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ABSTRACT: Warfarin use in patients with acute myocardial infarction (AMI) and atrial fibrillation (AF) remains challenging. We describe use of warfarin up to 1 year after hospitalization among patients with AMI and AF according to stroke and bleeding risk, and identify factors associated with long-term mortality in this population. Patients with AMI and AF who underwent cardiac catheterization during their AMI hospitalization in 1995-2007 were identified from the Duke Databank for Cardiovascular Disease. Warfarin use at discharge, 6 months, and 1 year as well as long-term vital status were assessed by surveys. Rates of warfarin use were presented according to CHADS2 and CHA2DS2VASc stroke and ATRIA bleeding risk scores. Cox proportional hazards modeling was used to determine whether warfarin use at discharge was independently associated with 1-year mortality. A total of 879 patients hospitalized with AMI with AF were identified. Median age was 72 (25th, 75th percentiles: 64, 79), and median follow-up was 4.1 years (1.3, 7.4). The rate of warfarin use at discharge was 24 % and did not differ by CHADS2, CHA2DS2VASc, or ATRIA risk scores. Warfarin use remained similar at 6 months (26 %) and 1 year (27 %). Long-term mortality was high and did not differ by whether warfarin was or was not prescribed at discharge (72 and 71 %, respectively). Factors associated with 1-year mortality were history of heart failure (HR 1.58, 95 % CI 1.32-1.90), higher Charlson comorbidity index (HR 1.19, 95 % CI 1.11-1.28), and older age (HR 1.03 per 1-year increase, 95 % CI 1.02-1.05). Warfarin use at discharge among patients hospitalized for AMI who had comorbid AF was low and remained low at 1 year. Warfarin use at hospital discharge was not associated with either 1-year mortality or long-term mortality.
Journal of Thrombosis and Thrombolysis 06/2013; · 1.48 Impact Factor
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ABSTRACT: Introduction: Traditional oral anticoagulants, such as warfarin, are effective but require frequent laboratory monitoring for dose adjustment and have several known interactions with food and other drugs. Oral direct factor Xa inhibitors are an emerging class of anticoagulants that do not require routine laboratory monitoring. We reviewed the pharmacokinetics and pharmacology as well as the clinical safety and efficacy of apixaban , an oral direct factor Xa inhibitor. Areas covered: Data from Phase II and III clinical trials and secondary analysis involving apixaban were included. Studies using apixaban for stroke prevention in patients with atrial fibrillation, for the prevention and treatment of venous thromboembolism, and for secondary prevention of ischemic events in patients with acute coronary syndromes are discussed. Expert opinion: Apixaban is a safe, effective, and attractive alternative to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. It is also a good option for the prevention of venous thromboembolic events after major orthopedic surgery and for the extended treatment of deep vein thrombosis and pulmonary embolism. Apixaban at a dose of 5 mg twice daily did not have a favorable risk/benefit profile for secondary prevention in high-risk patients with acute coronary syndromes.
Expert Opinion on Drug Safety 05/2013; · 3.02 Impact Factor
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Nature Reviews Cardiology 05/2013; · 8.83 Impact Factor
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ABSTRACT: : To review our current understanding of the epidemiology and pathogenesis of vein graft failure (VGF), give an overview of current preventive and interventional measures, and explore strategies that may improve vein graft patency.
: VGF and progression of native coronary artery disease limit the long-term efficacy of coronary artery bypass graft surgery.
: We reviewed the published literature on the pathophysiology, prevention, and/or treatment of VGF by searching the MEDLINE (January 1, 1966-January 1, 2012), EMBASE (January 1, 1980-January 1, 2012), and Cochrane (January 1, 1995-January 1, 2012) databases. In addition, we reviewed references from the selected articles for studies not identified in the initial search. Basic science and clinical studies were included; non-English language publications were excluded.
: Acute thrombosis, neointimal hyperplasia, and accelerated atherosclerosis are the 3 mechanisms that lead to VGF. Preventive measures include matching and quality assessment of conduit and target vessel, lipid-lowering drugs, antithrombotic therapy, and cessation of smoking. Treatment of VGF includes medical therapy, percutaneous intervention, and redo coronary artery bypass graft surgery. In patients undergoing graft intervention, the use of drug-eluting stents, antiplatelet agents, and embolic protection devices may improve clinical outcomes.
