| 1. |
|
|
| 2. |
|
|
| 3. |
- Bouyoucef, S E, et al.
(författare)
-
Poster Session 2 : Monday 4 May 2015, 08
- 2015
-
Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
-
Tidskriftsartikel (refereegranskat)
|
|
| 4. |
|
|
| 5. |
- Wijns, W, et al.
(författare)
-
Myocardial revascularization
- 2011
-
Ingår i: REVISTA PORTUGUESA DE CARDIOLOGIA. - : Elsevier BV. - 0870-2551 .- 2174-2049. ; 30:12, s. 951-1005
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 6. |
|
|
| 7. |
- O'Donoghue, M. L., et al.
(författare)
-
Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction: A Randomized Clinical Trial
- 2016
-
Ingår i: Jama. - : American Medical Association (AMA). - 0098-7484. ; 315:15, s. 1591-9
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: p38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and may improve outcomes. OBJECTIVE: To evaluate the efficacy and safety of losmapimod on cardiovascular outcomes in patients hospitalized with an acute myocardial infarction. DESIGN, SETTING, AND PATIENTS: LATITUDE-TIMI 60, a randomized, placebo-controlled, double-blind, parallel-group trial conducted at 322 sites in 34 countries from June 3, 2014, until December 8, 2015. Part A consisted of a leading cohort (n = 3503) to provide an initial assessment of safety and exploratory efficacy before considering progression to part B (approximately 22,000 patients). Patients were considered potentially eligible for enrollment if they had been hospitalized with an acute MI and had at least 1 additional predictor of cardiovascular risk. INTERVENTIONS: Patients were randomized to either twice-daily losmapimod (7.5 mg; n = 1738) or matching placebo (n = 1765) on a background of guideline-recommended therapy. Patients were treated for 12 weeks and followed up for an additional 12 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was the composite of cardiovascular death, MI, or severe recurrent ischemia requiring urgent coronary revascularization with the principal analysis specified at week 12. RESULTS: In part A, among the 3503 patients randomized (median age, 66 years; 1036 [29.6%] were women), 99.1% had complete ascertainment for the primary outcome. The primary end point occurred by 12 weeks in 123 patients treated with placebo (7.0%) and 139 patients treated with losmapimod (8.1%; hazard ratio, 1.16; 95% CI, 0.91-1.47; P = .24). The on-treatment rates of serious adverse events were 16.0% with losmapimod and 14.2% with placebo. CONCLUSIONS AND RELEVANCE: Among patients with acute MI, use of losmapimod compared with placebo did not reduce the risk of major ischemic cardiovascular events. The results of this exploratory efficacy study did not justify proceeding to a larger efficacy trial in the existing patient population. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02145468.
|
|
| 8. |
|
|
| 9. |
- Swedberg, Karl, 1944, et al.
(författare)
-
Successful treatment of heart failure with devices requires collaboration
- 2008
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 10:12, s. 1229-35
-
Tidskriftsartikel (refereegranskat)abstract
- Implanted biventricular pacemakers (cardiac resynchronisation therapy, CRT) with or without implantable cardioverter defibrillators (ICD) improve survival and morbidity in some patients with chronic heart failure (CHF) who are optimally treated with pharmacologic agents according to current guidelines. Correspondingly, ICDs improve survival. However, there is only limited evidence for device treatment in certain patient subgroups, such as the impact of ICD on outcomes in patients with reduced ejection fraction in New York Heart Association (NYHA) Class I or IV heart failure. Similarly, limited evidence exists for CRT in patients with only modest QRS prolongation or only modestly reduced ejection fraction. Despite evidence for a beneficial effect of device therapy in CHF, only a minority of eligible patients are currently offered these options. Multiple reasons contribute to the underuse of these potentially life-saving therapies. A lack of adherence to guidelines by health care professionals is an important barrier. Clearly, efforts should be made to improve the standard of care and to familiarise all physicians involved in managing CHF patients with the indications and potential efficacy of these devices. Increased collaboration between structured heart failure care and pacemaker clinics as well as between electrophysiologists, heart failure clinicians, and primary care physicians is required. Such team collaborations should lead to improved care with reduced mortality and morbidity and increased cost effectiveness. Treatment strategy should be based on a structured approach tailored to local practice and national priorities.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Bonaca, M. P., et al.
