Statins, safety

Law M, Rudnicka AR. Statin safety a systematic review. Am J Cardiol 2006 97 52-60C. 

Bottorff MB. Statin safety and drug interactions clinical implications. Am J Cardiol 2006 97(suppl) 27C-31C. 

McKenney JM, Davidson MH, Jacobsen TA, et al. Final conclusions of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006 97 (suppl) 89C-94C. 

In 2006 the National Lipid Association s Statin Safety Assessment Task Force concluded that chronic liver disease and compensated liver disease are not contraindications to the use of statins, but that they are contraindicated in decompensated disease or liver failure [2, 3] see Hepatic Adverse Effects. 

A 2006 review by the National Lipid Association s Statin Safety Assessment Task Force concluded that hepatic function does not appear to be compromised by statin use and that there was no apparent link between elevations in LFTs and the development of liver toxicity. They noted that TFT monitoring may itself be of little value in the absence of other symptoms of liver toxicity, but should be performed for medicolegal reasons, as it is recommended in the product SPCs. The expert group concluded that the use of statins is not contraindicated in chronic and compensated liver disease, but that it is contraindicated in decompensated disease or liver failure [2, 3]. 

Similarly, the National Lipid Association s Statin Safety Assessment Task Force recommends that LFTs be monitored at baseline, then at 12 weeks or after a dose increase, and periodically thereafter, particularly if the patient has symptoms indicative of liver toxicity. In... 

Cohen DE, Anania FA, Chalasani N (2006) An assessment of statin safety by hepatologists. Am J Cardiol 97 77C-81C. 

McKenneyJM, Davidson MH, Jacobson TA, Guyton JR. Final conclusions and recommendations of the national lipid association statin safety assessment task force. Am J Cardiol 2006 97(suppC) 89C-94C... 

Cholesterol Treatment Trialists (CTT) Collaborators (2005) Efficacy and safety of cholesterol-lowering treatment prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 366 1267-1278... 

Pasternak RC, Smith Jr, Bairey-Merz CN et al (2002) ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol 40 567-572... 

Montaner J, Chacon R Krupinski J, et al. Safety and efficacy of statins in the acute phase of ischemic stroke the mistics trial. Stroke 2004 35 293. 

Fibrates are being combined with statins to expand their potential in the dyslipidemia market. A recent clinical study examined the effects of rosuvastatin (10) and fenofibrate as mono and combination therapy in hyperlipidemic diabetic patients [43]. In late 2006, large scale Phase III clinical trials of rosuvastatin in combination with a next-generation fibrate, ABT 335, were initiated for evaluation of safety and efficacy in patients with mixed dyslipidemia. 

Crestor Astra-Zeneca) and lovastatin + niacin (Advicor Kos Pharmaceutical) — that can also cause rhabdomyolysis remain on the market. Although scientists agree that the other statins "seem to have essentially identical safety profiles and benefif-risk rafios," FDA said the ADRs associated with Baycol "have been reported significantly more frequently than for other approved statins." ... 

Lipitor molecule at active site. Source. Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG—CoA reductase, Science 292 1160 (2001). http //www.fda. gov/medwatch/SAFETY/2004/jul PI/Lipitor PI.pdf [accessed August 20, 2007]. Used with permission.)... 

Dr David Graham from the FDA, speaking to the US senate in 2004, controversially raised concerns (refuted by the respective Pharmaceutical Companies) over the safety of the retinoid, isotretinoin (used in the treatment of cancer), the statin, rosuvastatin (used to lower cholesterol), a long-acting p2-receptor antagonist, salmeterol (used in asthma therapy), and a selective serotonin reuptake inhibitor, paroxetine (used as an antidepressant) (21). 

With growing interest in the use of statins in women, the question naturally arises whether hormonal replacement could have any effect on their efficacy or safety. Data from the HERS (conducted in women with cardiac disorders) seem to have shown that there is no interaction (37). Estrogen replacement itself resulted in a significant increase in the early risk of primary events in women who did not use statins but not in statin users. Adjustment for statin use after randomization showed no adverse effect of estrogen on the efficacy of statins, in terms of either cardiovascular events or mortality. 

Athyros VG, Papageorgiou AA, Hatzikonstandinou HA, Didangelos TP, Carina MV, Kranitsas DF, Kontopoulos AG. Safety and efficacy of long-term statin-fibrate combinations in patients with refractory familial combined hyperlipidemia. Am J Cardiol 1997 80(5) 608-13. 

Armitage J. The safety of statins in clinical practice. Lancet 2007 370(9601) 1781-90. 

Vasudevan AR, Hamirani YS, Jones PH. Safety of statins effects on muscle and the liver. Cleve ClinJ Med. 2005 72 990-993, 996-1001. 

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