PMID- 19159124
OWN - NLM
STAT- MEDLINE
DCOM- 20090413
LR  - 20231105
IS  - 1175-3277 (Print)
IS  - 1175-3277 (Linking)
VI  - 8
IP  - 6
DP  - 2008
TI  - Statin adverse effects : a review of the literature and evidence for a 
      mitochondrial mechanism.
PG  - 373-418
LID - 10.2165/0129784-200808060-00004 [doi]
AB  - HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like 
      all medications, have potential for adverse effects (AEs). Here we review the 
      statin AE literature, first focusing on muscle AEs as the most reported problem 
      both in the literature and by patients. Evidence regarding the statin muscle AE 
      mechanism, dose effect, drug interactions, and genetic predisposition is 
      examined. We hypothesize, and provide evidence, that the demonstrated 
      mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs 
      in patients treated with statins. In meta-analyses of randomized controlled 
      trials (RCTs), muscle AEs are more frequent with statins than with placebo. A 
      number of manifestations of muscle AEs have been reported, with rhabdomyolysis 
      the most feared. AEs are dose dependent, and risk is amplified by drug 
      interactions that functionally increase statin potency, often through inhibition 
      of the cytochrome P450 3A4 system. An array of additional risk factors for statin 
      AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, 
      such as metabolic syndrome factors, thyroid disease, and genetic mutations linked 
      to mitochondrial dysfunction. Converging evidence supports a mitochondrial 
      foundation for muscle AEs associated with statins, and both theoretical and 
      empirical considerations suggest that mitochondrial dysfunction may also underlie 
      many nonmuscle statin AEs. Evidence from RCTs and studies of other designs 
      indicates existence of additional statin-associated AEs, such as cognitive loss, 
      neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician 
      awareness of statin AEs is reportedly low even for the AEs most widely reported 
      by patients. Awareness and vigilance for AEs should be maintained to enable 
      informed treatment decisions, treatment modification if appropriate, improved 
      quality of patient care, and reduced patient morbidity.
FAU - Golomb, Beatrice A
AU  - Golomb BA
AD  - Department of Medicine, University of California, San Diego, California 
      92093-0995, USA. bgolomb@ucsd.edu
FAU - Evans, Marcella A
AU  - Evans MA
LA  - eng
GR  - R01 HL063055-04/HL/NHLBI NIH HHS/United States
GR  - R01 HL063055-02/HL/NHLBI NIH HHS/United States
GR  - R01 HL063055-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL063055/HL/NHLBI NIH HHS/United States
GR  - R01 HL063055-05/HL/NHLBI NIH HHS/United States
GR  - R01 HL063055-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - New Zealand
TA  - Am J Cardiovasc Drugs
JT  - American journal of cardiovascular drugs : drugs, devices, and other 
      interventions
JID - 100967755
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
SB  - IM
MH  - Drug Interactions
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/metabolism
MH  - Meta-Analysis as Topic
MH  - Mitochondria/*metabolism
MH  - Mitochondria, Muscle/drug effects/metabolism
MH  - Muscular Diseases/*chemically induced/metabolism
MH  - Randomized Controlled Trials as Topic
MH  - Rhabdomyolysis/chemically induced/metabolism
MH  - Risk Factors
PMC - PMC2849981
MID - NIHMS163591
EDAT- 2009/01/23 09:00
MHDA- 2009/04/14 09:00
PMCR- 2010/04/06
CRDT- 2009/01/23 09:00
PHST- 2009/01/23 09:00 [entrez]
PHST- 2009/01/23 09:00 [pubmed]
PHST- 2009/04/14 09:00 [medline]
PHST- 2010/04/06 00:00 [pmc-release]
AID - 864 [pii]
AID - 10.2165/0129784-200808060-00004 [doi]
PST - ppublish
SO  - Am J Cardiovasc Drugs. 2008;8(6):373-418. doi: 10.2165/0129784-200808060-00004.