| 1. |
- Al-Faleh, Hussam, et al.
(författare)
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Unraveling the spectrum of left bundle branch block in acute myocardial infarction : insights from the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT 2 and 3) trials
- 2006
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 151:1, s. 10-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Left bundle branch block (LBBB) complicates the diagnosis of acute myocardial infarction (AMI). The Sgarbossa criteria were developed from GUSTO I to surmount this diagnostic challenge but have not been prospectively validated in a large population with presumed AMI. We evaluated their utility in the diagnosis and risk stratification of AMI patients in ASSENT 2 & 3. METHODS: Baseline electrocardiograms (ECG) of LBBB patients were scored using Sgarbossa's criteria (0-10) by 2 readers blinded to the CK/CK-MB data and clinical outcomes; 267 (1.2%) patients had LBBB on their baseline ECG. RESULTS: Among 253 LBBB patients with available peak CK/CK-MB data, 158 (62.5%) had peak CK/CK-MB levels > 2x ULN, thereby qualifying for the diagnosis of AMI. A Sgarbossa score of 3 was shown in 48.7% of LBBB patients with elevated CK/CK-MB versus in 12.6% of those without a CK/CK-MB rise (P < .001). Patients with higher Sgarbossa scores, ie, 3, had a higher mortality compared with those with a score < 3, (23.5% vs 7.7% at 30 days P < .001; and 33.7% vs 20.2% at 1 year, P < .001, respectively). CONCLUSIONS: Our findings validate the utility of Sgarbossa criteria for diagnosing AMI in the setting of LBBB. These criteria provide a simple and practical diagnostic approach to risk stratify this diagnostically challenging high-risk group and optimize risk-benefit of acute therapy.
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| 2. |
- Alexander, Karen P, et al.
(författare)
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Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity : Insights from the ARISTOTLE trial
- 2019
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 208, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin.METHODS: In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years.RESULTS: Multi-morbidity was present in 64% (n = 10,713) of patients; 51% (n = 8491) had moderate multi-morbidity, 13% (n = 2222) had high multi-morbidity, and 36% (n = 6087) had no multi-morbidity. Compared with the no multi-morbidity group, the high multi-morbidity group was older (74 vs 69 years), took twice as many medications (10 vs 5), and had higher CHA2DS2-VASc scores (4.9 vs 2.7) (all P < .001). Adjusted rates per 100 patient-years for stroke/systemic embolism, death, and major bleeding increased with multi-morbidity (Reference no multi-morbidity; moderate multi-morbidity 1.42 [1.24-1.64] and high multi-morbidity 1.92 [1.59-2.31]), with no interaction in relation to efficacy or safety of apixaban.CONCLUSIONS: Multi-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.
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| 3. |
- Aulin, Julia, et al.
(författare)
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Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multi-state model
- 2022
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 251, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAtrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.MethodsThe study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.ResultsBaseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P < .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events.ConclusionsIn anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.
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| 4. |
- Carlhed, Rickard, et al.
(författare)
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Improved adherence to Swedish national guidelines for acute myocardial infarction : the Quality Improvement in Coronary Care (QUICC) study
- 2006
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 152:6, s. 1175-1181
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The adherence to evidence-based treatment guidelines for acute myocardial infarction (AMI) is still suboptimal. Therefore, we designed a study to evaluate the effects of a collaborative quality improvement (QI) intervention on the adherence to AMI guidelines. The intervention used a national web-based quality registry to generate local and regular real-time performance feedback. METHODS: A 12-month baseline measurement of the adherence rates was retrospectively collected, comprising the period July 1, 2001, through June 30, 2002. During the intervention period of November 1, 2002, through April 30, 2003, multidisciplinary teams from 19 nonrandomized intervention hospitals were subjected to a multifaceted QI-oriented intervention. Another 19 hospitals, unaware of their status as controls, were matched to the intervention hospitals. During the postintervention measurement period of May 1, 2003, through April 30, 2004, a total of 6726 consecutive patients were included at the intervention (n = 3786) and control (n = 2940) hospitals. The outcome measures comprised 5 Swedish national guideline-derived quality indicators, compared between baseline and postintervention levels in the control and QUICC intervention hospitals. RESULTS: In the control and QI intervention hospitals, the mean absolute increase of patients receiving angiotensin-converting enzyme inhibitors was 1.4% vs 12.6% (P = .002), lipid-lowering therapy 2.3% vs 7.2% (P = .065), clopidogrel 26.3% vs 41.2% (P = .010), heparin/low-molecular weight heparin 5.3% vs 16.3% (P = .010), and coronary angiography 6.2% vs 16.8% (P = .027), respectively. The number of QI intervention hospitals reaching a treatment level of at least 70% in 4 or 5 of the 5 indicators was 15 and 5, respectively. In the control group, no hospital reached 70% or more in just 4 of the 5 indicators. CONCLUSIONS: By combining a systematic and multidisciplinary QI collaborative with a web-based national quality registry with functionality allowing real-time performance feedback, major improvements in the adherence to national AMI guidelines can be achieved.
