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Wallentin, Lars
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Publications (10 of 563) Show all publications
Brænne, I., Willenborg, C., Tragante, V., Kessler, T., Zeng, L., Reiz, B., . . . Schunkert, H. (2017). A genomic exploration identifies mechanisms that may explain adverse cardiovascular effects of COX-2 inhibitors. Scientific Reports, 7, Article ID 10252.
Open this publication in new window or tab >>A genomic exploration identifies mechanisms that may explain adverse cardiovascular effects of COX-2 inhibitors
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 10252Article in journal (Refereed) Published
Abstract [en]

Cyclooxygenase-2 inhibitors (coxibs) are characterized by multiple molecular off-target effects and increased coronary artery disease (CAD) risk. Here, we systematically explored common variants of genes representing molecular targets of coxibs for association with CAD. Given a broad spectrum of pleiotropic effects of coxibs, our intention was to narrow potential mechanisms affecting CAD risk as we hypothesized that the affected genes may also display genomic signals of coronary disease risk. A Drug Gene Interaction Database search identified 47 gene products to be affected by coxibs. We traced association signals in 200-kb regions surrounding these genes in 84,813 CAD cases and 202,543 controls. Based on a threshold of 1 x 10(-5) (Bonferroni correction for 3131 haplotype blocks), four gene loci yielded significant associations. The lead SNPs were rs7270354 (MMP9), rs4888383 (BCAR1), rs6905288 (VEGFA1), and rs556321 (CACNA1E). By additional genotyping, rs7270354 at MMP9 and rs4888383 at BCAR1 also reached the established GWAS threshold for genome-wide significance. The findings demonstrate overlap of genes affected by coxibs and those mediating CAD risk and points to further mechanisms, which are potentially responsible for coxib-associated CAD risk. The novel approach furthermore suggests that genetic studies may be useful to explore the clinical relevance of off-target drug effects.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-334934 (URN)10.1038/s41598-017-10928-4 (DOI)000408781200111 ()
Funder
AstraZenecaNovo NordiskEU, FP7, Seventh Framework Programme, 261123German Research Foundation (DFG)
Available from: 2017-12-01 Created: 2017-12-01 Last updated: 2017-12-01Bibliographically approved
Pagidipati, N. J., Hess, C. N., Clare, R. M., Akerblom, A., Tricoci, P., Wojdyla, D., . . . Roe, M. T. (2017). An examination of the relationship between serum uric acid level, a clinical history of gout, and cardiovascular outcomes among patients with acute coronary syndrome. American Heart Journal, 187, 53-61.
Open this publication in new window or tab >>An examination of the relationship between serum uric acid level, a clinical history of gout, and cardiovascular outcomes among patients with acute coronary syndrome
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2017 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 187, 53-61 p.Article in journal (Refereed) Published
Abstract [en]

Background Studies have suggested a relationship between higher baseline serum uric acid (sUA) levels and an elevated risk of subsequent ischemic cardiovascular outcomes among acute coronary syndrome (ACS) patients; this relationship may be modified by a clinical history of gout and has not been studied in large patient cohorts. We sought to understand the effect of sUA and gout on ACS outcomes. Methods Using PLATO and TRACER data on 27,959 ACS patients, we evaluated baseline sUA levels in relation to a composite of cardiovascular death, myocardial infarction (MI), or stroke. We assessed interaction terms to determine if a baseline clinical diagnosis of gout modified this putative relationship; 46% (n = 12,882) had sUA levels elevated >6.0 mg/dL. Results Patients with elevated levels were more often male with a history of prior MI, diabetes, and heart failure compared with those with sUA <6.0 mg/dL. The unadjusted risk of the composite endpoint increased with corresponding elevations in sUA levels (per 1 mg/dL increase) (HR = 1.23 [95% CI: 1.20-1.26]) above the statistical inflection point of 5.0 mg/dL. After adjustment, the association between sUA level and the composite outcome remained significant (HR = 1.07 [95% CI: 1.04-1.10]), and baseline gout did not modify this relationship. ' Conclusions In patients with ACS, increasing levels of sUA are associated with an elevated risk of cardiovascular events, regardless of a clinical diagnosis of gout. Further investigation is warranted to determine the mechanism behind this relationship and to delineate whether sUA is an appropriate therapeutic target to reduce cardiovascular risk.

Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2017
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-327059 (URN)10.1016/j.ahj.2017.02.023 (DOI)000401053600007 ()28454808 (PubMedID)
Available from: 2017-08-02 Created: 2017-08-02 Last updated: 2017-08-02Bibliographically approved
Westenbrink, B. D., Alings, M., Granger, C. B., Alexander, J. H., Lopes, R. D., Hylek, E. M., . . . van Gilst, W. H. (2017). Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. American Heart Journal, 185, 140-149.
Open this publication in new window or tab >>Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial
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2017 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 185, 140-149 p.Article in journal (Refereed) Published
Abstract [en]

Background Patients with atrial fibrillation (AF) are prone to cardiovascular events and anticoagulation-related bleeding complications. We hypothesized that patients with anemia are at increased risk for these outcomes. Methods We performed a post hoc analysis of the ARISTOTLE trial, which included >18,000 patients with AF randomized to warfarin (target international normalized ratio, 2.0-3.0) or apixaban 5 mg twice daily. Multivariable Cox regression analysis was used to determine if anemia (defined as hemoglobin <13.0 in men and <12.0 g/dL in women) was associated with future stroke, major bleeding, or mortality. Results Anemia was present at baseline in 12.6% of the ARISTOTLE population. Patients with anemia were older, had higher mean CHADS2 and HAS-BLED scores, and were more likely to have experienced previous bleeding events. Anemia was associated with major bleeding (adjusted hazard ratio [HR], 1.92; 95% CI, 1.62-2.28; P < .0001) and all-cause mortality (adjusted HR, 1.68; 95% CI, 1.46-1.93; P <. 0001) but not stroke or systemic embolism (adjusted HR, 0.92; 95% CI, 0.70-1.21). The benefits of apixaban compared with warfarin on the rates of stroke, mortality, and bleeding events were consistent in patients with and without anemia. Conclusions Chronic anemia is associated with a higher incidence of bleeding complications and mortality, but not of stroke, in anticoagulated patients with AF. Apixaban is an attractive anticoagulant for stroke prevention in patients with AF with or without anemia.

Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2017
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-320831 (URN)10.1016/j.ahj.2016.12.008 (DOI)000396386600016 ()28267467 (PubMedID)
Funder
GlaxoSmithKline (GSK)
Available from: 2017-04-26 Created: 2017-04-26 Last updated: 2017-04-26Bibliographically approved
Guimaraes, P. O., Wojdyla, D. M., Alexander, J. H., Thomas, L., Alings, M., Flaker, G. C., . . . Lopes, R. D. (2017). Anticoagulation therapy and clinical outcomes in patients with recently diagnosed atrial fibrillation: Insights from the ARISTOTLE trial. International Journal of Cardiology, 227, 443-449.
Open this publication in new window or tab >>Anticoagulation therapy and clinical outcomes in patients with recently diagnosed atrial fibrillation: Insights from the ARISTOTLE trial
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2017 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 227, 443-449 p.Article in journal (Refereed) Published
Abstract [en]