: Despite advances in management, VGF remains one of the leading causes of poor in-hospital and long-term outcomes after coronary artery bypass graft surgery. New developments in VGF prevention such as gene therapy, external graft support, fully tissue-engineered grafts, hybrid grafts, and synthetic conduits are promising but unproven. Future efforts to reduce VGF require a multidisciplinary approach with a primary focus on prevention.
Annals of surgery 05/2013; 257(5):824-33. · 7.90 Impact Factor
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ABSTRACT: Saphenous vein graft (SVG) failure is a common finding in patients following coronary artery bypass graft (CABG) surgery. In the literature SVG failure rates have been reported from 25 to over 50% within 10 years. Although common, it remains unclear to what extent SVG failure affects clinical outcome, due to differences in definition, patient selection and follow-up. Particularly the lack of agreement on a universal definition makes comparisons between studies, and therefore generalizability of associations with outcomes, challenging. We suggest using a definition of SVG failure that is based on imaging as well as clinical parameters, that includes reporting SVG failure on both graft and patient level. The use of non-invasive imaging may help improve follow-up rates, and provide a more accurate picture of the real incidence and clinical impact of SVG failure. Given the lack of supportive evidence showing a consistent association between SVG failure and major adverse cardiovascular events, SVG failure should not be considered a valid surrogate endpoint at this time.
American heart journal 05/2013; 165(5):639-43. · 4.65 Impact Factor
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ABSTRACT: With the large number of antithrombotic therapies available and under investigation for the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS), practice guidelines now stress the importance of selecting an antithrombotic strategy according to the efficacy and safety profiles of the chosen agent. Contemporary trials have incorporated bleeding along with ischemic end points into a composite end point commonly referred to as net clinical benefit, which allows for simultaneous evaluation of the differences between benefit and harm for an investigational antithrombotic therapy. However, incorporating major bleeding into a composite end point that includes ischemic events is not warranted and is associated with many pitfalls. In this article, we discuss the validity of combining efficacy and safety end points to form a net clinical benefit composite end point with the traditional time-to-event analysis for trials evaluating antithrombotic therapies for NSTE ACS. We describe alternative statistical approaches for concurrent assessment of the safety and efficacy of antithrombotic therapies used to treat patients with NSTE ACS.
American heart journal 05/2013; 165(5):644-654.e1. · 4.65 Impact Factor
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Sana M Al-Khatib,
Laine Thomas,
Lars Wallentin,
Renato D Lopes,
Bernard Gersh,
David Garcia,
Justin Ezekowitz,
Marco Alings,
Hongqui Yang, John H Alexander,
Gregory Flaker,
Michael Hanna,
Christopher B Granger
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ABSTRACT: AimsIt is uncertain whether the benefit from apixaban varies by type and duration of atrial fibrillation (AF).Methods and resultsA total of 18 201 patients with AF [2786 (15.3%) with paroxysmal and 15 412 (84.7%) with persistent or permanent] were randomized to apixaban or warfarin. In this pre-specified secondary analysis, we compared outcomes and treatment effect of apixaban vs. warfarin by AF type and duration. The primary efficacy endpoint was a composite of ischaemic or haemorrhagic stroke or systemic embolism. The secondary efficacy endpoint was all-cause mortality. There was a consistent reduction in stroke or systemic embolism (P for interaction = 0.71), all-cause mortality (P for interaction = 0.75), and major bleeding (P for interaction = 0.50) with apixaban compared with warfarin for both AF types. Apixaban was superior to warfarin in all studied endpoints, regardless of AF duration at study entry (P for all interactions >0.13). The rate of stroke or systemic embolism was significantly higher in patients with persistent or permanent AF than patients with paroxysmal AF (1.52 vs. 0.98%; P = 0.003, adjusted P = 0.015). There was also a trend towards higher mortality in patients with persistent or permanent AF (3.90 vs. 2.81%; P = 0.0002, adjusted P = 0.066).Conclusion
The risks of stroke, mortality, and major bleeding were lower with apixaban than warfarin regardless of AF type and duration. Although the risk of stroke or systemic embolism was lower in paroxysmal than persistent or permanent AF, apixaban is an attractive alternative to warfarin in patients with AF and at least one other risk factor for stroke, regardless of the type or duration of AF.