(författare)
-
Reduction in subtypes and sizes of myocardial infarction with ticagrelor in PEGASUS-TIMI 54
- 2018
-
Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:22
-
Tidskriftsartikel (refereegranskat)abstract
- Background-—Ticagrelor reduced cardiovascular death, myocardial infarction (MI), or stroke in patients with prior MI in PEGASUSTIMI 54 (Prevention of Cardiovascular Events [eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin). MI can occur in diverse settings and with varying severity; therefore, understanding the types and sizes of MI events prevented is of clinical importance. Methods and Results-—MIs were adjudicated by a blinded clinical events committee and categorized by subtype and fold elevation of peak cardiac troponin over the upper limit of normal. A total of 1042 MIs occurred in 898 of the 21 162 randomized patients over a median follow-up of 33 months. The majority of the MIs (76%) were spontaneous (Type 1), with demand MI (Type 2) and stent thrombosis (Type 4b) accounting for 13% and 9%, respectively; sudden death (Type 3), percutaneous coronary intervention–related (Type 4a) and coronary artery bypass graft–related (Type 5) each accounted for <1%. Half of MIs (520, 50%) had a peak troponin ≥10x upper limit of normal and 21% of MIs (220) had a peak troponin ≥1009 upper limit of normal. A total of 21% (224) were ST-segment–elevation MI STEMI. Overall ticagrelor reduced MI (4.47% versus 5.25%, hazard ratio 0.83, 95% confidence interval 0.72–0.95, P=0.0055). The benefit was consistent among the subtypes, including a 31% reduction in MIs with a peak troponin ≥1009 upper limit of normal (hazard ratio 0.69, 95% confidence interval 0.53–0.92, P=0.0096) and a 40% reduction in ST-segment elevation MI (hazard ratio 0.60, 95% confidence interval 0.46–0.78, P=0.0002). Conclusions-—In stable outpatients with prior MI, the majority of recurrent MIs are spontaneous and associated with a high biomarker elevation. Ticagrelor reduces the MI consistently among subtypes and sizes including large MIs and ST-segment elevation MI. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01225562. © 2018 The Authors.
|
|
| 14. |
- Cowie, M. R., et al.
(författare)
-
New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment
- 2017
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 19:6, s. 718-727
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure. The draft version of the Guideline was released for public consultation in January 2016. The Cardiovascular Round Table of the European Society of Cardiology (ESC), in partnership with the Heart Failure Association of the ESC, convened a dedicated two-day workshop to discuss three main topic areas of major interest in the field and addressed in this draft EMA guideline: (i) assessment of efficacy (i.e. endpoint selection and statistical analysis); (ii) clinical trial design (i.e. issues pertaining to patient population, optimal medical therapy, run-in period); and (iii) research approaches for testing novel therapeutic principles (i.e. cell therapy). This paper summarizes the key outputs from the workshop, reviews areas of expert consensus, and identifies gaps that require further research or discussion. Collaboration between regulators, industry, clinical trialists, cardiologists, health technology assessment bodies, payers, and patient organizations is critical to address the ongoing challenge of heart failure and to ensure the development and market access of new therapeutics in a scientifically robust, practical and safe way.
|
|
| 15. |
- Borer, J. S., et al.
(författare)
-
Effect of ivabradine on recurrent hospitalization for worsening heart failure in patients with chronic systolic heart failure: the SHIFT Study
- 2012
-
Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 33:22, s. 2813-2820
-
Tidskriftsartikel (refereegranskat)abstract
- AimsWe explored the effect of treatment with ivabradine, a pure heart rate-slowing agent, on recurrent hospitalizations for worsening heart failure (HF) in the SHIFT trial.Methods and resultsSHIFT was a double-blind clinical trial in which 6505 patients with moderate-to-severe HF and left ventricular systolic dysfunction, all of whom had been hospitalized for HF during the preceding year, were randomized to ivabradine or to placebo on a background of guideline-recommended HF therapy (including maximized beta-blockade). In total, 1186 patients experienced at least one additional HF hospitalization during the study, 472 suffered at least two, and 218 suffered at least 3. Patients with additional HF hospitalizations had more severe disease than those without. Ivabradine was associated with fewer total HF hospitalizations [902 vs. 1211 events with placebo; incidence rate ratio, 0.75, 95% confidence interval (CI), 0.65-0.87, P = 0.0002] during the 22.9-month median follow-up. Ivabradine-treated patients evidenced lower risk for a second or third additional HF hospitalization [hazard ratio (HR): 0.66, 95% CI, 0.55-0.79, P < 0.001 and HR: 0.71, 95% CI, 0.54-0.93, P = 0.012, respectively]. Similar observations were made for all-cause and cardiovascular hospitalizations.ConclusionTreatment with ivabradine, on a background of guidelines-based HF therapy, is associated with a substantial reduction in the likelihood of recurrent hospitalizations for worsening HF. This benefit can be expected to improve the quality of life and to substantially reduce health-care costs.
|
|
| 16. |
- Burr, S. P., et al.
