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Invasive treatment of coronary artery disease: Aspects on antithrombotic and percutaneous treatment options
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

The outcome after percutaneous coronary intervention (PCI) has improved considerably thanks to more effective antithrombotic treatment strategies and improved coronary stents. Stent thrombosis (ST) is a rare complication to PCI associated with considerable mortality and morbidity.

The general aim of this thesis was to add real-world evidence for antithrombotic and technical strategies in invasive treatment of coronary artery disease. Five observational studies were performed on a large, unselected, real-world population undergoing PCI. All studies were based on data from the national registry SWEDEHEART.

In 31,258 patients undergoing PCI for ST-elevation myocardial infarction (STEMI), the rate of definite early ST was low (0.84%, n=265) but ST was associated with very high mortality (21%, n=51) at one year.

Among 20,600 patients with STEMI, we compared the outcomes for those treated with heparin and those treated with bivalirudin during PCI. Rates of ST were low and similar with heparin and bivalirudin but all-cause mortality at 30 days and one year was significantly higher with heparin. We found no differences in rates of major bleeding, re-infarction and stroke.

A novel bioresorbable scaffold (Absorb), used in patients undergoing PCI for all indications, was associated with a four- to eightfold higher adjusted rate of definite ST over two years, compared with conventional modern drug-eluting stents (DES). One in four ST events occurred later than one year after PCI. Rates of in-stent restenosis were comparable with Absorb and DES. Suboptimal implantation technique and non-adherence to antiplatelet therapy guidelines was common among patients with bioresorbable scaffold thrombosis.

The novel parenteral and potent platelet inhibitor cangrelor was used nearly exclusively in STEMI (n=899), in early presenters with high-risk, often with cardiac arrest (18%) but was associated with low ST rates and no major bleeding events.

In an unselected population of 65,000 patients undergoing PCI for all indications, the Xience permanent polymer everolimus eluting stent (n=36,600) appears to be safe and effective with low event rates of ST and in-stent restenosis. Compared with a control group of other modern DES (n=167,000) including a high proportion of thinner struts and absorbable polymers, Xience exhibits similar results in all important endpoints.

All studies of this thesis provided important real-world evidence on antithrombotic and technical treatment strategies in invasive management of coronary artery disease.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. , p. 87
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1638
Keywords [en]
PCI, STEMI, stent thrombosis, bivalirudin, heparin, bioresorbable scaffold, cangrelor, drug eluting stent, DES
National Category
Medical and Health Sciences
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:uu:diva-403926ISBN: 978-91-513-0871-5 (print)OAI: oai:DiVA.org:uu-403926DiVA, id: diva2:1391970
Public defence
2020-03-27, H:son-Holmdahlsalen, Ing 100, Akademiska Sjukhuset, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2020-03-05 Created: 2020-02-06 Last updated: 2020-03-05
List of papers
1. Low real-world early stent thrombosis rates in ST-elevation myocardial infarction patients and the use of bivalirudin, heparin alone or glycoprotein IIb/IIIa inhibitor treatment: A nationwide Swedish registry report
Open this publication in new window or tab >>Low real-world early stent thrombosis rates in ST-elevation myocardial infarction patients and the use of bivalirudin, heparin alone or glycoprotein IIb/IIIa inhibitor treatment: A nationwide Swedish registry report
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2016 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 176, p. 78-82Article in journal (Refereed) Published
Abstract [en]

