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Compass Investigators - One of the best experts on this subject based on the ideXlab platform.
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Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial
Elsevier, 2018Co-Authors: Compass Investigators, Anand, Sonia SAbstract:BACKGROUND Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. METHODS This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). INTERPRETATION Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. FUNDING Bayer AG
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rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease an international randomised double blind placebo controlled trial
The Lancet, 2017Co-Authors: Compass InvestigatorsAbstract:Summary Background Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. Methods This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle–brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. Findings Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57–0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35–0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69–1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45–1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12–2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17–2·40; p=0·0043). Interpretation Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. Funding Bayer AG.
Katalin Keltai - One of the best experts on this subject based on the ideXlab platform.
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Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial
The Lancet, 2018Co-Authors: Sonia Anand, Jackie Bosch, John Eikelboom, Stuart Connolly, Rafael Diaz, Peter Widimsky, Victor Aboyans, Marco Alings, Ajay Kakkar, Katalin KeltaiAbstract:BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.
Emmanuel Di Valentin - One of the best experts on this subject based on the ideXlab platform.
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Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer
PLoS Medicine, 2015Co-Authors: Pamela Maris, Arnaud Blomme, Ana Perez Palacios, Brunella Costanza, Akeila Bellahcène, Elettra Bianchi, Stephanie Gofflot, Pierre Drion, Giovanna Elvi Trombino, Emmanuel Di ValentinAbstract:BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-β1 has been identified as a key driving force behind metastatic breast cancer, with promising therapeutic implications. METHODS AND FINDINGS: Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that Asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, Asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong Asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1β, secreted by TNBC cells, is responsible for inhibiting Asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of Asporin to inhibit TGF-β1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing Asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that Asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher Asporin expression (4-fold; p = 0.001). Assessment of Asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78-0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low Asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37-0.91; p = 0.017). Although these data highlight the potential of Asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort. CONCLUSIONS: Our data show that Asporin is a stroma-derived inhibitor of TGF-β1 and a tumor suppressor in breast cancer. High Asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing Asporin expression in TNBC as a promising strategy for targeted therapy.
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Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer.
Public Library of Science (PLoS), 2015Co-Authors: Pamela Maris, Arnaud Blomme, Ana Perez Palacios, Brunella Costanza, Akeila Bellahcène, Elettra Bianchi, Stephanie Gofflot, Pierre Drion, Giovanna Elvi Trombino, Emmanuel Di ValentinAbstract:Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-β1 has been identified as a key driving force behind metastatic breast cancer, with promising therapeutic implications.Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that Asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, Asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong Asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1β, secreted by TNBC cells, is responsible for inhibiting Asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of Asporin to inhibit TGF-β1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing Asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that Asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher Asporin expression (4-fold; p = 0.001). Assessment of Asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78-0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low Asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37-0.91; p = 0.017). Although these data highlight the potential of Asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort.Our data show that Asporin is a stroma-derived inhibitor of TGF-β1 and a tumor suppressor in breast cancer. High Asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing Asporin expression in TNBC as a promising strategy for targeted therapy
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High Asporin expression in human breast cancer matches with luminal-like tumor type and good patient outcome.
2015Co-Authors: Pamela Maris, Arnaud Blomme, Ana Perez Palacios, Brunella Costanza, Akeila Bellahcène, Elettra Bianchi, Stephanie Gofflot, Pierre Drion, Giovanna Elvi Trombino, Emmanuel Di ValentinAbstract:(A) Representative IHC staining of Asporin expression in human breast cancer tissues (upper panel). Box plots of Asporin expression in 180 breast cancer patients with different status of HER2, ER, and PR are also shown (lower panel). The black line denotes the median expression, and the red line the mean expression. Significant differences in Asporin expression were detected among all different subtypes of breast cancer. (B) Analysis of Asporin mRNA expression in breast cancer tumors from different molecular subtypes (n = 1,280) and evaluation of Asporin mRNA expression in breast cancer of different pathological grades (n = 1,411). (C) Representative IHC staining of Asporin expression (upper panel), box plot showing the IHC score (middle panel) in breast cancer tissues from 60 patients with different outcomes, and ROC curve analysis of data obtained from 60 patients with different outcome (lower panel). Scoring and statistics were performed as outlined in the Methods section. (D) Kaplan-Meier survival curve based on Asporin mRNA expression in untreated breast cancer with post-operative follow-up of 25 y (n = 375). Images in panels were taken at 100× magnification. All analyses outlined in (B) and (D) were performed using publicly deposited gene expression datasets [31,32] and according to procedures outlined in the Methods. AUC, area under the curve; HR, hazard ratio; SE, standard error.