European Heart Journal 04/2013; · 10.48 Impact Factor
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John J V McMurray,
Justin A Ezekowitz,
Basil S Lewis,
Bernard J Gersh,
Sean van Diepen,
John Amerena,
Jozef Bartunek,
Patrick Commerford,
Byung-Hee Oh,
Veli-Pekka Harjola,
Sana M Al-Khatib,
Michael Hanna, John H Alexander,
Renato D Lopes,
Daniel M Wojdyla,
Lars Wallentin,
Christopher B Granger
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ABSTRACT: BACKGROUND: -We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF)Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin. METHODS AND RESULTS: -The risk of a number of outcomes including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding or death ("net clinical benefit") were calculated in 3 patient groups: 1) No HF/no LVSD (n=8728) 2) HF/no LVSD (n=3207) and 3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24) and lowest in patients without HF or LVSD (1.54; 5.27); each comparison p<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death 0.89 (95% CI 0.81,0.98) p=0.02; for SSE, major bleed or death it was 0.85 (0.78,0.92); p<0.001. There was no heterogeneity of treatment-effect across the 3 groups. CONCLUSIONS: -Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
Circulation Heart Failure 04/2013; · 6.29 Impact Factor
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Judson B Williams,
Renato D Lopes,
Gail E Hafley,
T Bruce Ferguson,
Michael J Mack,
C Michael Gibson,
Robert A Harrington,
Eric D Peterson,
Peter K Smith,
Rajendra H Mehta, John H Alexander
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ABSTRACT: Dual antiplatelet therapy with both aspirin and clopidogrel is increasingly used after coronary artery bypass grafting (CABG); however, little is known about the safety or efficacy. We sought to determine the relationship between postoperative clopidogrel and clinical and angiographic outcomes following CABG. We evaluated 3,014 patients from PREVENT IV who underwent CABG at 107 US sites. Postoperative antiplatelet therapy was left to physician discretion. Risk-adjusted angiographic and clinical outcomes were compared in patients taking and not taking clopidogrel 30 days post-CABG. At 30 days, 633 (21 %) patients were taking clopidogrel. Clopidogrel users were more likely to have peripheral vascular (15 vs. 11 %) and cerebrovascular disease (17 vs. 11 %), prior myocardial infarction (MI) (46 vs. 41 %), and off-pump surgery (33 vs. 18 %). Clopidogrel use was associated with statistically insignificant higher graft failure (adjusted odds ratio 1.3; 95 % confidence interval [CI] [1.0, 1.7]; P = 0.05). At 5-year follow-up, clopidogrel use was associated with similar composite rates of death, MI, or revascularization (27 vs. 24 %; adjusted hazard ratio 1.1; 95 % CI [0.9, 1.4]; P = 0.38) compared with those not using clopidogrel. There was an interaction between use of cardiopulmonary bypass and clopidogrel with a trend toward lower 5-year clinical events with clopidogrel in patients undergoing off-pump CABG. In this observational analysis, clopidogrel use was not associated with better 5-year outcomes following CABG. There may be better outcomes with clopidogrel among patients having off-pump surgery. Adequately powered randomized clinical trials are needed to determine the role of dual antiplatelet therapy after CABG.
Journal of Thrombosis and Thrombolysis 04/2013; · 1.48 Impact Factor
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ABSTRACT: Background
Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting.Methods and resultsAll seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies.Conclusion
In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.