Background: Evidence supporting use of antithrombotic therapy in atrial fibrillation (AF) is based mainly on data from patients with permanent, persistent, or paroxysmal AF. Less is known about the risk following a new diagnosis of AF and the efficacy and safety of apixaban in these patients. Methods: Using data from ARISTOTLE, we assessed the relationship between timing of AF diagnosis and clinical outcomes and the efficacy and safety of apixaban versus warfarin in these patients. Recently diagnosed AF was defined as a new diagnosis of AF within 30 days prior to enrollment. Cox proportional hazards models were used to determine the association between recently diagnosed AF and clinical outcomes. We also assessed the efficacy and safety of apixaban versus warfarin according to time since AF diagnosis. Results: In ARISTOTLE, 1899 (10.5%) patients had recently diagnosed AF. After adjustment, patients with recently versus remotely diagnosed Al' had a similar risk of stroke/systemic embolism (HR = 1.07, 95% CI = 0.80-1.42; p 0.67), but higher mortality was seen in patients with recently diagnosed AF (adjusted HR = 1.21, 95% Cl 1.02-1.43; p 0.03). The beneficial effects of apixaban, compared with warfarin, on clinical outcomes were consistent, irrespective of timing of AI' diagnosis (all interaction p-values >0.12). Conclusion: Patients with recently diagnosed AF had a similar risk of stroke but higher mortality than patients with remotely diagnosed AF, suggesting that they are not at "low risk" and warrant stroke prevention strategies. The benefits of apixaban over warfarin were preserved, irrespective of timing of AF diagnosis.

Keyword
Apixaban, Anticoagulation, Atrial fibrillation, Recently diagnosed atrial fibrillation, Stroke prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-313928 (URN)10.1016/j.ijcard.2016.11.014 (DOI)000390480700077 ()27852444 (PubMedID)
Available from: 2017-04-05 Created: 2017-04-05 Last updated: 2017-11-29Bibliographically approved
Hijazi, Z., Oldgren, J., Siegbahn, A. & Wallentin, L. (2017). Application of Biomarkers for Risk Stratification in Patients with Atrial Fibrillation. Clinical Chemistry, 63(11), 152-164.
Open this publication in new window or tab >>Application of Biomarkers for Risk Stratification in Patients with Atrial Fibrillation
2017 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 11, 152-164 p.Article, review/survey (Refereed) Published
Abstract [en]

BACKGROUND: Atrial fibrillation is the most common sustained arrhythmia and an important contributor to cardiovascular morbidity and mortality. Several strategies have been proposed for prediction of outcomes and individualization of treatments to better balance the benefits of stroke prevention and risks of bleeding during anticoagulation. CONTENT: The availability of analytically more specific and sensitive methods to measure circulating biomarkers of cellular and organ stress and dysfunction has led to testing of their utility in several cardiovascular conditions. In patients with atrial fibrillation, biomarkers of myocardial injury (troponin) and cardiovascular stress and dysfunction (natriuretic peptides, growth differentiation factor 15), myocardial fibrosis (galectin-3), renal dysfunction (creatinine, cystatin C), inflammation (C reactive protein, cytokines) and coagulation activity (D-dimer) have been found associated with underlying pathophysiology, clinical outcomes and effects of treatment. Measurements of these markers might therefore expand the understanding of the pathophysiology, improve risk assessment and optimize treatment in individual patients with atrial fibrillation. SUMMARY: Biomarkers for risk stratification have potential roles as tools for evaluation of patients with atrial fibrillation and for selection of the best treatment strategies to prevent stroke, major bleeding, and mortality.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-319170 (URN)10.1373/clinchem.2016.255182 (DOI)000395048800024 ()
Funder
AstraZenecaGlaxoSmithKline (GSK)
Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2017-04-28Bibliographically approved
Ducrocq, G., Schulte, P. J., Budaj, A., Cornel, J. H., Held, C., Himmelmann, A., . . . Steg, P. G. (2017). Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes. American Heart Journal, 186, 91-99.
Open this publication in new window or tab >>Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes
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2017 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 186, 91-99 p.Article in journal (Refereed) Published
Abstract [en]

Background: Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality.

Methods: In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events.

