Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
Circulation. 2003;107:2908-2913
Published online before print June 9, 2003, doi: 10.1161/01.CIR.0000072771.11429.83
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
107/23/2908    most recent
01.CIR.0000072771.11429.83v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gurbel, P. A.
Right arrow Articles by O’Connor, C. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gurbel, P. A.
Right arrow Articles by O’Connor, C. M.
Related Collections
Right arrow Platelet function inhibitors
Right arrow Catheter-based coronary interventions: stents
Right arrow Platelets

(Circulation. 2003;107:2908.)
© 2003 American Heart Association, Inc.


Clinical Investigation and Reports

Clopidogrel for Coronary Stenting

Response Variability, Drug Resistance, and the Effect of Pretreatment Platelet Reactivity

Paul A. Gurbel, MD; Kevin P. Bliden, BS; Bonnie L. Hiatt, MD; Christopher M. O’Connor, MD

From the Sinai Center for Thrombosis Research (P.A.G., K.P.B., B.L.H.), Baltimore, Md, and Duke Clinical Research Institute (C.M.O.), Durham, NC.

Correspondence to Paul A. Gurbel, MD, Sinai Center for Thrombosis Research, Hoffberger Bldg, Suite 56, 2401 W Belvedere Ave, Baltimore, MD 21215. E-mail pgurbel{at}lifebridgehealth.org


*    Abstract
up arrowTop
*Abstract
down arrowIntroduction
down arrowMethods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Background— Clopidogrel is administered to prevent stent thrombosis; however, the uniformity of platelet inhibition after treatment and the influence of pretreatment reactivity on drug response have not been described.

Methods and Results— Platelet aggregation (5 and 20 µmol/L ADP), the activation of glycoprotein IIb/IIIa (PAC-1 antibody), and the expression of P-selectin were measured in patients undergoing elective coronary stenting (n=96) at baseline and at 2 hours, 24 hours, 5 days, and 30 days after stenting. All patients received aspirin (325 mg). Clopidogrel (300 mg) was administered in the catheterization laboratory and followed by 75 mg daily. There was marked interindividual variability in drug response as measured by all markers that showed a normal distribution. Resistance, defined as baseline aggregation (%) minus posttreatment aggregation (%) ≤10% by 5 µmol/L ADP, was present in 31% and 15% of patients at 5 and 30 days, respectively. Patients with the highest pretreatment platelet reactivity remained the most reactive at 24 hours after treatment (P<0.0001).

Conclusions— Interindividual variability in the platelet inhibitory response from clopidogrel occurs in patients undergoing elective coronary stenting. Patients with high pretreatment reactivity are least protected. Alternative pharmacological strategies and the association of adverse ischemic events should be investigated in these patients.


Key Words: drugs • platelets • stents


*    Introduction
up arrowTop
up arrowAbstract
*Introduction
down arrowMethods
down arrowResults
down arrowDiscussion
down arrowReferences
 
Clopidogrel with aspirin is the regimen of choice to prevent stent thrombosis.1 The CURE study (Clopidogrel in Unstable angina to prevent Recurrent Events) showed that combination clopidogrel and aspirin antiplatelet therapy reduces ischemic events compared with aspirin therapy alone.2 These findings are consistent with those of the CAPRIE study (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events), which showed superior reduction in ischemic events with clopidogrel therapy compared with aspirin, and which may be explained in part by aspirin resistance.3 However, the uniformity of inhibition after clopidogrel therapy and the incidence of drug resistance has not been investigated extensively. Interindividual variability in response to clopidogrel may affect clinical outcomes.4

We studied the individual responses to clopidogrel therapy in patients undergoing elective coronary artery stenting by measuring platelet aggregation and other markers of platelet activation by flow cytometry for 30 days after the procedure.5 The frequency of drug resistance is reported. We also studied the influence of pretreatment platelet reactivity on drug response.


*    Methods
up arrowTop
up arrowAbstract
up arrowIntroduction
*Methods
down arrowResults
down arrowDiscussion
down arrowReferences
 
This study was approved by the Investigational Review Board. Consecutive patients undergoing elective coronary stenting were enrolled after giving informed consent. All ages were included. The exclusion criteria were a history of bleeding diathesis, acute myocardial infarction within 48 hours, cerebrovascular event within 3 months, illicit drug or alcohol abuse, prothrombin time >1.5 times control, platelet count <100 000/mm3, hematocrit <25%, creatinine >4.0 mg/dL, and thienopyridine or glycoprotein (GP) IIb/IIIa use before the procedure.

Per protocol, GP IIb/IIIa inhibitors were not given. Clopidogrel (300 mg) was given to all patients in the catheterization laboratory after successful coronary artery stent implantation followed by 75 mg daily for 30 days. In addition, all patients had received at least 81 mg of aspirin for 7 days before the procedure (>90% received 325 mg) and were administered 325 mg on the day of the procedure and daily thereafter. Heparin to achieve an activated clotting time >300 seconds was administered as a bolus to all patients in the catheterization laboratory immediately before stenting.

Blood Sampling
Blood was collected in evacuated container tubes containing 3.8% trisodium citrate that were filled to capacity and then inverted 3 to 5 times for gentle mixing. Samples were obtained before clopidogrel administration (baseline) and at 2 hours, 24 hours, 5 days, and 30 days after stenting.

Platelet Aggregation
The blood-citrate mixture was centrifuged at 1200g for 2.5 minutes. The resulting platelet-rich plasma was kept at room temperature for use within 1 hour. The platelet count was determined in the platelet-rich plasma sample and adjusted to 3.5x108/mL with homologous platelet-poor plasma. Platelets were stimulated with ADP (5 and 20 µmol/L), and aggregation was assessed as described previously with a Chronolog Lumi-Aggregometer (model 560-Ca) with the AggroLink software package.6 Platelet aggregation was expressed as the maximal percent change in light transmittance from baseline, with platelet-poor plasma used as a reference. Curves were analyzed according to accepted standards.7

Flow Cytometry
The surface expression of platelet receptors was determined by flow cytometry with monoclonal antibodies. Briefly, the blood-citrate mixture (50 µL) was diluted with 450 µL of Tris buffered saline (10 mmol/L Tris, 0.15 mol/L sodium chloride) and mixed by inverting an Eppendorf tube gently 2 times. The corresponding antibody was then added (5 µL) and incubated at room temperature for 30 minutes. After incubation, 400 µL of 2% buffered paraformaldehyde was added for fixation. The samples were analyzed on a Becton Dickinson FACScan flow cytometer set up to measure fluorescent light scatter as described previously.8 All parameters were collected with four-decade logarithmic amplification. The data were collected in list-mode files and then analyzed. The PAC-1 antibody (Becton Dickinson) binds only to the active {alpha}IIbß3 receptor, and therefore the total amount of {alpha}IIbß3 is not determined.9 PAC-1 was expressed as log mean fluorescence intensity. P-selectin (Pharmingen) was measured after stimulation with 200 µmol/L ADP and is expressed as percent positivity (ie, the percentage of platelets positive for the antibody) as described previously.10 The dose of agonist was chosen on the basis of data reporting maximum expression of P-selectin induced by 100 µmol/L ADP in the absence of an ADP blocker.5

Drug Resistance Definition
Drug resistance was defined as an absolute difference between baseline aggregation and posttreatment aggregation ({Delta}aggregation [%]) of 10% or less with 5 µmol/L ADP used as the agonist. Because {Delta} aggregation (%) = baseline aggregation (%) - posttreatment aggregation (%), a negative {Delta} aggregation would indicate poststent platelet reactivity greater than baseline, and a positive {Delta} aggregation would indicate platelet inhibition.

