Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Lumbar Disk Herniation: Is Surgical Treatment Superior to Conservative Management?

The sport (Spine Patient Outcomes Research Trial) trial enrolled over 1,000 adults with lumbar disk disease-herniated disk, spinal stenosis, or spondylolisthesis-to compare outcomes between persons who were assigned to surgical treatment vs medical therapy. All study subjects underwent imaging to confirm pathology consonant with symptoms (97% had MRI).

The surgical intervention performed was open discectomy; medical therapy included exercise, education, and use of NSAIDs. The primary outcome measures were body pain and physical function (as measured on the SF-36) and degree of disability (as measured by the American Academy of Orthopedic Surgeons Oswestry Disability Index). End points were assessed at baseline, 3 months, 1 year, and 2 years.

For primary end points (by intention-to-treat analysis) there was no statistically significant difference between groups at any point during the study period. Although this would seem to confirm that surgery does not have advantage over conservative treatment, it must be recognized that the intention-to-treat analysis used in this trial does not necessarily function well because a large number of persons (40-45% in either group) originally assigned to one intervention ultimately crossed over to receive the other; ie, many patients randomized to surgery did not ultimately receive it, and vice versa. If one just looks at the data from the perspective of dividing the population into the treatment they actually received, outcomes favored surgery, but this does not reflect the original randomization process, and is hence subject to confounding.

Weinstein JN, et al. JAMA. 2006;296:2441-2450.

Rimonabant: An Answer to Obesity in Diabetes?

Obesity is a cause, concomitant, and consequence of diabetes. Clearly, overweight status increases the likelihood of developing diabetes, and is present at the time of diagnosis in most type 2 diabetics. Similarly, pharmacotherapy is often associated with weight gain, and diabetic consequences such as painful neuropathy may result in reduced activity levels, further exacerbating weight control dilemmas. Some weight loss agents such as orlistat (xenical) have shown favorable effects in diabetic subjects, but may be limited by tolerability.

Rimonabant (RBT) has been shown to produce statistically significant weight loss in non-diabetic overweight and obese subjects. Additionally, the weight loss has been noted to impact the critical abdominal visceral fat compartment. Scheen, et al, investigated the impact of RBT in overweight diabetic subjects.

Overweight/obese subjects with type 2 diabetes (n = 1,047) were randomized to receive RBT or placebo. All subjects were counseled in regard to diet and exercise, and followed for 1 year.

RBT at 5 mg/d or 20 mg/d was superior to placebo for weight loss at 1 year (2.3 kg or 5.3 kg vs 1.4 kg, respectively). RBT has shown a statistically significantly greater weight loss than diet and exercise alone in type 2 diabetics.

Scheen AJ, et al. Lancet. 2006;368:1660-1672.

Renin Inhibitors: A new Class of Antihypertensive Agents

Despite a diverse array of antihypertensive agents, less than half of Americans with hypertension (HTN) are aware of their condition, on treatment, and controlled to a BP of less than 140/90. New treatments, hence, are welcomed.

Aliskiren (ALISK) is the first potential member of a new class of oral gents: renin inhibitors. Although drugs like ACE inhibitors and ARBs impact the renin-angiotensin-aldosterone system, they typically induce a compensatory increase in renin. Combination of ACE/ARB and ALISK, on theoretical grounds, is sensible and appealing. Vaidyanathan et al report on four open-label studies (n = 87) evaluating the efficacy, safety, and tolerability of ALISK in combination with a representative agent from each of the 4 most commonly used antihypertensive classes: calcium channel blocker (amlodipine), ARB (Valsartan), diuretic (HCTZ), and ACE inhibitor (ramipril). It was anticipated that ALISK was unlikely to have significant drug interactions, since it is hepatically eliminated unchanged (ie, no p450 interactions), does not inhibit p450 enzymes, and is not highly protein bound.

ALISK therapy was not associated with any clinically relevant tolerability or safety issues. Mild headache, dizziness, and GI symptoms were reported, but differed minimally from adverse effect profiles seen with the other classes of agents when used as monotherapy. ALISK is currently pending FDA approval.

Vaidyanathan S, et al. Int J Clin Pract. 2006;60:1343-1356.