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.

Which is better for hypertension?

Source: Jamerson K, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high risk patients. N Engl J Med 2008;359:2417-2428.

JNC 7 is probably the consensus document most utilized by U.S. clinicians to make decisions about HTN. The ALLHAT trial was instrumental in establishing the equal efficacy of chlorthalidone, amlodipine, and lisinopril in reference to mortality, with some subgroups (CHF, stroke) showing superiority of chlorthalidone. These results led to the suggestion that diuretic therapy be a foundation of HTN treatment.

Clinical trials have consistently demonstrated that only a minority of patients are able to have their HTN controlled on monotherapy, and little direction has been available to guide therapy about which combination of agents provides best outcomes. The ACCOMPLISH trial was designed to compare outcomes in HTN patients (n = 11,506) considered to be high-risk because of substantial comorbidity (e.g., PAD, LVH, MI, stroke, CKD). The two regimens compared were ACE/CCB (benazepril/amlodipine) and ACE/HCTZ (benazepril/hydrochlorothiazide). The primary endpoint was a composite of CV death, nonfatal MI/stroke, hospitalization for angina, sudden death resuscitation, and revascularization.

The trial was stopped early at 36 months when the clear advantage of ACE/CCB was seen: a 20% relative risk reduction for the primary endpoint. In situations where clinicians are choosing combination therapy, ACE/CCB has been superior to ACE/HCTZ. Because HCTZ and chlorthalidone are not identical, there is some controversy over whether results would have been the same had chlorthalidone (the agent used in ALLHAT) been used instead. At the current time, since the vast majority of prescriptions for an antihypertensive diuretic in the United States employ HCTZ, these results should be generalizable to most practice situations.

Putting sunscreen to the test

Source: Sang SQ, et al. In vitro assessments of UVA protection by popular sunscreens available in the United States. J Am Acad Dermatol 2008; 59:934-942.

SPF stands for "sun protection factor," but if FDA recommendations change, the name will soon stand for "Sunburn Protection Factor" because of the recognition that current SPF testing reflects erythema effects of UVA light in the 320-340 nm and UVB light in the 290-320 nm wavelengths, but does not necessarily reflect efficacy for other photodamaging wavelengths. UVA light in the 340-400 nm range is also dermotoxic, but impact of sunscreen on this light component has not previously been included in labeling. In August 2007, the FDA suggested a new rating scale that includes a ratio of UVA 340-400 nm (termed UVA1) to total UV light absorption. Agents that have low efficacy for absorbing UVA1, even though they have good efficacy for other wavelengths, would be rated lower in overall efficacy.

An analysis of 13 OTC sunscreen products using the new FDA criteria found 8 to provide medium protection and 5 to provide high protection. All but one of the selected products had an SPF of at least 30. If the proposed FDA metric becomes widely accepted, consumers will have an opportunity to better appraise the overall efficacy of sunscreen products.

Triglycerides and risk of stroke

Source: Freiberg JJ, et al. Nonfasting triglycerides and risk of ischemic stroke in the general population. JAMA 2008;300:2142-2152.

The consistent and strong relationship between LDL and adverse CV events, coupled with widely replicated risk reduction achieved with statins, leaves little doubt about the risk-benefit ratio of such intervention. On the other hand, the relationship between triglycerides (TRGs) and CV events, and the benefits of lowering elevated TRGs, is much less well established.

The Copenhagen City Heart Study has been following approximately 14,000 men and women since 1976. Although TRGs are typically measured fasting, the authors of this paper measured non-fasting TRG (nf-TRG) to gain insight into associated CV risk.

An analysis was performed comparing 6 incremental levels of nf-TRG. The reference level was nf-TRG < 89 mg/dL. Risk for stroke was assessed for men and women, at increments of 89 mg/dL, from an nf-TRG level of 89 mg/dL to > 443 mg/dL. For both men and women, ischemic stroke increased with increasing levels of nf-TRG. For instance, individuals with nf-TRG > 443 mg/dL had a hazard ratio 2.5-3.8 times greater than persons with nf-TRG < 89 mg/dL.

These intriguing findings suggest that nf-TRG might be useful, in concert with LDL, as a target for CV risk reduction. Of course, whether intervention to modulate nf-TRG is appropriate will depend on future interventional trials documenting that reduction of nf-TRG is beneficial.