Statistical Analysis
The responders and nonresponders were compared with t tests. Standard regression analysis was used to correlate 5 and 20 µmol ADP/L-induced aggregation and 5- and 30-day aggregation and P-selectin expression (Statistica software).

To assess the effect of pretreatment reactivity on drug response, patients were divided into high, moderate, and low baseline reactivity.11 Two separate analyses were performed on the basis of aggregation and P-selectin expression. For 5 µmol/L ADP-induced aggregation, high reactivity was defined as percent aggregation >70%; moderate, 60% to 70%; and low, <60%. For P-selectin, high reactivity was defined as percent positivity >50%; moderate, 40% to 50%; and low, <40%. Comparisons were made between groups by 1-way ANOVA (Statistica software). The Wilks-Shapiro test was used to assess conformity with a normal distribution. Curves were plotted of the best fit to a normal distribution by Statistica software. Given the normal distribution of data, the mean±SD and mean±SE were used. P<0.05 was considered significant.


*    Results
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowMethods
*Results
down arrowDiscussion
down arrowReferences
 
Patient Data
Ninety-six patients had complete platelet studies performed at baseline, and of these patients, 92 had adequate poststent samples. The patient demographics on these 92 patients are shown with respect to the response to 5 µmol/L ADP-induced aggregation at day 5 in the Table. The patients were elderly, and most were males. Multiple cardiovascular risk factors were frequent. Concomitant drug use did not differ significantly between groups. A trend of higher calcium antagonist and ACE inhibitor use was observed in the nonresponders. Most patients were treated with 1 stent. There were no significant procedural differences between responders and nonresponders except for total stent length. Follow-up at 30 days revealed no cases of Q-wave myocardial infarction, stent thrombosis, target-vessel revascularization, cerebrovascular ischemic events, or death.


View this table:
[in this window]
[in a new window]
 
Demographics Based on Response to 5 µmol/L ADP at Day 5

Platelet Aggregation
Histograms of the response to clopidogrel are shown in Figures 1 and 2 Down. Baseline aggregation to 5 and 20 µmol/L ADP was 62±18% and 83±21%, respectively. The response to 5 and 20 µmol/L ADP showed a shift to the right between 2 and 24 hours after treatment, which indicates increased platelet inhibition. Aggregation by 5 µmol/L ADP was maximally inhibited by 24 hours (P<0.05 compared with baseline). Platelet aggregation was 58±22% at 2 hours, 37±22% at 24 hours, 32±18% at 5 days, and 31±15% at 30 days. At 2 hours after stenting, 63% of patients met the definition of resistance and platelet reactivity was greatest, with 42% of patients having greater aggregation than at baseline. At 24 hours, resistance fell to 31%, and 24% of patients still had greater aggregation than at baseline. No further changes were seen at 5 days, when resistance was observed in 31%. However, at 30 days after stenting, the incidence of resistance fell to 15%, but 11% still had aggregation greater than baseline.



View larger version (60K):
[in this window]
[in a new window]
 
Figure 1. Relationship between frequency of patients and absolute change in aggregation ({Delta}Aggregation [%]) in response to 5 µmol/L ADP at 2 hours (A), 24 hours (B), 5 days (C), and 30 days (D) after stenting. {Delta}Aggregation (%) is defined as baseline aggregation (%) minus posttreatment aggregation (%). Resistance, as defined herein, is {Delta} Aggregation (%) ≤10%. Resistance is present in those patients subtended by double-headed arrow. Curves represent normal distribution of data and were created by Statistica software.



View larger version (45K):
[in this window]
[in a new window]
 
Figure 2. Relationship between frequency of patients and absolute change in aggregation ({Delta}Aggregation [%]) in response to 20 µmol/L ADP at 2 hours (A), 24 hours (B), 5 days (C), and 30 days (D) after stenting. {Delta}Aggregation (%) is defined as baseline aggregation (%) minus posttreatment aggregation (%).

The response to 20 µmol/L ADP showed a similar pattern. Aggregation was 80±24% at 2 hours and fell to 60±25% at 24 hours (P<0.05 compared with baseline). At 5 days, aggregation remained stable (57±23%), with a nonsignificant decrease at 30 days (52±14%). A {Delta} aggregation of 10% or less was present in 53% of patients at 2 hours, 35% at 24 hours, 32% at 5 days, and 21% at 30 days. The correlation between the 5- and 20-µmol/L ADP aggregation response was strong (r=0.6).

Correlation of Responses at 5 and 30 Days
A strong correlation was observed between the 5- and 30-day responses to 5 µmol/L ADP (r=0.8). Moreover, strong correlations were also observed between 5- and 30-day responses for 20 µmol/L ADP (r=0.8) and P-selectin (r=0.7).

Platelet Receptor Expression
P-Selectin
Baseline stimulated P-selectin expression was 45±16% and fell over 24 hours, as indicated by a shift in the curve to the right (Figure 3). Maximum inhibition of P-selectin expression occurred within 24 hours (24±13%; P<0.05 compared with baseline) and was unchanged at 5 days (22±13%) and 30 days (23±10%), as observed in the aggregation studies. An absolute change in percent positivity of 10% or less was observed in 44% of patients at 2 hours, 25% at 24 hours, 12% at 5 days, and 29% at 30 days, which again suggests resistance to the standard clopidogrel regimen.



View larger version (44K):
[in this window]
[in a new window]
 
Figure 3. Relationship between frequency of patients and absolute change in % positivity of stimulated P-selectin expression ({Delta}% Positivity) at 2 hours (A), 24 hours (B), 5 days (C), and 30 days (D) after stenting. {Delta}% Positivity is defined as baseline positivity (%) minus posttreatment positivity (%).

PAC-1
PAC-1 binding showed similar response variability (Figure 4). Baseline expression was 14.9±13.1, and inhibition of the expression of active GP IIb/IIIa was maximal within 24 hours (8.5±5.1; P<0.05 compared with baseline). No significant changes as compared with 24 hours were observed at 5 days (8.1±3.7) or 30 days (8.6±5.3).



