Adverse drug reactions describe harm that happens after using a normal dose of a medicine. It is important to realize that in general, possible side effects (a theraputic or adverse effect that is not the intended treatment effect) may increase in risk as the dose is increased. Dose-related effects relate to how much of a medicine you have taken. This has recently been in the news with simvastatin (Zocor) and the FDA restricted the use of the 80 mg (highest dose) because it found that muscle injury was more likely with this dose than with lower doses. What also tends to happen with dose related effects is that the severity of problems and the number of problems tend to increase as the dose increases. An algorithm called the Naranjo Scale is a questionaire that can help decide if an adverse drug reaction is caused by a drug instead of other factors.
These terms can be confusing, but have come in to play as a new meta analysis shows a relationship between use of high dose Lipitor, Pravachol or Zocor and roughly a 12 % increased risk of diabetes. Data on the newest statin, pitavastatin (Livalo) is not yet available.
Some degree of associated risk with statins and diabetes was identified for one member of the cholesterol lowering drugs known as statins (what your doctor would call HMG-Co-A reductase inhibitors) appeared in the JUPITER study for Crestor (rosuvastatin) [Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statins trails. Lancet2010; 375:735-742]. What this meant was that Crestor appeared to be associated with about a 9% increased risk of diabetes.
The data that is now in the news was revealed when some researchers looked closely at 5 previously published studies and found what appears to be a further increased risk of diabetes when high doses of statins are used. This will be presented at the American Diabetes Association-ADA meeting (Preiss D, Sesshasai, SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared to moderate-dose statin therapy. JAMA 2011; 305:2556-2564) looked at 32,752 people.
The studies reviewed included A to Z, IDEAL, PROVE-IT, SEARCH and TNT. What this new analysis found was that high dose statin use (Lipitor-Atorvastatin, Pravachol-pravastatin and Zocor-simvastatin) appears to carry roughly a 12% increased diabetes risk. It is crucial to remember that overall, the benefits (avoiding heart disease and heart attack, etc.) outweigh the risk of diabetes for this family of medicines. Associations between the chemical structure of a statin and risk of diabetes, time to development and other key details are as yet, still generally not known. Livalo (pitavastatin) was not involved in the studies reviewed in this latest meta analysis.
The studies reviewed looked at Lipitor, Pravachol and Zocor. Prove IT compared 40 mg of Pravachol to 80 mg of Lipitor in 4,162 people. A to Z had a more complicated format, but looked at a given time of Zocor 40 mg then changed to 80 mg of Zocor in some patients. Other patients received 4 months of dietary counseling and placebo followed by 20 mg of Zocor for roughly 4,500 people. TNT was a large study of 15,464 people and involved treating to new targets and compared 80 mg of Lipitor to 10 mg of Lipitor. IDEAL looked at 8,888 people after a heart attack and compared 80 mg of Lipitor to 20 mg of Zocor. Finally, SEARCH looked at 80 mg of Zocor compared to 20 mg of Zocor and also tried to sort out the role of folic acid and vitamin B 12.
Concerns about diabetes, worsening function of the beta cells (cells in the pancreas that make insulin) can be addressed by talking to your doctor and getting some simple blood tests. Examples include a gylcosylated humoglobin (also known as A1C) which shows sugar control over the last few months and of course, checking a fasting and 2 hour after eating (post-prandial) sugar. Because of the risk of diabetes and risk of diabetes in general if you have a family history and are overweight, and if you are taking a pill from this family of medicines, it appears prudent to check A1C and sugar before starting a statin and periodically thereafter.
As always, talk to your doctor about any questions regarding your medicines BEFORE you make any changes in your treatments. Visit Amazon author central:
http://www.amazon.com/James-J.-Rybacki/e/B000APKNZM to find the EGPD update on statins and cholesterol with recommendations about diabetes testing and statin use.