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.

Efficacy and Safety of Benazepril for Advanced Chronic Renal Insufficiency

Ace inhibitors have been shown to improve renal outcomes in hypertension and to reduce proteinuria. By decreasing intraglomerular pressure, ACE inhibitors can produce a decline (usually transient) in renal function; clinicians sometimes are anxious about using ACE inhibitors in persons with chronic kidney disease, for fear of producing hyperkalemia or worsening renal function. This reluctance has been particularly prominent when creatinine levels rise above 2.0-2.5 mg/dL. Indeed, in the recent past, some textbooks have explicitly stated that ACE inhibitors are to be avoided when the creatinine surpasses 2.5 mg/dL. In contrast, studies have shown that the renal benefits of ACE inhibitors increase as the degree of renal impairment rises, but there has been a paucity of data from persons with creatinine > 3.0 mg/dL.

Hou et al studied subjects with CKD (n = 422) divided into Group 1 (baseline creatinine 1.5-3.0 mg/dL) and Group 2 (baseline creatinine 3.1-5.0 mg/dL). Group 1 received treatment with benazepril 20 mg/d; Group 2 was randomized to benazepril 20 mg/d or placebo. Both groups were treated for 3.4 years. Subjects were continued on their usual antihypertensive therapies.

The risk of the composite primary end point (doubling of serum creatinine, end-stage renal disease, or death) was reduced by 43% with benazepril, compared to placebo. Proteinuria and renal function decline were favorably affected. It is critical to recognize that the authors excluded subjects whose creatinine increased by > 30% or whose potassium rose over 5.6 mmoL/L during the initial 8 week run-in; clinicians would be wise to use similar boundaries.

Hou FF, et al. N Engl J Med. 2006; 354:131-140.


Prognostic Value of Thyroid Hormone Levels in Acute MI: Just an Epiphenomenon?

Acute illness may result in alterations in thyroid function tests commonly referred to as Sick Euthyroid Syndrome (SES). SES is characterized by lowered levels of T3 and T4, with a ‘normal' TSH: the peculiarity of the syndrome is that in normal circumstances, one would anticipate a rise in TSH when T3 and T4 drop. This aberrancy suggests a transient diminution in pituitary responsivity.

Cardiac tissue is exquisitely responsive to circulating thyroid hormone. In other disease states, SES has been shown to be associated with a poor outcome. Satar et al investigated the relationship between thyroid function status and outcomes in persons with acute myocardial infarction (AMI). Subjects were comprised of 95 patients with AMI, 26 patients with acute chest pain but no MI, and 114 controls (no chest pain, no MI).

In acute MI patients, a reduced T3 or T4 was associated with poorer survival, especially if accompanied by a higher TSH. Apparently, during AMI there is a downregulation of thyroid hormone production. Lower levels of T3 and T4 associated with AMI correlate with worse outcome.

Satar S, et al. Am Heart Hosp J. 2005;3:227-233.


Nonsteroidal Anti-inflammatory Drugs and the Risk of Actinic Keratoses and Squamous Cell Cancers of the Skin

Cyclo-oxygenase (COX) is overexpressed in some cancer cells, including squamous cell carcinoma of the skin (SCC) and actinic keratoses (AK). Basal cell carcinoma does not exhibit COX overexpression. Because recent animal studies have found COX inhibitors to have a favorable effect in SCC, an investigation in humans is timely.

Australians have a very high incidence of SCC and AK. In a small community in Queensland, SCC patients (n = 86) were compared with controls (n = 187) in reference to regular use of NSAIDs, defined as at least 2 NSAID tablets weekly. NSAID use was divided into ‘low frequency users' of NSAIDs (ie, at least 2 tablets/week) and ‘high frequency users' (ie, at least 8 tablets/week)

There was a dramatic difference in NSAID use between those with SCC or AK and those without. The odds ratio for high-frequency NSAID users having SCC was 0.07, or a 93% lesser odds ratio! Similarly, the number of AK lesions for regular NSAID users was approximately half that of non-users. NSAID use may have a favorable impact upon risk for both AK and SCC.

Butler GJ, et al. J Am Acad Dermatol. 2005;53:966-972.