Background In recent studies of primary percutaneous coronary intervention (PCI), bivalirudin compared with heparin has been associated with increased risk of stent thrombosis (ST). Our aim was to describe incidence and outcome of definite, early ST in a large contemporary primary PCI population divided in antithrombotic therapy subgroups. Methods and Results A prospective, observational cohort study of all 31,258 ST-elevation myocardial infarction patients who received a stent in Sweden from January 2007 to July 2014 in the SWEDEHEART registry was conducted. Patients were divided into 3 groups: bivalirudin, heparin alone, or glycoprotein IIb/IIIa inhibitor treated. Primary outcome measure was incidence of definite early ST (within 30 days of PCI). Secondary outcomes included all-cause mortality. Incidence of early ST was low, regardless of bivalirudin, heparin alone, or glycoprotein IIb/IIIa inhibitor treatment (0.84%, 0.94%, and 0.83%, respectively). All-cause mortality at 1 year was 20.7% for all ST patients (n = 265), compared with 9.1% in those without ST (n = 31,286; P < .001). Patients with ST days 2-30 had numerically higher all-cause mortality at 1 year compared with patients with ST days 0-1 (23% vs 16%, P =.20). Conclusion In this real-world observational study of 31,258 ST-elevation myocardial infarction patients, the incidence of early ST was low, regardless of antithrombotic treatment strategy. Early ST was associated with increased mortality. Numerically higher all-cause mortality at 1 year was noted with ST days 2-30 compared with ST days 0-1 post-PCI.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-299048 (URN)10.1016/j.ahj.2016.02.018 (DOI)000377472000014 ()27264223 (PubMedID)
Available from: 2016-07-13 Created: 2016-07-13 Last updated: 2020-02-06Bibliographically approved
2. Unfractionated heparin versus bivalirudin in patients undergoing primary percutaneous coronary intervention: a SWEDEHEART study
Open this publication in new window or tab >>Unfractionated heparin versus bivalirudin in patients undergoing primary percutaneous coronary intervention: a SWEDEHEART study
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2017 (English)In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 12, no 16, p. 2009-2017Article in journal (Refereed) Published
Abstract [en]

Aims: The aim of the stud was to compare outcomes in unfractionated heparin (UM) and bivalirudintreated patients undergoing primary percutaneous coronary intervention (PPCI). Methods and results: This observational study contained 20,612 PPCT patients treated with either GM monotherapv or bivalirudin with or without concomitant UFE. Patients with oral anticoagulant or glycoprotein IIb/IIIa inhibitor (GPI) treatment were excluded. The primary outcome measure was definite early stent thrombosis (Si) that occurred at low and similar rates in UNA only and bivalirudin-treated patients: 0.9% vs. 0.8% (adjusted hazard ratio [HR] 1.08, 95% confidence interval [CI]: 0.7-1.65). All-cause death at 30 days occurred in 6.9% vs. 5.4% of patients (adjusted HR 1.23, 95% Cl: 1.05-1.44) and within 365 days in 12.1% vs. 8.9% (adjusted HR 1.34, 95% CI: 1.19-1.52) in the two groups, respectively. The incidence of major bleeding within 30 days was 0.8% vs. 0.6% (adjusted HR 1.54, 95% CI: 0.97-2.45). The incidence of reinfarction within 365 days and stroke within 30 days was similar between groups. Conclusions: In this large, nationwide observational study we found low and similar rates of early ST in UFH only and bivalirudin-treated patients undergoing primary PCI. Mortality was higher in IJFH compared with bivalirudin-treated patients.

Keywords
adjunctive pharmacotherapy, drug-eluting stent, STEMI, stent thrombosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-320667 (URN)000397598300017 ()28044990 (PubMedID)
Available from: 2017-05-04 Created: 2017-05-04 Last updated: 2020-02-06Bibliographically approved
3. Outcome of percutaneous coronary intervention with the Absorb bioresorbable scaffold: data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
Open this publication in new window or tab >>Outcome of percutaneous coronary intervention with the Absorb bioresorbable scaffold: data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
Show others...
2017 (English)In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 13, no 11, p. 1304-1311, article id EIJ-D-17-00458Article in journal (Refereed) Published
Abstract [en]

Aims: Randomised trials indicate higher rates of stent thrombosis (ST) and target lesion failure (TLF) after percutaneous coronary intervention (PCI) with the Absorb bioresorbable scaffold (BRS) compared with modern drug-eluting stents (DES). We aimed to investigate the outcome of all Swedish patients treated with the Absorb BRS.