(författare)
-
Cell lineage-specific mitochondrial resilience during mammalian organogenesis
- 2023
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 186:6
-
Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mito-chondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic devel-opment. The compensatory pathways were both tissue and mutation specific and under the control of tran-scription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments.
|
|
| 17. |
- Delgado-Ortega, L., et al.
(författare)
-
PCV45 Health Economic Evaluation of Ticagrelor in Patients with Acute Coronary Patients (ACS) Based on the Plato Study from A Spanish Health Care Perspective
- 2011
-
Ingår i: Value in Health. - : Elsevier. - 1098-3015 .- 1524-4733. ; 14:7, s. A372-A372
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- ObjectivesPLATO was a multi centered, double blind, randomized study that included 18,624 ACS patients from 43 countries, comparing ticagrelor + aspirin versus clopidogrel + aspirin. The PLATO demonstrated that ticagrelor was superior on the primary composite endpoint: myocardial infarction, stroke, cardiovascular death (HR 0.84, 95% CI: 0.77 to 0.92) without an increase in major bleedings compared to clopidogrel, and whether the strategy of choice was invasive or conservative. The aim of this analysis is to estimate direct health care costs from a Spanish health care perspective (excluding drug costs because ticagrelor price has not yet been established).MethodsResource utilization was pre specified in the PLATO trial and included hospitalization bed days, investigations, interventions and blood products. Direct health care costs per patient at 12 months were estimated by multiplying the resource use with Spanish unit costs derived from the Spanish database e-salud, the GRDs of the Ministry of Health, published literature, and the CMBD 2008.ResultsTicagrelor resulted in numerically fewer bed days (mean difference per patient 0.21, 95% CI -0.16 to 0.59), PCIs (mean difference per patient 0.01, 95% CI -0.01 to 0.03) and CABGs (mean difference per patient 0.01, 95% CI: 0.00 to 0.01). Ticagrelor is associated with €341 reduction per patient (95% CI: 31 to 652) in healthcare costs at 12 months compared to clopidogrel. The reduction in healthcare costs was mainly due to fewer hospital days and cardiovascular interventions in the ticagrelor group. The reduction in cost increased over the 12-month treatment period consistent with the rate of clinical events over time in the PLATO study.ConclusionsTreatment with ticagrelor is associated with cost savings in patients with ACS at 12 months compared with clopidogrel (excluding drug costs) from a Spanish health care perspective. However, the total cost savings will depend on drug price, data not available yet.
|
|
| 18. |
- Kolh, P, et al.
(författare)
-
Guidelines on myocardial revascularization
- 2010
-
Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X .- 1010-7940. ; 3838 Suppl, s. S1-S52
-
Tidskriftsartikel (refereegranskat)
|
|
| 19. |
|
|
| 20. |
- Swedberg, Karl, 1944, et al.
(författare)
-
Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology
- 2005
-
Ingår i: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 26:11, s. 1115-40
-
Forskningsöversikt (refereegranskat)abstract
- Preamble Guidelines and Expert Consensus Documents aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) and by different organizations and other related societies. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing Guidelines and Expert Consensus Documents. In spite of the fact that standards for issuing good quality Guidelines and Expert Consensus Documents are well defined, recent surveys of Guidelines and Expert Consensus Documents published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilization of health resources. The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups, or consensus panels. The chosen experts in these writing panels are asked to provide disclosure statements of all relationships they may have which might be perceived as real or potential conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements. The Task Force has classified and ranked the usefulness or efficacy of the recommended procedure and/or treatments and the Level of Evidence as indicated in the tables on page 3.
|
|
| 21. |
|
|
| 22. |
- Bohm, M., et al.
(författare)
-
Non-adherence to ivabradine and placebo and outcomes in chronic heart failure: an analysis from SHIFT
- 2016
-
Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 18:6, s. 672-683
-
Tidskriftsartikel (refereegranskat)abstract
- AimsIn heart failure, non-adherence increases events; in turn, the effect of hospitalization on adherence is incompletely understood. We explored the relationship of non-adherence to outcomes, hospitalizations with non-adherence, and the influence of non-adherence on treatment effects of heart rate lowering with ivabradine. Methods and resultsIn the randomized, controlled Systolic Heart failure treatment with the If-inhibitor ivabradine Trial (SHIFT), we studied the effect of non-adherence (n = 1287) compared with adherence (n=5204) on cardiovascular outcomes. After adjustment, non-adherence was associated with the primary composite endpoint of cardiovascular death and heart failure hospitalization (hazard ratio 3.47, 95% confidence interval 2.91-4.13, P < 0.0001). No interaction with the treatment groups of placebo or ivabradine (P for interaction 0.54) occurred. Similar results for cardiovascular death and heart failure hospitalization, as well as for cardiovascular hospitalization, heart failure death, and total death were observed. The effect of ivabradine was maintained in patients being adherent or becoming non-adherent during the trial (P for interaction=0.54). Patients with a previous hospitalization were more likely to become non-adherent thereafter. ConclusionsNon-adherence identifies a group at particularly high cardiovascular event risk independent of treatment allocation. Non-adherent patients in the ivabradine group maintain a treatment benefit. Patients with previous hospitalizations are more likely to become non-adherent and represent a group of particularly high-risk patients in whom special attention to stimulate adherence may be valuable.
