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Wang, W. T., James, S. K. & Wang, T. Y. (2017). A review of sex-specific benefits and risks of antithrombotic therapy in acute coronary syndrome. European Heart Journal, 38(3), 165-171.
Open this publication in new window or tab >>A review of sex-specific benefits and risks of antithrombotic therapy in acute coronary syndrome
2017 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no 3, 165-171 p.Article in journal (Refereed) Published
Abstract [en]

Over the past decade, more men than women have shown improved outcomes from antithrombotic therapies after acute coronary syndrome (ACS), which raises the question of whether there are sex-specific differences in treatment patterns and response to therapy. Differences in presenting clinical characteristics, pathophysiologic profile, and disparities in treatment may contribute to this outcomes discrepancy. Analyses of large trials and registry data suggest that male and female ACS patients experience similar benefits from antithrombotic therapy without significant difference in treatment utilization rates, yet women are consistently at higher risk of bleeding than men. Bleeding may result in antithrombotic treatment disruption, which increases the risk of long-term thrombotic events. Additionally, female ACS patients are more likely to receive suboptimal medication dosing and have lower rates of long-term medication adherence. These differences have significant clinical implications for women, indicating the need for strategies that will optimize initial treatment and long-term management attuned to these recognized sex-specific gaps.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2017
Keyword
Acute coronary syndrome, Antithrombotic therapy, Sex-specific differences
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-319665 (URN)10.1093/eurheartj/ehv758 (DOI)000394009100013 ()28158545 (PubMedID)
Funder
GlaxoSmithKline (GSK)
Available from: 2017-04-07 Created: 2017-04-07 Last updated: 2017-11-29Bibliographically 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
Batra, G., Lindhagen, L., Andell, P., Erlinge, D., James, S., Spaak, J. & Oldgren, J. (2017). Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are associated with improved outcome but do not prevent new-onset atrial fibrillation after acute myocardial infarction. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 6(3), Article ID e005165.
Open this publication in new window or tab >>Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are associated with improved outcome but do not prevent new-onset atrial fibrillation after acute myocardial infarction
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2017 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 3, e005165Article in journal (Refereed) Published
Abstract [en]

Background Treatment with renin‐angiotensin system (RAS) inhibitors might restrain the structural/electrical remodeling associated with atrial fibrillation (AF). Limited evidence exists regarding the potential benefits of RAS inhibition post‐acute myocardial infarction (AMI) in patients with AF. This study sought to assess the association between RAS inhibition and all‐cause mortality and new‐onset AF in patients with/without congestive heart failure (CHF) post‐AMI.

Methods and Results Patients hospitalized for AMI between 2006 and 2012 were identified in Swedish registries. Patients were stratified in 4 subgroups; patients with CHF and AF (n=11 489); patients with CHF without AF (n=31 676); patients with AF without CHF (n=10 066); and patients without both CHF and AF (n=59 417). Patients exposed to RAS inhibition were compared to nontreated. Three‐year risk of all‐cause mortality and new‐onset AF was assessed using adjusted Cox regression analyses. At discharge, 83 291 (73.9%) patients received RAS inhibition. RAS inhibition was associated with lower 3‐year risk of all‐cause mortality in CHF patients with AF, adjusted hazard ratio (HR) with 95% CI 0.75 (0.70–0.81), CHF patients without AF, HR 0.65 (0.60–0.69), AF patients without CHF, HR 0.82 (0.75–0.90), and in patients without CHF and AF, HR 0.76 (0.72–0.81), respectively. RAS inhibition was not associated with lower 3‐year risk of new‐onset AF in patients without AF but with/without CHF; HR 0.96 (0.84–1.10) and 1.12 (1.02–1.22), respectively.

Conclusions RAS inhibition post‐AMI was associated with lower risk of all‐cause mortality. In patients with/without CHF, RAS inhibition was not associated with lower incidence of new‐onset AF.

