Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Sucampo Pharmaceuticals, Takeda, Boehringer Ingelheim; and is a consultant and on the speaker's bureau for Novo Nordisk, Lilly, Daiichi Sankyo, Forest Pharmaceuticals, Cephalon, Novartis, and Sanofi Aventis.

Thyroid hormone analogue for dyslipidemia

Source: Ladenson PW, et al. Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia. N Engl J Med 2010;362:906-916.

The role of statins in treatment of dyslipidemia is well established. There are, however, limitations of statins: Residual risk is substantial, not all persons can tolerate statins, and, even with full-dose statin treatment, some patients do not achieve lipid goals.

The role of the thyroid in lipid metabolism has long been a matter of scientific interest. It is recommended that patients with dyslipidemia undergo thyroid function testing since hypothyroidism, although only present in a small percentage of dyslipidemic patients, is readily correctable and offers meaningful lipid improvements. Enhancement of thyroid activity has favorable lipid effects. As far back as the 1960s, investigators were curious enough about thyroid hormone and vascular disease to enroll men in the Coronary Drug Project (1965) and randomize them to d-thyroxine, which was felt at the time (mistakenly) to have essentially no effect on sympathetic nervous system sensitivity, but favorable effects on lipids.

Eprotirome (EPR) is an analogue of thyroid hormone which has preferential affinity for thyroid receptors that modulate lipid lowering, as compared to cardiac receptors. A randomized placebo-controlled, double-blind study was done among patients on an NCEP step 1 diet and a statin (simvastatin or atorvastatin). Patients (n = 329) received statin plus either EPR or placebo for 12 weeks.

At the end of the trial, very favorable lipid effects were reported with the addition of EPR to a statin: a 22%-32% reduction in LDL, a 6- to 9-fold increase in patients achieving an LDL < 100 mg/dL, as well as favorable effects on triglycerides and apoB (all dose-dependent). A small reduction in HDL was seen. There was no change in heart rate or BP. Selective activation of thyroid receptors may one day provide an additional path for successful lipid modulation.

Diagnostic yield of elective coronary angiography

Source: Patel MR, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med 2010;362:886-895.

Current recommendations suggest that in stable persons under consideration for CAD evaluation, low-risk individuals be observed, high-risk patients be triaged to coronary angiography, and intermediate-risk persons be further stratified by means of non-invasive testing. Such guidance is structured to minimize unnecessary invasive investigations in low-risk individuals, and to identify — in the group of intermediate risk — those who merit follow-up with angiography.

The American College of Cardiology National Cardiovascular Data Registry provided information on patients without known CAD (n = 398,978) who received coronary angiography (electively) at hospitals in the United States during a 4-year interval commencing January, 2004.

Obstructive CAD was defined as at least 50% stenosis of the left main coronary artery (or greater degrees of stenosis of epicardial vessels). Catheterization determined that slightly more than one-third of patients had obstructive CAD. In addition to the disappointingly low percentage of individuals identified with CAD on angiography, this study also provided insights about the concordance of risk and use of non-invasive testing (i.e., stress testing). When non-invasive testing had preceded angiography, subjects' baseline risk category was at odds with the current recommendations focusing upon refinement of risk in persons at intermediate Framingham scores, in that those with high Framingham risk scores were disproportionately represented. The authors suggest that the diagnostic yield based upon current practice needs improvement.

Statins and risk of developing diabetes

Source: Sattar N, et al. Statins and risk of incident diabetes. Lancet 2010;375: 735-742.

There is little dispute regarding the beneficial reduction in CV events seen with statin treatment of dyslipidemic patients. At the same time, however, conflicting evidence has suggested that statin treatment might be associated with an increased risk of new-onset diabetes.

Sattar et al performed a meta-analysis of data from large statin clinical trials (n = 13), totalling almost 100,000 patients. During a mean follow-up of 4 years, 9% more individuals developed new diabetes on a statin than patients not treated with a statin. Since CV risk reduction was still favorably influenced by statin treatment, this small increased incidence of diabetes was either not sufficient to offset other beneficial vascular effects, or, once diabetes developed, statin protection was already on board, or perhaps both factors were influential.

You may recall that in hypertension treatment trials, a similar problem has been identified. Chlorthalidone (ALLHAT) had a significantly greater risk for incidence of new diabetes than comparators, yet this adverse effect did not seem to adversely affect CV event rates.

The mechanism by which statins increase risk for diabetes is obscure. This data analysis calculated that 255 subjects would have to be treated with a statin for 4 years to incur 1 additional new case of diabetes. Fortunately, if the small increase is real, it is strongly counterbalanced by well-documented reductions in CV events.