|
|
| 23. |
|
|
| 24. |
- De Caterina, Raffaele, et al.
(författare)
-
Heterogeneity of diabetes as a risk factor for major adverse cardiovascular events in anticoagulated patients with atrial fibrillation : an analysis of the ARISTOTLE trial.
- 2020
-
Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 8:3, s. 227-235
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: Whether diabetes without insulin therapy is an independent cardiovascular (CV) risk factor in atrial fibrillation (AF) has recently been questioned. We investigated the prognostic relevance of diabetes with or without insulin treatment in patients in the ARISTOTLE trial.METHODS AND RESULTS: Patients with AF and increased stroke risk randomized to apixaban vs. warfarin were classified according to diabetes status: no diabetes; diabetes on no diabetes medications; diabetes on non-insulin antidiabetic drugs only; or insulin-treated. The associations between such patient subgroups and stroke/systemic embolism (SE), myocardial infarction (MI), and CV death were examined by Cox proportional hazard regression, both unadjusted and adjusted for other prognostic variables. Patients with diabetes were younger and had a higher body mass index. Median CHA2DS2VASc score was 4.0 in patients with diabetes and 3.0 in patients without diabetes. We found no significant difference in stroke/SE incidence across patient subgroups. Compared with no diabetes, only insulin-treated diabetes was significantly associated with higher risk. When adjusted for clinical variables, compared with no diabetes, the hazard ratios (HRs) for MI (95% confidence intervals) were for diabetes on no medication: 1.15 (0.62-2.14); for diabetes on non-insulin antidiabetic drugs: 1.32 (0.90-1.94); for insulin-treated diabetes: 2.34 (1.43-3.82); interaction P = 0.008. HRs for CV death were for diabetes on no medication: 1.19 (0.86-166); for diabetes on non-insulin antidiabetic drugs: 1.12 (0.88-1.42); for insulin-treated diabetes 1.85 (1.36-2.53), interaction P = 0.001.CONCLUSION: In anticoagulated patients with AF, a higher risk of MI and CV death is largely confined to diabetes treated with insulin.
|
|
| 25. |
- Ezekowitz, Justin A., et al.
(författare)
-
Clinical outcomes of patients with diabetes and atrial fibrillation treated with apixaban : results from the ARISTOTLE trial
- 2015
-
Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : OXFORD UNIV PRESS. - 2055-6837 .- 2055-6845. ; 1:2, s. 86-94
-
Tidskriftsartikel (refereegranskat)abstract
- Aims We compared clinical outcomes in patients with AF with and without diabetes in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. Methods and results The main efficacy endpoints were SSE and mortality; safety endpoints were major and major/clinically relevant non-major bleeding. A total of 4547/18 201 (24.9%) patients had diabetes who were younger (69 vs. 70 years), more had coronary artery disease (39 vs. 31%), and higher mean CHADS(2) (2.9 vs. 1.9) and HAS-BLEDscores (1.9 vs. 1.7) (all P, 0.0001) than patients without diabetes. Patients with diabetes receiving apixaban had lower rates of SSE [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.53-1.05), all-cause mortality (HR 0.83, 95% CI 0.67-1.02), cardiovascular mortality (HR 0.89, 95% CI 0.66-1.20), intra-cranial haemorrhage (HR 0.49, 95% CI 0.25-0.95), and a similar rate of myocardial infarction (HR 1.02, 95% CI 0.62-1.67) compared with warfarin. For major bleeding, a quantitative interaction was seen (P-interaction = 0.003) with a greater reduction in major bleeding in patients without diabetes even after multivariable adjustment. Other measures of bleeding showed a consistent reduction with apixaban compared with warfarin without a significant interaction based on diabetes status. Conclusion Apixaban has similar benefits on reducing stroke, decreasing mortality, and causing less intra-cranial bleeding than warfarin in patients with and without diabetes.
|
|
| 26. |
|
|
| 27. |
|
|