Keyword
atrial fibrillation, myocardial infarction
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-317878 (URN)10.1161/JAHA.116.005165 (DOI)000399322900044 ()28320744 (PubMedID)
Funder
Swedish Foundation for Strategic Research
Available from: 2017-03-21 Created: 2017-03-21 Last updated: 2017-11-29Bibliographically approved
Fanaroff, A. C., Hasselblad, V., Roe, M. T., Bhatt, D. L., James, S. K., Steg, P. G., . . . Ohman, E. M. (2017). Antithrombotic agents for secondary prevention after acute coronary syndromes: A systematic review and network meta-analysis. International Journal of Cardiology, 241, 87-96.
Open this publication in new window or tab >>Antithrombotic agents for secondary prevention after acute coronary syndromes: A systematic review and network meta-analysis
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2017 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 241, 87-96 p.Article in journal (Refereed) Published
Abstract [en]

Background: Nine oral antithrombotic medications currently available in the United States and Europe have been studied in clinical trials for secondary prevention of cardiac events following acute coronary syndrome (ACS). Few combinations of these medications have been directly compared, and studies have used multiple different comparator regimens.

Methods: We performed a systematic review and network meta-analysis of randomized controlled trials evaluating one or more available oral antithrombotic therapies in patients with ACS or prior myocardial infarction (MI). Co-primary outcomes were all-cause and cardiovascular mortality compared with imputed placebo and aspirin monotherapy.

Results: Forty-seven studies (196,057 subjects) met inclusion criteria and were included in the systematic review. Almost all studies tested either aspirin monotherapy compared with placebo or a combination of antithrombotic agents that included aspirin. Nearly all regimens reduced all-cause and cardiovascular mortality compared with imputed placebo. However, compared with imputed aspirin monotherapy, only combination therapy with aspirin plus ticagrelor was associated with lower cardiovascular mortality (OR 0.80, 95% CI 0.68-0.93), and triple therapy with aspirin, clopidogrel, and very low dose rivaroxaban was associated with lower all-cause mortality (OR 0.67, 95% CI 0.49-0.90). Major bleeding was increased 45-95% with dual antithrombotic therapy, and 2-6-fold with triple therapy.

Conclusion: Few combinations of antithrombotic therapy were associated with a reduction inmortality compared with aspirin monotherapy, highlighting the difficulty in clinical interpretation of composite ischemic endpoints. Future studies may need to focus on limiting the number of antithrombotic therapies tested in combination to best balance ischemic event reduction and bleeding.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2017
Keyword
Acute coronary syndrome, Acute myocardial infarction, Antiplatelet agents, antithrombotic agents, Network meta-analysis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-331208 (URN)10.1016/j.ijcard.2017.03.046 (DOI)000405455200016 ()28320608 (PubMedID)
Available from: 2017-10-19 Created: 2017-10-19 Last updated: 2017-10-19Bibliographically 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. 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
De Silva, K., Myat, A., Cotton, J., James, S. K., Gershlick, A. & Stone, G. W. (2017). Bleeding associated with the management of acute coronary syndromes. Heart, 103(7), 546-562.
Open this publication in new window or tab >>Bleeding associated with the management of acute coronary syndromes
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2017 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 7, 546-562 p.Article in journal (Refereed) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-321346 (URN)10.1136/heartjnl-2015-307602 (DOI)000396232200015 ()28087588 (PubMedID)
Available from: 2017-05-31 Created: 2017-05-31 Last updated: 2017-05-31Bibliographically approved
Mohammad, M. A., Andell, P., Koul, S., James, S. K., Schersten, F., Gotberg, M. & Erlinge, D. (2017). Cangrelor in combination with ticagrelor provides consistent and potent P2Y12-inhibition during and after primary percutaneous coronary intervention in real-world patients with ST-segment-elevation myocardial infarction. Platelets, 28(4), 414-416.
Open this publication in new window or tab >>Cangrelor in combination with ticagrelor provides consistent and potent P2Y12-inhibition during and after primary percutaneous coronary intervention in real-world patients with ST-segment-elevation myocardial infarction
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2017 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 28, no 4, 414-416 p.Article in journal (Refereed) Published
Abstract [en]