European Heart Journal 03/2013; · 10.48 Impact Factor
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R D Lopes,
S M Al-Khatib,
H Yang,
Prof C B Granger,
J H Alexander,
Uppsala,
Prof L Wallentin,
Hill Lenox,
New Hospital,
Ny York, [......],
Justin A Ezekowitz,
Bernard J Gersh,
Christopher B Granger,
Stefan H Hohnloser,
John Horowitz,
Elaine M Hylek,
John J Mcmurray,
Puneet Mohan,
Dragos Vinereanu, John H Alexander
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ABSTRACT: Background The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism, causes less bleeding, and results in lower mortality. We assessed in this trial's participants how results diff ered according to patients' CHADS 2 , CHA 2 DS 2 VASc, and HAS-BLED scores, used to predict the risk of stroke and bleeding. Methods ARISTOTLE was a double-blind, randomised trial that enrolled 18 201 patients with atrial fi brillation in 39 countries. Patients were randomly assigned apixaban 5 mg twice daily (n=9120) or warfarin (target international normalised ratio 2·0–3·0; n=9081). The primary endpoint was stroke or systemic embolism. The primary safety outcome was major bleeding. We calculated CHADS 2 , CHA 2 DS 2 VASc, and HAS-BLED scores of patients at randomisation. Effi cacy analyses were by intention to treat, and safety analyses were of the population who received the study drug. ARISTOTLE is registered with ClinicalTrials.gov, number NCT00412984. Findings Apixaban signifi cantly reduced stroke or systemic embolism with no evidence of a diff erential eff ect by risk of stroke (CHADS 2 1, 2, or ≥3, p for interaction=0·4457; or CHA 2 DS 2 VASc 1, 2, or ≥3, p for interaction=0·1210) or bleeding (HAS-BLED 0–1, 2, or ≥3, p for interaction=0·9422). Patients who received apixaban had lower rates of major bleeding than did those who received warfarin, with no diff erence across all score categories (CHADS 2 , p for interaction=0·4018; CHA 2 DS 2 VASc, p for interaction=0·2059; HAS-BLED, p for interaction=0·7127). The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher (hazard ratio [HR] 0·22, 95% CI 0·10–0·48) than in those with HAS-BLED scores of 0–1 (HR 0·66, 0·39–1·12; p for interaction=0·0604). Interpretation Because apixaban has benefi ts over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS2, CHA2DS2VASc, and HAS-BLED scores, these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin. Further improvement in risk stratifi cation for both stroke and bleeding is needed, particularly for patients with atrial fi brillation at low risk for these events.
The Lancet 10/2012; · 38.28 Impact Factor
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Connie N Hess,
Samuel Broderick,
Jonathan P Piccini,
Karen P Alexander,
L Kristin Newby,
Linda K Shaw,
Kenneth W Mahaffey, John H Alexander,
Eric D Peterson,
Christopher B Granger,
Renato D Lopes
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ABSTRACT: Older patients with atrial fibrillation (AF) and coronary artery disease (CAD) face high risk of stroke and bleeding with antithrombotic therapy. Balancing safe and effective use of aspirin, clopidogrel, and warfarin in this population is important.
From the Duke Databank for Cardiovascular Disease, we identified patients with AF ≥65 years old with angiographically confirmed CAD from 2000 to 2010. Antithrombotic use was described across age and Congestive heart failure, Hypertension, Age >75 years, Diabetes, prior Stroke/transient ischemic attack (CHADS(2)) stroke risk and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding scores. Death and the composite of death, myocardial infarction, and stroke by antithrombotic strategy were reported.
Of 2,122 patients ≥65 years old with AF and CAD, 477 (22.5%) were ≥80 years old; 1,133 (53.4%) had acute coronary syndromes. Overall rates of aspirin, clopidogrel, and warfarin use were 83.4%, 34.6%, and 38.9%, respectively. Compared with patients 65 to 79 years old, more patients ≥80 years old were at high stroke risk (CHADS(2) ≥2, 84.7% vs 57.8%) and high bleeding risk (ATRIA 5-10, 55.8% vs 23.3%). Warfarin use in both age groups increased with higher CHADS(2) scores and decreased with higher ATRIA scores. Of patients ≥80 years old with CHADS(2) ≥2, 150 (38.2%) received warfarin. Antithrombotic strategy was not associated with improved 1-year adjusted outcomes.
Among older patients with AF and CAD, overall warfarin use was low. Patients ≥80 years old at highest stroke risk received warfarin in similar proportions to the overall cohort. Further investigation into optimizing antithrombotic strategies in this population is warranted.
