| 1. |
- Engstrøm, Thomas, et al.
(författare)
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Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients : A phase 2 randomised clinical trial
- 2018
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 104:19, s. 1593-1599
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI. Methods: In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months. Results: From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome. Conclusions: Administration of danegaptide to patients with STEMI did not improve myocardial salvage. Trial registration number: NCT01977755; Pre-results.
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| 2. |
- Kyhl, Kasper, et al.
(författare)
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Complete Revascularization Versus Culprit Lesion Only in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease : A DANAMI-3–PRIMULTI Cardiac Magnetic Resonance Substudy
- 2019
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Ingår i: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1936-8798. ; 12:8, s. 721-730
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to evaluate the effect of fractional flow reserve (FFR)–guided revascularization compared with culprit-only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) on infarct size, left ventricular (LV), function, LV remodeling, and the presence of nonculprit infarctions. Background: Patients with STEMI with multivessel disease might have improved clinical outcomes after complete revascularization compared with PCI of the infarct-related artery only, but the impact on infarct size, LV function, and remodeling as well as the risk for periprocedural infarction are unknown. Methods: In this substudy of the DANAMI-3 (Third Danish Trial in Acute Myocardial Infarction)–PRIMULTI (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization) randomized trial, patients with STEMI with multivessel disease were randomized to receive either complete FFR-guided revascularization or PCI of the culprit vessel only. The patients underwent cardiac magnetic resonance imaging during index admission and at 3-month follow-up. Results: A total of 280 patients (136 patients with infarct-related and 144 with complete FFR-guided revascularization) were included. There were no differences in final infarct size (median 12% [interquartile range: 5% to 19%] vs. 11% [interquartile range: 4% to 18%]; p = 0.62), myocardial salvage index (median 0.71 [interquartile range: 0.54 to 0.89] vs. 0.66 [interquartile range: 0.55 to 0.87]; p = 0.49), LV ejection fraction (mean 58 ± 9% vs. 59 ± 9%; p = 0.39), and LV end-systolic volume remodeling (mean 7 ± 22 ml vs. 7 ± 19 ml; p = 0.63). New nonculprit infarction occurring after the nonculprit intervention was numerically more frequent among patients treated with complete revascularization (6 [4.5%] vs. 1 [0.8%]; p = 0.12). Conclusions: Complete FFR-guided revascularization in patients with STEMI and multivessel disease did not affect final infarct size, LV function, or remodeling compared with culprit-only PCI.
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| 3. |
- Laursen, Peter Nørkjær, et al.
(författare)
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Comparison between patients included in randomized controlled trials of ischemic heart disease and real-world data. A nationwide study
- 2018
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 204, s. 128-138
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Tidskriftsartikel (refereegranskat)abstract
- Background: The objective was to compare patients with ischemic heart disease (IHD) undergoing percutaneous coronary intervention (PCI) who were included in randomized controlled trials (RCTs) (trial participants) with patients who were not included (nonparticipants) on a trial-by-trial basis and according to indication for PCI. Methods: In this cohort study, we compared patients with IHD who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011 and 2015 were considered as RCT-participants in this study. The RCT-participants were compared with contemporary nonparticipants with IHD undergoing PCI in the same period, and they were identified using unselected national registry data. The primary end point was all-cause mortality. Results: A total of 10,317 (30%) patients were included in 10 relevant RCTs (trial participants), and a total of 23,644 (70%) contemporary patients did not participate (nonparticipants). In all the included RCTs, nonparticipants had higher hazard ratios for mortality compared to trial participants (P <.001). Among all patients treated with PCI, the pooled estimates showed a significantly higher mortality rate for nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88-2.19) (P <.001). When patients were stratified according to indication for PCI, the pooled estimates showed a significantly lower mortality rate for trial participants compared to nonparticipants in all strata (P for all <.001). Conclusions: Trial participants in recently performed RCTs including patients undergoing PCI were not representative of the general population of patients with IHD treated with PCI according to clinical characteristics and mortality. The difference in mortality was found irrespective of the indication for PCI. Thus, results from RCTs including patients undergoing PCI should be extrapolated with caution to the general patient population.
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| 4. |
- Laursen, Peter Nørkjær, et al.