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Asporin binds to TGF-β1 and inhibits its downstream signaling and function.
2015Co-Authors: Pamela Maris, Arnaud Blomme, Ana Perez Palacios, Brunella Costanza, Akeila Bellahcène, Elettra Bianchi, Stephanie Gofflot, Pierre Drion, Giovanna Elvi Trombino, Emmanuel Di ValentinAbstract:(A) Western blot analysis of phospho-SMAD2 (p-SMAD2) and SMAD2 total protein extracts from MDA-MB-468 breast cancer cells treated for 15 min with TGF-β1 and/or human recombinant Asporin (Rec. ASPN). (B) Western blot analysis of p-SMAD2 in total protein extracts from MDA-MB-468 breast cancer cells treated with TGF-β1 and/or Asporin peptide corresponding to the 159–205 amino acid region (ASPNpep.). (C) Western blot analysis of p-SMAD2 and SMAD2 in total protein extracts from EpRAS cells treated for 15 min with TGF-β1 (5 ng/ml) and/or Asporin peptide. (D) EMT induction in EpRAS cells in the presence of TGF-β1 and/or Asporin peptide. EMT was monitored both at the phenotype level (upper panel) and using Western blot evaluation of VIM expression in total protein extracts from EpRAS cells (lower panel). (A–D): HSC70 was used as loading control. (E) Transwell migration assay of EpRAS cells pretreated with TGF-β1 (5 ng/ml) and/or Asporin peptide (10 μg/ml). (F) Quantification of the CSC population in EpRAS cells following TGF-β1 and/or Asporin peptide treatment. (E and F): The data are presented as mean ± SD. All panels: statistical significance was calculated using the Student’s t-test (as described in the Methods section). Western blots show representative data of three independent experiments.
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Asporin is overexpressed in breast cancer tissues.
2015Co-Authors: Pamela Maris, Arnaud Blomme, Ana Perez Palacios, Brunella Costanza, Akeila Bellahcène, Elettra Bianchi, Stephanie Gofflot, Pierre Drion, Giovanna Elvi Trombino, Emmanuel Di ValentinAbstract:(A) Tissue-specific pattern of mRNA expression of Asporin (ASPN), biglycan (BGN), and decorin (DCN). Source: BioGPS (http://biogps.org). The data are presented as mean ± standard deviation (SD). (B) Representative IHC staining of Asporin expression in ductal carcinoma and adjacent non-tumoral breast tissue (left panel) and normal breast tissue obtained from patients undergoing mammary reduction surgery (right panel). Asporin is almost exclusively expressed in breast cancer lesions, while a very low signal is detectable in the adjacent non-tumoral regions. Normal breast tissues are negative. Images of representative fields were taken at 100× and 400× magnification. (C) Western blot analysis of Asporin expression in tumoral breast cancer tissues (T) and the adjacent normal counterpart (AdN) of six ductal adenocarcinoma patients. Ponceau red staining was used as loading control.
Dick Heinegard - One of the best experts on this subject based on the ideXlab platform.
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Asporin competes with decorin for collagen binding binds calcium and promotes osteoblast collagen mineralization
Biochemical Journal, 2009Co-Authors: Sebastian Kalamajski, Anders Aspberg, Karin Lindblom, Dick Heinegard, Ake OldbergAbstract:The interactions of the ECM (extracellular matrix) protein Asporin with ECM components have previously not been investigated. Here, we show that Asporin binds collagen type I. This binding is inhibited by recombinant Asporin fragment LRR (leucine-rich repeat) 10-12 and by full-length decorin, but not by biglycan. We demonstrate that the polyaspartate domain binds calcium and regulates hydroxyapatite formation in vitro. In the presence of Asporin, the number of collagen nodules, and mRNA of osteoblastic markers Osterix and Runx2 were increased. Moreover, decorin or the collagen-binding Asporin fragment LRR 10-12 inhibited the pro-osteoblastic activity of full-length Asporin. Our results suggest that Asporin and decorin compete for binding to collagen and that the polyaspartate in Asporin directly regulates collagen mineralization. Therefore Asporin has a role in osteoblast-driven collagen biomineralization activity. We also show that Asporin can be expressed in Escherichia coli (Rosettagami (TM)) with correctly positioned cysteine bridges, and a similar system can possibly be used for the expression of other SLRPs (small LRR proteoglycans/proteins). (Less)
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identification and characterization of Asporin a novel member of the leucine rich repeat protein family closely related to decorin and biglycan
