Published online before print March 25, 2002, doi: 10.1161/01.CIR.0000013777.21160.07
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;105:1650.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Aspirin-Resistant Thromboxane Biosynthesis and the Risk of Myocardial Infarction, Stroke, or Cardiovascular Death in Patients at High Risk for Cardiovascular Events
From the Department of Medicine, University of Western Australia, Thrombosis and Haemophilia Unit, Royal Perth Hospital, Perth, Australia (J.W.E.); Hamilton Civic Hospitals Research Centre, Hamilton, Canada (J.H., J.I.W.); the Department of Medicine, McMaster University, Hamilton, Canada (J.H., J.I.W., S.Y.); Hemostasis Reference Laboratory, Hamilton Civic Hospitals, Hamilton, Canada (M.J.); the Biostatistics Department, Princess Margaret Hospital, Toronto, Canada (Q.Y.); and Population Health Institute, McMaster University, Hamilton, Canada (S.Y.).
Correspondence to Dr John Eikelboom, Thrombosis and Haemophilia Unit, Royal Perth Hospital, Wellington Street, Perth Box X2213 GPO, Perth WA 6897, Australia. E-mail john.eikelboom{at}health.wa.gov.au
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background— We studied whether aspirin resistance, defined as failure of suppression of thromboxane generation, increases the risk of cardiovascular events in a high-risk population.
Methods and Results— Baseline urine samples were obtained from 5529 Canadian patients enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study. Using a nested case-control design, we measured urinary 11-dehydro thromboxane B2 levels, a marker of in vivo thromboxane generation, in 488 cases treated with aspirin who had myocardial infarction, stroke, or cardiovascular death during 5 years of follow-up and in 488 sex- and age-matched control subjects also receiving aspirin who did not have an event. After adjustment for baseline differences, the odds for the composite outcome of myocardial infarction, stroke, or cardiovascular death increased with each increasing quartile of 11-dehydro thromboxane B2, with patients in the upper quartile having a 1.8-times-higher risk than those in the lower quartile (OR, 1.8; 95% CI, 1.2 to 2.7; P=0.009). Those in the upper quartile had a 2-times-higher risk of myocardial infarction (OR, 2.0; 95% CI, 1.2 to 3.4; P=0.006) and a 3.5-times-higher risk of cardiovascular death (OR, 3.5; 95% CI, 1.7 to 7.4; P<0.001) than those in the lower quartile.
Conclusions— In aspirin-treated patients, urinary concentrations of 11-dehydro thromboxane B2 predict the future risk of myocardial infarction or cardiovascular death. These findings raise the possibility that elevated urinary 11-dehydro thromboxane B2 levels identify patients who are relatively resistant to aspirin and who may benefit from additional antiplatelet therapies or treatments that more effectively block in vivo thromboxane production or activity.
Key Words: aspirin • thromboxane • atherosclerosis • myocardial infarction • stroke
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Aspirin reduces the risk of cardiovascular events by
25% in a broad category of patients with arterial vascular disease.1 However, its effectiveness is limited because 10% to 20% of patients with arterial thrombosis who are treated with aspirin have a recurrent vascular event during long-term follow-up.2 Aspirin exerts its major antithrombotic effect by irreversibly acetylating platelet cyclo-oxygenase-1, thereby inhibiting thromboxane A2 synthesis. Although other poorly defined effects of aspirin on platelet function have been described, their contribution to the antithrombotic effect of aspirin is uncertain.2,3
See p 1620
There are several possible explanations for the limited efficacy of aspirin. First, it is well recognized that platelets can be activated by pathways that are not blocked by aspirin.4–7 Second, it has been suggested that higher doses of aspirin than are currently used (75 to 325 mg/d) may be required in some patients to achieve the optimal antithrombotic effect of aspirin.8,9 However, low-dose aspirin blocks > 95% of platelet cyclooxygenase-1 activity,2,10 and there is no convincing evidence that the antithrombotic effect of aspirin is dose-related.11–13 Third, some patients may be able to generate thromboxane A2 despite usual therapeutic doses of aspirin and therefore fail to benefit from aspirin treatment.10 The clinical importance of this third mechanism is unclear.
All three potential causes of aspirin failure have been designated as aspirin resistance. For the purpose of the present study, we use the term to describe the third potential mechanism, namely, incomplete suppression of thromboxane generation with the usual dose of aspirin. The extent of inhibition of thromboxane A2 generation can be determined by measuring urinary levels of 11-dehydro thromboxane B2, a stable metabolite of thromboxane A2.14 Accordingly, baseline urinary 11-dehydro thromboxane B2 concentrations were measured in 976 aspirin-treated patients at high risk of cardiovascular events from Canadian centers who were enrolled in the Heart Outcomes Prevention Evaluation (HOPE) study to determine whether incomplete suppression of thromboxane generation is associated with an increased risk of recurrent cardiovascular events.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patients
The HOPE study15,16 was an international, randomized, placebo-controlled, 2x2 factorial trial of ramipril and vitamin E for the secondary prevention of cardiovascular disease. The institutional review committee at each participating center approved the study, and all subjects gave informed consent. A total of 9541 patients
55 years of age at the time of randomization who had a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes plus at least one other cardiovascular risk factor were assigned to one of four treatments: ramipril titrated up to 10 mg daily, 400 IU vitamin E daily, both, or neither. The study commenced in December 1993 and was terminated prematurely on March 22, 1999, because of clear evidence of a benefit of ramipril.
Urine Sample Collection
All study participants were asked to provide a first morning urine specimen at the time of randomization. Of the 9541 patients in the HOPE study, 9282 (97%) provided baseline urine samples.17 Samples (n=5529) from the 129 Canadian centers participating in this study were sent to the central laboratory in Hamilton, Canada, where they were stored at -80°C until analysis. Only samples from Canadian centers were used for the present study.
