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We-P11:237 Aspirin resistance is associated with aspirin dosage, mean platelet volume and platelet count in patients with acute coronary syndromes
Pl l
398
Wednesday, June 21, 2006: Poster Session Optinwtl atherosclerosis nwmagement ( lst part)
Objective: evaluation of TXA2 synthesis and platelet function in patients with vascular disease chronically treated with ASA (50-300) mg/day. M e t h o d s : We studied 455 patients: 291 with cerebrovascular and 164 with cardiovascular diseases, treated for more than a month and a control group of ASA-free normal subjects (n=110). After a personal interview, only patients that took ASA within 12-24 hours before evaluation were included. Platelet aggregation, recruitment, TXA2, and 14C-5HT release induced by collagen ( l l t g / m L ) were performed as described (Vall6s J et. al. Circulation 1998; 97:350-355). Results: Partial inhibition ( < 9 5 % ) of TXA2 was found in 39/455 (7.9%) (Group A), while the rest had an inhibition > 95% (Group B). Partial inhibition shows some dependence with the ASA dose. When Group A was evaluated again after a dose adjustment on therapeutic range, all patients reached optimal inhibition of TXA2. Importantly, Group A had a significant (p<0.01) increase of collagen-induced platelet aggregation, 14C-5HT release and platelet recruitment in whole blood vs. Group B. Conclusions: Despite compliance, optimal TXA2 inhibition was not achieved in 7.9% of the patients. This was due in our patients to insufficient daily dose of ASA, which resulted in a marked increase of platelet reactivity. This could reduce the protective effects of aspirin. (Grants FIS:03/0270 and C03/06/AVC AVCiT iT: G03/005).
We-P11:236
ACETYLSALICYLIC ACID AND CLOPIDOGREL RESISTANCE: POSSIBLE ROLE OF RISK FACTORS, M E D I C A T I O N A N D HEMORHEOLOGICAL VARIABLES
G. Feher, K. Koltai, E. Papp, Z. Keszthelyi, B. Alkonyi, E Kenyeres, H. Rapp, G. Kesmarky, K. Toth. 1st Department of Medicine, Universi~ of Pecs,
Medical School, Pets, Hungary Introduction: The aim of our present study was to compare the characteristics of patients with effective platelet inhibition by A S A and CLP to those with ineffective one. M e t h o d s : 599 patients taking 100-325 mg A S A daily and 157 patients taking 75 mg clopidogrel daily with chronic cardio- and cerebrovascular diseases were involved in our study. Platelet aggregation and hemorheological parameters were measured. Results: Patients with effective A S A inhibition had significantly lower plasma fibrinogen level (p < 0.05) and red blood cell aggregation values (p < 0.01). More of them suffered from hypertension (p < 0.05) compared to the other group. In the case of effective platelet aggregation beta-blockers and ACE inhibitors (p < 0.05), while in the group of ineffective platelet aggregation statins were taken more frequently (p < 0.05). Patients with effective CLP inhibition had lower BMI (p < 0.05) and in the case of ineffective platelet aggregation benzodiazepines and selective serotonin reuptake inhibitors were taken more frequently (p < 0.05). Conclusion: The background of ineffective antiplatelet medication has not yet been fully elucidated. Higher fibrinogen concentration increases red blood cell aggregation and can also result in increased platelet aggregation. An additive effect of several drugs may be involved in the effective therapy, on the other hand drug interactions may play a role in the inefficient antiplatelet bioavaJlability. The significant difference in BMI may suggest that clopidogrel therapy should be weight-adjusted. q
We-P11:237
/
A S P I R I N R E S I S T A N C E IS A S S O C I A T E D W I T H ASPIRIN DOSAGE, MEAN PLATELET VOLUME A N D P L A T E L E T C O U N T IN P A T I E N T S W I T H ACUTE CORONARY SYNDROMES
S. A d k e l , A. Yildirir, A. Aydinalp, U. Bal, G. Kaynar, K. Demirtas, B. Ozin, H. Muderrisoglu. Baskent Universi~ Facul~ of Medicine, Department of
Cardiology, Ankara, Turkey B a c k g r o u n d : Prior aspirin (ASA) use is an independent predictor of increased cardiovascular risk among patients with acute coronary syndromes (ACS). Clinical trials indicate that decreased responsiveness to aspirin therapy is associated with an increased risk of atherotrombotic events. In this study, we sought to assess factors affecting aspirin resistance in patients with ACS. M e t h o d s : Sixty seven patients who were on ASA therapy and hospitalized with the diagnosis ACS were included in the study. Platelet function was measured with the Platelet Function Analyzer (PFA)-100 on admission. ASA resistance by PFA-100 was defined as having a normal collagen and/or epinephrine closure time < 161 seconds. Demographic and clinical data were collected to analyze the predictors of A S A resistance.
