| 1. |
- Venetsanos, Dimitrios, et al.
(författare)
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Association between gender and short-term outcome in patients with ST elevation myocardial infraction participating in the international, prospective, randomised Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) trial: a prespecified analysis
- 2017
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Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To evaluate gender differences in outcomes in patents with ST-segment elevation myocardial infarction (STEMI) planned for primary percutaneous coronary intervention (PPCI). Settings A prespecified gender analysis of the multicentre, randomised, double-blind Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery. Participants Between September 2011 and October 2013, 1862 patients with STEMI and symptom duration amp;lt;6 hours were included. Interventions Patients were assigned to prehospital versus in-hospital administration of 180 mg ticagrelor. Outcomes The main objective was to study the association between gender and primary and secondary outcomes of the main study with a focus on the clinical efficacy and safety outcomes. Primary outcome: the proportion of patients who did not have 70% resolution of ST-segment elevation and did not meet the criteria for Thrombolysis In Myocardial Infarction (TIMI) flow 3 at initial angiography. Secondary outcome: the composite of death, MI, stent thrombosis, stroke or urgent revascularisation and major or minor bleeding at 30 days. Results Women were older, had higher TIMI risk score, longer prehospital delays and better TIMI flow in the infarct-related artery. Women had a threefold higher risk for all-cause mortality compared with men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 to 5.51). After adjustment, the difference was attenuated but remained statistically significant (HR 2.08, 95% CI 1.03 to 4.20). The incidence of major bleeding events was twofold to threefold higher in women compared with men. In the multivariable model, female gender was not an independent predictor of bleeding (Platelet Inhibition and Patient Outcomes major HR 1.45, 95% CI 0.73 to 2.86, TIMI major HR 1.28, 95% CI 0.47 to 3.48, Bleeding Academic Research Consortium type 3-5 HR 1.45, 95% CI 0.72 to 2.91). There was no interaction between gender and efficacy or safety of randomised treatment. Conclusion In patients with STEMI planned for PPCI and treated with modern antiplatelet therapy, female gender was an independent predictor of short-term mortality. In contrast, the higher incidence of bleeding complications in women could mainly be explained by older age and clustering of comorbidities.
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| 2. |
- Venetsanos, Dimitrios, et al.
(författare)
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Bivalirudin versus heparin with primary percutaneous coronary intervention
- 2018
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Ingår i: American Heart Journal. - Philadelphia, United States : Mosby, Inc.. - 0002-8703 .- 1097-6744. ; 201, s. 9-16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal adjunctive therapy in ST-segment elevation myocardial infarction (STEMI) patients treated with primary PCI (PPCI) remains a matter of debate. Our aim was to compare the efficacy and safety of bivalirudin to unfractionated heparin (UFH), with or without glycoprotein IIb/IIIa inhibitors (GPI) in a large real-world population, using data from the Swedish national registry, SWEDEHEART. Method: From 2008 to 2014 we identified 23,800 STEMI patients presenting within 12 hours from symptom onset treated with PPCI and UFH +/- GPI or bivalirudin +/- GPI. Primary outcomes included 30-day all-cause mortality and major in-hospital bleeding. Multivariable regression models and propensity score modelling were utilized to study adjusted association between treatment and outcome. Results: Treatment with UFH +/- GPI was associated with similar risk of 30-day mortality compared to bivalirudin +/- GPI (5.3% vs 5.5%, adjusted HR 0.94; 95% CI 0.82-1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between UFH +/- GPI and bivalirudin +/- GPI. In contrast, treatment with UFH +/- GPI was associated with a significant higher risk of major in-hospital bleeding (adjusted OR 1.62; 95% CI 1.30-2.03). When including GPI use in the multivariable analysis, the difference was attenuated and no longer significant (adjusted OR 1.25; 95% CI 0.92-1.70). Conclusion: Bivalirudin +/- GPI was associated with significantly lower risk for major in hospital bleeding but no significant difference in 30-day or one year mortality, stent thrombosis or re-infarction compared with UFH +/- GPI. The bleeding reduction associated with bivalirudin could be explained by the greater GPI use with UFH. (C) 2018 Elsevier Inc. All rights reserved.
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| 3. |
- Venetsanos, Dimitrios, et al.
(författare)
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Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets : The inhibition of platelet aggregation after administration of three different ticagrelor formulations (IPAAD-Tica) study, a randomised controlled trial.