American heart journal 10/2012; 164(4):607-15. · 4.65 Impact Factor
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Renato D Lopes,
Sana M Al-Khatib,
Lars Wallentin,
Hongqiu Yang,
Jack Ansell,
M Cecilia Bahit,
Raffaele De Caterina,
Paul Dorian,
J Donald Easton,
Cetin Erol,
Justin A Ezekowitz,
Bernard J Gersh,
Christopher B Granger,
Stefan H Hohnloser,
John Horowitz,
Elaine M Hylek,
John Jv McMurray,
Puneet Mohan,
Dragos Vinereanu, John H Alexander
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ABSTRACT: BACKGROUND: The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism, causes less bleeding, and results in lower mortality. We assessed in this trial's participants how results differed according to patients' CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, used to predict the risk of stroke and bleeding. METHODS: ARISTOTLE was a double-blind, randomised trial that enrolled 18 201 patients with atrial fibrillation in 39 countries. Patients were randomly assigned apixaban 5 mg twice daily (n=9120) or warfarin (target international normalised ratio 2·0-3·0; n=9081). The primary endpoint was stroke or systemic embolism. The primary safety outcome was major bleeding. We calculated CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores of patients at randomisation. Efficacy analyses were by intention to treat, and safety analyses were of the population who received the study drug. ARISTOTLE is registered with ClinicalTrials.gov, number NCT00412984. FINDINGS: Apixaban significantly reduced stroke or systemic embolism with no evidence of a differential effect by risk of stroke (CHADS(2) 1, 2, or ≥3, p for interaction=0·4457; or CHA(2)DS(2)VASc 1, 2, or ≥3, p for interaction=0·1210) or bleeding (HAS-BLED 0-1, 2, or ≥3, p for interaction=0·9422). Patients who received apixaban had lower rates of major bleeding than did those who received warfarin, with no difference across all score categories (CHADS(2), p for interaction=0·4018; CHA(2)DS(2)VASc, p for interaction=0·2059; HAS-BLED, p for interaction=0·7127). The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher (hazard ratio [HR] 0·22, 95% CI 0·10-0·48) than in those with HAS-BLED scores of 0-1 (HR 0·66, 0·39-1·12; p for interaction=0·0604). INTERPRETATION: Because apixaban has benefits over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS2, CHA2DS2VASc, and HAS-BLED scores, these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin. Further improvement in risk stratification for both stroke and bleeding is needed, particularly for patients with atrial fibrillation at low risk for these events. FUNDING: Bristol-Myers Squibb and Pfizer.
The Lancet 10/2012; · 38.28 Impact Factor
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Renato D Lopes,
Judson B Williams,
Rajendra H Mehta,
Eric M Reyes,
Gail E Hafley,
Keith B Allen,
Michael J Mack,
Eric D Peterson,
Robert A Harrington,
C Michael Gibson,
Robert M Califf,
Nicholas T Kouchoukos,
T Bruce Ferguson,
Todd J Lorenz, John H Alexander
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ABSTRACT: Edifoligide, an E2F transcription factor decoy, does not prevent vein graft failure or adverse clinical outcomes at 1 year in patients undergoing coronary artery bypass grafting (CABG). We compared the 5-year clinical outcomes of patients in PREVENT IV treated with edifoligide and placebo to identify predictors of long-term clinical outcomes.
A total of 3,014 patients undergoing CABG with at least 2 planned vein grafts were enrolled. Kaplan-Meier curves were generated to compare the long-term effects of edifoligide and placebo. A Cox proportional hazards model was constructed to identify factors associated with 5-year post-CABG outcomes. The main outcome measures were death, myocardial infarction (MI), repeat revascularization, and rehospitalization through 5 years.
Five-year follow-up was complete in 2,865 patients (95.1%). At 5 years, patients randomized to edifoligide and placebo had similar rates of death (11.7% and 10.7%, respectively), MI (2.3% and 3.2%), revascularization (14.1% and 13.9%), and rehospitalization (61.6% and 62.5%). The composite outcome of death, MI, or revascularization occurred at similar frequency in patients assigned to edifoligide and placebo (26.3% and 25.5%, respectively; hazard ratio 1.03 [95% CI 0.89-1.18], P = .721). Factors associated with death, MI, or revascularization at 5 years included peripheral and/or cerebrovascular disease, time on cardiopulmonary bypass, lung disease, diabetes mellitus, and congestive heart failure.
