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.

Predicting Stroke Risk after TIA

Stroke remains the third lead ing cause of death in America. Risk of stroke after TIA is greatly magnified, such that as many as 20% will suffer a stroke within 90 days, disproportionately occurring within the first 48 hours post-TIA. Scoring systems to enhance prediction of stroke after TIA have been devised and validated, and include the ABCD score and the California score. These scores had different boundaries (the ABCD score predicted 7 day risk; the California score looked at 90 day risk), and because of questions about generalizability (the ABCD was validated on Greek and British populations, vs the California Score which was developed from an American cohort), it would be desirable to evolve a single score capturing the best aspects of both the ABCD and California scoring systems.

Based on logistic regression, the authors derived a "unified ABCD" score and validated it upon a large population of individuals (n = 4,809) from American and British populations. The new scale, which they term the ABCD2 is so-named because it predicts risk in the 2 days post-TIA. Components of the ABCD2 include age, diabetes, blood pressure, duration of TIA, speech impairment, and focal weakness. The new scale predicts high risk patients in the first 48 hours better than either of the component scores from which it was derived. The authors offer this scale as "a new standard of care" model for identifying highest risk TIA patients who may benefit from more intensive investigation and treatment.

Johnston SC, et al Lancet. 2007;369:283-292.

Which is the Better Study in Acute Stroke: CT or MRI?

Common wisdom suggests that for acute stroke, MRI is preferred to CT. Sometimes, however, patients who present with neurologic syndromes may suffer disorders other than/in addition to stroke. Hence, clinicians would prefer to know which imaging modality provides best information about stroke (ischemic and hemorrhagic), as well as other cerebrovascular maladies.

It is already recognized that CT is less valuable for detecting ischemic stroke than ruling out hemorrhagic stroke. Yet, there has been little comparison to determine whether CT or MRI is actually superior to detect CNS hemorrhage.

In a prospective blind comparison of CT and MRI in presents presenting with suspected acute stroke, MRI was significantly more sensitive for both ischemic and hemorrhagic stroke detection. When assessed comparatively relative to the final clinical diagnosis, the sensitivity of MRI was substantially greater than CT (83% vs 26%). Unless cost or availability precludes its use, MRI should be the preferred study in patients presenting with symptoms suggesting acute stroke.

Chalela JA, et al. Lancet. 2007;369:293-298.

Comparison of a DPP-4 and TZD for Monotherapy in Type 2 Diabetes

Glucagon-like peptide-1 (GLP) is one of a family of agents known as incretins (FYI, correctly pronounced in-KREE-tins, since your author has heard it repeatedly mispronounced "IN-creh-tins" at professional meetings of late). Incretins have numerous favorable physiologic effects in patients with type 2 diabetes (DM2), including enhanced glucose-dependent insulin secretion, activation of insulin biosynthesis and gene transcription, suppression of glucagon, slowed gastric emptying, induction of satiety, and inhibition of beta cell apoptosis. Until very recently, we have not been able to capitalize upon these physiologic attributes because the actions of GLP are very short lived. DPP4 inhibitors block the enzyme that degrades GLP, resulting in a prolonged GLP effect. Sitagliptin (Januvia) is the only currently approved DDP4 inhibitor, but others are pending FDA approval.

The potency of the DPP4 inhibitor vildagliptin (VIL) was compared in a double-blind fashion with rosiglitazone (Avandia) in type 2 diabetics. A population of newly diagnosed diabetics (n = 786) were randomized to VIL 50 mg b.i.d. vs rosiglitazone 8 mg qd and followed for 6 months. The primary outcome was change from baseline A1C (baseline = 8.7).

Both agents were similar in mean reduction of A1C at 24 weeks (1.1-1.3%), proving statistical noninferiority of vildagliptin to rosiglitazone. Additionally, amongst persons with higher baseline A1C (eg, > 9.0%), pharmacotherapy impact was correspondingly larger (A1C decrease 1.8%).

Because they are not associated with weight gain, and show similar potency to agents popularly used to treat DM2, the availability of this new class of oral agents is welcome.

Rosenstock J, et al Diabetes Care. 2007;30(2):217-223.