Results: The mean age of the study population was 67-4-11 years and 27 (40%) were females, 51 (76.1%) were dyslipidemic, 30 (44.8%) were diabetic.ASA resistance was noted in 22 (32.8%) and high platelet volume (> 10.2 r ) was noted in 16 (23.9%) patients. Baseline clinical characteristics of ASA resistant and ASA responsive patients were similar (p>0.05). ASA resistance group had lower aspirin dose (154-4-91 mg/day vs 233-4-95 mg/day, p=0.02), higher platelet volume (45% vs 15%, p:0.004), mean platelet volume (MPV) (9,86-4-1.4 fl vs 8,9-4-0.6 r, p=0.003) and platelet count (× 1000/mm 3) (284-t- 83 vs 238-t- 78, p=0.04) than ASA responsive group. Conclusion: ASA resistance is associated with aspirin dosage, MPV and platelet count in ACS. Large-scale studies are needed to evalute the efficacy of alternative antiplatelet agents in ASA-resistant patients. I
I We-P11:238 I EFFECT OF TWO DIFFERENT DOSES OF ASPIRIN ON PLATELET AGGREGATION AND T H R O M B O X A N E F O R M A T I O N IN P A T I E N T S UNDERGOING CABG i
M. Brambilla;'2, A. A n s e l m o ; , C. Centenaxo;, E. Tremoli 1,2, A. Paxolaxi 1, M. Camera 1'2 . 1Centro Cardiologico Monzino, Milan, Italy." 2Dept.
Phat'macological Sciences, Universi~ of Milan, Milan, Italy Aspirin is the most widely used antiplatelet agent that prevents the formation of TXA2 by inhibition of COX-1. Despite cleax benefit from aspirin (ASA) in patients with cardiovascular disease, evidence of heterogeneity in the individual response has given rise to the concept of aspirin failure to prevent a thrombotic event. Objective: To investigate platelet function and the antiplatelet effect of ASA in 44 patients undergoing CABG and randomly assigned to 100 or 325 mg/d A S A treatment. M e t h o d s : Venous blood was collected before, 3 and 5 days after surgical intervention. Collagen induced aggregation of platelet rich plasma (PRP) and TXB2 levels in PRP and in serum were evaluated. Results: Before surgery the two groups of patients were comparable in terms of platelet aggregation and thromboxane B2 levels. After 2 days of A S A treatment, collagen-induced aggregation was inhibited by 38% in both groups of patients and a similar degree of inhibition was recorded 5 days after surgery. 3 days after surgery serum TXB2 levels were reduced by 95% and 90% in patients receiving 325 or 100 mg/d A S A with residual TXB2 of 10.8-t-2.2 and 24.6-t-3.7 ng/ml (p<0.02), respectively. No significant differences in the levels of TXB2 were observed after 5 days. Measurement of TXB2 in collagen stimulated PRP showed a 80% reduction in patients treated with 100 mg ASA and 95% in those treated with 325 mg/d. C o n d u s i o n s : In patients undergoing CABG A S A 325mg/d led to an almost complete inhibition of TXB2 production, whereas A S A 100mg/d showed a residual amount of this metabolite. Inhibition of platelet aggregation was comparable with the two treatments.