Journal of Biological Chemistry, 2001Co-Authors: Pilar Lorenzo, Anders Aspberg, Patrik Onnerfjord, Michael T Bayliss, Peter J Neame, Dick HeinegardAbstract:Asporin, a novel member of the leucine-rich repeat family of proteins, was partially purified from human articular cartilage and meniscus. Cloning of human and mouse Asporin cDNAs revealed that the protein is closely related to decorin and biglycan. It contains a putative propeptide, 4 amino-terminal cysteines, 10 leucine-rich repeats, and 2 C-terminal cysteines. In contrast to decorin and biglycan, Asporin is not a proteoglycan. Instead, Asporin contains a unique stretch of aspartic acid residues in its amino-terminal region. A polymorphism was identified in that the number of consecutive aspartate residues varied from 11 to 15. The 8 exons of the human Asporin gene span 26 kilobases on chromosome 9q31.1-32, and the putative promoter region lacks TATA consensus sequences. The Asporin mRNA is expressed in a variety of human tissues with higher levels in osteoarthritic articular cartilage, aorta, uterus, heart, and liver. The deduced amino acid sequence of Asporin was confirmed by mass spectrometry of the isolated protein resulting in 84% sequence coverage. The protein contains an N-glycosylation site at Asn(281) with a heterogeneous oligosaccharide structure and a potential O-glycosylation site at Ser(54). The name Asporin reflects the aspartate-rich amino terminus and the overall similarity to decorin.
Chupak Lau - One of the best experts on this subject based on the ideXlab platform.
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aspirin resistance and adverse clinical events in patients with coronary artery disease
The American Journal of Medicine, 2007Co-Authors: Waihong Chen, Xi Cheng, Puiyin Lee, Jeanette Yatyin Kwok, Hungfat Tse, Chupak LauAbstract:Abstract Purpose We sought to determine the clinical significance of aspirin resistance measured by a point-of-care assay in stable patients with coronary artery disease (CAD). Methods We used the VerifyNow Aspirin (Accumetrics Inc, San Diego, Calif) to determine aspirin responsiveness of 468 stable CAD patients on aspirin 80 to 325 mg daily for ≥4 weeks. Aspirin resistance was defined as an Aspirin Reaction Unit ≥550. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), unstable angina requiring hospitalization, stroke, and transient ischemic attack. Results Aspirin resistance was noted in 128 (27.4%) patients. After a mean follow-up of 379±200 days, patients with aspirin resistance were at increased risk of the composite outcome compared to patients who were aspirin-sensitive (15.6% vs 5.3%, hazard ratio [HR] 3.12, 95% confidence intervals [CI], 1.65-5.91, P P = .007). Conclusions Aspirin resistance, defined by an aggregation-based rapid platelet function assay, is associated with an increased risk of adverse clinical outcomes in stable patients with CAD.
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low dose aspirin increases aspirin resistance in patients with coronary artery disease
The American Journal of Medicine, 2005Co-Authors: Puiyin Lee, Waihong Chen, Xi Cheng, Jeanette Yatyin Kwok, Hungfat Tse, Chupak LauAbstract:Abstract Purpose We sought to investigate the association of aspirin dose and aspirin resistance in stable coronary artery disease patients measured by a point-of-care assay. Methods We studied 468 consecutive stable coronary artery disease patients in a referral cardiac center who were taking aspirin 80 to 325 mg daily for ≥4 weeks. The VerifyNow Aspirin (Ultegra RPFA-ASA, Accumetrics Inc, San Diego, Calif) was used to determine aspirin responsiveness. An aspirin reaction unit (ARU) ≥550 indicates the absence of aspirin-induced platelet dysfunction, based on correlation with epinephrine-induced light transmission aggregometry. Demographic and clinical data were collected to analyze the predictors of aspirin resistance. Results Aspirin resistance was noted in 128 (27.4%) patients. Univariate predictors of aspirin resistance include elderly ( P = 0.002), women ( P P P = 0.009) and aspirin dose ≤100mg ( P = 0.004). Multivariate analysis revealed hemoglobin (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.51 to 0.69; P P = 0.022) to be independent predictors of aspirin resistance. Daily aspirin dose ≤ 100 mg was associated with increased prevalence of aspirin resistance compared with 150 mg and 300 mg daily (30.2% vs 16.7% vs 0%, P = 0.0062). Conclusion A 100 mg or less daily dose of aspirin, which may have lower side effects, is associated with a higher incidence of aspirin resistance in patients with coronary artery disease. Prospective randomized studies are warranted to elucidate the optimal aspirin dosage for preventing ischemic complications of atherothrombotic disease.
