The trusted source for
healthcare information and
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Abbott, AstraZeneca, Boehringer Ingelheim, Daiichi, Sankyo, Forest Pharmaceuticals, Lilly, Novo Nordisk, Takeda.
Fibrates: Generally safe, but do they improve outcomes?
Source: Jun M, et al. Effects of fibrates on cardiovascular outcomes: A systematic review and meta-analysis. Lancet 2010;375:1875-1884.
According to this meta-analysis, the answer to the question above very much depends upon which outcome you believe is important. Conclusions are derived from 18 trials (45,058 participants) between 1950 and 2010. Although the results of individual fibrate (i.e., gemfibrozil, fenofibrate) trials have been somewhat disappointing, the combined data look more encouraging.
For instance, in the pooled data there was a 10% relative risk reduction for major cardiovascular (CV) events, and an almost 20% relative risk reduction for non-fatal coronary events in trials of fibrate vs placebo. Surprisingly, despite these favorable effects upon CV endpoints, there was no statistically significant reduction in all-cause mortality, CV death, or cardiac death.
When compared with other interventions to reduce CV risk (e.g., BP reduction, statins, antiplatelet therapies), the degree of absolute risk reduction achieved through fibrate therapy is substantially less. As might be anticipated, in trials where subjects had a higher baseline triglyceride level, risk reduction was greater.
Most at-risk patients in the United States are already receiving statins. The ACCORD trial was the only large trial in which patients that were already being treated with a statin then received a fibrate; no additional benefit from the fibrate was discerned. Nonetheless, fibrates will continue to have a role in high-risk patients, and in patients with marked triglyceride elevation at risk for pancreatitis.
Glucosamine and low back pain
Source: Wilkens P, et al. Effect of glucosamine on pain-related disability in patients with chronic low back pain and degenerative lumbar osteoarthritis: A randomized controlled trial. N Engl J Med 2010;304:45-52.
The burden of suffering attributed to low back pain (LBP) is readily identified by all who practice primary care. Indeed, it is recognized as the largest single component of dollars expended on long-term disability in the United States. Unfortunately, there is little evidence that supports any currently available interventions to alter the natural history of LBP and restore functionality. Because glucosamine has shown promise in other forms of osteoarthritis, and because lumber osteoarthritis is commonplace in persons with LBP, a trial of glucosamine for patients with both disorders was intuitively appealing.
In this randomized, double-blind trial, subjects were randomized to either 1500 mg/day glucosamine sulfate or placebo for 6 months. Outcomes were assessed at 6 months (end of active therapy) and again 6 months later (after a 6-month hiatus in treatment).
The Roland Morris Disability Questionnaire is specifically designed to address functional status in persons suffering LBP. In addition to this metric, degree of pain reduction and quality of life were assessed.
Although glucosamine was well tolerated, it did not produce a statistically significant improvement at either the 6-month or 12-month follow-up. Unless there exists another indication for the use of glucosamine, clinicians remain without supportive data to employ it for LBP associated with lumbar osteoarthritis.
Effects of allopurinol upon exercise in patients with angina
Source: Noman A, et al. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: A randomised, placebo controlled crossover trial. Lancet 2010;375:2161-2167.
Allopurinol has been shown, in heart failure, to reduce myocardial oxygen demand. The mechanism by which this occurs is not certain, nor is it known whether such favorable effects occur in persons without heart failure. If, during exercise, an intervention could similarly reduce myocardial oxygen demand, it could prove useful in persons with angina.
To address this question, the authors randomized subjects (n = 65) with chronic stable exercise-induced angina to high-dose allopurinol (600 mg/day) or placebo. Inclusion criteria required consistency of time to ischemia on baseline Bruce protocol exercise treadmill testing. Subjects received 600 mg/day allopurinol for 6 weeks (or placebo) and were then crossed over.
Allopurinol did produce a statistically significant increase in time to ST depression, as well as time to onset of chest pain, with no adverse effects. As a result, the authors suggest that there may be a role for allopurinol based upon cost, efficacy, and safety. Before embarking upon utilization of allopurinol for angina, clinicians must recognize that allopurinol is known to cause (rarely) a hypersensitivity vasculitis, which has a case fatality rate of approximately 25%.