Follow-Up and Ascertainment of Clinical Outcomes
All patients in the HOPE study were followed at 1 month, 6 months, and 6-month intervals thereafter until completion of the study. At each follow-up, clinical outcomes were recorded and medication use, including aspirin, was documented. The primary outcome was the composite of myocardial infarction, stroke, and death from cardiovascular causes, as previously defined.15,16
Selection of Cases and Control Subjects
Of patients with available urine samples (n=5529), only those who were taking aspirin at the time of commencement of the run-in phase (before randomization), at randomization (coinciding with the time of urine collection), and at each follow-up visit were eligible for inclusion. Aspirin-treated patients who provided an adequate baseline sample of urine and had a confirmed myocardial infarction, stroke, or cardiovascular death after randomization were defined as cases. Control subjects were randomly selected from aspirin-treated patients who provided an adequate baseline urine sample but did not have myocardial infarction, stroke, or cardiovascular death after randomization. Control subjects were matched according to sex and age (±5 years) in a 1:1 ratio with cases.
Laboratory Analysis
For each case and control subject, urine collected and stored at baseline was thawed and assayed for 11-dehydro thromboxane B2 levels with a commercially available enzyme immunoassay (Cayman Chemical) that has interassay and intra-assay coefficients of variation of 12.1% and 10%, respectively. Assays were performed by laboratory staff blinded to patient status as case or control subject. In addition, case and control specimens were assayed in random order, thereby reducing the possibility of systematic bias.
Statistical Analysis
Means or proportions for baseline demographics and risk factors were calculated for cases and control subjects. The significance of any difference between cases and control subjects was tested by means of Student’s paired t test for means and McNemar 
2 test for proportions, which takes into account the matching between cases and control subjects. Because 11-dehydro thromboxane B2 values are skewed, geometric means were calculated after log transformation of the raw data; the significance of any differences in geometric mean values between cases and control subjects was tested by means of Student’s paired t test. Median concentrations also were calculated, and levels in cases and control subjects were compared by means of Wilcoxon’s rank-sum test.
Tests for trend were used to assess any association between increasing baseline urinary 11-dehydro thromboxane B2 concentrations and risk of myocardial infarction, stroke, or cardiovascular death after dividing the samples into quartiles defined by the distribution of the complete cohort. Adjusted estimates of the association between increasing baseline urinary 11-dehydro thromboxane B2 concentrations and risk of myocardial infarction, stroke, or cardiovascular death were obtained by means of conditional logistic regression modeling that accounted for the matching variables and controlled for the random treatment assignment and baseline differences between cases and control subjects. A separate multivariable regression model was used to examine the association between baseline patient characteristics, including age, sex, heart rate, blood pressure, body mass index, past history of vascular disease, conventional vascular risk factors, lipid-lowering therapy, ß-blockers, diuretics, and randomized treatment allocation (ramipril or vitamin E) and urinary 11-deydro thromboxane B2 concentrations in the urine.
All probability values are 2-sided; confidence intervals were calculated at the 95% level.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Baseline characteristics of cases and control subjects are shown in Table 1. As expected, patients in whom myocardial infarction, stroke, or cardiovascular death subsequently developed had a higher mean body mass index and baseline blood pressure and were more likely than those who remained free of these events to be current smokers or have a history of hypertension, diabetes, myocardial infarction, or peripheral vascular disease. Cases also were more often treated with diuretics or calcium channel blockers at baseline and less often treated with lipid-lowering drugs or randomized to ramipril therapy. Because of the matching, the age and sex of cases and control subjects were similar.
|
Geometric mean and median urinary concentrations of 11-dehydro thromboxane B2 at baseline were significantly higher among patients who had subsequent development of the composite outcome of myocardial infarction, stroke, or cardiovascular death compared with those who remained free of these events (Table 2). The difference between cases and control subjects was greatest in those who had a myocardial infarction (24.5 versus 20.9 ng/mmol creatinine, P=0.003) or died of a cardiovascular cause (25.6 versus 20.4 ng/mmol creatinine, P<0.001). Baseline urinary concentrations of 11-dehydro thromboxane B2 were not significantly different between cases who had subsequent development of stroke and their matched control group (25.0 versus 27.4 ng/mmol creatinine, P=0.47).
|
The adjusted odds for the composite outcome of myocardial infarction, stroke, or cardiovascular death increased with each increasing quartile of baseline urinary 11-dehydro thromboxane B2 concentration (P for trend across quartiles, 0.01), with patients in the highest quartile having a risk 1.8-fold higher than those in the lowest quartile (OR, 1.8; 95% CI, 1.2 to 2.9; P=0.009) (Figure). A similar association was seen with myocardial infarction (P for trend across quartiles, 0.005) and cardiovascular death (P for trend across quartiles, 0.001) but not for stroke (P for trend across quartiles, 0.20) (Table 3). Results were similar with or without adjustment for baseline differences between cases and control subjects, including conventional vascular risk factors, cointerventions, and randomized treatment allocation.
|
|
To evaluate whether increased baseline urinary 11-dehydro thromboxane B2 concentrations were associated with early rather than late cardiovascular events, we performed separate analyses in patients who had an event within the first 12 months of study entry and those whose event occurred >12 months after study entry. The adjusted odds for the composite outcome of myocardial infarction, stroke, or cardiovascular death that was associated with the highest quartile of urinary 11-dehydro thromboxane B2 as compared with the lowest quartile was 2.9 (95% CI, 0.9 to 9.1) for events occurring with the first 12 months and 1.7 (95% CI, 1.0 to 2.7) for events occurring after the first 12 months.