IWe-P11:2391 EB RL OY OT HDRCOECLYLT EC ODUENFTO RAMR EA BAISLSIOT YC I AATNEDD WWHI ITTHE i
A S P I R I N R E S I S T A N C E IN H I G H - R I S K V A S C U L A R PATIENTS L. Mannini I , R. Marcucci 1 , R. Paniccia 1 , E. Antonucci I , L. Evangelisti I , L. Lucarini 1 , A.M. Gori 1 , D. Prisco 1 , G.F. Gensini 1'2 , R. Abbate 1 .
1Department of Medical and Surgical Critical Care, Thrombosis Centre, Universi~ of Florence, Florence, Italy." 2 Centro S. Maria Agli Ulivi, Fon&tzione Don Carlo Gnocchi, Onlus IRCCS, bttpruneta, Italy Recently the phenomenon of aspirin resistance has been object of several studies, but no data axe available on the possible role of the haemorheologic parameters in affecting platelets function and resistance to antiplatelet agents. A i m of our study was to evaluate platelet function and haemorheology in patients with acute coronary syndromes (ACS), receiving double antiplatelet therapy with aspirin and clopidogrel. The study population included 301 (231 M/70 F; age: 66-4-13 yrs) consecutive adult patients admitted to the Coronary Care Unit of the Azienda Ospedaliero-Universitaria Careggi, with diagnosis of acute myocardial infarction or unstable angina. We assessed: whole blood viscosity (WBV) at shear rates of 0.512 s 1 and 94.5 s 1 , plasma viscosity (PLV) at 94.5 s 1 shear rate, erythrocyte deformability index (DI) and PFA-100 closure times with ADP (PFA/ADP) and epinephrine (PFA/EPI). We considered any PFA-100-EPI result <203 sec (95th percentile of control distribution) to be indicative of aspirin resistance. 104/301 patients (34.5%) had PFA/EPI CTs in the reference range (Group 1) whereas the remaining had values higher than 203 sec.
XIV bztentational Symposium on Atherosclerosis, Rome, Italy, June 18-22, 2006
398
Wednesday, June 21, 2006: Poster Session Optinwtl atherosclerosis nwmagement ( lst part)
Objective: evaluation of TXA2 synthesis and platelet function in patients with vascular disease chronically treated with ASA (50-300) mg/day. M e t h o d s : We studied 455 patients: 291 with cerebrovascular and 164 with cardiovascular diseases, treated for more than a month and a control group of ASA-free normal subjects (n=110). After a personal interview, only patients that took ASA within 12-24 hours before evaluation were included. Platelet aggregation, recruitment, TXA2, and 14C-5HT release induced by collagen ( l l t g / m L ) were performed as described (Vall6s J et. al. Circulation 1998; 97:350-355). Results: Partial inhibition ( < 9 5 % ) of TXA2 was found in 39/455 (7.9%) (Group A), while the rest had an inhibition > 95% (Group B). Partial inhibition shows some dependence with the ASA dose. When Group A was evaluated again after a dose adjustment on therapeutic range, all patients reached optimal inhibition of TXA2. Importantly, Group A had a significant (p<0.01) increase of collagen-induced platelet aggregation, 14C-5HT release and platelet recruitment in whole blood vs. Group B. Conclusions: Despite compliance, optimal TXA2 inhibition was not achieved in 7.9% of the patients. This was due in our patients to insufficient daily dose of ASA, which resulted in a marked increase of platelet reactivity. This could reduce the protective effects of aspirin. (Grants FIS:03/0270 and C03/06/AVC AVCiT iT: G03/005).