View larger version (37K):
[in this window]
[in a new window]
 
Figure 4. Relationship between frequency of patients and absolute change in mean fluorescence intensity (MFI) of PAC-1 binding ({Delta}MFI) at 2 hours (A), 24 hours (B), 5 days (C), and 30 days (D) after stenting. {Delta}MFI is defined as baseline MFI minus posttreatment MFI.

Effect of Pretreatment Platelet Reactivity on Drug Response
High pretreatment reactivity, defined by the response to 5 µmol/L ADP, was present in 31 patients, moderate reactivity in 25 patients, and low reactivity in 40 patients. High-reactivity patients had a greater incidence of diabetes (71%; P<0.05) than those with moderate (24%) and low (40%) reactivity. Patient weight, gender, age, statin use, smoking history, incidence of hyperlipidemia, history of prior infarction, total contrast load, procedure duration, and number of vessels treated were not significantly different between groups.

Platelet Aggregation
At baseline, by definition, the high-reactivity group had markedly greater reactivity (78±6%) than the moderate (65±3%; P<0.00001) and low (48±9%; P<0.00001) groups (Figure 5A). At day 1 after stenting, the high-reactivity group continued to have the most reactive platelets (67±11%; P=0.004 versus moderate [56±15%] and P<0.0001 versus low [52±15%]). By day 5, platelet reactivity by this marker was similar among groups.



View larger version (28K):
[in this window]
[in a new window]
 
Figure 5. A, ADP-induced platelet aggregation (5 µmol/L ADP) in high-, moderate-, and low-reactivity groups at baseline and at 1 and 5 days after clopidogrel therapy. High-reactivity patients were defined as pretreatment percent aggregation >70%; moderate, 60% to 70%; and low, <60%. B, Stimulated P-selectin expression in high-, moderate-, and low-reactivity groups at baseline and at 1 and 5 days after clopidogrel therapy. High-reactivity patients were defined as pretreatment percent positivity >50%; moderate, 40% to 50%; and low, <40%.

P-Selectin Expression
At baseline, the high-reactivity group had greater expression (67±7%) than the moderate (44±3%; P<0.00001) and low (29±6%; P<0.00001) groups (Figure 5B). The effect that pretreatment reactivity had on the inhibitory response to clopidogrel at day 1 was remarkably similar to findings with ADP-induced light-transmittance aggregometry. At day 1, patients with high pretreatment P-selectin expression remained the most reactive (P<0.001 versus low reactivity). At day 5 of therapy, patients in the high-reactivity group had a trend to greater P-selectin expression than the moderate (31±12% versus 19±13%; P=0.06) and low (20±7%; P=0.04) groups.


*    Discussion
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowMethods
up arrowResults
*Discussion
down arrowReferences
 
The present study illustrates the variable platelet inhibitory response to the standard administered dose of clopidogrel. The platelet aggregation studies used 2 agonist concentrations that showed a strong correlation. In addition, platelet receptor expression showed similar findings. These uniform observations, irrespective of the methodology chosen to detect inhibition, strengthen our conclusions that the response to clopidogrel therapy is indeed heterogeneous and that drug resistance occurs. Our observations are in agreement with one other report of 18 patients with stable angina treated with the same clopidogrel regimen after coronary intervention.12 Those investigators demonstrated variable inhibition of ADP-induced fibrinogen binding on day 2 after stenting.

Our definition of drug resistance was empirical because there have been no extensive reports on this subject among patients treated with clopidogrel. Clopidogrel inhibits aggregation in response to ADP, and therefore, we studied the response to 2 different concentrations of this agonist with light-transmittance aggregometry. Moreover, we assessed the expression of an established marker of platelet activation (P-selectin) in response to a maximal agonist concentration and studied the response of a sensitive platelet activation–dependent marker (PAC-1 binding) in nonstimulated blood.5,9

The present study suggests that the maximum inhibitory response to a 300-mg loading dose followed by 75 mg/d occurs within 24 hours. These findings are consistent with reports in healthy volunteers and in patients undergoing coronary stenting.13,14

The response to clopidogrel appears to be patient specific. The robust correlations demonstrated that in most patients, the 30-day inhibitory response from clopidogrel was predicted by the 5-day response. Of equal importance, the present investigation also suggests that resistance to clopidogrel does not accrue over time.

The present study is the first to demonstrate that the level of platelet reactivity after the standard clopidogrel regimen for coronary stenting is critically dependent on the pretreatment reactivity. The present in vitro tests suggest that patients with the greatest pretreatment platelet activity have the least antithrombotic protection, particularly within the first 24 hours of therapy. The level of platelet reactivity has been correlated with adverse events by others.4 Moreover, an examination of P-selectin expression suggests that this relationship is true even after 5 days of therapy, when those patients with the greatest baseline expression of this activation-dependent receptor tended to be more reactive than those with baseline low or moderate expression. The present findings may help to explain why ticlopidine without a loading dose did not prevent stent thrombosis in the first 3 days after the procedure.15 The similar findings at 24 hours using 2 different established markers of platelet activity strengthen our conclusion that the response to clopidogrel therapy is indeed dependent on pretreatment reactivity. Previous investigations using aggregometry and P-selectin expression as markers of reactivity have shown that loading doses higher than 300 mg may enhance and accelerate platelet inhibition in patients undergoing coronary interventions.16–19 Similar strategies may particularly benefit patients with high pretreatment reactivity.

Limitations
The present study included patients undergoing elective coronary stenting, which is known to increase platelet reactivity.8 Because pretreatment reactivity affected the reactivity measured after antiplatelet therapy, postdrug platelet reactivity may be less in studies of healthy volunteers and in patients with stable coronary artery disease. Our definition of resistance involves the amplitude of maximal platelet aggregation and can be influenced by various factors, including intrapatient variability. The current rates of stent thrombosis observed in elective stenting are much lower than the incidence of clopidogrel resistance in the present study, which suggests that our definition may be an overestimate or that resistance to clopidogrel is not a primary factor influencing stent thrombosis in these patients. However, the present data imply that nonresponders with high pretreatment reactivity may be at greatest risk.

In conclusion, the platelet inhibitory response to the standard dosing regimen of clopidogrel for coronary stenting is variable, follows a normal distribution, and appears stable over 30 days. Patients with high pretreatment reactivity are the least protected within the first 5 days of treatment. Further study is necessary to investigate the mechanisms of these findings and how they correlate with the occurrence of ischemic events. The present work would also support further investigations to determine whether higher clopidogrel doses may overcome interindividual differences in drug response.


*    Acknowledgments
 
Supported by the Sinai Center for Thrombosis Research and Platelet and Thrombosis Research, LLC.

Received January 29, 2003; revision received March 20, 2003; accepted March 21, 2003.


