess of mostly mild muscle pain. Most (>90%) of all reports of muscle symptoms by participants allocated statin therapy were not due to the statin.”
The authors go on to state that when a patient reports muscle symptoms while taking a statin, they are unlikely to be caused by the drug. The investigators note that there was substantial variation in how the studies defined and reported muscle symptoms. Nevertheless, the authors believe that muscle pain experienced during statin treatment is mostly imaginary or due to aging and not brought on by the drugs.
The Media Amplifies the Message: Statin Side Effects Are Imaginary:
Hear are some headlines from the past week:
“Many patients stop taking statins because of muscle pain, but statins aren’t causing it, new study says” CNN Health, Aug. 30, 2022
“Statin pills rarely cause muscle pain or problems, study finds” BBC News, Aug. 29, 2022
“Scientists find no association between statins and pain, urge patients to continue taking pills” WISHTV.COM8, Aug. 30, 2022
“Statin myths debunked: Cholesterol-busting pills don’t cause memory loss or diabetes” Daily Mail, Aug. 31, 2022
This is not the first time the media has advanced the message that:
Statin Side Effects Are Not Real
Here are some headlines from 2014:
“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 older 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.”
Do Statin-Type Cholesterol-Lowering Drugs Cause ANY Side Effects?
So, what are we to make of all 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, elevated blood sugar, 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 and even that is questionable according to the United States Preventive Services Task Force.
Pretty much ignored by the press has been a section in the European Journal of Preventing Cardiology 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 journal articles 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.
See No Evil, Speak No Evil:
Think of it this way. If you are not looking for something you may not find it. We cannot tell you how many adverse drug reactions have been overlooked over the decades because researchers did not make a connection.
One of the most glaring examples has to do with fluoroquinolone (FQ) antibiotics. For 25 years doctors prescribed drugs like ciprofloxacin (Cipro) and levofloxacin (Levaquin) without much concern.
Then there was a gradual realization that FQ antibiotics can cause life-threatening aortic aneurysms. In this situation the main artery that carries blood from the heart can develop a weak spot or rupture. These drugs can also cause severe nerve, joint and muscle pain, tendon tears and damage heart valves. You can learn more about fluoroquinolone complications at this link.
Statin Side Effects Are Real…or Imaginary?
People’s Pharmacy Analysis:
Randomized clinical trials, especially those designed to obtain FDA approval, are not really 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 results.
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.
Priming the Pump:
There is another often-ignored factor that may skew results in clinical trials. If the investigators ask all the patients in a clinical trial if they have experienced a headache, a lot of people will say yes. Just priming the pump, so to speak, can trigger an affirmative answer. That’s true for both the placebo arm as well as the drug arm. Headaches are quite common and asking about them can get people thinking about the possibility of a recent headache.
We suspect that this may also be relevant for statin trials. 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
We would love your feedback. Tell your story below. To read others, click here. Many of the comments you will read below were posted after the original article was published in The European Journal of Preventive Cardiology (March, 2014). Now that there are new articles published in JAMA (Aug. 23/30, 2022) and in The Lancet (Aug. 29, 2022) discounting statin side effects, we suspect that many physicians will dismiss reports of adverse reactions to statins.
Please share your experience with statins in the comment section. If you have never experienced any adverse reactions we want to hear from you. That is also true if you believe that statin side effects are real.
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