| 1. |
- Kappetein, Arie Pieter, et al.
(författare)
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Design and rationale for a randomised comparison of everolimus-eluting stents and coronary artery bypass graft surgery in selected patients with left main coronary artery disease : the EXCEL trial
- 2016
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Ingår i: EuroIntervention. - 1774-024X .- 1969-6213. ; 12:7, s. 861-872
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Coronary artery bypass graft (CABG) surgery is the standard of care for revascularisation of patients with left main coronary artery disease (LMCAD). Recent studies have suggested that percutaneous coronary intervention (PCI) with drug-eluting stents (DES) may provide comparable outcomes in selected patients with LMCAD without extensive CAD. We therefore designed a trial to investigate whether PCI with XIENCE cobalt-chromium everolimus-eluting stents (CoCr-EES) would result in non-inferior or superior clinical outcomes to CABG in selected patients with LMCAD. Methods and results: The Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial is a prospective, open-label, multicentre, international study of 1,900 randomised subjects. Patients with significant LMCAD with a SYNTAX score <= 32 and local Heart Team consensus that the subject is appropriate for revascularisation by both PCI and CABG are consented and randomised 1:1 to undergo PCI using CoCr-EES or CABG. All patients undergo follow-up for five years. The primary endpoint is the three-year composite rate of death, stroke or myocardial infarction, assessed at a median follow-up of at least three years (with at least two-year follow-up in all patients), powered for sequential non-inferiority and superiority testing. Conclusions: The EXCEL study will define the contemporary roles of CABG and PCI using XIENCE CoCr-EES in patients with LMCAD disease with low and intermediate SYNTAX scores.
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| 2. |
- Landray, Martin J., et al.
(författare)
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Improving public health by improving clinical trial guidelines and their application
- 2017
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 38:21, s. 1632-1637B
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Tidskriftsartikel (refereegranskat)abstract
- Evidence generated from randomized controlled trials forms the foundation of cardiovascular therapeutics and has led to the adoption of numerous drugs and devices that prolong survival and reduce morbidity, as well as the avoidance of interventions that have been shown to be ineffective or even unsafe. Many aspects of cardiovascular research have evolved considerably since the first randomized trials in cardiology were conducted. In order to be large enough to provide reliable evidence about effects on major outcomes, cardiovascular trials may now involve thousands of patients recruited from hundreds of clinical sites in many different countries. Costly infrastructure has developed to meet the increasingly complex organizational and operational requirements of these clinical trials. Concerns have been raised that this approach is unsustainable, inhibiting the reliable evaluation of new and existing treatments, to the detriment of patient care. These issues were considered by patients, regulators, funders, and trialists at a meeting of the European Society of Cardiology Cardiovascular Roundtable in October 2015. This paper summarizes the key insights and discussions from the workshop, highlights subsequent progress, and identifies next steps to produce meaningful change in the conduct of cardiovascular clinical research.
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| 3. |
- Matsumoto, Shingo, et al.
(författare)
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Underutilization of Mineralocorticoid Antagonists in Patients With Heart Failure With Reduced Ejection Fraction
- 2023
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Ingår i: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY. - 0735-1097 .- 1558-3597. ; 82:11, s. 1080-1091
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND It is unknown how the efficacy and safety of mineralocorticoid receptor antagonists vary according to duration of heart failure with reduced ejection fraction (HFrEF).OBJECTIVES In this study, we sought to evaluate the safety and efficacy of eplerenone according to duration of HFrEF. METHODS In the EMPHASIS-HF trial, 3 patient groups were created according to HFrEF duration: <1 year, 1 to <5 years, and >= 5 years. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Outcomes were adjusted for prespecified prognostic variables and examined with the use of Cox regression models.RESULTS The numbers of patients in each group were: 975, <1 year; 769, 1 to <5 years; and 988, >= 5 years. Patients with longer-standing HF were older and more frequently had cardiovascular and noncardiovascular comorbidities. The rate of the primary outcome (per 100 person-years) increased with HFrEF duration: 9.8 (95% CI: 8.4-11.4) for <1 year, 13.5 (95% CI: 11.6-15.7) for 1 to <5 years, and 17.6 (95% CI: 15.6-19.8) for >= 5 years. The benefits of eplerenone were consistent across HF duration: HRs for the primary outcome were 0.57 (95% CI: 0.42-0.79) for <1 year, 0.81 (95% CI: 0.60-1.10) for 1 to <5 years, and 0.61 (95% CI: 0.48-0.78) for >= 5 years; Pinteraction 1/4 0.24. The absolute benefit was greatest in the longest-duration group: the number needed to treat for the primary outcome was 14 for <1 year, 13 for 1 to <5 years, and 10 for >= 5 years duration. CONCLUSIONS Patients with longer-standing HFrEF had worse clinical status and a higher rate of events, but the benefit of eplerenone was consistent regardless of HFrEF duration. (A Comparison of Outcomes in Patients in NYHA Class II Heart Failure When Treated With Eplerenone or Placebo in Addition to Standard Heart Failure Medicines [EMPHASIS-HF]; NCT00232180) (J Am Coll Cardiol 2023;82:1080-1091)
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| 4. |
- Capodanno, Davide, et al.