*    References
up arrowTop
up arrowAbstract
up arrowIntroduction
up arrowMethods
up arrowResults
up arrowDiscussion
*References
 
1. Gurbel PA, O’Connor CM, Cummings CC, et al. Clopidogrel: the future choice for preventing platelet activation during coronary stenting? Pharm Res. 1999; 65: 109–123.

2. Yusuf S, Zhao F, Mehta SR, et al, for the Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001; 345: 494–502.[Abstract/Free Full Text]

3. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996; 348: 1329–1339.[CrossRef][Medline] [Order article via Infotrieve]

4. Steinhubl SR, Talley JD, Braden GA, et al. Point of care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study. Circulation. 2001; 103: 2528–2530.[Free Full Text]

5. Shattil SJ, Cunningham M, Hoxie JA. Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry. Blood. 1987; 70: 307–315.[Abstract/Free Full Text]

6. Gurbel PA, Serebruany VL, Shustov AR, et al. Effects of reteplase and alteplase on platelet aggregation and major receptor expression during the first 24 hours of acute myocardial infarction treatment. J Am Coll Cardiol. 1998; 31: 1466–1473.[Abstract/Free Full Text]

7. Ruggeri ZM. New insights into the mechanisms of platelet adhesion and aggregation. Semin Hematol. 1994; 31: 29–39.[Medline] [Order article via Infotrieve]

8. Gurbel PA, Cummings CC, Bell CR, et al. Onset and extent of platelet inhibition by clopidogrel loading in patients undergoing elective coronary stenting: the Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial. Am Heart J. 2003; 145: 239–247.[CrossRef][Medline] [Order article via Infotrieve]

9. Gawaz M, Neumann FJ, Schomig A. Evaluation of platelet membrane glycoproteins in coronary artery disease: consequences for diagnosis and therapy. Circulation. 1999; 99: E1–E11.[Medline] [Order article via Infotrieve]

10. Gurbel PA, Kereiakes DJ, Dalesandro MR, et al. Role of soluble and platelet-bound p-selectin in discriminating cardiac from non-cardiac chest pain at presentation in the emergency department. Am Heart J. 2000; 139: 320–328.[Medline] [Order article via Infotrieve]

11. Serebruany VL, Gurbel PA, Shustov AR, et al. Heterogeneity of platelet aggregation and major surface receptor expression in patients with acute myocardial infarction. Am Heart J. 1998; 136: 398–405.[CrossRef][Medline] [Order article via Infotrieve]

12. Jaremo P, Lindahl TL, Fransson SG, et al. Individual variations of platelet inhibition after loading doses of clopidogrel. J Intern Med. 2002; 252: 233–238.[CrossRef][Medline] [Order article via Infotrieve]

13. Savcic M, Hauert J, Bachmann F, et al. Clopidogrel loading dose regimens: kinetic profile of pharmacodynamic response in healthy subjects. Semin Thromb Hemost. 1999; 25: 15–19.[Medline] [Order article via Infotrieve]

14. Gurbel PA, Malinin AI, Callahan KP, et al. Effect of loading with clopidogrel at the time of coronary stenting on platelet aggregation and GP IIb/IIIa expression and platelet-leukocyte aggregate formation. Am J Cardiol. 2002; 90: 312–315.[CrossRef][Medline] [Order article via Infotrieve]

15. Schuhlen H, Kastrati A, Dirschinger J, at al. Intracoronary stenting and risk for major adverse cardiac events during the first month. Circulation. 1998; 98: 104–111.[Abstract/Free Full Text]

16. Seyfarth HJ, Koksch M, Roethig G, et al. Effect of 300- and 450-mg clopidogrel loading doses on membrane and soluble P-selectin in patients undergoing coronary stent implantation. Am Heart J. 2002; 143: 118–123.[CrossRef][Medline] [Order article via Infotrieve]

17. Claeys MJ, Van Der Planken MG, Michiels JJ, et al. Comparison of antiplatelet effect of loading dose of clopidogrel versus abciximab during coronary intervention. Blood Coagul Fibrinolysis. 2002; 13: 283–288.[CrossRef][Medline] [Order article via Infotrieve]

18. Gawaz M, Seyfarth M, Muller I, et al. Comparison of effects of clopidogrel versus ticlopidine on platelet function in patients undergoing coronary stent placement. Am J Cardiol. 2001; 87: 332–336.[CrossRef][Medline] [Order article via Infotrieve]

19. Muller I, Seyfarth M, Rudiger S, et al. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart. 2001; 85: 92–93.[Free Full Text]




This article has been cited by other articles:


Home page
HeartHome page
N. Chapman and M. Schachter
Clopidogrel and calcium-channel blockers: a clinically important interaction?
Heart, February 1, 2010; 96(3): 179 - 180.
[Full Text] [PDF]


Home page
J Clin PharmacolHome page
N. A. Farid, A. Kurihara, and S. A. Wrighton
Metabolism and Disposition of the Thienopyridine Antiplatelet Drugs Ticlopidine, Clopidogrel, and Prasugrel in Humans
J. Clin. Pharmacol., February 1, 2010; 50(2): 126 - 142.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
T. Geisler, C. Zurn, R. Simonenko, M. Rapin, H. Kraibooj, A. Kilias, B. Bigalke, K. Stellos, M. Schwab, A. E. May, et al.
Early but not late stent thrombosis is influenced by residual platelet aggregation in patients undergoing coronary interventions
Eur. Heart J., January 1, 2010; 31(1): 59 - 66.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll Cardiol IntvHome page
F. Mangiacapra, B. De Bruyne, O. Muller, C. Trana, A. Ntalianis, J. Bartunek, G. Heyndrickx, G. Di Sciascio, W. Wijns, and E. Barbato
High Residual Platelet Reactivity After Clopidogrel: Extent of Coronary Atherosclerosis and Periprocedural Myocardial Infarction in Patients With Stable Angina Undergoing Percutaneous Coronary Intervention
J. Am. Coll. Cardiol. Intv., January 1, 2010; 3(1): 35 - 40.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
J. S. Berger, D. L. Bhatt, C. P. Cannon, Z. Chen, L. Jiang, J. B. Jones, S. R. Mehta, M. S. Sabatine, S. R. Steinhubl, E. J. Topol, et al.
The relative efficacy and safety of clopidogrel in women and men a sex-specific collaborative meta-analysis.
J. Am. Coll. Cardiol., November 17, 2009; 54(21): 1935 - 1945.
[Abstract] [Full Text] [PDF]


Home page
Circ Cardiovasc GenetHome page
G. Rudez, H. J. Bouman, J. W. van Werkum, F. W.G. Leebeek, A. Kruit, H. J.T. Ruven, J. M. ten Berg, M. P.M. de Maat, and C. M. Hackeng
Common Variation in the Platelet Receptor P2RY12 Gene Is Associated With Residual On-Clopidogrel Platelet Reactivity in Patients Undergoing Elective Percutaneous Coronary Interventions
Circ Cardiovasc Genet, October 1, 2009; 2(5): 515 - 521.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
M. P. Bonaca, P. G. Steg, L. J. Feldman, J. F. Canales, J. J. Ferguson, L. Wallentin, R. M. Califf, R. A. Harrington, and R. P. Giugliano
Antithrombotics in acute coronary syndromes.
J. Am. Coll. Cardiol., September 8, 2009; 54(11): 969 - 984.
[Abstract] [Full Text] [PDF]