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| 5. |
- Carnicelli, Anthony P, et al.
(författare)
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Individual Patient Data from the Pivotal Randomized Controlled Trials of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (COMBINE AF) : Design and Rationale
- 2021
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; Mar:233, s. 48-58
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are the preferred class of medications for prevention of stroke and systemic embolism in patients with atrial fibrillation unless contraindications exist. Five large, international, randomized, controlled trials of NOACs versus either warfarin or aspirin have been completed to date.DESIGN: COMBINE AF incorporates de-identified individual patient data from 77,282 patients with atrial fibrillation at risk for stroke randomized to NOAC, warfarin, or aspirin from 5 pivotal randomized controlled trials. All patients randomized in the constituent trials are included. Variables common to ≥3 of the constituent trials are included in the master database. Individual trial data sets from the 4 coordinating centers were combined at the Duke Clinical Research Institute. The final database will be securely shared with the 4 academic coordinating centers. The combined master database will be used to perform statistical analyses aimed at better understanding underlying risk factors and outcomes in patients with atrial fibrillation treated with oral anticoagulants, with a special focus on patient subgroups and uncommon outcomes. The initial analysis from COMBINE AF will be a network meta-analysis investigating the relative efficacy and safety of pooled higher-dose NOACs versus pooled lower-dose NOACs versus warfarin with respect to multiple time-to-event efficacy and safety outcomes. COMBINE AF is registered with PROSPERO (CRD42020178771).CONCLUSIONS: In conclusion, COMBINE AF provides a rich and robust database consisting of individual patient data and will offer opportunities to investigate oral anticoagulants across many patient subgroups. Data sharing and collaboration across academic institutions and investigators will serve as overarching themes.
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| 6. |
- Cornel, Jan H., et al.
(författare)
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Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes-Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
- 2012
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 164:3, s. 334-342
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Tidskriftsartikel (refereegranskat)abstract
- Background Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits.Methods Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses.Results Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 [95% CI, 1.07-1.94]); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P = .50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P = .61).Conclusions In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.
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| 7. |
- Ducrocq, Gregory, et al.
(författare)
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Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes
- 2017
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 186, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Pathophysiologic mechanisms of persistent cardiac troponin I elevation in stabilized patients after an episode of acute coronary syndrome
- 2008
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 156:3, s. 588-594
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently, a high prevalence of small persistent cardiac troponin I (cTnI) elevations has been reported in patients who had been stabilized after a recent episode of acute coronary syndrome (ACS). We now have studied the associations of persistently elevated cTnI levels to cardiac performance, inflammation, coagulation, coronary status, and treatment strategy in these patients. METHODS AND RESULTS: Cardiac troponin I was determined at 6 weeks, 3 months, and 6 months after randomization in 898 stabilized ACS patients from the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC) II trial and using the high-sensitive Access AccuTnI assay (Beckman Coulter, Fullerton, CA). All patients were followed up for at least 5 years. Persistent cTnI elevation >0.01 microg/L at the 3 measurement instances was detected in 233 patients (26%). N-terminal pro-brain natriuretic peptide (NT-proBNP) at 6 months (OR 2.5, 95% CI 2.0-3.1), male sex (OR 2.2, 95% CI 1.4-3.7), and randomization to an early invasive strategy (OR 1.8, 95% CI 1.2-2.7) independently predicted persistently elevated cTnI levels. Persistently cTnI-positive patients in the invasive cohort had significantly lower NT-proBNP levels compared to noninvasively treated patients, indicating that the mechanisms causing cTnI elevation in this group may be prognostically less harmful. No independent associations were found for markers of inflammation or coagulation. CONCLUSION: Persistent cTnI elevation occurs frequently late after an ACS. The NT-proBNP level at 6 months was the strongest predictor for elevated cTnI levels that thus appear to be predominantly related to impaired left ventricular function.