We-P11:236
ACETYLSALICYLIC ACID AND CLOPIDOGREL RESISTANCE: POSSIBLE ROLE OF RISK FACTORS, M E D I C A T I O N A N D HEMORHEOLOGICAL VARIABLES
G. Feher, K. Koltai, E. Papp, Z. Keszthelyi, B. Alkonyi, E Kenyeres, H. Rapp, G. Kesmarky, K. Toth. 1st Department of Medicine, Universi~ of Pecs,
Medical School, Pets, Hungary Introduction: The aim of our present study was to compare the characteristics of patients with effective platelet inhibition by A S A and CLP to those with ineffective one. M e t h o d s : 599 patients taking 100-325 mg A S A daily and 157 patients taking 75 mg clopidogrel daily with chronic cardio- and cerebrovascular diseases were involved in our study. Platelet aggregation and hemorheological parameters were measured. Results: Patients with effective A S A inhibition had significantly lower plasma fibrinogen level (p < 0.05) and red blood cell aggregation values (p < 0.01). More of them suffered from hypertension (p < 0.05) compared to the other group. In the case of effective platelet aggregation beta-blockers and ACE inhibitors (p < 0.05), while in the group of ineffective platelet aggregation statins were taken more frequently (p < 0.05). Patients with effective CLP inhibition had lower BMI (p < 0.05) and in the case of ineffective platelet aggregation benzodiazepines and selective serotonin reuptake inhibitors were taken more frequently (p < 0.05). Conclusion: The background of ineffective antiplatelet medication has not yet been fully elucidated. Higher fibrinogen concentration increases red blood cell aggregation and can also result in increased platelet aggregation. An additive effect of several drugs may be involved in the effective therapy, on the other hand drug interactions may play a role in the inefficient antiplatelet bioavaJlability. The significant difference in BMI may suggest that clopidogrel therapy should be weight-adjusted. q
We-P11:237
/
A S P I R I N R E S I S T A N C E IS A S S O C I A T E D W I T H ASPIRIN DOSAGE, MEAN PLATELET VOLUME A N D P L A T E L E T C O U N T IN P A T I E N T S W I T H ACUTE CORONARY SYNDROMES
S. A d k e l , A. Yildirir, A. Aydinalp, U. Bal, G. Kaynar, K. Demirtas, B. Ozin, H. Muderrisoglu. Baskent Universi~ Facul~ of Medicine, Department of
Cardiology, Ankara, Turkey B a c k g r o u n d : Prior aspirin (ASA) use is an independent predictor of increased cardiovascular risk among patients with acute coronary syndromes (ACS). Clinical trials indicate that decreased responsiveness to aspirin therapy is associated with an increased risk of atherotrombotic events. In this study, we sought to assess factors affecting aspirin resistance in patients with ACS. M e t h o d s : Sixty seven patients who were on ASA therapy and hospitalized with the diagnosis ACS were included in the study. Platelet function was measured with the Platelet Function Analyzer (PFA)-100 on admission. ASA resistance by PFA-100 was defined as having a normal collagen and/or epinephrine closure time < 161 seconds. Demographic and clinical data were collected to analyze the predictors of A S A resistance.
Results: The mean age of the study population was 67-4-11 years and 27 (40%) were females, 51 (76.1%) were dyslipidemic, 30 (44.8%) were diabetic.ASA resistance was noted in 22 (32.8%) and high platelet volume (> 10.2 r ) was noted in 16 (23.9%) patients. Baseline clinical characteristics of ASA resistant and ASA responsive patients were similar (p>0.05). ASA resistance group had lower aspirin dose (154-4-91 mg/day vs 233-4-95 mg/day, p=0.02), higher platelet volume (45% vs 15%, p:0.004), mean platelet volume (MPV) (9,86-4-1.4 fl vs 8,9-4-0.6 r, p=0.003) and platelet count (× 1000/mm 3) (284-t- 83 vs 238-t- 78, p=0.04) than ASA responsive group. Conclusion: ASA resistance is associated with aspirin dosage, MPV and platelet count in ACS. Large-scale studies are needed to evalute the efficacy of alternative antiplatelet agents in ASA-resistant patients. I
I We-P11:238 I EFFECT OF TWO DIFFERENT DOSES OF ASPIRIN ON PLATELET AGGREGATION AND T H R O M B O X A N E F O R M A T I O N IN P A T I E N T S UNDERGOING CABG i
M. Brambilla;'2, A. A n s e l m o ; , C. Centenaxo;, E. Tremoli 1,2, A. Paxolaxi 1, M. Camera 1'2 . 1Centro Cardiologico Monzino, Milan, Italy." 2Dept.