Home page
JAMAHome page
A. R. Shuldiner, J. R. O'Connell, K. P. Bliden, A. Gandhi, K. Ryan, R. B. Horenstein, C. M. Damcott, R. Pakyz, U. S. Tantry, Q. Gibson, et al.
Association of Cytochrome P450 2C19 Genotype With the Antiplatelet Effect and Clinical Efficacy of Clopidogrel Therapy
JAMA, August 26, 2009; 302(8): 849 - 857.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
A. Perez de Prado, C. Cuellas, A. Diego, A. de Miguel, and F. Fernandez-Vazquez
Platelet reactivity and stent thrombosis: still some issues to solve.
J. Am. Coll. Cardiol., August 11, 2009; 54(7): 666 - 667.
[Full Text] [PDF]


Home page
Eur Heart JHome page
L. Wallentin
P2Y12 inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use
Eur. Heart J., August 2, 2009; 30(16): 1964 - 1977.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
C. Verstuyft, T. Simon, and R. B. Kim
Personalized medicine and antiplatelet therapy: ready for prime time?
Eur. Heart J., August 2, 2009; 30(16): 1943 - 1963.
[Full Text] [PDF]


Home page
HeartHome page
L Bonello, A De Labriolle, M Scheinowitz, G Lemesle, P Roy, D H Steinberg, T L Pinto Slottow, R Pakala, A D Pichard, P Barragan, et al.
Emergence of the concept of platelet reactivity monitoring of response to thienopyridines
Heart, August 1, 2009; 95(15): 1214 - 1219.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
E. Braunwald
Adventures in Cardiovascular Research
Circulation, July 14, 2009; 120(2): 170 - 180.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
D. R. Holmes Jr, D. J. Kereiakes, N. S. Kleiman, D. J. Moliterno, G. Patti, and C. L. Grines
Combining Antiplatelet and Anticoagulant Therapies.
J. Am. Coll. Cardiol., July 7, 2009; 54(2): 95 - 109.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
A. D. Michelson, A. L. Frelinger III, E. Braunwald, W. E. Downey, D. J. Angiolillo, N. P. Xenopoulos, J. A. Jakubowski, Y. Li, S. A. Murphy, J. Qin, et al.
Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial
Eur. Heart J., July 2, 2009; 30(14): 1753 - 1763.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
M. Valgimigli, G. Campo, N. de Cesare, E. Meliga, P. Vranckx, A. Furgieri, D. J. Angiolillo, M. Sabate, M. Hamon, A. Repetto, et al.
Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention: Results From the Double-Blind, Prospective, Randomized Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel Study
Circulation, June 30, 2009; 119(25): 3215 - 3222.
[Abstract] [Full Text] [PDF]


Home page
HeartHome page
A. Prasad and D. R Holmes
Update on dual antiplatelet therapy for percutaneous coronary intervention
Heart, June 1, 2009; 95(11): 861 - 865.
[Full Text] [PDF]


Home page
CirculationHome page
J. L. Mega, S. L. Close, S. D. Wiviott, L. Shen, R. D. Hockett, J. T. Brandt, J. R. Walker, E. M. Antman, W. L. Macias, E. Braunwald, et al.
Cytochrome P450 Genetic Polymorphisms and the Response to Prasugrel: Relationship to Pharmacokinetic, Pharmacodynamic, and Clinical Outcomes
Circulation, May 19, 2009; 119(19): 2553 - 2560.
[Abstract] [Full Text] [PDF]


Home page
J Clin PharmacolHome page
N. F. Ford
Clopidogrel Resistance: Pharmacokinetic or Pharmacogenetic?
J. Clin. Pharmacol., May 1, 2009; 49(5): 506 - 512.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
N. R. Desai, J. L. Mega, S. Jiang, C. P. Cannon, and M. S. Sabatine
Interaction Between Cigarette Smoking and Clinical Benefit of Clopidogrel
J. Am. Coll. Cardiol., April 14, 2009; 53(15): 1273 - 1278.
[Abstract] [Full Text] [PDF]


Home page
Journal of Pharmacy PracticeHome page
A. Veverka and J. M. Hammer
Prasugrel: A New Thienopyridine Inhibitor
Journal of Pharmacy Practice, April 1, 2009; 22(2): 158 - 165.
[Abstract] [PDF]


Home page
Br J AnaesthHome page
T. C. Collyer, D. J. Gray, R. Sandhu, J. Berridge, and G. Lyons
Assessment of platelet inhibition secondary to clopidogrel and aspirin therapy in preoperative acute surgical patients measured by Thrombelastography(R) Platelet MappingTM
Br. J. Anaesth., April 1, 2009; 102(4): 492 - 498.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
E. Mahla, M. J. Antonino, U. S. Tantry, and P. A. Gurbel
Point-of-care platelet function analysis ready for prime time?
J. Am. Coll. Cardiol., March 10, 2009; 53(10): 857 - 859.
[Full Text] [PDF]


Home page
AMERICAN JOURNAL OF LIFESTYLE MEDICINEHome page
J. Hopkins and M. Limacher
The Role of Aspirin in Cardiovascular Disease Prevention in Women
American Journal of Lifestyle Medicine, March 1, 2009; 3(2): 123 - 134.
[Abstract] [PDF]


Home page
NEJMHome page
J. L. Mega, S. L. Close, S. D. Wiviott, L. Shen, R. D. Hockett, J. T. Brandt, J. R. Walker, E. M. Antman, W. Macias, E. Braunwald, et al.
Cytochrome P-450 Polymorphisms and Response to Clopidogrel
N. Engl. J. Med., January 22, 2009; 360(4): 354 - 362.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
D. X. Zhao, M. Leacche, J. M. Balaguer, K. D. Boudoulas, J. A. Damp, J. P. Greelish, J. G. Byrne, and the Writing Group on behalf of the Cardiac Surgery
Routine intraoperative completion angiography after coronary artery bypass grafting and 1-stop hybrid revascularization results from a fully integrated hybrid catheterization laboratory/operating room.
J. Am. Coll. Cardiol., January 20, 2009; 53(3): 232 - 241.
[Abstract] [Full Text] [PDF]


Home page
Annals of Clinical & Laboratory ScienceHome page
H. Kim, H. K. Lee, K. Han, and H.-K. Jeon
Prevalence and Risk Factors for Aspirin and Clopidogrel Resistance in Patients with Coronary Artery Disease or Ischemic Cerebrovascular Disease
Ann. Clin. Lab. Sci., January 1, 2009; 39(3): 289 - 294.
[Abstract] [Full Text] [PDF]