Methods and results: The Absorb BRS (n=810) was compared with commonly used modern DES (n=67,909). The main outcome measure was definite ST; mean follow-up was two years. Despite being implanted in a younger, lower-risk population compared with modern DES, the Absorb BRS was associated with a higher crude incidence of definite ST at stent level: 1.5 vs. 0.6%, hazard ratio (HR) 2.38 (95% confidence interval [CI]: 1.34-4.23), adjusted HR 4.34 (95% CI: 2.37-7.94); p<0.001. The patient level adjusted HR was 4.44 (95% CI: 2.25-8.77). Rates of in-stent restenosis were similar for BRS and DES. Non-compliance with dual antiplatelet therapy (DAPT) guidelines was noted in six out of 12 BRS ST events. Three very late ST events occurred with the Absorb BRS.

Conclusions: In this real-world observational study, the Absorb BRS was associated with a significantly higher risk of definite ST compared with modern DES. Non-compliance with DAPT guideline recommendations was common among Absorb definite ST events.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-342850 (URN)10.4244/EIJ-D-17-00458 (DOI)000424327500013 ()28781242 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research Council
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2020-02-06Bibliographically approved
4. Clinical use of cangrelor: nationwide experience from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
Open this publication in new window or tab >>Clinical use of cangrelor: nationwide experience from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)
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2019 (English)In: European Heart Journal - Cardiovascular Pharmacotherapy, ISSN 2055-6837, E-ISSN 2055-6845, Vol. 5, no 3, p. 151-157Article in journal (Refereed) Published
Abstract [en]

Aims This nationwide study aimed to analyse the first 2 years of routine clinical use of cangrelor in all Swedish patients undergoing percutaneous coronary intervention (PCI). Methods and results This observational Swedish Coronary Angiography and Angioplasty Registry (SCAAR) study identified 915 cangrelor-treated patients. As 899 were ST-segment elevation myocardial infarction (STEMI)-patients undergoing primary PCI, we decided to exclude all non-STEMI patients (n=16) from the following analysis. We then identified all primary PCI patients, January 2016 to January 2018 (n=10816). Excluding hospitals without cangrelor use, tailoring time frames from first cangrelor use per hospital, patients treated with cangrelor (n=899) were compared with those without cangrelor treatment (n=4614). A separate analysis was performed for cardiac arrest STEMI patients (n=273). Cangrelor-use in primary PCI varied greatly between hospitals (4-36%, mean 16%). At variance with randomized trials, cangrelor was used nearly exclusively in STEMI, often with cardiac arrest (19%). Cangrelor was combined with ticagrelor in two-thirds of patients, among which >50% was prehospital. Cangrelor was used more frequently in high-risk patients: left main PCI, thrombus aspiration, and cardiac arrest. Despite cangrelor being used in more high-risk patients, crude definite stent thrombosis rates at 30days were low and similar in cangrelor (0.7%) and non-cangrelor treated patients (0.8%). Conclusion Cangrelor was used nearly exclusively in primary PCI STEMI patients, predominantly with ticagrelor. Despite being used in very high-risk patients, often with cardiac arrest, cangrelor treatment was associated with low stent thrombosis rates.

Place, publisher, year, edition, pages
Oxford University Press, 2019
Keywords
Cangrelor, Primary PCI, STEMI, Cardiac arrest
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-394654 (URN)10.1093/ehjcvp/pvz002 (DOI)000484382600005 ()30698669 (PubMedID)
Available from: 2019-10-15 Created: 2019-10-15 Last updated: 2020-02-06Bibliographically approved
5. Outcome of PCI with Xience versus other commonly used modern drug eluting stents: a SCAAR report
Open this publication in new window or tab >>Outcome of PCI with Xience versus other commonly used modern drug eluting stents: a SCAAR report
Show others...
(English)Manuscript (preprint) (Other academic)
Keywords
Drug eluting stent, PCI, outcome
National Category
Medical and Health Sciences Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:uu:diva-402887 (URN)
Available from: 2020-01-21 Created: 2020-01-21 Last updated: 2020-02-06Bibliographically approved

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