(författare)
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Trial Design Principles for Patients a High Bleeding Risk Undergoing PCI JACC Scientific Expert Panel
- 2020
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 76:12, s. 1468-1483
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Tidskriftsartikel (refereegranskat)abstract
- Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of this consensus-based document, the second initiative from the Academic Research Consortium for HBR, is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI. The authors discuss the designs of trials in HBR patients undergoing PCI and various aspects of trial design specific to HBR patients, including target populations, intervention and control groups, primary and secondary outcomes, and timing of endpoint reporting. (C) 2020 by the American College of Cardiology Foundation.
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| 6. |
- Damman, Peter, et al.
(författare)
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Long-Term Cardiovascular Mortality after Procedure-Related or Spontaneous Myocardial Infarction in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome : A Collaborative Analysis of Individual Patient Data from the FRISC II, ICTUS, and RITA-3 Trials (FIR)
- 2012
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 125:4, s. 568-576
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To investigate the long-term prognostic impact of procedure-related and spontaneous myocardial infarction (MI) on cardiovascular mortality in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS AND RESULTS: Five-year follow-up after procedure-related or spontaneous MI was investigated in the individual patient-pooled dataset of the FRISC-II, ICTUS and RITA-3 (FIR) NSTE-ACS trials. The principal outcome was cardiovascular death up to 5 years of follow-up. Cumulative event rates were estimated with the Kaplan-Meier method, hazard ratios (HR) were calculated with time-dependent Cox proportional-hazards models. Adjustments were made for the variables associated with long-term outcomes. Of the 5467 patients, 212 endured a procedure-related MI within 6 months after enrolment. A spontaneous MI occurred in 236 patients within 6 months. The cumulative cardiovascular death rate was 5.2% in patients who endured a procedure-related MI and comparable to patients without a procedure-related MI (HR 0.66, 95%CI: 0.36-1.20, P=0.17). In patients who endured a spontaneous MI within 6 months, the cumulative cardiovascular death rate was 22.2% and higher than patients without a spontaneous MI (HR 4.52, 95%CI: 3.37-6.06, P<0.001). These HRs did not materially alter after risk adjustments. CONCLUSIONS: Five-year follow-up of NSTE-ACS patients from the three FIR trials showed no association between a procedure-related MI and long-term cardiovascular mortality. In contrast there was a substantially raised long-term mortality after a spontaneous MI.
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| 7. |
- Damman, Peter, et al.
(författare)
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Timing of Angiography With a Routine Invasive Strategy and Long-Term Outcomes in Non-ST-Segment Elevation Acute Coronary Syndrome : A Collaborative Analysis of Individual Patient Data From the FRISC II (Fragmin and Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction) Trials
- 2012
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Ingår i: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1936-8798. ; 5:2, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study sought to investigate long-term outcomes after early or delayed angiography in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS) undergoing a routine invasive management. Background The optimal timing of angiography in patients with nSTE-ACS is currently a topic for debate.Methods: Long-term follow-up after early (within 2 days) angiography versus delayed (within 3 to 5 days) angiography was investigated in the FRISC-II (Fragmin and Fast Revascularization During Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction) (FIR) nSTE-ACS patient-pooled database. The main outcome was cardiovascular death or myocardial infarction up to 5-year follow-up. Hazard ratios (HR) were calculated with Cox regression models. Adjustments were made for the FIR risk score, study, and the propensity of receiving early angiography using inverse probability weighting.Results: Of 2,721 patients originally randomized to the routine invasive arm, consisting of routine angiography and subsequent revascularization if suitable, 975 underwent early angiography and 1,141 delayed angiography. No difference was observed in 5-year cardiovascular death or myocardial infarction in unadjusted (HR: 1.06, 95% confidence interval [CI]: 0.79 to 1.42, p = 0.61) and adjusted (HR: 0.93, 95% CI: 0.75 to 1.16, p = 0.54) Cox regression models.Conclusions: In the FIR database of patients presenting with nSTE-ACS, the timing of angiography was not related to long-term cardiovascular mortality or myocardial infarction. (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes [ICTUS]; ISRCTN82153174. Intervention Versus Conservative Treatment Strategy in Patients With Unstable Angina or Non-ST Elevation Myocardial Infarction [the Third Randomised Intervention Treatment of Angina Trials (RITA-3)]; ISRCTN07752711)
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| 8. |
- Damman, Peter, et al.