Up to a quarter of patients undergoing CABG will have a major cardiac event or repeat revascularization procedure within 5 years of surgery. Edifoligide does not affect outcomes after CABG; however, common identifiable baseline and procedural risk factors are associated with long-term outcomes after CABG.
American heart journal 09/2012; 164(3):379-386.e1. · 4.65 Impact Factor
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Stefan H Hohnloser,
Ziad Hijazi,
Laine Thomas, John H Alexander,
John Amerena,
Michael Hanna,
Matyas Keltai,
Fernando Lanas,
Renato D Lopes,
Jose Lopez-Sendon,
Christopher B Granger,
Lars Wallentin
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ABSTRACT: AimsAtrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the ARISTOTLE trial. We evaluated these outcomes in relation to renal function.Methods and resultsBaseline glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations as well as cystatin C measurements. According to baseline Cockcroft-Gault, there were 7518 patients (42%) with an estimated GFR (eGFR) of >80 mL/min, 7587 (42%) between >50 and 80 mL/min, and 3017 (15%) with an eGFR of ≤50 mL/min. The rate of cardiovascular events and bleeding was higher at impaired renal function (≤80 mL/min). Apixaban was more effective than warfarin in preventing stroke or systemic embolism and reducing mortality irrespective of renal function. These results were consistent, regardless of methods for GFR estimation. Apixaban was associated with less major bleeding events across all ranges of eGFRs. The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft-Gault {hazard ratio (HR) 0.50 [95% confidence interval (CI) 0.38-0.66], interaction P = 0.005} or CKD-EPI equations [HR 0.48 (95% CI 0.37-0.64), interaction P = 0.003].Conclusion
In patients with AF, renal impairment was associated with increased risk of cardiovascular events and bleeding. When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function. Patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban.
European Heart Journal 08/2012; · 10.48 Impact Factor
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Thomas J Povsic,
John P Vavalle,
Laura H Aberle,
Jaroslaw D Kasprzak,
Mauricio G Cohen,
Roxana Mehran,
Christoph Bode,
Christopher E Buller,
Gilles Montalescot,
Jan H Cornel,
Andrzej Rynkiewicz,
Michael E Ring,
Uwe Zeymer,
Madhu Natarajan,
Nicolas Delarche,
Steven L Zelenkofske,
Richard C Becker, John H Alexander
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ABSTRACT: AimsWe sought to determine the degree of anticoagulation reversal required to mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent ischaemic events in acute coronary syndrome (ACS) patients managed with an early invasive approach. REG1 consists of pegnivacogin, an RNA aptamer selective factor IXa inhibitor, and its complementary controlling agent, anivamersen. REG1 has not been studied in invasively managed patients with ACS nor has an optimal level of reversal allowing safe sheath removal been defined.Methods and resultsNon-ST-elevation ACS patients (n = 640) with planned early cardiac catheterization via femoral access were randomized 2:1:1:2:2 to pegnivacogin with 25, 50, 75, or 100% anivamersen reversal or heparin. The primary endpoint was total ACUITY bleeding through 30 days. Secondary endpoints included major bleeding and the composite of death, myocardial infarction, urgent target vessel revascularization, or recurrent ischaemia. Enrolment in the 25% reversal arm was suspended after 41 patients. Enrolment was stopped after three patients experienced allergic-like reactions. Bleeding occurred in 65, 34, 35, 30, and 31% of REG1 patients with 25, 50, 75, and 100% reversal and heparin. Major bleeding occurred in 20, 11, 8, 7, and 10% of patients. Ischaemic events occurred in 3.0 and 5.7% of REG1 and heparin patients, respectively.Conclusion
At least 50% reversal is required to allow safe sheath removal after cardiac catheterization. REG1 appears a safe strategy to anticoagulate ACS patients managed invasively and warrants further investigation in adequately powered clinical trials of patients who require short-term high-intensity anticoagulation. Clinical Trials Registration: ClinicalTrials.gov NCT00932100.