Home page
ESC Textbook of Cardiovascular MedicineHome page
C. W. Hamm, H. Möllmann, J.-P. Bassand, and F. van de Werf
CHAPTER 16 Acute Coronary Syndromes
ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
D. Erlinge, C. Varenhorst, O. O. Braun, S. James, K. J. Winters, J. A. Jakubowski, J. T. Brandt, A. Sugidachi, A. Siegbahn, and L. Wallentin
Patients With Poor Responsiveness to Thienopyridine Treatment or With Diabetes Have Lower Levels of Circulating Active Metabolite, but Their Platelets Respond Normally to Active Metabolite Added Ex Vivo
J. Am. Coll. Cardiol., December 9, 2008; 52(24): 1968 - 1977.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
J. Saw, E. H. Madsen, S. Chan, and E. Maurer-Spurej
The ELAPSE (Evaluation of Long-Term Clopidogrel Antiplatelet and Systemic Anti-Inflammatory Effects) Study
J. Am. Coll. Cardiol., December 2, 2008; 52(23): 1826 - 1833.
[Abstract] [Full Text] [PDF]


Home page
Ther Adv Cardiovasc DisHome page
L. Ang and E. Mahmud
Monitoring oral antiplatelet therapy: is it justified?
Therapeutic Advances in Cardiovascular Disease, December 1, 2008; 2(6): 485 - 496.
[Abstract] [PDF]


Home page
J Am Coll Cardiol IntvHome page
P. Gladding, M. Webster, I. Zeng, H. Farrell, J. Stewart, P. Ruygrok, J. Ormiston, S. El-Jack, G. Armstrong, P. Kay, et al.
The Antiplatelet Effect of Higher Loading and Maintenance Dose Regimens of Clopidogrel: The PRINC (Plavix Response in Coronary Intervention) Trial
J. Am. Coll. Cardiol. Intv., December 1, 2008; 1(6): 612 - 619.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll Cardiol IntvHome page
P. Gladding, M. Webster, I. Zeng, H. Farrell, J. Stewart, P. Ruygrok, J. Ormiston, S. El-Jack, G. Armstrong, P. Kay, et al.
The Pharmacogenetics and Pharmacodynamics of Clopidogrel Response: An Analysis From the PRINC (Plavix Response in Coronary Intervention) Trial
J. Am. Coll. Cardiol. Intv., December 1, 2008; 1(6): 620 - 627.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll Cardiol IntvHome page
N. S. Kleiman
Searching for the Ceiling: New Reflections on the Disposition and Metabolism of Clopidogrel
J. Am. Coll. Cardiol. Intv., December 1, 2008; 1(6): 628 - 630.
[Full Text] [PDF]


Home page
J Am Coll Cardiol IntvHome page
B. Aleil, L. Jacquemin, F. De Poli, M. Zaehringer, J.-P. Collet, G. Montalescot, J.-P. Cazenave, M.-C. Dickele, J.-P. Monassier, and C. Gachet
Clopidogrel 150 mg/day to Overcome Low Responsiveness in Patients Undergoing Elective Percutaneous Coronary Intervention: Results From the VASP-02 (Vasodilator-Stimulated Phosphoprotein-02) Randomized Study
J. Am. Coll. Cardiol. Intv., December 1, 2008; 1(6): 631 - 638.
[Abstract] [Full Text] [PDF]


Home page
Anesth. Analg.Home page
C. Velik-Salchner, S. Maier, P. Innerhofer, W. Streif, A. Klingler, C. Kolbitsch, and D. Fries
Point-of-Care Whole Blood Impedance Aggregometry Versus Classical Light Transmission Aggregometry for Detecting Aspirin and Clopidogrel: The Results of a Pilot Study
Anesth. Analg., December 1, 2008; 107(6): 1798 - 1806.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart J SupplHome page
G. De Luca
Adjunctive antithrombotic therapy during primary percutaneous coronary intervention
Eur. Heart J. Suppl., December 1, 2008; 10(suppl_J): J2 - J14.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
N. S. Kleiman
Clopidogrel and Calcium-Channel Antagonists: Another Drug-Drug Interaction for the Ever-Wary Clinician?
J. Am. Coll. Cardiol., November 4, 2008; 52(19): 1564 - 1566.
[Full Text] [PDF]


Home page
J Am Coll CardiolHome page
G. Patti, A. Nusca, F. Mangiacapra, L. Gatto, A. D'Ambrosio, and G. Di Sciascio
Point-of-Care Measurement of Clopidogrel Responsiveness Predicts Clinical Outcome in Patients Undergoing Percutaneous Coronary Intervention: Results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) Study
J. Am. Coll. Cardiol., September 30, 2008; 52(14): 1128 - 1133.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
D. O. Williams and J. D. Abbott
What to Do With Patients Receiving Long-Term Clopidogrel: Reload or Relax?
Circulation, September 16, 2008; 118(12): 1219 - 1222.
[Full Text] [PDF]


Home page
J Am Coll CardiolHome page
K. P. Bliden, J. DiChiara, L. Lawal, A. Singla, M. J. Antonino, B. A. Baker, W. L. Bailey, U. S. Tantry, and P. A. Gurbel
The Association of Cigarette Smoking With Enhanced Platelet Inhibition by Clopidogrel
J. Am. Coll. Cardiol., August 12, 2008; 52(7): 531 - 533.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Neuroradiol.Home page
J.P.P. Peluso, W.J. van Rooij, M. Sluzewski, and G.N. Beute
A New Self-Expandable Nitinol Stent for the Treatment of Wide-Neck Aneurysms: Initial Clinical Experience
AJNR Am. J. Neuroradiol., August 1, 2008; 29(7): 1405 - 1408.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Neuroradiol.Home page
D.H. Lee, A. Arat, H. Morsi, H. Shaltoni, J.R. Harris, and M.E. Mawad
Dual Antiplatelet Therapy Monitoring for Neurointerventional Procedures Using a Point-of-Care Platelet Function Test: A Single-Center Experience
AJNR Am. J. Neuroradiol., August 1, 2008; 29(7): 1389 - 1394.
[Abstract] [Full Text] [PDF]


Home page
Anesth. Analg.Home page
L. T. Newsome, M. A. Kutcher, and R. L. Royster
Coronary Artery Stents: Part I. Evolution of Percutaneous Coronary Intervention
Anesth. Analg., August 1, 2008; 107(2): 552 - 569.
[Abstract] [Full Text] [PDF]


Home page
Eur. J. Cardiothorac. Surg.Home page
N. Zimmermann, E. Gams, and T. Hohlfeld
Aspirin in coronary artery bypass surgery: new aspects of and alternatives for an old antithrombotic agent.
Eur. J. Cardiothorac. Surg., July 1, 2008; 34(1): 93 - 108.
[Abstract] [Full Text] [PDF]


