RESUMO
BACKGROUND: Secretory phospholipase A(2) (sPLA(2)) may play a role in myonecrosis after elective percutaneous coronary intervention (PCI). Inhibition of this enzyme may have a beneficial effect. The central hypothesis of this study was that treatment with varespladib, a small-molecule inhibitor of sPLA(2) would reduce postprocedural release of cardiac biomarkers after elective percutaneous coronary intervention. METHODS AND RESULTS: Between October 2007 and June 2009, 144 stable patients were randomized in a phase II trial to receive varespladib 500 mg PO BID or placebo 3 to 5 days before and for 5 days after elective percutaneous coronary intervention. The primary end point was elevation of troponin I or creatine kinase-MB above the upper limit of normal at 6 to 8 or 18 to 24 hours after percutaneous coronary intervention. Mean age was 63±10 and 64±10 years, with 38% and 42% with diabetes mellitus and 29% and 28% with prior myocardial infarction for the varespladib and placebo groups, respectively. The primary end point occurred in 75% of varespladib and 63% of placebo patients (P=0.14). Troponin I 3 times the upper limit of normal was observed in 57% and 50% (P=0.39) and creatine kinase-MB 2 times the upper limit of normal in 14% and 3% (P=0.018). Median (first and third quartiles) change in high-sensitivity C-reactive protein in these 2 groups was 0.65 mg/L (-0.18 and 1.48) and 0.70 mg/L (0.00 and 1.50) at 18 to 24 hours (P=0.81) and 0.20 mg/L (-0.70 and 1.40) and 0.60 mg/L (-0.12 and 1.72) at 3 to 5 days (P=0.23), whereas change in sPLA(2) activity at 3 to 5 days in a subset was -2.85 ng/ml (-3.40 and -1.85) and 0.25 ng/ml (-0.20 and 0.85) (P<0.001). CONCLUSIONS: Inhibition of sPLA(2) by varespladib administered for 3 to 5 days before the procedure does not reduce periprocedural myonecrosis associated with elective percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00533039.
Assuntos
Acetatos/uso terapêutico , Síndrome Coronariana Aguda/enzimologia , Angioplastia/efeitos adversos , Indóis/uso terapêutico , Fosfolipases A2 Secretórias/antagonistas & inibidores , Fosfolipases A2 Secretórias/metabolismo , Acetatos/farmacologia , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Biomarcadores/sangue , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Indóis/farmacologia , Cetoácidos , Masculino , Pessoa de Meia-Idade , Fosfolipases A2 Secretórias/sangueRESUMO
PURPOSE: To investigate the clinical applicability of a physical principle that suggests that a large globe offers less resistance to applanation than a smaller one. SETTING: Referral practice, Bridgeport, Connecticut, USA. METHODS: The correlation between axial length and applanation tonometry in 513 adult eyes, arbitrarily chosen from a referral practice, was examined using regression analysis. RESULTS: A statistically significant negative correlation was found; that is, for every 1.0 mm increase in axial length, the tonometry value was 0.29 units lower (P =.0002). In women, the mean axial length was 1.04 mm shorter and the mean intraocular pressure 0.54 mm Hg higher than in men. CONCLUSIONS: Globe size influenced applanation tonometry readings. Hence, when the tonometry record does not fit the clinical findings, axial length measurement may help interpret its significance.