(författare)
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Usefulness of the Admission Electrocardiogram to Predict Long-Term Outcomes After Non-ST-Elevation Acute Coronary Syndrome (from the FRISC II, ICTUS, and RITA-3 [FIR] Trials)
- 2012
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 109:1, s. 6-12
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the independent prognostic value of qualitative and quantitative admission electrocardiographic (ECG) analysis regarding long-term outcomes after non-ST-segment elevation acute coronary syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were included in this analysis. The main outcome was 5-year cardiovascular death or myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression models, and adjustments were made for established outcome predictors. The additional discriminative value was assessed with the category-less net reclassification improvement and integrated discrimination improvement indexes. In the 5,420 patients, the presence of ST-segment depression (≥1 mm; adjusted HR 1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long-term cardiovascular death or myocardial infarction. Risk increases were short and long term. On quantitative ECG analysis, cumulative ST-segment depression (≥5 mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or ≥6 leads with inverse T waves (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long-term outcomes. No interaction was observed with treatment strategy. No improvements in net reclassification improvement and integrated discrimination improvement were observed after the addition of quantitative characteristics to a model including qualitative characteristics. In conclusion, in the FRISC II, ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics provided long-term prognostic value for cardiovascular death or myocardial infarction. Quantitative ECG characteristics provided no incremental discrimination compared to qualitative data.
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| 9. |
- Fox, Keith A. A., et al.
(författare)
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Long-Term Outcome of a Routine Versus Selective Invasive Strategy in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome A Meta-Analysis of Individual Patient Data
- 2010
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 55:22, s. 2435-2445
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study was designed to determine: 1) whether a routine invasive (RI) strategy reduces the long-term frequency of cardiovascular death or nonfatal myocardial infarction (MI) using a meta-analysis of individual patient data from all randomized studies with 5-year outcomes; and 2) whether the results are influenced by baseline risk. BACKGROUND: Pooled analyses of randomized trials show early benefit of routine intervention, but long-term results are inconsistent. The differences may reflect differing trial design, adjunctive therapies, and/or limited power. This meta-analysis (n = 5,467 patients) is designed to determine whether outcomes are improved despite trial differences. METHODS: Individual patient data, with 5-year outcomes, were obtained from FRISC-II (Fragmin and Fast Revascularization during Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Randomized Trial of a Conservative Treatment Strategy Versus an Interventional Treatment Strategy in Patients with Unstable Angina) trials for a collaborative meta-analysis. A Cox regression analysis was used for a multivariable risk model, and a simplified integer model was derived. RESULTS: Over 5 years, 14.7% (389 of 2,721) of patients randomized to RI strategy experienced cardiovascular death or nonfatal MI versus 17.9% (475 of 2,746) in the selective invasive (SI) strategy (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.71 to 0.93; p = 0.002). The most marked treatment effect was on MI (10.0% RI strategy vs. 12.9% SI), and there were consistent trends for cardiovascular deaths (HR: 0.83, 95% CI: 0.68 to 1.01; p = 0.068) and all deaths (HR: 0.90, 95% CI: 0.77 to 1.05). There were 2.0% to 3.8% absolute reductions in cardiovascular death or MI in the low and intermediate risk groups and an 11.1% absolute risk reduction in highest risk patients. CONCLUSIONS: An RI strategy reduces long-term rates of cardiovascular death or MI and the largest absolute effect in seen in higher-risk patients.
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