- 2017
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 149, s. 88-94
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To provide pharmacodynamic data of crushed and chewed ticagrelor tablets, in comparison with standard integral tablets.METHODS: Ninety nine patients with stable angina were randomly assigned, in a 3:1:1 fashion, to one of the following 180mg ticagrelor loading dose (LD) formulations: A) Integral B) Crushed or C) Chewed tablets. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60min after LD. High residual platelet reactivity (HRPR) was defined as >208 P2Y12 reaction units (PRU).RESULTS: There was no significant difference in PRU values at baseline. PRU 20min after LD were 237 (182-295), 112 (53-238) and 84 (29-129) and 60min after LD, 56 (15-150), 51 (18-85) and 9 (7-34) in integral, crushed and chewed ticagrelor LD, respectively (p<0.01 for both). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60min. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20min whereas no difference was observed at 60min. At 20min, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01).CONCLUSION: With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared to standard integral tablets. We also show that administration of chewed tablets is feasible and provides faster inhibition than either crushed or integral tablets.CLINICAL TRIAL REGISTRATION: European Clinical Trial Database (EudraCT number 2014-002227-96).
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| 4. |
- Venetsanos, Dimitrios, et al.
(författare)
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Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR
- 2015
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Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 5:9, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To validate the performance of the most commonly used formulas for estimation of glomerular filtration rate (GFR) against measured GFR during the index hospitalisation for ST-elevation myocardial infarction (STEMI). Setting: Single centre, methodological study. Participants: 40 patients with percutaneous coronary intervention-treated STEMI were included between November 2011 and February 2013. Patients on dialysis, cardiogenic shock or known allergy to iodine were excluded. Outcome measures: Creatinine and cystatin C were determined at admission and before discharge in 40 patients with STEMI. Clearance of iohexol was measured (mGFR) before discharge. We evaluated and compared the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rG-CystC) with GFR regarding correlation, bias, precision and accuracy (P30). Agreement between eGFR and mGFR to discriminate CKD was assessed by Cohens. statistics. Results: MDRD-IDMS and CKD-EPI demonstrated good performance to estimate GFR (correlation 0.78 vs 0.81%, bias -1.3% vs 1.5%, precision 17.9 vs 17.1 mL/min 1.73 m(2) and P30 82.5% vs 82.5% for MDRD-IDMS vs CKD-EPI). CKD was best classified by CKD-EPI (. 0.83). CG showed the worst performance (correlation 0.73%, bias -1% to 3%, precision 22.5 mL/min 1.73 m(2) and P30 75%). The rG-CystC formula had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03). At arrival, CKD-EPI and rG-CystC had almost perfect agreement in CKD classification (kappa=0.87), whereas at discharge agreement was substantially lower (kappa=0.59) and showed a significant discrepancy in CKD classification (p=0.02). Median cystatin C concentration increased by 19%. Conclusions: In acute STEMI, CKD-EPI showed the best CKD-classification ability followed by MDRD-IDMS, whereas CG performed the worst. STEMI altered the performance of the cystatin C equation during the acute phase, suggesting that other factors might be involved in the rise of cystatin C.
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| 5. |
- Venetsanos, Dimitrios
(författare)
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Improving management of STEMI patients treated with primary PCI : Pharmacotherapy, renal function estimation and gender perspective
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis focused on the acute management of patients with ST-segment elevation myocardial infarction (STEMI) in an effort to provide information that may improve outcome. The aim was to evaluate the efficacy and safety of bivalirudin versus unfractionated heparin (UFH) in STEMI patients during primary PCI. Furthermore, to provide pharmacodynamic data of novel ways of ticagrelor administration compared to standard tivcagrelor. Additionally, to identify subgroups of patients, such as women who may derive greater benefit from specific antithrombotic strategies due to their risk/benefit profile. Finally, to evaluate current formulas for estimation of renal function in the acute phase of STEMI.In Paper I, all STEMI patients in Sweden between 2008 and 2014, treated with primary PCI and UFH or bivalirudin were included in our analysis. Of the total population of 23 800 patients, 8 783 (36.9%) were included in the UFH group and 15 017 (63.1%) in the bivalirudin group. Concomitant GPI administration was 68.5% in the UFH arm compared to 3.5% in the bivalirudin arm (p<0.01).The adjusted incidence of 30-day mortality was not significant different between the two groups (UFH vs bivalirudin, adjusted HR 0.94; 95% CI 0.82 -1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between the two groups. In contrast, patients treated with UFH had a significantly higher incidence of major in-hospital bleeding (adjusted OR 1.62; 95%CI 1.30 -2.03).In Paper II pharmacodynamic data of chewed or crushed ticagrelor compared to standard ticagrelor loading dose (LD) was assessed in 99 patients with stable angina. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60 minutes after LD. High Residual platelet reactivity (HRPR) was defined as > 208 P2Y12 reaction units (PRU). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60 minutes. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20 minutes whereas no difference was observed at 60 minutes. At 20 minutes, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01).In Paper III we presented a pre-specified gender analysis of the ATLANTIC trial including 1 862 STEMI patients that were randomly assigned to pre-hospital versus in-hospital administration of 180mg ticagrelor. Women were older and had higher TIMI risk score. Women had a 3-fold higher risk for all-cause mortality compared to men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 – 5.51). However, after adjustment for baseline characteristics, the difference was lesser and no longer significant (HR 1.98, 95% CI 0.97 – 4.04). Female gender was not an independent predictor of risk for bleeding after multivariable adjustments (BARC type 3-5 HR 1.52, 95% CI 0.74-3.09). There was no interaction between gender and efficacy or safety of randomised treatment.In Paper IV, forty patients with PCI- treated STEMI were included between November 2011 and February 2013. We validated the performance of the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rGCystC) equations for estimation of GFR against measured GFR (mGFR) during the index hospitalisation for STEMI.MDRD-IDMS and CKD-EPI demonstrated a good performance to estimate GFR with accuracy within 30% (P30) 82.5% vs 82.5%, respectively. CKD was best classified by CKD-EPI (Kappa 0.83). CG showed the worst performance with the lowest P30. The rG-CystC equation had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03).Conclusions – In STEMI patients treated with primary PCI, bivalirudin should be preferred in patient at high risk for bleeding. With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared with standard integral tablets. In STEMI patients, fast and potent platelet inhibition with chewed ticagrelor may reduce the risk of early stent thrombosis and patients treated with a less aggressive antithrombotic strategy, such as UFH or bivalirudin monotherapy, may derive a greater benefit. Although gender differences in adverse outcomes could mainly be explained by older age and clustering of comorbidities in women, a bleedreduction strategy in women with high risk characteristics is warranted in order to improve their outcome. Regardless the choice of antithrombotic strategy, dose adjustment of drugs cleared by kidneys based on GFR estimation is of crucial importance. MDRD and CKD-EPI should be the formulas used for estimation of GFR in STEMI patients
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| 6. |
- Venetsanos, Dimitrios, et al.
(författare)
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Long-term efficacy of drug coated balloons compared with new generation drug-eluting stents for the treatment of de novo coronary artery lesions
- 2018
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Ingår i: Catheterization and Cardiovascular Interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 92:5, s. 317-326
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 Wiley Periodicals, Inc. Background: Studies comparing drug coated balloons (DCB) with new generation drug-eluting stents (nDES) for the treatment of de novo coronary artery lesions are lacking. Methods: From 2009 to 2016, DCB or nDES used for treatment of de novo coronary lesions at our institution were included, in total 1,197 DEB and 6,458 nDES. We evaluated target lesions restenosis (TLR) and definite target lesion thrombosis (TLT). Propensity score modeling were utilized to study adjusted associations between treatment and outcomes. Results: Median follow-up was 901days. DCB patients were older, with higher cardiovascular risk profile. Bailout stenting after DCB was performed in 8% of lesions. The cumulative rate of TLR and TLT was 7.0 vs. 4.9% and 0.2 vs. 0.8% for DCB vs. nDES, respectively. Before adjustment, DCB was associated with a higher risk of TLR [hazard ratio (HR) 1.44; 95% confidence interval (CI) 1.07-1.94] and a non-significantly lower risk of TLT (HR 0.30; 95% CI 0.07-1.24), compared to nDES. In the propensity matched population consisted of 1,197 DCB and 1,197 nDES, treatment with DCB was associated with similar risk for TLR (adjusted HR 1.05; 95% CI 0.72-1.53) but significantly lower risk for TLT (adjusted HR 0.18; 95% CI 0.04-0.82) compared to nDES. Conclusions: Treatment with DCB was associated with a similar risk of TLR and a lower risk of definite TLT compared with nDES. In selected cases, DCB appears as a good alternative to nDES for the treatment of de novo coronary lesions.
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| 7. |
- Venetsanos, Dimitrios, et al.
