Very low LDL-C with statins safe regarding major known side effects, but caution urged

   In a post-hoc analysis of data from the JUPITER trial of statin therapy, achieving LDL-C levels <30 mg/dL appeared safe as concerns the major side effects known to be associated with the drugs.

   Brendan Everett, MD, MPH, and colleagues at Brigham and Women's Hospital and Harvard Medical School, Boston, USA, noted that of study participants with baseline LDL-C <130 mg/dL who were administered the study drug at 20 mg, 767 achieved at least one on-treatment LDL-C of <30 mg/dL during a median follow-up of two years; 7,387 did not.

   The rates of any adverse event, myalgia, nervous system disorders, creatinine kinase elevations, liver function test abnormalities, or cancer were not significantly different between participants achieving LDL-C <30 mg/dL or >/=30 mg/dL (all P >0.05). According to Dr. Everett and colleagues, exploratory analyses evaluating a broad spectrum of potential adverse effects showed an increase in total renal or urinary disorders (adjusted relative risk [RR] 1.49; 95% confidence interval [CI], 1.19 to 1.86), which appeared to primarily reflect an increase in hematuria (RR 2.20; CI, 1.47 to 3.28). The researchers also noted that "other hypotheses generating findings of uncertain pathobiology" include possible increases in psychiatric (RR 1.43; CI, 1.09 to 1.88) and hepatobiliary disorders (RR 1.68; CI, 1.09 to 2.60).    

   Considering the potential adverse effects on less well described pathways, close monitoring in future trials of very low LDL-C reduction is warranted, the researchers concluded.