| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Metra, M., et al.
(author)
-
Effects of low-dose oral enoximone administration on mortality, morbidity, and exercise capacity in patients with advanced heart failure: the randomized, double-blind, placebo-controlled, parallel group ESSENTIAL trials
- 2009
-
In: European Journal of Heart Failure. - 1522-9645. ; 30:24, s. 3015-26
-
Journal article (peer-reviewed)abstract
- AIMS: Use of inotropic agents in patients with heart failure (HF) has been limited by adverse effects on outcomes. However, administration of positive inotropes at lower doses and concomitant treatment with beta-blockers might increase benefit-risk ratio. We investigated the effects of low doses of the positive inotrope enoximone on symptoms, exercise capacity, and major clinical outcomes in patients with advanced HF who were also treated with beta-blockers and other guideline-recommended background therapy. METHODS AND RESULTS: The Studies of Oral Enoximone Therapy in Advanced HF (ESSENTIAL) programme consisted of two identical, randomized, double-blind, placebo-controlled trials that differed only by geographic location (North and South America: ESSENTIAL-I; Europe: ESSENTIAL-II). Patients with New York Heart Association class III-IV HF symptoms, left ventricular ejection fraction < or = 30%, and one hospitalization or two ambulatory visits for worsening HF in the previous year were eligible for participation in the trials. The trials had three co-primary endpoints: (i) the composite of time to all-cause mortality or cardiovascular hospitalization, analysed in the two ESSENTIAL trials combined; (ii) the 6 month change from baseline in the 6 min walk test distance (6MWTD); and (iii) the Patient Global Assessment (PGA) at 6 months, both analysed in each trial separately. ESSENTIAL-I and -II randomized 1854 subjects at 211 sites in 16 countries. In the combined trials, all-cause mortality and the composite, first co-primary endpoint did not differ between the two treatment groups [hazard ratio (HR) 0.97; 95% confidence interval (CI) 0.80-1.17; and HR 0.98; 95% CI 0.86-1.12, respectively, for enoximone vs. placebo]. The two other co-primary endpoints were analysed separately in the two ESSENTIAL trials, as prospectively designed in the protocol. The 6MWTD increased with enoximone, compared with placebo, in ESSENTIAL-I (P = 0.025, not reaching, however, the pre-specified criterion for statistical significance of P < 0.020), but not in ESSENTIAL-II. No difference in PGA was observed in either trial. CONCLUSION: Although low-dose enoximone appears to be safe in patients with advanced HF, major clinical outcomes are not improved.
|
|
| 12. |
- Wijns, W, et al.
(author)
-
Myocardial revascularization
- 2011
-
In: REVISTA PORTUGUESA DE CARDIOLOGIA. - : Elsevier BV. - 0870-2551 .- 2174-2049. ; 30:12, s. 951-1005
-
Journal article (other academic/artistic)
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Cavender, M. A., et al.
(author)
-
Vorapaxar in Patients With Diabetes Mellitus and Previous Myocardial Infarction Findings From the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 Trial
- 2015
-
In: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 131:12, s. 1047-1053
-
Journal article (peer-reviewed)abstract
- Background-Vorapaxar reduces cardiovascular death, myocardial infarction (MI), or stroke in patients with previous MI while increasing bleeding. Patients with diabetes mellitus (DM) are at high risk of recurrent thrombotic events despite standard therapy and may derive particular benefit from antithrombotic therapies. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 trial was a randomized, double-blind, placebo-controlled trial of vorapaxar in patients with stable atherosclerosis. Methods and Results-We examined the efficacy of vorapaxar in patients with and without DM who qualified for the trial with a previous MI. Because vorapaxar is contraindicated in patients with a history of stroke or transient ischemic attack, the analysis (n=16 896) excluded such patients. The primary end point of cardiovascular death, MI, or stroke occurred more frequently in patients with DM than in patients without DM (rates in placebo group: 14.3% versus 7.6%; adjusted hazard ratio, 1.47; P<0.001). In patients with DM (n=3623), vorapaxar significantly reduced the primary end point (11.4% versus 14.3%; hazard ratio, 0.73 [95% confidence interval, 0.60-0.89]; P=0.002) with a number needed to treat to avoid 1 major cardiovascular event of 29. The incidence of moderate/severe bleeding was increased with vorapaxar in patients with DM (4.4% versus 2.6%; hazard ratio, 1.60 [95% confidence interval, 1.07-2.40]). However, net clinical outcome integrating these 2 end points (efficacy and safety) was improved with vorapaxar (hazard ratio, 0.79 [95% confidence interval, 0.67-0.93]). Conclusions-In patients with previous MI and DM, the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of recurrent ischemic events.
|
|
| 17. |
- Donaldson, M., et al.
(author)
-
Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy
- 2019
-
In: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 91:3, s. 153-163
-
Journal article (peer-reviewed)abstract
- Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17 beta-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17 beta-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions. (C) 2019 S. Karger AG, Basel
|
|
| 18. |
- Fox, K., et al.