(författare)
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Unreported exclusion and sampling bias in interpretation of randomized controlled trials in patients with STEMI
- 2019
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 289, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To assess the impact of sampling bias due to reported as well as unreported exclusion of the target population in a multi-center randomized controlled trial (RCT)of ST-elevation myocardial infarction (STEMI). Methods and Results: We compared clinical characteristics and mortality between participants in the DANAMI-3 trial to contemporary non-participants with STEMI using unselected registries. A total of 179 DANAMI-3 participants (8%)and 617 contemporary non-participants (22%)had died (Log-Rank: P < 0.001)after a median follow-up of 1333 days (range: 1–2021 days). In an unadjusted Cox regression model all groups of non-participants had a higher hazard ratio to predict mortality compared to participants: eligible excluded (n = 144)(hazard ratio: 3.41 (95% CI: (2.69–4.32)), ineligible excluded (n = 472)(hazard ratio: 3.42 (95% CI: (2.44–4.80), eligible non-screened (n = 154)(hazard ratio: 3.37 (95% CI: (2.36–4.82)), ineligible non-screened (n = 154)(hazard ratio: 6.48 (95% CI: (4.77–8.80). Conclusion: Sampling bias had occurred due to both reported and unreported exclusion of eligible patients and the difference in mortality between participants and non-participants could not be explained only by the trial exclusion criteria. Thus, screening logs may not be suited to address the risks of sampling bias.
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| 5. |
- Nepper-Christensen, Lars, et al.
(författare)
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Benefit From Reperfusion With Primary Percutaneous Coronary Intervention Beyond 12 Hours of Symptom Duration in Patients With ST-Segment-Elevation Myocardial Infarction
- 2018
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Ingår i: Circulation. Cardiovascular Interventions. - 1941-7632. ; 11:9, s. 006842-006842
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Guidelines recommend primary percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI) presenting ≥12 hours of symptom onset in the presence of ongoing ischemia. However, data supporting this recommendation are limited. We evaluated the effect of primary PCI on reperfusion success, using cardiac magnetic resonance, in STEMI patients with signs of ongoing ischemia presenting 12 to 72 hours after symptom onset compared with STEMI patients presenting <12 hours.METHODS AND RESULTS: We included 865 STEMI patients who underwent cardiac magnetic resonance just after index PCI and 3 months later. Despite equal area at risk (34±12% versus 33±12%; P=0.370), patients presenting late (n=58) had larger final infarct size (13% [interquartile range, 9-24] versus 11% [interquartile range, 4-19]; P=0.037) and smaller myocardial salvage index (0.58 [interquartile range, 0.39-0.71] versus 0.65 [interquartile range, 0.49-0.84]; P=0.021) compared with patients presenting <12 hours after symptom onset (n=807). However, 65% of late-presenting patients achieved substantial myocardial salvage ≥0.50, and area under the curve for symptom onset to PCI as predictor of a myocardial salvage index ≥0.50 was poor (0.58 [95% CI, 0.53-0.63]; P<0.001). In addition, final infarct size, salvage index and left ventricular function correlated weakly with duration from symptom onset to primary PCI ( R2 values <0.05).CONCLUSIONS: STEMI patients with signs of ongoing ischemia treated with primary PCI 12 to 72 hours after symptom onset had less myocardial salvage and developed larger infarcts. However, a large proportion achieved substantial myocardial salvage indicating a benefit from primary PCI in late-presenting patients.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01435408 and NCT01960933.
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| 6. |
- Nepper-Christensen, Lars, et al.
(författare)
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Impact of diagnostic ECG-to-wire delay in STEMI patients treated with primary PCI : A DANAMI-3 substudy
- 2018
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Ingår i: EuroIntervention. - 1774-024X. ; 14:6, s. 700-707
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We aimed to evaluate the impact of delay from diagnostic pre-hospital electrocardiogram (ECG) to wiring of the infarct-related vessel (ECG-to-wire) >120 minutes on cardiovascular magnetic resonance (CMR) markers of reperfusion success and clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI). Methods and results: We included 1,492 patients in the analyses of clinical outcome. CMR was performed in 748 patients to evaluate infarct size and myocardial salvage. In total, 304 patients (20%) had ECG-to-wire >120 minutes, which was associated with larger acute infarct size (18% [interquartile range (IQR), 10-28] vs. 15% [8-24]; p=0.022) and smaller myocardial salvage (0.42 [IQR 0.28-0.57] vs. 0.50 [IQR 0.34-0.70]; p=0.002). However, 33% of the patients with ECG-to-wire >120 minutes still had a substantial myocardial salvage ≥0.50. In a multivariable analysis, ECG-to-wire >120 minutes was associated with an increased risk of all-cause mortality and heart failure (hazard ratio 1.61, 95% confidence interval [CI] 1.14-2.26, p=0.007). Conclusions: ECG-to-wire >120 minutes was associated with larger infarct size, smaller myocardial salvage and a poorer clinical outcome in STEMI patients transferred for primary percutaneous coronary intervention. However, myocardial salvage was still substantial in one third of patients treated beyond 120 minutes of delay.
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