Using linear multivariable regression modeling, variables that were found to be independently associated with baseline urinary 11-dehydro thromboxane B2 concentrations in the urine were female sex (P=0.004), body mass index (P=0.001), history of peripheral vascular disease (P=0.01), current cigarette smoking (P=0.09), use of calcium channel blockers (P=0.08), and randomization to vitamin E (P=0.04). However, these variables combined were able to predict <5% of the variation in urinary 11-dehydro thromboxane B2 concentrations (R2=0.045).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This is the first study to demonstrate an association between aspirin resistance, defined as failure of suppression of thromboxane generation, and cardiovascular risk. In a well-defined cohort of aspirin-treated patients at high risk of cardiovascular events, increasing baseline urinary concentrations of 11-dehydro thromboxane B2 were associated with an increasing risk of cardiovascular events, particularly myocardial infarction and cardiovascular death. This association was strong, graded, and independent of conventional vascular risk factors, including elevated body mass index, blood pressure, hypertension, diabetes, smoking, and previous history of vascular disease. Moreover, the strength of the association was not modified by differences between cases and control subjects in the proportion of patients receiving lipid-lowering or antihypertensive therapy or by randomization to vitamin E or ACE inhibitors.
Several mechanisms can be proposed to account for the incomplete suppression of thromboxane generation by aspirin.2 First, polymorphisms or mutations of the cyclooxygenase-1 gene that make it relatively resistant to inhibition by aspirin may provide a molecular basis for aspirin resistance. However, to our knowledge, such a mutation has not been identified. Second, nucleated cells such as monocytes or vascular endothelial cells can provide prostaglandin H2 to platelets to bypass platelet cyclooxygenase-1 or can use prostaglandin H2 to synthesize their own thromboxane A2 because they are endowed with substantial amounts of thromboxane synthase.4,18–20 Arachidonate conversion to prostaglandin H2 is catalyzed by cyclooxygenase-1 or -2. Although low-dose aspirin permanently and completely blocks cyclooxygenase-1 in platelets, nucleated cells can regenerate the enzyme. Consequently, these cells can produce prostaglandin H2 even in the face of aspirin treatment. In addition to cyclooxygenase-1–mediated prostaglandin H2 generation, nucleated cells can also produce prostaglandin H2 through cyclooxygenase-2.20,21 Whereas cyclooxygenase-1 is blocked by 80 to 325 mg of aspirin, doses similar to that used in the HOPE trial, inhibition of cyclooxygenase-2 requires doses of aspirin in excess of 500 mg daily.2 Unlike cyclooxygenase-1, which is constitutively expressed, cyclooxygenase-2 expression in nucleated cells is augmented 10- to 20-fold by inflammatory stimuli. Augmented cyclooxygenase-2 expression may contribute to aspirin resistance in patients with ischemic heart disease because atherosclerosis is an inflammatory disease.21–23
Our finding of an independent albeit weak association between history of peripheral vascular disease and urinary 11-dehydro thromboxane B2 levels in the urine is consistent with prior reports suggesting that the severity of atherosclerosis is an important determinant of thromboxane generation.14,24 In patients being treated with aspirin, differences in the extent or severity of atherosclerosis are unlikely to affect de novo platelet thromboxane production because even very low doses of aspirin completely and irreversibly block platelet cyclooxygenase-1.25 Upregulation of cyclooxygenase-2 has been demonstrated in atherosclerotic tissue24 and may be associated with greater synthesis and transfer of prostaglandin H2 to platelets, thereby bypassing platelet cyclooxygenase-1 and leading to aspirin-insensitive thromboxane biosynthesis in these patients. However, our study cannot distinguish between failure of suppression of platelet cyclooxygenase-1 and upregulation of COX-2 expression as the cause for the observed differences in 11-dehydro thromboxane B2 excretion between cases and control subjects.
The reason for the lack of an association between urinary 11-dehydro thromboxane B2 and risk of stroke is unclear. Aspirin reduces the risk of stroke in a broad category of high-risk patients1,2; elevated urinary concentrations of 11-dehydro thromboxane B2 have been reported in patients after stroke,26 and failure of aspirin to suppress "platelet reactivity"’ or inhibit platelet aggregation in response to various platelet agonists also has been documented in patients after stroke.27–29 In our study, the mean urinary concentration of 11-dehydro thromboxane B2 in cases who had a stroke was similar to that in all cases (25.0 versus 24.5 ng/mmol creatinine), but the corresponding urinary concentration in matched stroke control subjects with was higher than the concentration in all control subjects (27.4 versus 21.5 ng/mmol creatinine). However, the number of stroke cases and matched control subjects was relatively small (n=80). Given the clear and graded association between urinary 11-dehydro thromboxane B2 concentration and the composite outcome of myocardial infarction, stroke, or cardiovascular death, as well as other individual components of this outcome, the absence of a demonstrable association between stroke risk and urinary concentration of 11-dehydro thromboxane B2 probably reflects a play of chance.
Our study has several potential limitations. First, there were important differences between cases and control subjects with regard to potentially important confounders, including body mass index, systolic blood pressure, hypertension, diabetes, smoking, history of vascular disease, and cointerventions. However, even after adjustment for these differences, a clear association between urinary 11-dehydro thromboxane B2 concentrations and risk of death, myocardial infarction, and stroke was demonstrated. The weak association between baseline patient characteristics and urinary 11-dehydro thromboxane B2 concentrations further supports the conclusion that confounding did not account for our results. Second, urinary 11-dehydro thromboxane B2 concentrations may have been influenced by recent acute thrombotic events, such as myocardial infarction or stroke, processes that are known to be associated with platelet activation and enhanced urinary excretion of thromboxane metabolites. However, patients who had a myocardial infarction or stroke within the previous 7 weeks were not randomized into the HOPE study, making this explanation less likely. Third, single baseline determinations of urinary 11-dehydro thromboxane B2 concentrations may not accurately reflect the extent of platelet activation over long periods of time. However, the association between elevated urinary 11-dehydro thromboxane B2 concentrations at baseline and subsequent risk of cardiovascular events was evident both during the first 12 months after randomization and beyond 12 months, indicating a stable association over an extended period of time. Fourth, we did not confirm patient compliance with aspirin therapy by measuring salicylate levels in the blood or urine. However, we specifically assessed compliance with aspirin therapy at each follow-up visit and only considered patients for inclusion who were taking aspirin before randomization and at 6-month follow-up visits. Patients who discontinued aspirin at any time during the study were not included. Finally, the extent of biological variation in urinary 11-dehydro thromboxane B2 levels is unknown but could potentially limit the value of this marker to predict the risk of future cardiovascular events in an individual patient.
