Abstract 1422: Safety and Efficacy of Achieving Very Low Low-Density Lipoprotein Cholesterol Levels With Rosuvastatin in the JUPITER Trial
Introduction Although CV benefits of aggressively lowering LDL-C have been confirmed in clinical trials, health consequences ranging from neuropsychiatric conditions to cancer have also been ascribed to very low cholesterol.
Hypothesis Achieving very low LDL-C with rosuvastatin (RSV) is safe.
Methods We randomized men (age >50y) and women (age >60y) with LDL-C<130 mg/dL to rosuvastatin (RSV) 20 mg/d or placebo. Those with LDL-C<50 mg/dL at any visit were considered to have very low LDL-C. Adverse events (AEs) during follow up (median 2y, range up to 5y) were centrally coded to MedDRA preferred terms with automated system overread by trained coders blinded to therapy assignment. Rates of AEs were compared by χ2 tests without multiplicity adjustment. Independent predictors of very low LDL-C were identified by logistic regression. Occurrence of major CV events (MI/stroke/CV death/revascularization/unstable angina) was assessed in Cox proportional hazard models.
Results In subjects with at least 1 postrandomization lipid profile, median LDL-C at year 1 was 110 mg/dL in placebo group and 51 mg/dL in RSV group (70 and 44 mg/dL, respectively, in RSV-treated subjects without and with very low LDL-C). Independent predictors of attaining very low LDL-C included older age, lower baseline LDL-C, higher BMI and medication adherence (all p<0.0001). Although rate of myalgia was higher in RSV group overall than in placebo group (p=0.015), there was no difference in rate of occurrence of muscle weakness, myopathy, mood disorders, peripheral neuropathy or cancer and no evidence that achieving LDL-C<50 mg/dL with RSV was associated with increase in any of these AEs (Table⇓). Risk of major CV events was also lower in those achieving LDL-C<50 mg/dL than in those not attaining very low LDL-C (HR 0.49, 95% CI 0.34 – 0.72; p=0.0003).
Conclusion RSV-treated subjects with very low LDL-C (<50 mg/dL) had a reassuring safety profile and fewer CV events compared with those not attaining very low LDL-C.