(author)
-
Effect of ivabradine in patients with left-ventricular systolic dysfunction: a pooled analysis of individual patient data from the BEAUTIFUL and SHIFT trials
- 2013
-
In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:29, s. 2263-2270
-
Journal article (peer-reviewed)abstract
- AimsTo test the effect of ivabradine on the outcomes in a broad population with left-ventricular (LV) systolic dysfunction with coronary artery disease (CAD) and/or heart failure (HF).Methods and resultsIndividual trial data from BEAUTIFUL and SHIFT were pooled to evaluate the effect of ivabradine on the outcomes in patients with LV dysfunction and heart rate >/=70 b.p.m. The pooled population (n = 11 897; baseline age 62.3 +/- 10.4 years, heart rate 79.6 +/- 9.2 b.p.m., and LV ejection fraction 30.3 +/- 5.6%) was well treated according to current recommendations (87% beta-blockers, 90% renin-angiotensin system inhibitors). Median follow-up was 21 months. Treatment with ivabradine was associated with a 13% relative risk reduction for the composite of cardiovascular mortality or HF hospitalization (P < 0.001 vs. placebo); this was driven by HF hospitalizations (19%, P < 0.001). There were also significant relative risk reductions for the composite of cardiovascular mortality, HF hospitalizations, or myocardial infarction (MI) hospitalization (15%, P < 0.001); cardiovascular mortality and non-fatal MI (10%, P = 0.023); and MI hospitalization (23%, P = 0.009). Similar results were found in patients with differing clinical profiles. Ivabradine was well tolerated.ConclusionIvabradine may be important for the improvement of clinical outcomes in patients with LV systolic dysfunction and heart rate >/=70 b.p.m., whatever the primary clinical presentation (CAD or HF) or clinical status (NYHA class).
|
|
| 19. |
|
|
| 20. |
- Eisen, A., et al.
(author)
-
High-Sensitivity Troponin I in Stable Patients with Atherosclerotic Disease in the TRA 2 degrees P - TIMI 50 Trial
- 2017
-
In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 63:1, s. 307-315
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Cardiac troponin I, measured with a high-sensitivity assay (hs-TnI), is well-established for risk prediction in acute coronary syndromes. However, its prognostic role in stable atherosclerotic disease, particularly for future myocardial infarction (MI), is less well defined. METHODS: We measured hs-TnI (Abbott ARCHITECT) in 15 833 patients with prior MI, ischemic stroke, or peripheral arterial disease from the placebo controlled Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P) Thrombolysis in Myocardial Infarction (TIMI) 50 trial of the platelet inhibitor vorapaxar, excluding patients with recent MI (<30 days). hs-TnI was categorized into 5 groups based on the detection limit (1.9 ng/L), 99th percentile reference limit (26 ng/L), and tertiles in between (1.9-26 ng/L), as well as sex-specific reference limits. RESULTS: Higher hs-TnI concentration was associated with older age, male sex, and increased atherosclerosis burden. hs-TnI identified a graded 3-year risk of cardiovascular death, MI, or stroke from 5.0% to 18.6% (P < 0.001), driven by cardiovascular death and MI (P < 0.001). This risk was independent of established clinical risk indicators, B-type natriuretic peptide and C-reactive protein [adjusted hazard ratio 2.70 (95% CI, 1.96-3.71), P < 0.001 for hs-TnI >26 ng/L vs <1.9 ng/L]. In patients with prior MI, there was a pattern of greater absolute benefit with vorapaxar in patients with an increased hs-TnI (absolute risk difference 1.9% with hs-TnI >26 ng/L vs 0.3% with hs-TnI <1.9 ng/L; P interaction = 0.82). CONCLUSIONS: In stable patients with established atherosclerosis, hs-TnI concentrations effectively stratified the risk of new or recurrent cardiovascular (CV) events, in particular CV death and MI. High-risk patients with prior MI identified by increased hs-TnI had a substantial absolute improvement in net clinical outcome with vorapaxar. (C) 2016 American Association for Clinical Chemistry
|
|
| 21. |
- Hamill, V., et al.