(författare)
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Pretreatment with ticagrelor may offset additional inhibition of platelet and coagulation activation with bivalirudin compared to heparin during primary percutaneous coronary intervention
- 2018
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 171, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- Background: It remains unknown if bivalirudin compared to heparin confers any additional inhibition of platelet and coagulation activation during primary percutaneous coronary intervention (PPCI) after pretreatment with ticagrelor. Methods: In this substudy of VALIDATE-SWEDEHEART trial, 103 patients pretreated with ticagrelor were randomized before PPCI to heparin or bivalirudin. Blood samples were collected before and 1 and 12 h after PPCI. We measured platelet reactivity (PR) using Multiplate, soluble P-selectin, thrombin-antithrombin complexes (TAT) and prothrombin fragments 1 + 2 (F1 + 2) as markers of platelet and coagulation activation. Results: The median (IQR) time from ticagrelor administration to randomization was 63 (29) vs 60 (24) minutes, p = 0.28. ADP-induced PR did not significantly differ between groups over time (heparin vs bivalirudin, AUC 73 (62) vs 74 (68), p = 0.74, 32 (42) vs 43 (51), p = 0.38, 15 (15) vs 19 (15), p = 0.29, before, 1 and 12 h after PPCI). Soluble P-selectin did not significantly differ between groups. At 1 h TAT significantly increased with bivalirudin (3.0 (1.3) to 4.3 (4.2) ug/L; p < 0.01), but not with UFH (3.1 (2.1) to 3.5 (1.6) ug/L, p = 0.24). F1 + 2 increased in both groups but the rise was numerically higher with bivalirudin (170 (85) to 213 (126) pmol/L vs 168 (118) to 191 (103) pmol/L). At 12 h, a comparable significant increase in thrombin generation was observed in both groups. Conclusion: In patients treated with ticagrelor, we found no major differences between bivalirudin and heparin in platelet aggregation or coagulation markers, which is in agreement with the neutral clinical results of the VALIDATE-SWEDEHEART study.
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| 8. |
- Venetsanos, Dimitrios, et al.
(författare)
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Sex-related response to bivalirudin and unfractionated heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention : A subgroup analysis of the VALIDATE-SWEDEHEART trial
- 2019
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Ingår i: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 8:6, s. 502-509
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients.METHODS: This study was a prespecified analysis of the Bivalirudin versus Heparin in ST-Segment and Non ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days.RESULTS: There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60-1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89-1.26), p for interaction 0.05). The observed difference was primarily due to lower risk of major bleeding (Bleeding Academic Research Consortium definition 2, 3 or 5) associated with bivalirudin in women (8.9% vs 11.8%, hazard ratio 0.74 (0.54-1.01)) but not in men (8.5% vs 7.3%, hazard ratio 1.16 (0.94-1.43) in men, p for interaction 0.02). Conversely, no significant difference in the risk of Bleeding Academic Research Consortium 3 or 5 bleeding, associated with bivalirudin, was found in women 4.5% vs 5.4% (hazard ratio 0.84 (0.54-1.31)) or men 2.9% vs 2.1% (hazard ratio 1.36 (0.93-1.99)). Bleeding Academic Research Consortium 2 bleeding occurred significantly less often in women assigned to bivalirudin than to unfractionated heparin. The risk of death or myocardial infarction did not significantly differ between randomised treatments in men or women.CONCLUSION: In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.
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| 9. |
- Wilander, Henrik, et al.
(författare)
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Nationwide observational study of incidence, management and outcome of spontaneous coronary artery dissection: a report from the Swedish Coronary Angiography and Angioplasty register.
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to conduct a nationwide all comer description of incidence, contemporary management and outcome in Swedish spontaneous coronary artery dissection (SCAD) patients. The incidence of SCAD as well as the management and outcome of these patients is not well described.A nationwide observational study.All patients with SCAD registered in the Swedish Coronary Angiography and Angioplasty Register from 2015 to 2017 were included. The index angiographies of patients with registered SCAD were re-evaluated at each centre to confirm the diagnosis. Patients with non-SCAD myocardial infarction (MI) (n=32 601) were used for comparison.Outcomes included all-cause mortality, reinfarction or acute coronary reangiography.This study found 147 SCAD patients, rendering an incidence of 0.74 per 100 000 per year and a prevalence of 0.43% of all MIs. The average age was 52.9 years, 75.5% were women and 47.6% presented with ST-segment elevation MI. Median follow-up time for major adverse cardiac event was 17.3 months. Percutaneous coronary intervention was attempted in 40.1% of SCAD patients and 30.6% received stent. The use of antithrombotic agents was similar between the groups and there was no difference regarding outcomes, 10.9% vs 13.4%, p=0.75. Mortality was lower in SCAD patients, 2.7% vs 8.0%, p=0.03, whereas SCAD patients more often underwent acute reangiography, 9.5% vs 4.6%, p<0.01.In this nationwide, all comer Swedish study, the overall incidence of SCAD was low, including 25% men which is more and in contrast to previous studies. Compared with non-SCAD MI, SCAD patients were younger, with lower cardiovascular risk burden, yet suffered substantial mortality and morbidity and more frequently underwent acute coronary reangiography.
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