Highlights
- •Approximately 10% of participants in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin achieved low-density lipoprotein cholesterol (LDL-C) <30 mg/dl on rosuvastatin.
- •The rate of adverse events in those with LDL-C <30 mg/dl on a statin was low.
- •However, there was a modest increase in diabetes and hematuria in patients with LDL-C <30 mg/dl.
- •No increased risk of diabetes or hematuria was seen for patients with large (≥70) percent reductions in LDL-C.
Recent US guidelines expand the indications for high-intensity statin therapy, yet
data on the safety of attaining very low-density lipoprotein cholesterol (LDL-C) levels
are scarce. Among 16,304 participants in the Justification for the Use of Statins
in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) with on-treatment
LDL-C levels, we identified 767 who did and 7,387 who did not achieve LDL-C <30 mg/dl
on rosuvastatin 20 mg daily and 718 participants who did and 7,436 who did not achieve
LDL-C reductions of ≥70% on rosuvastatin, and 8,150 allocated to placebo. In participants
with an LDL-C <30 mg/dl, we observed an increase in the risk of physician-reported
type 2 diabetes with an adjusted hazard ratio (95% confidence interval) of 1.56 (1.09
to 2.23, p = 0.01) and physician-reported hematuria (hazard ratio 2.10 [1.39 to 3.19],
p <0.001) compared with rosuvastatin-treated participants with LDL-C ≥30 mg/dl. There
was also an increased risk of certain musculoskeletal, hepatobiliary, and psychiatric
disorders. No difference in renal failure, cancer, memory impairment, or hemorrhagic
stroke was observed, although there were few events in these categories. In rosuvastatin-treated
participants, achieving LDL-C reduction ≥70% versus <70% did not appear to be associated
with increased risk of hepatobiliary, renal, or urinary disorders. In conclusion,
in this post hoc analysis in the JUPITER, achieving LDL-C levels <30 mg/dl with high-intensity
statin therapy appeared to be generally well tolerated but associated with certain
adverse events, including more physician-reported diabetes, hematuria, hepatobiliary
disorders, and insomnia. These data may guide the monitoring of patients on intensive
statin therapy and adverse events in trials of therapies that lead to very low LDL-C
levels.
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Article Info
Publication History
Published online: September 14, 2014
Accepted:
August 15,
2014
Received in revised form:
August 15,
2014
Received:
July 18,
2014
Footnotes
Clinical Trial Registration: (Clinicaltrials.gov NCT00239681).
See page 1688 for disclosure information.
Identification
Copyright
© 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