(author)
-
Repeated Heart Rate Measurement and Cardiovascular Outcomes in Left Ventricular Systolic Dysfunction
- 2015
-
In: American Journal of Medicine. - : Elsevier BV. - 0002-9343. ; 128:10, s. 1102-1108
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Elevated resting heart rate is associated with increased cardiovascular risk, particularly in patients with left ventricular systolic dysfunction. Heart rate is not monitored routinely in these patients. We hypothesized that routine monitoring of heart rate would increase its prognostic value in patients with left ventricular systolic dysfunction. METHODS: We analyzed the relationship between heart rate measurements and a range of adverse cardiovascular outcomes, including hospitalization for worsening heart failure, in the pooled placebo-treated patients from the morBidity-mortality EvAlUaTion of the I-f inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction (BEAUTIFUL) trial and Systolic Heart failure treatment with the I-f inhibitor ivabradine (SHIFT) Trial, using standard and time-varying covariate Cox proportional hazards models. By adjusting for other prognostic factors, models were fitted for baseline heart rate alone or for time-updated heart rate (latest heart rate) alone or corrected for baseline heart rate or for immediate previous time-updated heart rate. RESULTS: Baseline heart rate was strongly associated with all outcomes apart from hospitalization for myocardial infarction. Time-updated heart rate increased the strengths of associations for all outcomes. Adjustment for baseline heart rate or immediate previous time-updated heart rate modestly reduced the prognostic importance of time-updated heart rate. For hospitalization for worsening heart failure, each 5 beats/min increase in baseline heart rate and time-updated heart rate was associated with a 15% (95% confidence interval, 12-18) and 22% (confidence interval, 19-40) increase in risk, respectively. Even after correction, the prognostic value of time-updated heart rate remained greater. CONCLUSIONS: In patients with left ventricular systolic dysfunction, time-updated heart rate is more strongly related with adverse cardiovascular outcomes than baseline heart rate. Heart rate should be measured to assess cardiovascular risk at all assessments of patients with left ventricular systolic dysfunction. (C) 2015 Elsevier Inc. All rights reserved.
|
|
| 22. |
- Kosova, E. C., et al.
(author)
-
Vorapaxar in patients with coronary artery bypass grafting: Findings from the TRA 2 degrees P-TIMI 50 trial
- 2017
-
In: European heart journal. Acute cardiovascular care. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 6:2, s. 164-172
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Vorapaxar is a first-in-class protease-activated receptor-1 antagonist indicated for the reduction of cardiovascular death, myocardial infarction, and stroke in stable patients with prior atherothrombosis, who have not had a prior stroke or transient ischemic attack. The aims of this study were to investigate: 1) the role of vorapaxar in patients with severe coronary artery disease treated previously with coronary artery bypass grafting (CABG); and 2) safety in patients undergoing CABG while receiving vorapaxar. METHODS: TRA 2 degrees P-TIMI 50 was a randomized, double-blinded, placebo-controlled trial of vorapaxar in 26,449 stable patients with prior atherothrombosis followed for a median of 30 months. We 1) investigated the efficacy of vorapaxar among patients with a history of CABG prior to randomization (n=2942); and 2) assessed the safety among 367 patients who underwent a new CABG during the trial. RESULTS: Patients with a prior CABG were at higher risk for cardiovascular death, myocardial infarction, or stroke at three years compared with patients without a prior CABG (13.7% vs. 7.8%, p<0.001). Among patients with a prior CABG, vorapaxar significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke (11.9% vs. 15.6%, hazard ratio 0.71, 95% confidence interval 0.58-0.88, p=0.001; number-needed-to-treat = 27). In patients undergoing CABG while receiving vorapaxar, the rate of Thrombolysis in Myocardial Infarction CABG major bleeding was 6.3% vs. 4.1% with placebo (hazard ratio 1.53, 95% confidence interval 0.58-4.01, p=0.39). CONCLUSIONS: In patients with a prior CABG, vorapaxar significantly reduced the risk of recurrent major cardiovascular events. In patients undergoing CABG while receiving vorapaxar, bleeding risk appeared similar to that seen in the overall trial population.
|
|
| 23. |
- McMurray, J. J., et al.
(author)
-
Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF)
- 2013
-
In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 15:3, s. 334-341
-
Journal article (peer-reviewed)abstract
- AIMS: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. METHODS AND RESULTS: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m(2)). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106-117) g/L. CONCLUSION: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.
|
|
| 24. |
- McMurray, J. J., et al.
(author)
-
Design of the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF): a Phase III, anaemia correction, morbidity-mortality trial
- 2009
-
In: European Journal of Heart Failure. - 1879-0844. ; 11:8, s. 795-801
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non-anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown. OBJECTIVE: The Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF; Clinical Trials.gov NCT 003 58215) was designed to evaluate the effect of the long-acting erythropoietin-stimulating agent darbepoetin alfa on mortality and morbidity (and quality of life) in patients with HF and anaemia. METHODS: Approximately 2600 patients with New York Heart Association class II-IV, an ejection fraction < or =40%, and a haemoglobin (Hb) consistently < or =12.0 g/dL but > or =9.0 g/dL will be enrolled. Patients are randomized 1:1 to double-blind subcutaneous administration of darbepoetin alfa or placebo. Investigators are also blinded to Hb measurements and darbepoetin alfa is dosed to achieve an Hb concentration of 13.0 g/dL (but not exceeding 14.5 g/dL) with sham adjustments of the dose of placebo. The primary endpoint is the time to death from any cause or first hospital admission for worsening HF, whichever occurs first. The study will complete when approximately 1150 subjects experience a primary endpoint.
|
|
| 25. |
|
|