Patients pretreated with ticagrelor with less than 1 hour from percutaneous coronary intervention (PCI) or receiving ticagrelor in cath lab were prospectively included and received cangrelor. Cangrelor was infused for 2 hours and platelet function was assessed as P2Y12 reactivity units (PRU) with the VerifyNow P2Y12 function assay before start of infusion, 15 min after the start of infusion, and 30 min after the end of infusion. A total of n = 32 patients with an average age of 68 (+/- 13) years with n = 22 (69%) males were included. The level of P2Y12 inhibition before cangrelor infusion was started was 249 PRU (IQR 221-271). After 15 min of cangrelor infusion the P2Y12 reactivity was markedly decreased to 71 PRU (IQR 52-104, p < 0.001). At 30 min after end of infusion PRU remained within the therapeutic range, 89 PRU (IQR 50-178; p < 0.001 for comparison with preinfusion) with only n = 4 (12.5%) patients with PRU > 225. Results were consistent between patients receiving ticagrelor prehospital or in the cath lab and no statistical differences in PRU were noted between the two groups in any of the three measurements. In conclusion, cangrelor in combination with ticagrelor results in consistent and strong P2Y12 inhibition during and after infusion and cangrelor may bridge the gap until oral P2Y12 inhibitors achieve effect in real-world STEMI patients undergoing primary PCI.

Keyword
Cangrelor, myocardial infarction, PCI
National Category
Cardiac and Cardiovascular Systems Hematology
Identifiers
urn:nbn:se:uu:diva-331911 (URN)10.1080/09537104.2016.1246714 (DOI)000405498700014 ()27885888 (PubMedID)
Funder
Swedish Heart Lung FoundationKnut and Alice Wallenberg FoundationSwedish Research CouncilSwedish Foundation for Strategic Research Region Skåne
Available from: 2017-10-23 Created: 2017-10-23 Last updated: 2017-10-23Bibliographically approved
Ohman, E. M., Roe, M. T., Steg, P. G., James, S. K., Povsic, T. J., White, J., . . . Gibson, C. M. (2017). Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial. The Lancet, 389(10081), 1799-1808.
Open this publication in new window or tab >>Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial
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2017 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 389, no 10081, 1799-1808 p.Article in journal (Refereed) Published
Abstract [en]

Background Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2.5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months.

Methods In this double-blind, multicentre, randomised trial (GEMINI-ACS-1) done at 371 clinical centres in 21 countries, eligible patients were older than 18 years with unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), with positive cardiac biomarkers and either ischaemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography. Participants were randomly assigned (1: 1) within 10 days after admission for the index acute coronary syndromes event to either aspirin or rivaroxaban based on a computer-generated randomisation schedule. Randomisation was balanced by using randomly permuted blocks with size of four and was stratified based on the background P2Y12 inhibitor (clopidogrel or ticagrelor) intended to be used at the time of randomisation. Investigators and patients were masked to treatment assignment. Patients received a minimum of 180 days of double-blind treatment with rivaroxaban 2.5 mg twice daily or aspirin 100 mg daily. The choice of clopidogrel or ticagrelor during trial conduct was not randomised and was based on investigator preference. The primary endpoint was thrombolysis in myocardial infarction (TIMI) clinically significant bleeding not related to coronary artery bypass grafting (CABG; major, minor, or requiring medical attention) up to day 390. Primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02293395.

Findings Between April 22, 2015, and Oct 14, 2016, 3037 patients with acute coronary syndromes were randomly assigned; 1518 to receive aspirin and 1519 to receive rivaroxaban. 1704 patients (56%) were in the ticagrelor and 1333 (44%) in the clopidogrel strata. Median duration of treatment was 291 days (IQR 239-354). TIMI non-CABG clinically significant bleeding was similar with rivaroxaban versus aspirin therapy (total 154 patients [5%]; 80 participants [5%] of 1519 vs 74 participants [5%] of 1518; HR 1.09 [95% CI 0.80-1.50]; p=0.5840).

Interpretation A dual pathway antithrombotic therapy approach combining low-dose rivaroxaban with a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes had similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor. A larger, adequately powered trial would be required to definitively assess the efficacy and safety of this approach.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-322520 (URN)10.1016/S0140-6736(17)30751-1 (DOI)000400549300029 ()28325638 (PubMedID)
Available from: 2017-05-29 Created: 2017-05-29 Last updated: 2017-05-29Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-4413-9736

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