European Heart Journal 08/2012; · 10.48 Impact Factor
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Judson B Williams,
Eric D Peterson,
J Matthew Brennan,
Art Sedrakyan,
Dale Tavris, John H Alexander,
Renato D Lopes,
Rachel S Dokholyan,
Yue Zhao,
Sean M O'Brien,
Robert E Michler,
Vinod H Thourani,
Fred H Edwards,
Hesha Duggirala,
Thomas Gross,
Danica Marinac-Dabic,
Peter K Smith
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ABSTRACT: The safety and durability of endoscopic vein graft harvest in coronary artery bypass graft (CABG) surgery has recently been called into question.
To compare the long-term outcomes of endoscopic vs open vein-graft harvesting for Medicare patients undergoing CABG surgery in the United States.
An observational study of 235,394 Medicare patients undergoing isolated CABG surgery between 2003 and 2008 at 934 surgical centers participating in the Society of Thoracic Surgeons (STS) national database. The STS records were linked to Medicare files to allow longitudinal assessment (median 3-year follow-up) through December 31, 2008.
All-cause mortality. Secondary outcome measures included wound complications and the composite of death, myocardial infarction, and revascularization.
Based on Medicare Part B coding, 52% of patients received endoscopic vein-graft harvesting during CABG surgery. After propensity score adjustment for clinical characteristics, there were no significant differences between long-term mortality rates (13.2% [12,429 events] vs 13.4% [13,096 events]) and the composite of death, myocardial infarction, and revascularization (19.5% [18,419 events] vs 19.7% [19,232 events]). Time-to-event analysis for those patients receiving endoscopic vs open vein-graft harvesting revealed adjusted hazard ratios [HRs] of 1.00 (95% CI, 0.97-1.04) for mortality and 1.00 (95% CI, 0.98-1.05) for the composite outcome. Endoscopic vein-graft harvesting was associated with lower harvest site wound complications relative to open vein-graft harvesting (3.0% [3654/122,899 events] vs 3.6% [4047/112,495 events]; adjusted HR, 0.83; 95% CI, 0.77-0.89; P < .001).
Among patients undergoing CABG surgery, the use of endoscopic vein-graft harvesting compared with open vein-graft harvesting was not associated with increased mortality.
JAMA The Journal of the American Medical Association 08/2012; 308(5):475-84. · 30.03 Impact Factor
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ABSTRACT: Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome initiated by heparin exposure and characterized by thrombocytopenia and paradoxical thrombophilia. HIT is mediated by the formation of antibodies against the platelet factor 4/heparin complex, which leads to platelet activation, thrombin generation, and potentially fatal thrombotic sequelae. The clinical presentation of HIT is variable and can be easily overlooked. Although a number of functional and antigen-based immunoassays have been developed to detect the presence of HIT antibodies, initial diagnosis is often based on recognition of thrombocytopenia in the appropriate clinical context and later confirmed with immunologic testing. Given the serious clinical consequences of HIT, immediate cessation of heparin products and administration of non-heparin anticoagulants are crucial components of treatment. We provide a review of the clinical syndrome and practical summary of treatment recommendations from the most recent 2012 American College of Chest Physicians evidence-based guidelines for the treatment and prevention of HIT.
Journal of Thrombosis and Thrombolysis 07/2012; 34(4):552-61. · 1.48 Impact Factor
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J Donald Easton,
Renato D Lopes,
M Cecilia Bahit,
Daniel M Wojdyla,
Christopher B Granger,
Lars Wallentin,
Marco Alings,
Shinya Goto,
Basil S Lewis,
Mårten Rosenqvist,
Michael Hanna,
Puneet Mohan, John H Alexander,
Hans-Christoph Diener
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ABSTRACT: In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA.
Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984.
Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA.
The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population.
Bristol-Myers Squibb and Pfizer.
The Lancet Neurology 05/2012; 11(6):503-11. · 23.46 Impact Factor
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American heart journal 04/2012; 163(4):e25. · 4.65 Impact Factor