We conclude that among aspirin-treated patients at high risk of cardiovascular events, persistent thromboxane generation predicts the risk of the composite outcome of myocardial infarction, stroke, or cardiovascular death, independent of other cardiovascular risk factors. These data raise the possibility that high urinary levels of 11-dehydro thromboxane B2 can prospectively identify patients who are relatively resistant to conventional antithrombotic doses of aspirin and who may benefit from additional antiplatelet therapies or treatments that more effectively block thromboxane production or activity.
|
Acknowledgments |
|---|
Professor Weitz is the recipient of a Career Investigator Award from the Heart and Stroke Foundation of Canada and holds the Heart and Stroke Foundation of Ontario/J. Fraser Mustard Chair in Cardiovascular Research and the Canada Research Chair in Thrombosis. Professor Yusuf is the recipient of a Canadian Institute of Health Research Senior Scientist Award and holds a Heart and Stroke Foundation of Ontario Research Chair.
Received December 27, 2001; revision received January 25, 2002; accepted January 31, 2002.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy, I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ. 1994; 308: 81–106.
2. Patrono C, Coller B, Dalen JE, et al. Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest. 2001; 119: 39S–63S.
3. Awtry EH, Loscalzo J, Aspirin. Circulation. 2000; 101: 1206–1208.
4. Maclouf J, Folco G, Patrono C. Eicosanoids and iso-eicosanoids: constitutive, inducible and transcellular biosynthesis in vascular disease. Thromb Haemost. 1998; 79: 691–705.
5. Valles J, Santos MT, Aznar J, et al. Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality: the effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity. Circulation. 1998; 97: 350–355.
6. Santos MT, Moscardo A, Valles J, et al. Participation of tyrosine phosphorylation in cytoskeletal reorganization, alpha(IIb)beta(3) integrin receptor activation, and aspirin-insensitive mechanisms of thrombin-stimulated human platelets. Circulation. 2000; 102: 1924–1930.
7. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in preventing major vascular events in patients with acute coronary syndromes without ST elevation. N Engl J Med. 2001; 345: 494–502.
8. Patrono C. Prevention of myocardial infarction and stroke by aspirin: different mechanisms? Different dosage? Thromb Res. 1998; 92: S7–S12.
9. Dyken ML, Barnett HJM, Easton JD, et al. Low-dose aspirin and stroke: "it ain’t necessarily so." Stroke. 1992; 23: 1395–1400.
10. Vejar M, Fragasso G, Hackett D, et al. Dissociation of platelet activation and spontaneous myocardial ischemia in unstable angina. Thromb Haemost. 1990; 63: 163–168.
11. Taylor DW, Barnett HJ, Haynes RB, et al. Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial: ASA and Carotid Endarterectomy (ACE) Trial Collaborators. Lancet. 1999; 353: 2179–2184.
12. Dutch TIA Trial Study Group. A comparison of two doses of aspirin (30 mg vs 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. N Engl J Med. 1991; 325: 1261–1266.
13. Farrell B, Godwin J, Richards S, et al. The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. J Neurol Neurosurg Psychiatry. 1991; 54: 1044–1054.
14. Catella F, Healy D, Lawson J, et al. 11-Dehydrothromboxane B2: a quantitative index of thromboxane A2 formation in the human circulation. Proc Natl Acad Sci U S A. 1986; 83: 5861–5865.
15. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000; 342: 145–153.
16. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000; 342: 154–160.
17. Gerstein HC, Mann JF, Pogue J, et al. Prevalence and determinants of microalbuminuria in high-risk diabetic and nondiabetic patients in the Heart Outcomes Prevention Evaluation Study: the HOPE Study Investigators. Diabetes Care. 2000; 23 (suppl 2): B35–B39.
18. Marcus AJ, Weksler BB, Jaffe EA, et al. Synthesis of prostacyclin from platelet-derived endoperoxides by cultured human endothelial cells. J Clin Invest. 1980; 66: 979–986.
19. Schafer AI, Crawford DD, Gimbrone MA. Unidirectional transfer of prostaglandin endoperoxides between platelets and endothelial cells. J Clin Invest. 1984; 73: 1105–1112.
20. Karim S, Habib A, Levy-Toledano S, et al. Cyclooxygenase-1 and -2 of endothelial cells utilize exogenous or endogenous arachidonic acid for transcellular production of thromboxane. J Biol Chem. 1996; 271: 12042–12048.
21. Cipollone F, Patrignani P, Greco A, et al. Differential suppression of thromboxane biosynthesis by indobufen and aspirin in patients with unstable angina. Circulation. 1997; 96: 1109–1116.
22. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999; 340: 115–126.
23. Cipollone F, Prontera C, Pini B, et al. Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability. Circulation. 2001; 104: 921–927.
24. Belton O, Byrne D, Kearney D, et al. Cyclooxygenase-1 and -2-dependent prostacyclin formation in patients with atherosclerosis. Circulation. 2000; 102: 840–845.
25. Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. 1994; 330: 1287–1294.
26. van Kooten F, Ciabattoni G, Koudstaal PJ, et al. Increased platelet activation in the chronic phase after cerebral ischemia and intracerebral hemorrhage. Stroke. 1999; 30: 546–549.