Results: A total of 822 patients (4.4%) had >= 1 spontaneous ischemic event; 485 patients (2.6%), >= 1 spontaneous PLATO major bleed, 282 (1.5%), >= 1 spontaneous TIMI major bleed; and 207 (1.1%), >= 1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% Cls) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P > 0.05)

Conclusions: In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem "prognostically equivalent" to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2017
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-324336 (URN)10.1016/j.ahj.2017.01.010 (DOI)000401053500011 ()28454837 (PubMedID)
Available from: 2017-06-16 Created: 2017-06-16 Last updated: 2017-06-16Bibliographically approved
Lindholm, D., Lindbäck, J., Armstrong, P. W., Budaj, A., Cannon, C. P., Granger, C. B., . . . Wallentin, L. (2017). Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease. Journal of the American College of Cardiology, 70(7), 813-826.
Open this publication in new window or tab >>Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease
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2017 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 70, no 7, 813-826 p.Article in journal (Refereed) Published
Abstract [en]

Background Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD).Objectives This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD.Methods In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study.Results During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This “ABC-CHD” model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts.Conclusions This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903)

Place, publisher, year, edition, pages
Elsevier, 2017
Keyword
cardiac troponin, low-density lipoprotein cholesterol, N-terminal pro-B-type natriuretic peptide, risk prediction
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-327281 (URN)10.1016/j.jacc.2017.06.030 (DOI)000407028500001 ()28797349 (PubMedID)
Available from: 2017-08-08 Created: 2017-08-08 Last updated: 2017-11-23Bibliographically approved
Lindholm, D. P., James, S. K., Bertilsson, M., Becker, R. C., Cannon, C. P., Giannitsis, E., . . . Wallentin, L. (2017). Biomarkers and Coronary Lesions Predict Outcomes after Revascularization in Non-ST-Elevation Acute Coronary Syndrome. Clinical Chemistry, 63(2), 573-584.
Open this publication in new window or tab >>Biomarkers and Coronary Lesions Predict Outcomes after Revascularization in Non-ST-Elevation Acute Coronary Syndrome
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2017 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 2, 573-584 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Risk stratification in non-ST-elevation acute coronary syndrome (NSTE-ACS) is currently mainly based on clinical characteristics. With routine invasive management, angiography findings and biomarkers are available and may improve prognostication. We aimed to assess if adding biomarkers [high-sensitivity cardiac troponin T (cTnT-hs), N-terminal probrain-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15)] and extent of coronary artery disease (CAD) might improve prognostication in revascularized patients with NSTE-ACS.

METHODS: In the PLATO (Platelet Inhibition and Patient Outcomes) trial, 5174 NSTE-ACS patients underwent initial angiography and revascularization and had cTnT-hs, NT-proBNP, and GDF-15 measured. Cox models were developed adding extent of CAD and biomarker levels to established clinical risk variables for the composite of cardiovascular death (CVD)/spontaneous myocardial infarction (MI), and CVD alone. Models were compared using c-statistic and net reclassification improvement (NRI).

RESULTS: For the composite end point and CVD, prognostication improved when adding extent of CAD, NT-proBNP, and GDF-15 to clinical variables (c-statistic 0.685 and 0.805, respectively, for full model vs 0.649 and 0.760 for clinical model). cTnT-hs did not contribute to prognostication. In the full model (clinical variables, extent of CAD, all biomarkers), hazard ratios (95% CI) per standard deviation increase were for cTnT-hs 0.93(0.81-1.05), NT-proBNP 1.32(1.13-1.53), GDF-15 1.20(1.07-1.36) for the composite end point, driven by prediction of CVD by NT-proBNP and GDF-15. For spontaneous MI, there was an association with NT-proBNP or GDF-15, but not with cTnT-hs.

CONCLUSIONS: In revascularized patients with NSTE-ACS, the extent of CAD and concentrations of NT-proBNP and GDF-15 independently improve prognostication of CVD/spontaneous MI and CVD alone. This information may be useful for selection of patients who might benefit from more intense and/or prolonged antithrombotic treatment.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-315774 (URN)10.1373/clinchem.2016.261271 (DOI)000393360000020 ()27932413 (PubMedID)
Funder
AstraZeneca
Note

Författarna företräder The PLATO Investigators.

Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2017-11-29Bibliographically approved
Erlinge, D., Omerovic, E., Fröbert, O., Linder, R., Danielewicz, M., Hamid, M., . . . James, S. (2017). Bivalirudin versus Heparin Monotherapy in Myocardial Infarction. New England Journal of Medicine, 377(12), 1132-1142.
Open this publication in new window or tab >>Bivalirudin versus Heparin Monotherapy in Myocardial Infarction
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2017 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 12, 1132-1142 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y 12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y(12) inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P = 0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P = 0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P = 0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P = 0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P = 0.76). CONCLUSIONS Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others;

Place, publisher, year, edition, pages
MASSACHUSETTS MEDICAL SOC, 2017
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-336480 (URN)10.1056/NEJMoa1706443 (DOI)000411348500007 ()28844201 (PubMedID)
Available from: 2017-12-18 Created: 2017-12-18 Last updated: 2017-12-18Bibliographically approved
Gaglia, M. A. ., Lipinski, M. J., Lhermusier, T., Steinvil, A., Kiramijyan, S., Pokharel, S., . . . Waksman, R. (2017). Comparison of Platelet Reactivity in Black Versus White Patients With Acute Coronary Syndromes After Treatment With Ticagrelor. American Journal of Cardiology, 119(8), 1135-1140.
Open this publication in new window or tab >>Comparison of Platelet Reactivity in Black Versus White Patients With Acute Coronary Syndromes After Treatment With Ticagrelor
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2017 (English)In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 119, no 8, 1135-1140 p.Article in journal (Refereed) Published
Abstract [en]

Ticagrelor, a potent platelet inhibitor, has primarily been studied in white patients. Platelet reactivity among black patients with acute coronary syndrome (ACS) on ticagrelor, however, is unknown. Our objective was to compare platelet reactivity in black versus white patients with ACS treated with ticagrelor. We conducted a prospective, pharmacodynamic study of 29 black patients with ACS treated with ticagrelor. Platelet reactivity was assessed at 1, 4, and 8 hours after a loading dose of ticagrelor 180 mg and at 30 days on a maintenance dose of ticagrelor 90 mg twice daily. Assays included light transmission aggregometry, VerifyNow P2Y12, and vasodilator-stimulated phosphoprotein. We provided comparison with a historical white cohort. Platelet reactivity among blacks with ACS on ticagrelor was similar to that in whites, except that blacks had lower values at 4 hours, 8 hours, and on maintenance therapy for light transmission aggregometry with 20 mu mol/L adenosine diphosphate. Among blacks, high-on-treatment platelet reactivity for all 3 assays was uncommon at 1 hour and nonexistent at 4 hours, 8 hours, and while on maintenance therapy. Blacks preloaded with clopidogrel (n = 17) had significantly lower results of VerifyNow (64 +/- 65 vs 198 +/- 86, p<0.001) and vasodilator-stimulated phosphoprotein (12.8 +/- 21.6 vs 58.9 +/- 19.9, p<0.001) at 1 hour compared with those with no clopidogrel prelOad. In conclusion, among patients with ACS receiving ticagrelor, levels of platelet reactivity in blacks are similar to that in whites. This suggests that the cardiovascular benefits of ticagrelor observed in the platelet inhibition and patient outcomes (PLATO) trial are likely to be observed in blacks and whites.

Place, publisher, year, edition, pages
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC, 2017
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-322180 (URN)10.1016/j.amjcard.2017.01.002 (DOI)000399515000002 ()
Funder
AstraZenecaGlaxoSmithKline (GSK)
Available from: 2017-05-17 Created: 2017-05-17 Last updated: 2017-05-17Bibliographically approved
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