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Earth to JUPITER: How a Potent Statin May Actually Be Detrimental For Lifestyle-Associated Diseases

Efthimiadis asserted that rosuvastatin, the strongest statin, hold the initial promises in the prevention of cardiovascular disease. Indeed, the results of the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER trial) has been recently published and received a great publicity in the lay press. In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin 20 mg daily significantly reduced the incidence of major cardiovascular events, although with small absolute numbers, the rates of the primary end point being 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively. We suggest that the translation in clinical practice of the JUPITER trial is not so straightforward. Individuals enrolled in the JUPITER trial led an unhealthy lifestyle; at baseline, mostly were overweight or obese (the baseline median body mass index was 28.3 with interquartile range 25.3-32.0). However, before enrolment, no attempt was made to alter their habits. Furthermore, although it was announced that the study was stopped early because there was unequivocal evidence of a reduction in cardiovascular morbidity and mortality among patients who received rosuvastatin when compared to placebo, a closer look at the mortality data says that the sum of fatal strokes and fatal myocardial infarctions was 12 in both rosuvastatin and placebo group. Moreover, data on overall vascular mortality were not given, and termination of the study after 1.9 years is too short to assess correctly the side effects, especially if we look at the Kaplan-Meier curve for all-cause mortality. It has recently been reported that statins may not only have detrimental effects on muscle degradation but they also diminish or block pathways in skeletal muscle that favors muscle hypertrophy or muscle oxidative metabolism. This is particularly worrisome, because physical activity should have been regarded as the most cost-effective way to prevent cardiovascular and metabolic diseases in participants enrolled in the JUPITER trial. In fact, when dealing with individuals at risk of contracting lifestyle-associated diseases, it is unrealistic to imagine that one can prevent or treat the overt clinical complications of an unhealthy lifestyle merely by means of drugs. Therefore, it is particularly concerning that rosuvastatin significantly increased the incidence of diabetes, a pathology closely related to unhealthy lifestyles. As such, it may represent the results of a ‘‘justification’’ to continue self-destructive habits.