Home page
Am J Health Syst PharmHome page
M. J. Price
New antiplatelet therapies in development
Am. J. Health Syst. Pharm., July 1, 2008; 65(13_Supplement_5): S11 - S15.
[Abstract] [Full Text] [PDF]


Home page
HeartHome page
T Geisler, M Kapp, K Gohring-Frischholz, K Daub, C Dosch, B Bigalke, H Langer, C Herdeg, and M Gawaz
Residual platelet activity is increased in clopidogrel- and ASA-treated patients with coronary stenting for acute coronary syndromes compared with stable coronary artery disease
Heart, June 1, 2008; 94(6): 743 - 747.
[Abstract] [Full Text] [PDF]


Home page
ChestHome page
C. Patrono, C. Baigent, J. Hirsh, and G. Roth
Antiplatelet Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Chest, June 1, 2008; 133(6_suppl): 199S - 233S.
[Abstract] [Full Text] [PDF]


Home page
ChestHome page
J. I. Weitz, J. Hirsh, and M. M. Samama
New Antithrombotic Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Chest, June 1, 2008; 133(6_suppl): 234S - 256S.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
D. Trenk, W. Hochholzer, M. F. Fromm, L.-E. Chialda, A. Pahl, C. M. Valina, C. Stratz, P. Schmiebusch, H.-P. Bestehorn, H. J. Buttner, et al.
Cytochrome P450 2C19 681G>A Polymorphism and High On-Clopidogrel Platelet Reactivity Associated With Adverse 1-Year Clinical Outcome of Elective Percutaneous Coronary Intervention With Drug-Eluting or Bare-Metal Stents
J. Am. Coll. Cardiol., May 20, 2008; 51(20): 1925 - 1934.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
L. Bonello, L. Camoin-Jau, S. Arques, C. Boyer, D. Panagides, O. Wittenberg, M.-C. Simeoni, P. Barragan, F. Dignat-George, and F. Paganelli
Adjusted Clopidogrel Loading Doses According to Vasodilator-Stimulated Phosphoprotein Phosphorylation Index Decrease Rate of Major Adverse Cardiovascular Events in Patients With Clopidogrel Resistance: A Multicenter Randomized Prospective Study
J. Am. Coll. Cardiol., April 8, 2008; 51(14): 1404 - 1411.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
N. S. Kleiman
Will Measuring Vasodilator-Stimulated Phosphoprotein Phosphorylation Help Us Optimize the Loading Dose of Clopidogrel?
J. Am. Coll. Cardiol., April 8, 2008; 51(14): 1412 - 1414.
[Full Text] [PDF]


Home page
Eur Heart JHome page
M. J. Price, S. Endemann, R. R. Gollapudi, R. Valencia, C. T. Stinis, J. P. Levisay, A. Ernst, N. S. Sawhney, R. A. Schatz, and P. S. Teirstein
Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation
Eur. Heart J., April 2, 2008; 29(8): 992 - 1000.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
D. R. Holmes Jr
Resistance to what, does it matter? How do we study it?
Eur. Heart J., April 2, 2008; 29(8): 957 - 958.
[Full Text] [PDF]


Home page
Am. J. Neuroradiol.Home page
S. Muller-Schunk, J. Linn, N. Peters, M. Spannagl, M. Deisenberg, H. Bruckmann, and T.E. Mayer
Monitoring of Clopidogrel-Related Platelet Inhibition: Correlation of Nonresponse with Clinical Outcome in Supra-Aortic Stenting
AJNR Am. J. Neuroradiol., April 1, 2008; 29(4): 786 - 791.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll Cardiol IntvHome page
D. J. Kereiakes and P. A. Gurbel
Peri-Procedural Platelet Function and Platelet Inhibition in Percutaneous Coronary Intervention
J. Am. Coll. Cardiol. Intv., April 1, 2008; 1(2): 111 - 121.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
P. L. L'Allier, G. Ducrocq, N. Pranno, S. Noble, R. Ibrahim, J. C. Gregoire, F. Azzari, A. Nozza, C. Berry, S. Doucet, et al.
Clopidogrel 600-mg double loading dose achieves stronger platelet inhibition than conventional regimens: results from the PREPAIR randomized study.
J. Am. Coll. Cardiol., March 18, 2008; 51(11): 1066 - 1072.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
R. D. McBane II, R. J. Leadley Jr, S. M. Baxi, K. Karnicki, and W. Wysokinski
Iliac Venous Stenting: Antithrombotic Efficacy of PD0348292, an Oral Direct Factor Xa Inhibitor, Compared With Antiplatelet Agents in Pigs
Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 413 - 418.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
A. D. Michelson
P2Y12 Antagonism: Promises and Challenges
Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): s33 - s38.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
J. S. Li, E. Yow, K. Y. Berezny, P. M. Bokesch, M. Takahashi, T. P. Graham Jr, S. P. Sanders, D. Sidi, D. Bonnet, P. Ewert, et al.
Dosing of Clopidogrel for Platelet Inhibition in Infants and Young Children: Primary Results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) Trial
Circulation, January 29, 2008; 117(4): 553 - 559.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
M. Gilard, B. Arnaud, J.-C. Cornily, G. Le Gal, K. Lacut, G. Le Calvez, J. Mansourati, D. Mottier, J.-F. Abgrall, and J. Boschat
Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study
J. Am. Coll. Cardiol., January 22, 2008; 51(3): 256 - 260.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
P. A. Gurbel, W. C. Lau, and U. S. Tantry
Omeprazole: A Possible New Candidate Influencing the Antiplatelet Effect of Clopidogrel
J. Am. Coll. Cardiol., January 22, 2008; 51(3): 261 - 263.
[Full Text] [PDF]