27. Grotemeyer KH, Scharafinski HW, Husstedt IW. Two-year follow-up of aspirin responder and aspirin non responder: a pilot-study including 180 post-stroke patients. Thromb Res. 1993; 71: 397–403.
28. Helgason CM, Bolin KM, Hoff JA, et al. Development of aspirin resistance in persons with previous ischemic stroke. Stroke. 1994; 25: 2331–2336.
29. Helgason CM, Tortorice KL, Winkler SR, et al. Aspirin response and failure in cerebral infarction. Stroke. 1993; 24: 345–350.
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
|
|
F. Marin, R. Gonzalez-Conejero, P. Capranzano, T. A. Bass, V. Roldan, and D. J. Angiolillo Pharmacogenetics in cardiovascular antithrombotic therapy. J. Am. Coll. Cardiol., September 15, 2009; 54(12): 1041 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sun, A. Swaim, J. E. Herrera, D. Becker, L. Becker, K. Srivastava, L. E. Thompson, M. R. Shero, A. Perez-Tamayo, B. Suktitipat, et al. Platelet Kainate Receptor Signaling Promotes Thrombosis by Stimulating Cyclooxygenase Activation Circ. Res., September 11, 2009; 105(6): 595 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-P. Collet and G. Montalescot Review: Platelet Function Testing and Implications for Clinical Practice Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2009; 14(3): 157 - 169. [Abstract] [PDF]
|
|
|
|
 |
|
 A R Muir, M F McMullin, C Patterson, and P P McKeown Assessment of aspirin resistance varies on a temporal basis in patients with ischaemic heart disease Heart, August 1, 2009; 95(15): 1225 - 1229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 J. Smout, A. Dyker, M. Cleanthis, G. Ford, P. Kesteven, and G. Stansby Platelet Function Following Acute Cerebral Ischemia Angiology, June 1, 2009; 60(3): 362 - 369. [Abstract] [PDF]
|
|
|
|
 |
|
 S. M. Davis and G. A. Donnan Antiplatelet Activity Stroke, June 1, 2009; 40(6): 2275 - 2275. [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Steinhubl, D. L. Bhatt, D. M. Brennan, G. Montalescot, G. J. Hankey, J. W. Eikelboom, P. B. Berger, E. J. Topol, and on behalf of the CHARISMA Investigators Aspirin to Prevent Cardiovascular Disease: The Association of Aspirin Dose and Clopidogrel With Thrombosis and Bleeding Ann Intern Med, March 17, 2009; 150(6): 379 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Lev Aspirin resistance transient laboratory finding or important clinical entity? J. Am. Coll. Cardiol., February 24, 2009; 53(8): 678 - 680. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bevilacqua, A. A. Alkodami, E. Volpi, A. G. Cerillo, S. Berti, M. Glauber, and J. Gianetti Risk Stratification After Coronary Artery Bypass Surgery by a Point-of-Care Test of Platelet Function. Ann. Thorac. Surg., February 1, 2009; 87(2): 496 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. M. Akay, Z. Canturk, E. Akin, C. Bal, and Z. Gulbas Aspirin-Resistance Frequency: A Prospective Study in 280 Healthy Turkish Volunteers Clinical and Applied Thrombosis/Hemostasis, February 1, 2009; 15(1): 98 - 102. [Abstract] [PDF]
|
|
|
|
 |
|
 D. M. Scott, R. M Norwood, and D. Parra P2Y12 Inhibitors in Cardiovascular Disease: Focus on Prasugrel Ann. Pharmacother., January 1, 2009; 43(1): 64 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
J. W. Eikelboom, G. J. Hankey, J. Thom, D. L. Bhatt, P. G. Steg, G. Montalescot, S. C. Johnston, S. R. Steinhubl, K.-H. Mak, J. D. Easton, et al. Incomplete Inhibition of Thromboxane Biosynthesis by Acetylsalicylic Acid: Determinants and Effect on Cardiovascular Risk Circulation, October 21, 2008; 118(17): 1705 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Kapoor Enteric Coating Is a Possible Cause of Aspirin Resistance J. Am. Coll. Cardiol., October 7, 2008; 52(15): 1276 - 1277. [Full Text] [PDF]
|
|
|
|
|
|
D. Trenk and F.-J. Neumann Aspirin Resistance: An Underestimated Risk in Patients With Drug-Eluting Stents? J. Am. Coll. Cardiol., August 26, 2008; 52(9): 740 - 742. [Full Text] [PDF]
|
|
|
|
|
|
S. Guthikonda, C. L. Alviar, M. Vaduganathan, M. Arikan, A. Tellez, T. DeLao, J. F. Granada, J.-F. Dong, N. S. Kleiman, and E. I. Lev Role of Reticulated Platelets and Platelet Size Heterogeneity on Platelet Activity After Dual Antiplatelet Therapy With Aspirin and Clopidogrel in Patients With Stable Coronary Artery Disease J. Am. Coll. Cardiol., August 26, 2008; 52(9): 743 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Santilli, M. Romano, A. Recchiuti, A. Dragani, A. Falco, G. Lessiani, F. Fioritoni, S. Lattanzio, D. Mattoscio, R. De Cristofaro, et al. Circulating endothelial progenitor cells and residual in vivo thromboxane biosynthesis in low-dose aspirin-treated polycythemia vera patients Blood, August 15, 2008; 112(4): 1085 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Herrera-Galeano, D. M. Becker, A. F. Wilson, L. R. Yanek, P. Bray, D. Vaidya, N. Faraday, and L. C. Becker A Novel Variant in the Platelet Endothelial Aggregation Receptor-1 Gene Is Associated With Increased Platelet Aggregability Arterioscler Thromb Vasc Biol, August 1, 2008; 28(8): 1484 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 Y. Yano, T. Ohmori, S. Hoshide, S. Madoiwa, K. Yamamoto, T. Katsuki, T. Mitsuhashi, J. Mimuro, K. Shimada, K. Kario, et al. Determinants of thrombin generation, fibrinolytic activity, and endothelial dysfunction in patients on dual antiplatelet therapy: involvement of factors other than platelet aggregability in Virchow's triad Eur. Heart J., July 2, 2008; 29(14): 1729 - 1738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Kamphuisen Thrombogenicity in patients with percutaneous coronary artery intervention and dual antiplatelet treatment Eur. Heart J., July 2, 2008; 29(14): 1699 - 1700. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Natarajan, A. G Zaman, and S. M Marshall Platelet hyperactivity in type 2 diabetes: role of antiplatelet agents Diabetes and Vascular Disease Research, June 1, 2008; 5(2): 138 - 144. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Thachil The implications of aspirin resistance in renal failure NDT Plus, June 1, 2008; 1(3): 192 - 193. [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