Phat'macological Sciences, Universi~ of Milan, Milan, Italy Aspirin is the most widely used antiplatelet agent that prevents the formation of TXA2 by inhibition of COX-1. Despite cleax benefit from aspirin (ASA) in patients with cardiovascular disease, evidence of heterogeneity in the individual response has given rise to the concept of aspirin failure to prevent a thrombotic event. Objective: To investigate platelet function and the antiplatelet effect of ASA in 44 patients undergoing CABG and randomly assigned to 100 or 325 mg/d A S A treatment. M e t h o d s : Venous blood was collected before, 3 and 5 days after surgical intervention. Collagen induced aggregation of platelet rich plasma (PRP) and TXB2 levels in PRP and in serum were evaluated. Results: Before surgery the two groups of patients were comparable in terms of platelet aggregation and thromboxane B2 levels. After 2 days of A S A treatment, collagen-induced aggregation was inhibited by 38% in both groups of patients and a similar degree of inhibition was recorded 5 days after surgery. 3 days after surgery serum TXB2 levels were reduced by 95% and 90% in patients receiving 325 or 100 mg/d A S A with residual TXB2 of 10.8-t-2.2 and 24.6-t-3.7 ng/ml (p<0.02), respectively. No significant differences in the levels of TXB2 were observed after 5 days. Measurement of TXB2 in collagen stimulated PRP showed a 80% reduction in patients treated with 100 mg ASA and 95% in those treated with 325 mg/d. C o n d u s i o n s : In patients undergoing CABG A S A 325mg/d led to an almost complete inhibition of TXB2 production, whereas A S A 100mg/d showed a residual amount of this metabolite. Inhibition of platelet aggregation was comparable with the two treatments.
IWe-P11:2391 EB RL OY OT HDRCOECLYLT EC ODUENFTO RAMR EA BAISLSIOT YC I AATNEDD WWHI ITTHE i
A S P I R I N R E S I S T A N C E IN H I G H - R I S K V A S C U L A R PATIENTS L. Mannini I , R. Marcucci 1 , R. Paniccia 1 , E. Antonucci I , L. Evangelisti I , L. Lucarini 1 , A.M. Gori 1 , D. Prisco 1 , G.F. Gensini 1'2 , R. Abbate 1 .
1Department of Medical and Surgical Critical Care, Thrombosis Centre, Universi~ of Florence, Florence, Italy." 2 Centro S. Maria Agli Ulivi, Fon&tzione Don Carlo Gnocchi, Onlus IRCCS, bttpruneta, Italy Recently the phenomenon of aspirin resistance has been object of several studies, but no data axe available on the possible role of the haemorheologic parameters in affecting platelets function and resistance to antiplatelet agents. A i m of our study was to evaluate platelet function and haemorheology in patients with acute coronary syndromes (ACS), receiving double antiplatelet therapy with aspirin and clopidogrel. The study population included 301 (231 M/70 F; age: 66-4-13 yrs) consecutive adult patients admitted to the Coronary Care Unit of the Azienda Ospedaliero-Universitaria Careggi, with diagnosis of acute myocardial infarction or unstable angina. We assessed: whole blood viscosity (WBV) at shear rates of 0.512 s 1 and 94.5 s 1 , plasma viscosity (PLV) at 94.5 s 1 shear rate, erythrocyte deformability index (DI) and PFA-100 closure times with ADP (PFA/ADP) and epinephrine (PFA/EPI). We considered any PFA-100-EPI result <203 sec (95th percentile of control distribution) to be indicative of aspirin resistance. 104/301 patients (34.5%) had PFA/EPI CTs in the reference range (Group 1) whereas the remaining had values higher than 203 sec.
XIV bztentational Symposium on Atherosclerosis, Rome, Italy, June 18-22, 2006