What to Believe and Do About Statin-Associated Adverse Effects
The Statin craze is a long way from dead yet but the medical establishment is gradually coming to terms with the bad side-effects of statin use. At one time they denied any bad side-effects. So the article excerpted below is interesting. It is particularly interesting for the two sentences I have highlighted below. Basically, medical researchers just didn't want to know about side-effects from their new wonder drug.
And they still don't. The summary below does not capture well, for instance, the mental effects of statins. These are widely reported by patients but are virtually dismissed below. Statins can give you Alzheimer-type symptoms so it is possible that the upsurge in Alzheimers in recent years is in fact misidentified statin use.
So the report below does serve as a warning but should be regarded as a minimal warning. The problems are undoubtedly greater than the author, Paul D. Thompson, acknowledges. Thompson is of course convinced that the benefits of Statins outweigh the problems but on my reading of the literature, that only applies to people who already have experienced heart problems: angina, stroke, heart attacks. Dosing up people with statins as a general preventive measure seems on my reading to be devoid of ANY benefit and likely to do harm. As another curent article in JAMA says: Statins for Primary Prevention; The Debate Is Intense, but the Data Are Weak
Possible statin-associated adverse effects include diabetes mellitus, hemorrhagic stroke, decreased cognition, tendon rupture, interstitial lung disease, as well as muscle-related symptoms.1 Statins increase the risk of diabetes consistent with the observation that low cholesterol levels increase diabetes risk.1 Although statins reduce total stroke, they increase the risk of hemorrhagic stroke consistent with the observation that low cholesterol levels are associated with an increase in hemorrhagic stroke.1 Statins appear to reduce or have no effect on cognitive decline.1 Tendinopathies and interstitial lung disease have possible mechanistic links to statins, but their association with statins is based solely on a small case series.1 The frequency of these possible drug-related complications is unknown but is low and outweighed by the vascular benefits of statins therapy.
Statin-associated muscle symptoms are the most frequent statin-related symptoms. Experts agree that statins can cause muscle symptoms with marked increases in creatine kinase (CK) levels, usually defined as 10 times the upper limits of normal because this has been observed in randomized clinical trials (RCTs) with an estimated occurrence of 1 additional case per 10 000 individuals treated each year.2 In addition, statins can cause a necrotizing myopathy with antibodies against hydroxyl-methyl-glutaryl Co-A reductase.1 This condition must be recognized promptly because it can lead to persistent myopathy. These patients present with muscle pain and weakness plus marked increases in CK levels that do not resolve with drug cessation. Statin-associated necrotizing myopathy is newly recognized and rare but may be more frequently diagnosed now that a commercial test for the antibody is available.
In contrast, there is considerable debate as to whether statins can produce milder symptoms such as myalgia, muscle cramps, or weakness with little or no increase in CK levels. Collins et al2 reviewed the possible adverse effects found in RCTs of statin therapy and concluded that statin-associated muscle symptoms without marked CK elevations do not exist or are extremely rare because they are not reported in the statin RCTs. These authors suggested that these symptoms may be inappropriately attributed to statins due in part to patients being warned of such possible adverse effects by their clinicians.
Most clinicians, however, are convinced that these symptoms exist and are caused by statins. The incidence of statin myalgia has been estimated at 10% from observational studies.1 The Effect of Statins on Skeletal Muscle Performance (STOMP) study is the only randomized, controlled double-blind study designed specifically to examine the effects of statins on skeletal muscle.3 The STOMP trial had predefined criteria for statin myalgia, which included onset of symptoms during treatment, persistence for 2 weeks, symptom resolution within 2 weeks of treatment cessation, and symptom reappearance within 4 week of restarting treatment. Nineteen of 203 patients treated with statins and 10 of 217 patients treated with placebo met the study definition of myalgia (9.4% vs 4.6%, P = .054). This finding did not reach statistical significance, but it indicates a 94.6% probability that statins were responsible for the symptoms. This result occurred even though the study participants were young (mean age, 44.1 years), healthy, and treated with statins for only 6 months. Creatine kinase values were not different between the 2 groups. These results not only suggest that the true incidence of statin myalgia is approximately 5% but also support the observation that approximately 10% of patients will report symptoms of myalgia. Collins et al2 reanalyzed the STOMP trial data after including 29 patients treated with atorvastatin and 10 with placebo who discontinued participation because of personal reasons, yielding a P value of .08 and used this finding to support their assertion that statins do not cause muscle symptoms without markedly increased CK levels.
Diagnosing true statin-associated muscle symptoms is difficult. In the Goal Achievement After Utilizing an Anti PCSK9 Antibody in Statin Intolerant Subjects (GAUSS-3) study,4 the presence of statin myalgia was determined by randomly assigning patients with presumed statin muscle symptoms to receive either 20 mg of atorvastatin or placebo each day for 10 weeks followed by a 2-week hiatus before crossover to the alternative treatment. Only 209 patients (42.6%) developed muscle symptoms during atorvastatin treatment. An additional 130 (26.5%) developed muscle symptoms during placebo-only treatment, 48 (9.6%) developed muscle symptoms during both treatments, and 85 (17.3%) did not develop symptoms during either treatment.
Other evidence supports the idea that statins can cause skeletal muscle symptoms without abnormal CK values. Muscle biopsies show differences in gene expression among patients with statin-associated muscle symptoms during statin treatment and compared them with asymptomatic controls.5 Statins also produce slight increases in average CK levels and augment the increase in CK observed after exercise.1 Rhabdomyolysis is more frequent in participants in RCTs who are receiving statins and have variants in the gene for solute carrier organic anion transporter family member 1B1 (SLCO1B1),2 which regulates hepatic statin uptake. The SLCO1B1 gene variants that reduce hepatic uptake allow more statin to escape the liver and enter the extra portal circulation and ultimately skeletal muscle. The SLCO1B1 variants are also associated with mild muscle adverse effects in study participants treated with statins.6
How could the statin RCTs miss detecting mild statin-related muscle adverse effects such as myalgia? By not asking. A review of 44 statin RCTs reveals that only 1 directly asked about muscle-related adverse effects.7 In the STOMP trial, investigators called patients twice monthly to ask specifically about muscle symptoms.