Frequencing of Amyotrophic Lateral Sclerosis (ALS) associated with statin usage

This publication –– concerning drug efficacy vs possible association with long-term undesirable drug toxicity –– has been ruminating in my mind for some weeks, so I asked for input on the statistical analysis. Statin cholesterol-lowering drugs are among the most widely prescribed drugs in the world today. The benefits (lowering cholesterol and therefore reducing risk of coronary heart disease) seem to be so fantastic that some have actually proposed adding statins to our drinking water.

Like all drugs, statins have the potential to produce adverse drug reactions (ADRs). Particular focus has been on muscle effects (i.e. pain, weakness, and increased fatigue), but occasionally more serious effects such as rhabdomyolysis (destruction of striated muscle), necrotizing autoimmune myopathy (abnormalities of skeletal muscle structure & metabolism), and triggering (or ‘unmasking’) mitochondrial myopathy. Concerns have also been raised about possible increases in occurrence of amyotrophic lateral sclerosis (ALS)-like muscle-wasting conditions associated with statin use. ALS is a fatal neurodegenerative disease –– affecting muscle-controling neurons that characteristically leads to rapidly progressive paralysis –– ending in death, usually from respiratory failure or aspiration of food material.

In the attached study, authors examined US FDA Adverse Event Reporting System (FAERS) data –– to compare reporting odds ratios (RORs) of ALS and ALS-like conditions in patients taking the various statins. They looked at disproportionate rates of reported ALS and ALS-related conditions for each statin agent, separately. RORs ranged from 9.09 (range 6.57–12.6) and 16.2 (range 9.56–27.5) for rosuvastatin and pravastatin (hydrophilic, i.e. relatively water-soluble) to 17.0 (range 14.1–20.4), 23.0 (range 18.3–29.1), and 107 (range 68.5–167) for atorvastatin, simvastatin, and lovastatin (lipophilic, i.e. relatively fat-soluble), respectively. These data extend previous evidence, which suggests that differences in increased risk of ALS depends on which statin is studied.

Critique: The association of ALS and ALS-like events with statin usage appears to be real, and this association might be causal because it is supported by other studies including studies in mice. However, the present result is not new –– although this study had a larger sample-size than previous studies. Authors concluded that hydrophilic statins exhibit lower risk than lipophilic statins [e.g. the two extremes were rosuvastatin (ROR of 9) vs lovastatin (ROR of 107)]. This observation can be influenced by many confounding factors (i.e. caveats) not explicitly considered in this study, especially the duration of statin usage and age of each patient. Obviously, the “older” statins should have higher risks because they have been used longer and in older patients (also, probably patients of lower social economical status, because the older statins are cheaper than the new statins). All these issues might contribute to the risk factors for ALS.

Drug Safety Apr 2o18; 41: 403–413

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