A. Y. Gasparyan, T. Watson, and G. Y.H. Lip The Role of Aspirin in Cardiovascular Prevention: Implications of Aspirin Resistance J. Am. Coll. Cardiol., May 13, 2008; 51(19): 1829 - 1843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Aradi, A. Konyi, L. Palinkas, T. Berki, T. Pinter, T. Tahin, I. Horvath, L. Papp, and A. Komocsi Thienopyridine Therapy Influences Late Outcome After Coronary Stent Implantation Angiology, May 1, 2008; 59(2): 172 - 178. [Abstract] [PDF]
|
|
|
|
 |
|
 E. C. Bruce, Y. Guo, K. C. Lawson, A. K. Manatunga, S. F. Auyeung, W. M. McDonald, N. Rushing, A. R. Brown, N. Gilles, M. Emery, et al. Platelet Thromboxane A2 Secretion in Patients With Major Depression Responsive to Electroconvulsive Therapy Psychosom Med, April 1, 2008; 70(3): 319 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Gengo, M. Rainka, M. Robson, M. F. Gengo, A. Forrest, M. Hourihane, and V. Bates Prevalence of Platelet Nonresponsiveness to Aspirin in Patients Treated for Secondary Stroke Prophylaxis and in Patients With Recurrent Ischemic Events J. Clin. Pharmacol., March 1, 2008; 48(3): 335 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Krasopoulos, S. J Brister, W S. Beattie, and M. R Buchanan Aspirin "resistance" and risk of cardiovascular morbidity: systematic review and meta-analysis BMJ, January 26, 2008; 336(7637): 195 - 198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 I. Avalos, C. P. Chung, A. Oeser, G. L. Milne, H. Borntrager, J. D. Morrow, P. Raggi, J. Solus, and C. M. Stein Aspirin therapy and thromboxane biosynthesis in systemic lupus erythematosus Lupus, December 1, 2007; 16(12): 981 - 986. [Abstract] [PDF]
|
|
|
|
 |
|
 J. DiChiara, K. P. Bliden, U. S. Tantry, M. S. Hamed, M. J. Antonino, T. A. Suarez, O. Bailon, A. Singla, and P. A. Gurbel The Effect of Aspirin Dosing on Platelet Function in Diabetic and Nondiabetic Patients: An Analysis From the Aspirin-Induced Platelet Effect (ASPECT) Study Diabetes, December 1, 2007; 56(12): 3014 - 3019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. M. Cholette, J. S. Rubenstein, G. M. Alfieris, M. P. McDermott, W. G. Harmon, R. Vermilion, M. P. Eaton, J. J. Gangemi, and N. B. Lerner Elevated Risk of Thrombosis in Neonates Undergoing Initial Palliative Cardiac Surgery Ann. Thorac. Surg., October 1, 2007; 84(4): 1320 - 1325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Snoep, M. M. C. Hovens, J. C. J. Eikenboom, J. G. van der Bom, and M. V. Huisman Association of Laboratory-Defined Aspirin Resistance With a Higher Risk of Recurrent Cardiovascular Events: A Systematic Review and Meta-analysis Arch Intern Med, August 13, 2007; 167(15): 1593 - 1599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lordkipanidze, C. Pharand, E. Schampaert, J. Turgeon, D. A. Palisaitis, and J. G. Diodati A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease Eur. Heart J., July 2, 2007; 28(14): 1702 - 1708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P. A. Gurbel, K. P. Bliden, J. DiChiara, J. Newcomer, W. Weng, N. K. Neerchal, T. Gesheff, S. K. Chaganti, A. Etherington, and U. S. Tantry Evaluation of Dose-Related Effects of Aspirin on Platelet Function: Results From the Aspirin-Induced Platelet Effect (ASPECT) Study Circulation, June 26, 2007; 115(25): 3156 - 3164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Faraday, L. R. Yanek, R. Mathias, J. E. Herrera-Galeano, D. Vaidya, T. F. Moy, M. D. Fallin, A. F. Wilson, P. F. Bray, L. C. Becker, et al. Heritability of Platelet Responsiveness to Aspirin in Activation Pathways Directly and Indirectly Related to Cyclooxygenase-1 Circulation, May 15, 2007; 115(19): 2490 - 2496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 C. L. Campbell, S. Smyth, G. Montalescot, and S. R. Steinhubl Aspirin Dose for the Prevention of Cardiovascular Disease: A Systematic Review JAMA, May 9, 2007; 297(18): 2018 - 2024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Howard-Alpe, J. de Bono, L. Hudsmith, W. P. Orr, P. Foex, and J. W. Sear Coronary artery stents and non-cardiac surgery Br. J. Anaesth., May 1, 2007; 98(5): 560 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 B. T. Ivandic, E. Giannitsis, P. Schlick, P. Staritz, H. A. Katus, and T. Hohlfeld Determination of Aspirin Responsiveness by Use of Whole Blood Platelet Aggregometry Clin. Chem., April 1, 2007; 53(4): 614 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Fitzgerald and A. Maree Aspirin and Clopidogrel Resistance Hematology, January 1, 2007; 2007(1): 114 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Michelson, A. L. Frelinger, and