58 Cilostazol or Pentoxifylline for Claudication?
David L. Dawson, Wilford Hall Med Ctr, Lackland AFB, AK; Hugh G. Beebe, Jobst Vascular Ctr, Toledo, OH; Michael H. Davidson, Chicago Ctr for Clin Res, Chicago, IL; David A. Chinoy, Jacksonville CV Ctr, Jacksonville, FL; J Alan Herd, Baylor Coll of Medicine, Houston, TX; William R. Hiatt, Univ of Colorado, Denver, CO; Jeffrey D. Heckman, Enoch B. Bortey, William P. Forbes, Otsuka America Pharm, Inc., Rockville, MD
Background: Pentoxiphylline (PTX) is the only FDA approved drug for treating claudication symptoms in patients with peripheral arterial disease (PAD), but a series of US trials has demonstrated efficacy of a new drug, cilostazol (CLZ). The present study compared these two drugs. Methods: A 24 week, multicenter, randomized, double-blind, placebo and active-controlled parallel group study was conducted to assess the relative efficacy and safety of CLZ 100 mg bid, PTX 400 mg tid, and placebo (PLC) for the treatment of claudication secondary to PAD. Results: Fifty-four centers enrolled 698 patients with stable claudication. Efficacy was evaluated using a constant speed, variable-grade treadmill protocol at baseline and every 4 weeks. Compared to PLC, CLZ significantly increased Maximum Walking Distance (MWD) and Pain Free Walking Distance (PFD), but PTX did not. There were 6 deaths in the study (CLZ=2, PTX=3, PLC=1). Serious adverse events were equal in each treatment group (CLZ 11.9%, PTX 13.4%, PLC 13.0%). The most common non-serious adverse events were headache (CLZ 27.8%, PTX 11.2%, PLC 11.7%), abnormal stools (CLZ 14.5%, PTX 5.2%, PLC 2.9%), and palpitations (CLZ 17.2%, PTX 2.2%, PLC 1.3%). Conclusion: CLZ is an effective and well-tolerated alternative for treating symptoms of claudication. PTX did not significantly improve treadmill-measured walking distance, compared to PLC.⇓
3694 Thromboembolic Risk in Atrial Flutter: preliminary results of the italian multicenter FLASIEC study
Giovanni Corrado, Ospedale Valduce, Como Italy; Aurelio Sgalambro, Ospedale Civico, Codogno Italy; Francesco Gentile, Ospedale Bassini, Milano Italy; Antonio Mantero, Ospedale Niguarda, Milano Italy; Mauro Santarone, Ospedale Valduce, Como Italy; Maurizio Gasparini, Rosaria Bufalino, Istituto Humanitas, Milano Italy; Alberto Morabito, Istituto di Statistica e Biometria. Universita’ degli Studi, Milano Italy; Ketty Savino, Cattedra di Cardiologia. Universita’ di Perugia., Perugia Italy; Riccardo Schiavina, Ospedale San Gerardo, Monza Italy; Rolando Mangia, Ospedale Cardinale Panico, Tricase Italy
Patients with atrial flutter (AFL) are believed to be at lower risk of thromboembolism (TE) than pts with atrial fibrillation. However the incidence of atrial thrombi (AT) and the need of anticoagulation (AC) in pts with AFL is not well established. We prospectively evaluated in the Italian multicenter FLASIEC (Flutter Atriale Società Italiana di Ecografia Cardiovascolare) study 98 pts with AFL (69 m., aged 71±10 yrs); exclusion criteria were history of atrial fibrillation, mitral stenosis and prosthetic mitral valve. AFL duration was <1 day in 8 pts, 12±26 days in 46 pts and was unknown in 44 pts. 90/98 pts underwent transesophageal echocardiogram (TEE). Left atrial spontaneous echocontrast (SEC) was found in 39/90 pts (43%). Left atrial thrombi were found in 7 pts (8%), right atrial thrombi in 3 pts (3%). SEC and left atrial thrombi were correlated with AC status, age, sex, previous TE, AFL duration, AFL cycle length, organic heart disease, hypertension, left atrium diameter, left ventricular ejection fraction and left atrial appendage contractility (emptying/filling velocities, emptying fraction and eyeball evaluation). SEC correlated with left atrial appendage filling vel. (Odds ratio=0.97, p<0.02) and with eyeball reduced or absent left atrial appendage contractility (OR=3.25, p<0.005). No predictors of the presence of left atrial thrombi could be elucidated through data analysis. Conclusions: 1) Atrial thrombi and SEC are not uncommon in patients with AFL. 2) We were unable to find clinical and echocardiographic predictors of the presence of left atrial thrombi. 3) AC should be considered in pts with AFL candidates to cardioversion.
Young Investigator Prize in Thrombosis
An Altered Responsiveness to Thromboxane A2 Production Mediates an Increased Aspirin in PlA2 Platelets
Glen E. Cooke, Ohio State University; Paul F. Bray, Jeanette D. Hamlington, Johns Hopkins University School of Medicine; Youm M. Pham, Pascal J. Goldschmidt-Clermont, Ohio State University.
Aspirin (ASA) reduces the rates of first myocardial infarction (MI) and recurrent MI by 25% to 50%. We have previously reported that the PIA2 polymorphism of the GPIIIa subunit of the fibrinogen receptor (GPIIb-IIIa) represents a risk factor for unstable coronary events. The study population consisted of healthy male volunteers (15 PIA1/A1 and 11 PIA1/A2). Venous blood samples were obtained between 7 and 9 am in the fasting state. Platelet-rich plasma (PRP) was used for platelet aggregation by the Born methods with epinephrine as an agonist. Various concentrations of ASA (0.053 to 53 μmol/L) were tested on epinephrine-induced aggregation. In addition, thromboxane B2 was measured by enzyme immunoassay with baseline aggregation and during aggregation influenced by ASA. Baseline aggregation was similar between PIA1/A1 and PIA1/A2 platelets [82.8±2.2% (mean±SEM) vs 76.2±2.8%, respectively. P>0.05]. PIA1/A2 platelets were significantly more sensitive to ASA inhibition than PIA1/A1 platelets at ASA concentrations of 0.53 μmol/L (51.5±6.3% vs 73.2±5.1%, respectively, P=0.02) and 5.3 μmol/L (39.0±5.3% vs 60.8±5.7%, respectively, P=0.01). The IC50 for ASA in PIA1/A2 platelets (2.3±1.2 μmol/L) was significantly lower than the IC50 for ASA in PIA1/A1 platelets (22.8±5.8 μmol/L, P=0.004). Thromboxane B2 levels were not significantly different between PIA1/A1 and PIA1/A2 platelets either during baseline aggregation or with aggregation in the presence of various concentrations of ASA. The inhibitory action of ASA in vitro is heightened on platelets displaying the PIA2 polymorphism of the glycoprotein IIIa of the fibrinogen receptor (GPIIb-IIIa). This significant difference in ASA efficacy between PIA1/A1 and PIA1/A2 was seen at concentrations routinely found in patients (0.6 to 14 μmol/L). In addition, a 10-fold reduction in the IC50 of ASA was measured on PIA1/A2 platelets relative to PIA1/A1 platelets. Furthermore, our data indicate that the difference between PIA1 and PIA2 is not related to the activity of COX-1 but seems to be mediated by a mechanism downstream from thromboxane A2.
[Corrections for Vol 98, Number 17, October 27, 1998. Pages I-1–I-1016.]
- Copyright © 1999 by American Heart Association