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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.
BNP to guide treatment of heart failure
Source: Pfisterer M, et al. BNP-guided vs symptom-guided heart failure therapy: JAMA 2009;301:383-392.
For persons aged 65 or older in the United States, congestive heart failure (CHF) remains the most common diagnosis for hospital admission. Despite advances, the outcome of CHF remains daunting, with 5-year mortality rates as high as many malignancies. Because brain natriuretic peptide (BNP) reflects left ventricular wall stress, it can be useful to assist in diagnosis of CHF. Additionally, some, but not all, clinical trials have suggested that intensification of therapy to achieve optimization of BNP is associated with improved outcomes. The TIME-CHF study was devised to provide a more definitive comparison between the success of treatment intensification based upon symptoms vs level of BNP.
Patients with CHF (n = 499) were randomized to BNP-directed management (titrate treatment until BNP < 400 ng/mL) vs symptomatic management (intensify treatment until NYHA class II symptoms or better). Follow-up for the primary endpoint - hospitalization-free survival - was 18 months.
The BNP group experienced more use of aldosterone antagonists as well as more frequent increases in dose and utilization of ACE inhibitors and ARBs. However, there was no difference in the primary endpoint. In subjects age < 75 years, there was a reduction in mortality favoring BNP-directed management; however, because this was a secondary endpoint and the primary endpoint did not achieve statistical significance, it must be considered exploratory rather than established. BNP-guided intensification of treatment is no more effective than standard symptom-directed clinical methods.
Clopidogrel and CV events
Source: Simon T, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009;360:363-375.
Utilization of clopidogrel (CPG) in patients with acute coronary syndromes (ACS) is well established. Similarly, long-term prophylaxis with CPG for secondary prevention of CV events is evidence-based: The CAPRIE trial indicated that CPG is marginally superior to aspirin for endpoint reduction, and the PROFESS trial demonstrated that ER-dipyridamole/aspirin (Aggrenox®) failed to meet the non-inferiority threshold when compared to CPG for stroke prevention.
Residual risk in persons receiving CPG remains substantial, suggesting that perhaps the efficacy of CPG is not universal; might some subjects metabolize CPG differently than others, leading to different levels of efficacy (or adverse effects)?
The FAST-MI study enrolled ACS patients on CPG, and studied the relationship of genetic variants that result in variations in absorption, activation, and biologic activity of CPG. Next, the relationship between these genetic variants and adverse outcomes (death, stroke, MI) were studied.
The most important genetic variant appeared to be at the P450 2C19 gene. Persons with two loss-of-function 2C19 genes were almost 4 times as likely to have a CV event over the next year as persons without. The 2C19 gene is utilized for metabolism of CPG to its active metabolite; lesser antiplatelet activity would be anticipated in persons with impaired 2C19 activity. These results further support the findings of another trial in the same issue of The New England Journal of Medicine that identified increased CV risk in persons with reduced 2C19 P450 functionality.
Vicks VapoRub revisited
Source: Abanses JC, et al. Vicks VapoRub induces mucin secretion, decreases ciliary beat frequency, and increases tracheal mucus transport in the ferret trachea. Chest 2009;135:143-148.
Those of us in the baby-boomer generation may recall the application of a generous quantity of some Vicks® VapoRub®-type salve (VvR) to the chest wall as a time-honored remedy that grandma suggested for folks in distress with the common cold. Toxicity of VvR, rather than efficacy, was the subject of this publication.
As with essentially any therapeutic agent, there is always the potential for adverse effects. Based upon a single case report of a toddler who developed respiratory distress subsequent to peri-nasal application of VvR, Abanses et al investigated potential adverse physiologic effects of VvR by experiments in ferrets.
VvR resulted in increased mucin secretion and decreased ciliary beat frequency (observed by video microscopy), the combination of which could lead to small-airway obstruction. The authors report upon studies of menthol (an ingredient of VvR) in adults. Despite a decrease in nasal airflow, subjects universally report improved nasal symptoms, attributed to the cooling effect of menthol in the nasal passages, which the brain interprets as increased airflow across the nostrils.
VvR appears to be a generally safe remedy, but case reports of adverse effects suggest caution in young children. The case report presented here was initially treated as asthma; clinicians might consider inquiring about VvR use in children who present with new, otherwise unexplained symptoms of respiratory distress.