M. I. Furman Resistance to antiplatelet drugs Eur. Heart J. Suppl., October 1, 2006; 8(suppl_G): G53 - G58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. O'Kennedy, L. Crosbie, S. Whelan, V. Luther, G. Horgan, J. I Broom, D. J Webb, and A. K Duttaroy Effects of tomato extract on platelet function: a double-blinded crossover study in healthy humans. Am. J. Clinical Nutrition, September 1, 2006; 84(3): 561 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Cox, A. O. Maree, M. Dooley, R. Conroy, M. F. Byrne, and D. J. Fitzgerald Effect of Enteric Coating on Antiplatelet Activity of Low-Dose Aspirin in Healthy Volunteers Stroke, August 1, 2006; 37(8): 2153 - 2158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fosburgh Aspirin and Clopidogrel Resistance Mayo Clin. Proc., July 1, 2006; 81(7): 989 - 989. [Full Text] [PDF]
|
|
|
|
|
|
E. D. Michos, R. Ardehali, R. S. Blumenthal, R. A. Lange, and H. Ardehali Aspirin and Clopidogrel Resistance-Reply-I Mayo Clin. Proc., July 1, 2006; 81(7): 990 - 990. [Full Text] [PDF]
|
|
|
|
|
|
L. H Cavallari, C. M Helgason, L. D Brace, M. A. Viana, and E. A Nutescu Sex Difference in the Antiplatelet Effect of Aspirin in Patients with Stroke Ann. Pharmacother., May 1, 2006; 40(5): 812 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Michos, R. Ardehali, R. S. Blumenthal, R. A. Lange, and H. Ardehali Aspirin and Clopidogrel Resistance Mayo Clin. Proc., April 1, 2006; 81(4): 518 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. H. Wang, D. L. Bhatt, and E. J. Topol Aspirin and clopidogrel resistance: an emerging clinical entity Eur. Heart J., March 2, 2006; 27(6): 647 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P Raghavan, D. W Laight, K. M Shaw, and M. H Cummings Review: Aspirin and diabetes The British Journal of Diabetes & Vascular Disease, March 1, 2006; 6(2): 74 - 82. [Abstract] [PDF]
|
|
|
|
|
|
E. I. Lev, R. T. Patel, K. J. Maresh, S. Guthikonda, J. Granada, T. DeLao, P. F. Bray, and N. S. Kleiman Aspirin and Clopidogrel Drug Response in Patients Undergoing Percutaneous Coronary Intervention: The Role of Dual Drug Resistance J. Am. Coll. Cardiol., January 3, 2006; 47(1): 27 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Poston, J. Gu, J. M. Brown, J. S. Gammie, C. White, L. Nie, R. N. Pierson III, and B. P. Griffith Endothelial injury and acquired aspirin resistance as promoters of regional thrombin formation and early vein graft failure after coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., January 1, 2006; 131(1): 122 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Lev, R. T. Patel, K. J. Maresh, S. Guthikonda, J. Granada, T. DeLao, P. F. Bray, and N. S. Kleiman Aspirin and Clopidogrel Drug Response in Patients Undergoing Percutaneous Coronary Intervention: The Role of Dual Drug Resistance J. Am. Coll. Cardiol., December 13, 2005; (2005) j.jacc.2005.08.058v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Gurbel, K. P. Bliden, W. Samara, J. A. Yoho, K. Hayes, M. Z. Fissha, and U. S. Tantry Clopidogrel Effect on Platelet REactivity in Patients With Stent Thrombosis: Results of the CREST Study J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1827 - 1832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. S. Tantry, K. P. Bliden, and P. A. Gurbel Overestimation of Platelet Aspirin Resistance Detection by Thrombelastograph Platelet Mapping and Validation by Conventional Aggregometry Using Arachidonic Acid Stimulation J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1705 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Williams, M. J. Coffey, B. Coles, S. Sanchez, J. D. Morrow, J. R. Cockcroft, M. J. Lewis, and V. B. O'Donnell In vivo aspirin supplementation inhibits nitric oxide consumption by human platelets Blood, October 15, 2005; 106(8): 2737 - 2743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Mason, A. K. Jacobs, and J. E. Freedman Aspirin Resistance and Atherothrombotic Disease J. Am. Coll. Cardiol., September 20, 2005; 46(6): 986 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. F. McAdam, D. Byrne, J. D. Morrow, and J. A. Oates Contribution of Cyclooxygenase-2 to Elevated Biosynthesis of Thromboxane A2 and Prostacyclin in Cigarette Smokers Circulation, August 16, 2005; 112(7): 1024 - 1029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Angiolillo, A. Fernandez-Ortiz, E. Bernardo, C. Ramirez, M. Sabate, P. Jimenez-Quevedo, R. Hernandez, R. Moreno, J. Escaned, F. Alfonso, et al. Platelet Function Profiles in Patients With Type 2 Diabetes and Coronary Artery Disease on Combined Aspirin and Clopidogrel Treatment Diabetes, August 1, 2005; 54(8): 2430 - 2435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Saseen ASHP Therapeutic Position Statement on the Daily Use of Aspirin for Preventing Cardiovascular Events Am. J. Health Syst. Pharm., July 1, 2005; 62(13): 1398 - 1405. [Full Text] [PDF]
|
|
|
|
|
|
S. R. Steinhubl, R. Charnigo, and D. J. Moliterno Resistance to Antiplatelet Resistance: Is it Justified? J. Am. Coll. Cardiol., June 7, 2005; 45(11): 1757 - 1758. [Full Text] [PDF]
|
|
|
|
|
|
