Author + information
- Received April 6, 2006
- Revision received January 16, 2007
- Accepted January 22, 2007
- Published online May 1, 2007.
- ↵⁎Reprint requests and correspondence:
Dr. Michael H. Davidson, Radiant Research, Rush Medical College, Rush University Medical Center, 1725 West Harrison Street, Suite 1159, Chicago, Illinois.
Data from recent clinical trials of high- versus moderate-dose statin therapy support the recommendation to achieve a low-density lipoprotein (LDL) <100 mg/dl in high-risk patients and reveal that many patients will require a high-dose statin to achieve this goal. Overall, low rates of serious musculoskeletal (<0.6%) and hepatic (<1.3%) toxicity have been observed with high-dose statin therapy. In the long-term trials, atorvastatin 80 mg had higher rates of persistent transaminase elevations but rates of myopathy and rhabdomyolysis similar to lower doses of statins. The rate of myopathy and rhabdomyolysis for simvastatin 80 mg, although still low, was about 4× higher than for atorvastatin 80 mg and lower doses of statin. A similar margin of safety would be expected in properly selected patients with characteristics similar to those who participated in the clinical trials. High-dose statin therapy or combination therapy will be required for the large majority of very high-risk patients to achieve the optional LDL goal of <70 mg/dl. While the combination of ezetimibe, bile-acid sequestering agents, niacin, and fenofibrate with moderate dose statins appears to be reasonably safe, the long-term safety of combination with high-dose statins remains to be established. In order to optimize patient outcomes, clinicians should be aware of specific patient characteristics, such as advancing age, gender, body mass index, or glomerular filtration rate, which predict muscle and hepatic statin toxicity.
Dr. Davidson has been on the Speakers’ Bureau for Abbott Laboratories, AstraZeneca Pharmaceuticals, Kos Pharmaceuticals, Merck, Merck/Schering-Plough, Pfizer, Inc., Reliant Pharmaceuticals, Inc., Sankyo Pharma, and Takeda Pharmaceuticals. Dr. Davidson has also been a consultant for Abbott Laboratories, AstraZeneca Pharmaceuticals, Kos Pharmaceuticals, Merck, Merck/Schering-Plough, Pfizer, Inc., Novartis, Reliant Pharmaceuticals, Inc., Roche Pharmaceuticals, Sankyo Pharma, Sumitomo Pharmaceuticals, and Takeda Pharmaceuticals. Dr. Davidson has received grants/research from Abbott Laboratories, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Kos Pharmaceuticals, Merck, Merck/Schering-Plough, Pfizer, Inc., Novartis, Reliant Pharmaceuticals, Inc., Roche Pharmaceuticals, Sankyo Pharma, and Takeda Pharmaceuticals. Dr. Robinson has received grants/research from Abbott, Andrx Labs, AstraZeneca, Atherogenics, Inc., Bristol-Myers Squibb, GlaxoSmithKline, Hoffman La Roche, Merck, Pfizer, Inc., Procter & Gamble, Schering-Plough, Sankyo, Takeda, and Wyeth Ayerst. Dr. Robinson has also received speaker honoraria from Merck and Pfizer, Inc. and has been a consultant for Merck, Pfizer, Inc., and Proliant.
- Received April 6, 2006.
- Revision received January 16, 2007.
- Accepted January 22, 2007.
- American College of Cardiology Foundation