Posts Tagged ‘observational studies’
One of the more interesting aspects of having a blog is getting comments from readers. It is always nice to get responses that enjoy the posts or that value my views. Of course, there are also some that suggest I don’t know what I’m talking about. I received one such comment last week which I believe merits a considered response. A couple of weeks ago, I wrote a piece entitled: “Disease Creep or Good Medical Practice?” Essentially, I was challenging the view that the use of statins to lower LDL cholesterol is an example of “disease creep” – the conversion of a risk-factor to an actual disease. Briefly, my view is that high cholesterol, while not a disease itself, is a strong predictor of heart disease in people with multiple cardiovascular risk factors and thus needs to be treated if diet and exercise aren’t sufficient to lower LDL cholesterol to recommended levels.
A few days later, I received a comment that began: “Did none of you receive the message that statin use was associated with the onset of type 2 diabetes?” The writer was referring to recent data from the Women’s Health Initiative (WHI) reported in the online edition of “Archives of Internal Medicine.” The investigation included 153,840 post-menopausal women aged 50 – 79 who were not diabetic at the start of the study. Over the course of the next 6 – 7 years, 10,242 women developed type 2 diabetes. After taking into account factors like lack of exercise and weight gain, it was determined by the WHI researchers that those on statins were 48% more likely to become diabetic than those not on statins at all.
Does this mean that statins can make older women more susceptible to diabetes? That is hard to say. It is possible that statins have effects on muscles and the liver that cause improper glucose metabolism, which could lead to diabetes. However, the WHI study is an observational study, not a prospective one and there are uncontrolled factors in an observational study. For example, women on statins may feel that they are protected from heart disease and may be eating more starches and sugars. Post-menopausal women don’t metabolize sugars well and this may be contributing to the increase in incidences of diabetes seen in this study.
Observational studies can yield wildly different results. Some, like the WHI study suggest negative effects of statins, others show unexpected benefits. It is interesting to note that a recent observational study suggests that taking statins may prevent death from flu. In a study entitled “Association Between Use of Statins and Mortality Among Patients Hospitalized With Laboratory-Confirmed Influenza Virus Infection: A Multistate Study” published in The Journal of Infectious Diseases (January 1, 2012), the authors reviewed the records of 3,043 older adults hospitalized with the flu in 2007/2008. Those who were on statins were 41% less likely to die from the flu over 30 days compared to those who weren’t, independent of age or flu vaccination status. An accompanying editorial to this article stated the dilemma that all observational studies pose: while there is a scientific rationale as to why statins could reduce mortality, the results might also be explained by a “healthy user bias” in that “statin users are more apt to be discriminating users of healthcare.” The editorial emphasized the need for a double-blind, placebo-controlled randomized trial of acute statin therapy in hospitalized statin-naïve, influenza infected patients to provide a definitive answer as to whether statins have protective benefits in flu patients.
Randomized prospective studies do exist for statins in diabetics. One of note is CARDS (Collaborative Atorvastatin Diabetes Study). CARDS was designed as a 6-year study and was made up of 2838 diabetes patients aged 40 – 75 with no history of heart disease. The patients were randomized to receive 10mg of atorvastatin or placebo. Over time, the LDL cholesterol levels of those on placebo remained unchanged (at about 120mg/dL, whereas those on atorvastatin had dropped to 77mg/dL on average. Surprisingly, the Data Safety Monitoring Board (DSMB) halted CARDS after only 4 years when it was found that those on atorvastatin had 35% fewer cardiovascular events, 48% fewer strokes and a death rate lowering of 27%. When the results of CARDS were reported in The Lancet (Vol. 364, 685 – 696, 2004), the authors concluded: “The debate about whether all patients with type 2 diabetes warrant statin treatment should now focus on whether any patients can reliably be identified as being at sufficiently low risk for this safe and efficacious treatment to be withheld.”
Statins are important drugs. But like any drug, they can have risks and need to be used appropriately.