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.

Does it matter how we lower LDL?

Source: Taylor AJ, et al. N Engl J Med 2009;361:2113-2122.

Based upon a presumed direct relationship with LDL lowering and reduction in CV events for persons with vasculopathy, many clinicians enthusiastically embraced the combination of ezetimibe with statins, especially when therapeutic LDL goals were difficult to attain with a statin alone. After the ENHANCE trial, which questioned the ability of ezetimibe to effectively regress carotid atherosclerosis, clinicians began to rethink the issue, fueled additionally by disappointing data from the trials of torceptrapib, an HDL-raising drug, which not only did not prove to reduce CV events, but actually worsened CV risk and was subsequently withdrawn from consideration for FDA approval.

A single clinical trial, the Coronary Drug Project, showed CV risk reduction with niacin in long-term follow-up. Because of adverse effects that limit more universal use of niacin, agents that were much better tolerated (like ezetimibe) appeared to be a more suitable choice.

A clinical trial was performed to evaluate the comparative efficacy of extended-release niacin with ezetimibe in persons with known coronary disease or with a CHD risk equivalent (e.g., diabetes mellitus). All subjects were already on a statin and had achieved an LDL < 100 mg/dL. Over 14 months, the performance of niacin to regress carotid intima-media thickness was significantly greater than ezetimibe. Indeed, the incidence of CV events was significantly lower in the niacin group also (1% vs 5%).

Although ezetimibe is effective in reducing LDL, it has not been shown to have a favorable effect upon CV or vascular surrogate endpoints; hence, its use must be reconsidered.

Identifying risk factors for falls in seniors

Source: Leveille SG, et al. JAMA 2009; 302:2214-2221.

Among older adults, falls remain in the top 10 causes of death. Risk factors for falls include vitamin D status, cognitive status, physical decline, and mobility impairment. The epidemiologic magnitude of fall risk has motivated the search for other risk factors.

Leveille et al studied a population of community-dwelling senior citizens (age > 70 years) in the greater Boston area. Each participant (n = 749) was assessed for chronic pain, and reassessed on a monthly basis for 18 months. During this interval, subjects reported 1029 falls.

Subjects were stratified into pain scores by tertile. Most pain syndromes were associated with disorders like osteoarthritis, and included individuals with a single painful area as well as multiple symptomatic sites.

There was a linear relationship between pain scores and risk for falls. Subjects with two or more painful sites had approximately 20% greater risk of falls when compared to persons without pain. Although one might think that analgesic use prompted by joint pain might explain a greater incidence of falls, such a relationship was not demonstrable in this population.

Why pain is associated with falls is uncertain. Perhaps pain leads to deconditioning, leading to falls. There is also some support for cognitive effects of chronic pain that might lead to lesser executive alacrity, impairing the ability to respond to precipitants of a fall. It remains to be shown whether superior pain control will reduce fall risk.

Prevention of diabetes: The long-term outlook

Source: Diabetes Prevention Program Research Group; et al. Lancet 2009; 374:1677-1686.

Numerous randomized clinical trials show that a variety of interventions can prevent the development of type 2 diabetes in subjects with prediabetes (i.e., impaired glucose tolerance, defined as a 2-hour post-load glucose of 140-199 mg/dL). Lifestyle interventions (i.e., intensive diet and exercise programs) are generally at least as effective as pharmacotherapy (e.g., metformin, rosiglitazone, orlistat). Some experts quibble with the term "prevent," preferring instead to indicate that our prediabetes interventions simply "delay" diabetes. Since persons at high risk for type 2 diabetes are likely to remain in a high-risk group indefinitely, the long-term picture of interventions to prevent type 2 diabetes is important.

The Diabetes Prevention Program (DPP) was one of the largest diabetes prevention trials ever performed. At 2.8 years, incidence of type 2 diabetes was reduced 58% with lifestyle, and 31% with metformin (compared to placebo). A recent report by the Diabetes Prevention Program Research Group provides a window of insight into data 10 years from the date of randomization.

Compared to placebo, subjects in the lifestyle intervention group had a 34% reduction in new onset type 2 diabetes; the metformin group had an 18% risk reduction.

Follow-up of subjects enrolled in the DPP indicates a long-term risk reduction in development of type 2 diabetes attained with lifestyle or metformin intervention. Whether you call it prevention or delay, less type 2 diabetes at 10 years is a good thing.