People on statins are 9% more likely to develop diabetes according to a meta-analysis

From Reuters:

This small risk is outweighed by the drugs' heart-protecting properties but it could prompt a rethink among those with low cardiovascular risk factors who are tempted to take statins to prevent future heart disease.

"It will stop us putting statins in the water, as it were, and mean we give them when appropriate for the right reasons."

Lovastatin, a compound isolated from Aspergillus terreus, was the first statin to be marketed for lowering cholesterol. Image source: Wikipedia, public domain.

Statins are among the most successful drugs of all time and have been credited with preventing millions of heart attacks and strokes.

This Lancet meta-analysis included 13 large randomised controlled trials involving more than 91,000 patients.

Treating 255 patients with statins for 4 years would result in only one extra case of diabetes.

Giving statins to the same group would avoid 5.4 deaths or heart attacks over 4 years, and nearly the same number of strokes.

Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease should not change.

References:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61965-6/fulltext

http://www.reuters.com/article/idUSTRE61G00P20100217

Related:
Statins Don't Cause Diabetes. Dr. Mintz' Blog.

Beyond statins: Thyromimetic eprotirome decreases LDL

Dyslipidemia increases the risk of atherosclerotic cardiovascular disease and is incompletely reversed by statin therapy alone in many patients. Thyroid hormones lower levels of serum low-density lipoprotein (LDL) cholesterol and has other potentially favorable actions on lipoprotein metabolism. Consequently, thyromimetic drugs hold promise as lipid-lowering agents if adverse effects can be avoided.

In this 12-week trial, the thyroid hormone analogue eprotirome was associated with decreases in levels of atherogenic lipoproteins in patients receiving treatment with statins.

Similar reductions were seen in levels of serum LDL, apolipoprotein B, triglycerides, and Lp(a) lipoprotein. No change in levels of serum thyrotropin or triiodothyronine was detected, although the thyroxine level decreased in patients receiving eprotirome.

References:

Use of the Thyroid Hormone Analogue Eprotirome in Statin-Treated Dyslipidemia. NEJM, 2010.

Image source: Wikipedia, public domain.

Statins Use in Presence of Elevated Liver Enzymes: What to Do?

The beneficial role of statins in primary and secondary prevention of coronary heart disease has resulted in their frequent use in clinical practice.

However, safety concerns, especially regarding hepatotoxicity, have driven multiple trials, which have demonstrated the low incidence of statin-related hepatic adverse effects. The most commonly reported hepatic adverse effect is the phenomenon known as transaminitis, in which liver enzyme levels are elevated in the absence of proven hepatotoxicity.

"Ttransaminitis" is usually asymptomatic, reversible, and dose-related.


Lovastatin, a compound isolated from Aspergillus terreus, was the first statin to be marketed for lowering cholesterol. Image source: Wikipedia, public domain.

The increasing incidence of chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis C, has created a new challenge when initiating statin treatment. These diseases result in abnormally high liver biochemistry values, discouraging statin use.

A PubMed/MEDLINE search of the literature (1994-2008) was performed for this Mayo Clinic Proceedings review. The review supports the use of statin treatment in patients with high cardiovascular risk whose elevated aminotransferase levels have no clinical relevance or are attributable to known stable chronic liver conditions.

References:
Statins in the Treatment of Dyslipidemia in the Presence of Elevated Liver Aminotransferase Levels: A Therapeutic Dilemma. Rossana M. Calderon, MD, Luigi X. Cubeddu, MD, Ronald B. Goldberg, MD and Eugene R. Schiff, MD. Mayo Clinic Proceedings April 2010 vol. 85 no. 4 349-356.

Statins slightly increase risk of cataracts, liver dysfunction, kidney failure and muscle weakness

Statins do NOT prevent a long list of diseases

Statins were not significantly associated with risk of Parkinson’s disease, rheumatoid arthritis, venous thromboembolism, dementia, osteoporotic fracture, gastric cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer.

Statins may decrease risk of esophageal cancer

Statin use was associated with decreased risks of oesophageal cancer.

Statins slightly increase the risk of liver dysfunction, kidney failure, muscle weakness and cataracts

Statin use was associated with increased risks of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataract.

Is the risk the same with all statins?

Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin.

A dose-response effect was apparent for acute renal failure and liver dysfunction. All increased risks persisted during treatment and were highest in the first year.

How long does the risk last?

After stopping treatment the risk of cataract returned to normal within a year in men and women. Risk of acute renal failure returned to normal within 1-3 years in men and women, and liver dysfunction within 1-3 years in women and from three years in men.

What was the NNT and NNH?

Based on the 20% threshold for cardiovascular risk, for women the NNT with any statin to prevent one case of cardiovascular disease over five years was 37 and for oesophageal cancer was 1266 and for men the respective values were 33 and 1082.

In women the NNH for an additional case of acute renal failure over five years was 434, of moderate or severe myopathy was 259, of moderate or severe liver dysfunction was 136, and of cataract was 33. Overall, the NNHs and NNTs for men were similar to those for women, except for myopathy where the NNH was 91.

Conclusion

Claims of unintended benefits of statins, except for oesophageal cancer, remain unsubstantiated, although potential adverse effects at population level were confirmed and quantified.

Interestingly, the BMJ abstract did not mention increased diabetes risk that was reported in a previous study published in The Lancet.

References:

Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ 2010; 340:c2197 doi: 10.1136/bmj.c2197 (Published 20 May 2010).

Balancing the intended and unintended effects of statins. BMJ 2010; 340:c2240 doi: 10.1136/bmj.c2240 (Published 20 May 2010).

People on statins are 9% more likely to develop diabetes according to a meta-analysis
Cholesterol drug side effects need watching: study. Reuters.

Image source: Simvastatin. Wikipedia, public domain.