Home page
Eur Heart J SupplHome page
A. K. Gitt and A. Betriu
Antiplatelet therapy in acute coronary syndromes
Eur. Heart J. Suppl., January 1, 2008; 10(suppl_A): A4 - A12.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart J SupplHome page
R. F. Storey
Variability of response to antiplatelet therapy
Eur. Heart J. Suppl., January 1, 2008; 10(suppl_A): A21 - A27.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart J SupplHome page
C. Gachet and B. Aleil
Testing antiplatelet therapy
Eur. Heart J. Suppl., January 1, 2008; 10(suppl_A): A28 - A34.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
S. D. Wiviott, D. Trenk, A. L. Frelinger, M. O'Donoghue, F.-J. Neumann, A. D. Michelson, D. J. Angiolillo, H. Hod, G. Montalescot, D. L. Miller, et al.
Prasugrel Compared With High Loading- and Maintenance-Dose Clopidogrel in Patients With Planned Percutaneous Coronary Intervention: The Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation Thrombolysis in Myocardial Infarction 44 Trial
Circulation, December 18, 2007; 116(25): 2923 - 2932.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
P. A. Gurbel, R. C. Becker, K. G. Mann, S. R. Steinhubl, and A. D. Michelson
Platelet Function Monitoring in Patients With Coronary Artery Disease
J. Am. Coll. Cardiol., November 6, 2007; 50(19): 1822 - 1834.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
C. P. Cannon, S. Husted, R. A. Harrington, B. M. Scirica, H. Emanuelsson, G. Peters, R. F. Storey, and for the DISPERSE-2 Investigators
Safety, Tolerability, and Initial Efficacy of AZD6140, the First Reversible Oral Adenosine Diphosphate Receptor Antagonist, Compared With Clopidogrel, in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: Primary Results of the DISPERSE-2 Trial
J. Am. Coll. Cardiol., November 6, 2007; 50(19): 1844 - 1851.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
R. F. Storey, S. Husted, R. A. Harrington, S. Heptinstall, R. G. Wilcox, G. Peters, M. Wickens, H. Emanuelsson, P. Gurbel, P. Grande, et al.
Inhibition of Platelet Aggregation by AZD6140, A Reversible Oral P2Y12 Receptor Antagonist, Compared With Clopidogrel in Patients With Acute Coronary Syndromes
J. Am. Coll. Cardiol., November 6, 2007; 50(19): 1852 - 1856.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
D. J. Angiolillo, E. Bernardo, M. Sabate, P. Jimenez-Quevedo, M. A. Costa, J. Palazuelos, R. Hernandez-Antolin, R. Moreno, J. Escaned, F. Alfonso, et al.
Impact of Platelet Reactivity on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
J. Am. Coll. Cardiol., October 16, 2007; 50(16): 1541 - 1547.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
G. Campo, M. Valgimigli, D. Gemmati, G. Percoco, L. Catozzi, A. Frangione, F. Federici, F. Ferrari, M. Tebaldi, S. Luccarelli, et al.
Poor Responsiveness to Clopidogrel: Drug-Specific or Class-Effect Mechanism?: Evidence From a Clopidogrel-to-Ticlopidine Crossover Study
J. Am. Coll. Cardiol., September 18, 2007; 50(12): 1132 - 1137.
[Abstract] [Full Text] [PDF]


Home page
J CARDIOVASC PHARMACOL THERHome page
G. J. Weerakkody, J. A. Jakubowski, J. T. Brandt, C. D. Payne, H. Naganuma, and K. J. Winters
Greater Inhibition of Platelet Aggregation and Reduced Response Variability With Prasugrel Versus Clopidogrel: An Integrated Analysis
Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2007; 12(3): 205 - 212.
[Abstract] [PDF]


Home page
StrokeHome page
D. A. Payne, C. I. Jones, P. D. Hayes, A. R. Naylor, and A. H. Goodall
Therapeutic Benefit of Low-Dose Clopidogrel in Patients Undergoing Carotid Surgery Is Linked to Variability in the Platelet Adenosine Diphosphate Response and Patients' Weight
Stroke, September 1, 2007; 38(9): 2464 - 2469.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
N. von Beckerath, A. Kastrati, A. Wieczorek, G. Pogatsa-Murray, D. Sibbing, I. Graf, and A. Schomig
A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days
Eur. Heart J., August 1, 2007; 28(15): 1814 - 1819.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart J SupplHome page
C. Bode and M. Zehender
The use of antiplatelet agents following percutaneous coronary intervention: focus on late stent thrombosis
Eur. Heart J. Suppl., August 1, 2007; 9(suppl_D): D10 - D19.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
Authors/Task Force Members, J.-P. Bassand, C. W. Hamm, D. Ardissino, E. Boersma, A. Budaj, F. Fernandez-Aviles, K. A.A. Fox, D. Hasdai, E. M. Ohman, et al.
Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology
Eur. Heart J., July 1, 2007; 28(13): 1598 - 1660.
[Full Text] [PDF]


Home page
Circ. Res.Home page
T. A. Meadows and D. L. Bhatt
Clinical Aspects of Platelet Inhibitors and Thrombus Formation
Circ. Res., May 11, 2007; 100(9): 1261 - 1275.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
A. O. Maree and D. J. Fitzgerald
Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease
Circulation, April 24, 2007; 115(16): 2196 - 2207.
[Full Text] [PDF]


Home page
J Am Coll CardiolHome page
D. J. Angiolillo, A. Fernandez-Ortiz, E. Bernardo, F. Alfonso, C. Macaya, T. A. Bass, and M. A. Costa
Variability in Individual Responsiveness to Clopidogrel: Clinical Implications, Management, and Future Perspectives
J. Am. Coll. Cardiol., April 10, 2007; 49(14): 1505 - 1516.
[Abstract] [Full Text] [PDF]


Home page
ANN INTERN MEDHome page
S. Eshaghian, S. Kaul, S. Amin, P. K. Shah, and G. A. Diamond
Role of Clopidogrel in Managing Atherothrombotic Cardiovascular Disease
Ann Intern Med, March 20, 2007; 146(6): 434 - 441.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
K. P. Bliden, J. DiChiara, U. S. Tantry, A. K. Bassi, S. K. Chaganti, and P. A. Gurbel
Increased Risk in Patients With High Platelet Aggregation Receiving Chronic Clopidogrel Therapy Undergoing Percutaneous Coronary Intervention: Is the Current Antiplatelet Therapy Adequate?
J. Am. Coll. Cardiol., February 13, 2007; 49(6): 657 - 666.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
D. J. Angiolillo, S. B. Shoemaker, B. Desai, H. Yuan, R. K. Charlton, E. Bernardo, M. M. Zenni, L. A. Guzman, T. A. Bass, and M. A. Costa
Randomized Comparison of a High Clopidogrel Maintenance Dose in Patients With Diabetes Mellitus and Coronary Artery Disease: Results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) Study
Circulation, February 13, 2007; 115(6): 708 - 716.
[Abstract] [Full Text] [PDF]


Home page
Hum Exp ToxicolHome page
G Kocabay, I Okcular, V Akkaya, and K. Guler
Suicide attempt with clopidogrel
Human and Experimental Toxicology, December 1, 2006; 25(12): 731 - 734.
[Abstract] [PDF]


Home page
CirculationHome page
M. O'Donoghue and S. D. Wiviott
Clopidogrel Response Variability and Future Therapies: Clopidogrel: Does One Size Fit All?
Circulation, November 28, 2006; 114(22): e600 - e606.
[Full Text] [PDF]


This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
107/23/2908    most recent
01.CIR.0000072771.11429.83v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gurbel, P. A.
Right arrow Articles by O’Connor, C. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gurbel, P. A.
Right arrow Articles by O’Connor, C. M.
Related Collections
Right arrow Platelet function inhibitors
Right arrow Catheter-based coronary interventions: stents
Right arrow Platelets