Clinical Briefs By Louis Kuritzky, MD
Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Sucampo Pharmaceuticals, Takeda, Boehringer Ingelheim; and is a consultant and on the speaker's bureau for Novo Nordisk, Lilly, Daiichi Sankyo, Forest Pharmaceuticals, Cephalon, Novartis, and Sanofi Aventis.
PPIs and Clopidogrel: Do We Have to Worry?
Source: O'Donoghue ML, et al. Lancet 2009;374:989-997.
The antiplatelet effect of clopidogrel is dependent upon its conversion and activation through the 2C19 pathway of the P450 system. Blockade of this pathway occurs because of genetics, in persons who do not have sufficiently active 2C19, and pharmacotherapies that specifically block 2C19. Proton pump inhibitors (PPIs), particularly omeprazole, are recognized to be 2C19 inhibitors. Is there reason for concern?
Although the in vitro aspects of PPI-antiplatelet interactions are of interest, it is probably more important to see whether such interactions affect the bottom line: CV events. Fortunately, there is a large - and largely reassuring - database from which to glean the impact of the PPI-antiplatelet interaction.
The PRINCIPLE-TIMI and TRITON-TIMI are acute coronary syndrome trials in which clopidogrel and/or prasugrel were used. In both of these trials, some participants were also using PPIs, providing an opportunity to see if concomitant utilization of a platelet inhibitor and PPI affected outcomes.
Subjects who were on clopidogrel who also were receiving PPIs showed less effective platelet inhibition compared to clopidogrel alone (in vitro testing). This effect was less pronounced among prasugrel recipients, consistent with its lesser dependence upon the P450 system for full activity.
Although platelet aggregometry demonstrated diminished antiplatelet effect, in these 2 trials (total n > 15,000), there was no signal of increased adverse outcomes in subjects concomitantly receiving a PPI and clopidogrel or prasugrel. PPIs provide important GI protection for persons on NSAIDs, as well as excellent symptomatic relief for GERD patients. These data suggest that PPIs need not be avoided when treating acute coronary syndromes with clopidogrel or prasugrel.
Beyond Diabetes Prevention
Source: Perreault L, et al. Diabetes Care 2009;32:1583-1588.
Most individuals with predia-betes, defined as either impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both, will go on to develop diabetes unless an intervention is instituted. To date, diet, exercise, and pharmacotherapy have all been shown to reduce progression to diabetes by as much as 60%, with diet + exercise being the clearest winner. Although prevention (or delay) of diabetes is important, many persons who do not progress to overt diabetes during a diabetes prevention trial remain prediabetic, which is still a high-risk category. The report by Perreault et al describes factors which were associated, during intervention for diabetes prevention, with restoration to normal glucose regulation.
The Diabetes Prevention Program was the largest diabetes prevention trial to date (n = 3234). Prediabetes subjects were randomized to intensive lifestyle intervention (diet + exercise), metformin (850 mg bid), or placebo, with a mean follow-up of 3 years.
Within the categories of impaired fasting glucose (glucose = 100-125 mg/dL) and impaired glucose tolerance (glucose = 140-199 mg/dL on oral glucose tolerance testing), persons with lesser baseline impairments were more likely to enjoy restoration to normal glucose regulation. Similarly, younger subjects and those who successfully lost weight regained euglycemia more often.
We can encourage our patients that efforts to prevent diabetes can do that and, in some cases, even restore glucose regulation to normal.
Influenza Vaccine Efficacy: Flu Shot vs Nasal Mist
Source: Monto AS, et al. N Engl J Med 2009;361:1260-1267.
Is influenza management getting more complicated, or is it just me? Dealing with vagaries of virus antigenic shift and drift, the moving target of antiviral resistance, insufficiently sen-sitive point-of-care testing for influ-enza, and the ever-evolving designa-tion of appropriate risk groups for "seasonal" (regular) vs "novel" (pandemic) influenza prevention is a daunting challenge.
Two major categories of trivalent influenza vaccine are available to prevent seasonal flu: inactivated (SHOT) and live attenuated (NASAL). A randomized double-blind placebo-controlled trial compared the efficacy of SHOT and NASAL vaccine to prevent influenza. Adults 18-49 years (excluding persons with contraindications to live vaccine) received one vaccine or placebo, and recorded respiratory symptoms through the 2007-2008 flu season; throat swabs were obtained for confirmation of influenza during periods of respiratory symptoms.
Among the 1963 subjects in this study, 6.1% experienced laboratory-confirmed influenza. SHOT efficacy vs placebo was 68% compared to NASAL efficacy of 36%. In the 2007-2008 influenza season, risk reduction of influenza was almost twice as great with SHOT.
The antiplatelet effect of clopidogrel is dependent upon its conversion and activation through the 2C19 pathway of the P450 system. Blockade of this pathway occurs because of genetics, in persons who do not have sufficiently active 2C19, and pharmacotherapies that specifically block 2C19. Proton pump inhibitors (PPIs), particularly omeprazole, are recognized to be 2C19 inhibitors. Is there reason for concern?Subscribe Now for Access
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