| 1. |
- Bhatt, Deepak L., et al.
(författare)
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Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
- 2019
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
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Tidskriftsartikel (refereegranskat)abstract
- In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
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| 2. |
- Govsyeyev, Nicholas, et al.
(författare)
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Etiology and outcomes of amputation in patients with peripheral artery disease in the EUCLID trial
- 2022
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Ingår i: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 75:2, s. 660-670e3
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Amputation remains a frequent and feared outcome in patients with peripheral artery disease (PAD). Although typically characterized as major or minor on the extent of tissue loss, the etiologies and outcomes after amputation by extent are not well-understood. In addition, emerging data suggest that the drivers and outcomes of amputation in patients with PAD may differ in those with and without diabetes mellitus (DM).Methods: The EUCLID trial randomized 13,885 patients with symptomatic PAD, including 5345 with concomitant diabetes, to ticagrelor or clopidogrel and followed them for long-term outcomes. Amputations were prospectively reported by trial investigators. Their primary and contributing drivers were adjudicated using safety data, including infection, ischemia, or multifactorial etiologies. Outcomes following major and minor amputations were analyzed, including recurrent amputation, major adverse limb events, adverse cardiovascular events, and mortality. Multivariable logistic regression models were used to identify independent predictors of minor amputations. Analyses were performed overall and stratified by the presence or absence of DM at baseline.Results: Of the patients randomized, 398 (2.9%) underwent at least one lower extremity nontraumatic amputation, for a total of 511 amputations (255 major and 256 minor) over a median of 30 months. A history of minor amputation was the strongest independent predictor for a subsequent minor amputation (odds ratio, 7.29; 95% confidence interval, 5.17-10.30; P <.001) followed by comorbid DM (odds ratio, 4.60; 95% confidence interval, 3.16-6.69; P <.001). Compared with patients who had a major amputation, those with a minor amputation had similar rates of subsequent major amputation (12.2% vs 13.6%), major adverse limb events (15.1% vs 14.9%), and major adverse cardiovascular events (17.6% vs 16.3%). Ischemia alone was the primary driver of amputation (51%), followed by infection alone (27%), and multifactorial etiologies (22%); however, infection was the most frequent driver in those with DM (58%) but not in those without DM (15%).Conclusions: Outcomes after amputation remain poor regardless of whether they are categorized as major or minor. The pattern of amputation drivers in PAD differs by history of DM, with infection being the dominant etiology in those with DM and ischemia in those without DM. Greater focus is needed on the prognostic importance of minor amputation and of the multifactorial etiologies of amputation in PAD. Nomenclature with anatomical description of amputations and eliminating terms "major" or "minor" would seem appropriate.
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| 3. |
- Hess, Connie N., et al.
(författare)
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A Structured Review of Antithrombotic Therapy in Peripheral Artery Disease with a Focus on Revascularization : A TASC (InterSociety Consensus for the Management of Peripheral Artery Disease) Initiative
- 2017
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Ingår i: Circulation. - 0009-7322. ; 135:25, s. 2534-2555
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Forskningsöversikt (refereegranskat)abstract
- Peripheral artery disease affects >200 million people worldwide and is associated with significant limb and cardiovascular morbidity and mortality. Limb revascularization is recommended to improve function and quality of life for symptomatic patients with peripheral artery disease with intermittent claudication who have not responded to medical treatment. For patients with critical limb ischemia, the goals of revascularization are to relieve pain, help wound healing, and prevent limb loss. The baseline risk of cardiovascular and limb-related events demonstrated among patients with stable peripheral artery disease is elevated after revascularization and related to atherothrombosis and restenosis. Both of these processes involve platelet activation and the coagulation cascade, forming the basis for the use of antiplatelet and anticoagulant therapies to optimize procedural success and reduce postprocedural cardiovascular risk. Unfortunately, few high-quality, randomized data to support use of these therapies after peripheral artery disease revascularization exist, and much of the rationale for the use of antiplatelet agents after endovascular peripheral revascularization is extrapolated from percutaneous coronary intervention literature. Consequently, guideline recommendations for antithrombotic therapy after lower limb revascularization are inconsistent and not always evidence-based. In this context, the purpose of this structured review is to assess the available randomized data for antithrombotic therapy after peripheral arterial revascularization, with a focus on clinical trial design issues that may affect interpretation of study results, and highlight areas that require further investigation.
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| 4. |
- Hiatt, William R, et al.
(författare)
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Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease
- 2017
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Ingår i: The New England journal of medicine. - 0028-4793 .- 1533-4406. ; 376, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease.METHODS: In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months.RESULTS: The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49).CONCLUSIONS: In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).
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| 8. |
- Norgren, Lars, et al.
(författare)
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Outcomes of Patients with Critical Limb Ischaemia in the EUCLID Trial
- 2018
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 55:1, s. 109-117
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Critical limb ischaemia (CLI) implies an increased risk of cardiovascular morbidity and mortality, and the optimal antithrombotic treatment is not established.Design, Materials, Methods: The EUCLID trial investigated the effect of monotherapy with ticagrelor versus clopidogrel in 13,885 patients with peripheral artery disease (PAD); the primary endpoint was cardiovascular death, myocardial infarction, or ischaemic stroke. Patients planned for revascularisation or amputation within 3 months, were excluded. This analysis focuses on the subgroup with CLI, defined by rest pain (58.8%), major (9.0%) or minor (32.2%) tissue loss.Results: In EUCLID, 643 patients (4.6%) had CLI at baseline. Diabetes mellitus was more common in the CLI group, while coronary disease, carotid disease, and hypertension were more common in the non-CLI group. A majority of CLI patients (62.1%) had only lower extremity PAD. In patients enrolled on the ankle brachial index (ABI) criteria, ABI was 0.55 +/- 0.21 (mean +/- SD) for those with CLI versus 0.63 +/- 0.15 for those without CLI. The primary efficacy endpoint significantly increased among patients with CLI compared with those without CLI with a rate of 8.85 versus 4.28/100 patient years (adjusted for baseline characteristics hazard ratio [HR] 1.43 [95% CI 1.16-1.76]; p = 0.0009). When acute limb ischaemia requiring hospitalisation was added to the model, significant differences remained (adjusted HR 1.38, [95% CI 1.13-1.69]; p = 0.0016). The 1 year mortality was 8.9%. A trend towards increased lower limb revascularisation among those with CLI was observed. Bleeding (TIMI major, fatal, intracranial) did not differ between those with and without CLI.Conclusions: Nearly 5% of patients enrolled in EUCLID had CLI at baseline. Milder forms of CLI dominated, a result of the trial design. Patients with CLI had a significantly higher rate of cardiovascular mortality and morbidity versus those without CLI. Further efforts are required to reduce the risk of cardiovascular events in PAD, especially in patients with CLI.
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| 9. |
- Norgren, Lars, et al.
(författare)
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TASC II section F on revascularization in PAD
- 2007
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Ingår i: Journal of Endovascular Therapy. - : SAGE Publications. - 1526-6028 .- 1545-1550. ; 14:5, s. 743-744
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Norgren, Lars, et al.
(författare)
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Why TASC II?
- 2007
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Ingår i: Vascular Medicine. - London : Arnold. - 1358-863X .- 1477-0377. ; 12:4, s. 327-
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Tidskriftsartikel (refereegranskat)
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