E. Papp, V. Havasi, J. Bene, K. Komlosi, L. Czopf, E. Magyar, C. Feher, G. Feher, B. Horvath, Z. Marton, et al. Glycoprotein IIIA Gene (PlA) Polymorphism and Aspirin Resistance: Is There Any Correlation? Ann. Pharmacother., June 1, 2005; 39(6): 1013 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Harrison, H. Segal, K. Blasbery, C. Furtado, L. Silver, and P. M. Rothwell Screening for Aspirin Responsiveness After Transient Ischemic Attack and Stroke: Comparison of 2 Point-of-Care Platelet Function Tests With Optical Aggregometry Stroke, May 1, 2005; 36(5): 1001 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Mikkelsson, M. Perola, and P. J. Karhunen Genetics of Platelet Glycoprotein Receptors: Risk of Thrombotic Events and Pharmacogenetic Implications Clinical and Applied Thrombosis/Hemostasis, April 1, 2005; 11(2): 113 - 125. [Abstract] [PDF]
|
|
|
|
|
|
S. Sanderson, J. Emery, T. Baglin, and A.-L. Kinmonth Narrative Review: Aspirin Resistance and Its Clinical Implications Ann Intern Med, March 1, 2005; 142(5): 370 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gonzalez-Conejero, J. Rivera, J. Corral, C. Acuna, J. A. Guerrero, and V. Vicente Biological Assessment of Aspirin Efficacy on Healthy Individuals: Heterogeneous Response or Aspirin Failure? Stroke, February 1, 2005; 36(2): 276 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fries and T. Grosser The Cardiovascular Pharmacology of COX-2 Inhibition Hematology, January 1, 2005; 2005(1): 445 - 451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Michelson Platelet Function Testing in Cardiovascular Diseases Circulation, November 9, 2004; 110(19): e489 - e493. [Full Text] [PDF]
|
|
|
|
|
|
M. Cattaneo Aspirin and Clopidogrel: Efficacy, Safety, and the Issue of Drug Resistance Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 1980 - 1987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.P. Collet, G. Montalescot, B. Blanchet, M.L. Tanguy, J.L. Golmard, R. Choussat, F. Beygui, L. Payot, N. Vignolles, J.P. Metzger, et al. Impact of Prior Use or Recent Withdrawal of Oral Antiplatelet Agents on Acute Coronary Syndromes Circulation, October 19, 2004; 110(16): 2361 - 2367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Hennekens, K. Schror, S. Weisman, and G. A. FitzGerald Terms and Conditions: Semantic Complexity and Aspirin Resistance Circulation, September 21, 2004; 110(12): 1706 - 1708. [Full Text] [PDF]
|
|
|
|
|
|
C. Patrono, B. Coller, G. A. FitzGerald, J. Hirsh, and G. Roth Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 234S - 264S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fiorucci, A. Mencarelli, A. Meneguzzi, A. Lechi, B. Renga, P. del Soldato, A. Morelli, and P. Minuz Co-administration of nitric oxide-aspirin (NCX-4016) and aspirin prevents platelet and monocyte activation and protects against gastric damage induced by aspirin in humans J. Am. Coll. Cardiol., August 4, 2004; 44(3): 635 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Tanaka, F. Szlam, N. Katori, A. Tsuda, and J. H. Levy In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasoconstriction in human internal mammary artery Br. J. Anaesth., August 1, 2004; 93(2): 257 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Schieffer, C. Bunte, J. Witte, K. Hoeper, R. H. Boger, E. Schwedhelm, and H. Drexler Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease J. Am. Coll. Cardiol., July 21, 2004; 44(2): 362 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. van Ryn, M. Kink-Eiband, I. Kuritsch, U. Feifel, G. Hanft, G. Wallenstein, G. Trummlitz, and M. Pairet Meloxicam Does Not Affect the Antiplatelet Effect of Aspirin in Healthy Male and Female Volunteers J. Clin. Pharmacol., July 1, 2004; 44(7): 777 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Wiviott and E. M. Antman Clopidogrel Resistance: A New Chapter in a Fast-Moving Story Circulation, June 29, 2004; 109(25): 3064 - 3067. [Full Text] [PDF]
|
|
|
|
|
|
F. Cipollone, E. Toniato, S. Martinotti, M. Fazia, A. Iezzi, C. Cuccurullo, B. Pini, S. Ursi, G. Vitullo, M. Averna, et al. A Polymorphism in the Cyclooxygenase 2 Gene as an Inherited Protective Factor Against Myocardial Infarction and Stroke JAMA, May 12, 2004; 291(18): 2221 - 2228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Dogne, J. Hanson, X. de Leval, P. Kolh, V. Tchana-Sato, L. de Leval, S. Rolin, A. Ghuysen, P. Segers, B. Lambermont, et al. Pharmacological Characterization of N-tert-Butyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl]urea (BM-573), a Novel Thromboxane A2 Receptor Antagonist and Thromboxane Synthase Inhibitor in a Rat Model of Arterial Thrombosis and Its Effects on Bleeding Time J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 498 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Danchin Acute coronary syndromes: should women receive less antithrombotic medication than men? Heart, April 1, 2004; 90(4): 363 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Quinn, H. D. Aronow, R. M. Califf, D. L. Bhatt, S. Sapp, N. S. Kleiman, R. A. Harrington, D. F. Kong, D. E. Kandzari, and E. J. Topol Aspirin dose and six-month outcome after an acute coronary syndrome J. Am. Coll. Cardiol., March 17, 2004; 43(6): 972 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. M. Pulcinelli, P. Pignatelli, A. Celestini, S. Riondino, P. P. Gazzaniga, and F. Violi Inhibition of platelet aggregation by aspirin progressively decreases in long-term treated patients J. Am. Coll. Cardiol., March 17, 2004; 43(6): 979 - 984. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||