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| 9. |
- Eggers, Kai M., 1962-, et al.
(författare)
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ST2 and mortality in non-ST-segment elevation acute coronary syndrome
- 2010
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 159:5, s. 788-794
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: ST2 is a member of the interleukin-1 receptor family that is up-regulated in conditions associated with increased myocardial strain. ST2 has been shown to be independently predictive of adverse outcome in heart failure and ST-segment elevation myocardial infarction, but its prognostic value in non-ST-elevation acute coronary syndrome (NSTE-ACS) has not been established. METHODS: We measured ST2 at randomization and after 24, 48, and 72 hours in 403 NSTE-ACS patients from the GUSTO IV study, and studied its kinetics and its associations to clinical baseline factors and 1-year mortality. RESULTS: Median ST2 levels decreased from 28.4 U/mL at randomization to 21.8 U/mL at 72 hours (P < .001). Peak levels were noted 6 to 17 hours after symptom onset. Randomization ST2 levels were independently associated to N-terminal pro-B-type natriuretic peptide but otherwise exhibited only weak relations to cardiovascular risk factors and comorbidities, and biomarkers of myocardial necrosis or inflammation. ST2 was related to 1-year mortality independently of clinical risk indicators (odds ratio 2.3 [95% CI 1.1-4.6], P = .03) but lost its predictive value after additional adjustment for prognostic biomarkers, in particular N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: ST2 levels are elevated early in NSTE-ACS and predict 1-year mortality. Our data indicate that ST2 represents an interesting novel pathophysiologic pathway in the setting of ischemia-related myocardial dysfunction. However, future prospective evaluations in larger populations are needed before the clinical utility of ST2 can be determined.
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| 10. |
- Ezekowitz, Michael D., et al.
(författare)
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Rationale and design of RE-LY : randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran
- 2009
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 157:5, s. 805-810
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin K antagonists (VKAs) are effective for stroke prevention in patients with atrial fibrillation (AF) but are difficult to use. Dabigatran etexilate is a prodrug that is rapidly converted to the active direct thrombin inhibitor dabigatran. It is administered in a fixed dose without laboratory monitoring and is being compared with warfarin (international normalized ratio 2-3) in the RE-LY trial. Two doses of dabigatran (110 and 150 mg BID) are being evaluated. RE-LY is a phase 3, prospective, randomized, open-label multinational (44 countries) trial of patients with nonvalvular AF and at least 1 risk factor for stroke. Recruitment concluded with a total of 18,113 patients. Patients who were VKA-naive and experienced are included in balanced proportions. The primary outcome is stroke (including hemorrhagic) or systemic embolism. Safety outcomes are bleeding, liver function abnormalities, and other adverse events. Adjudication of end points is blinded to drug assignment. The trial is expected to accrue a minimum of 450 events with a minimum 1-year of follow-up. RE-LY is the largest AF stroke prevention trial yet undertaken. It is unique because it includes equal numbers of VKA-experienced and naive patients and evaluates 2 different dosages of dabigatran, which may allow tailoring of dosing to individual patient needs. The worldwide site distribution and broad range of stroke risk further increase the general applicability of the trial. Results are expected in 2009.
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