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- 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. |
- Sultanian, Pedram, et al.
(författare)
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Cardiac arrest in COVID-19 : characteristics and outcomes of in- and out-of-hospital cardiac arrest. A report from the Swedish Registry for Cardiopulmonary Resuscitation.
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 42:11, s. 1094-1106
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the characteristics and outcome among cardiac arrest cases with COVID-19 and differences between the pre-pandemic and the pandemic period in out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA).METHOD AND RESULTS: We included all patients reported to the Swedish Registry for Cardiopulmonary Resuscitation from 1 January to 20 July 2020. We defined 16 March 2020 as the start of the pandemic. We assessed overall and 30-day mortality using Cox regression and logistic regression, respectively. We studied 1946 cases of OHCA and 1080 cases of IHCA during the entire period. During the pandemic, 88 (10.0%) of OHCAs and 72 (16.1%) of IHCAs had ongoing COVID-19. With regards to OHCA during the pandemic, the odds ratio for 30-day mortality in COVID-19-positive cases, compared with COVID-19-negative cases, was 3.40 [95% confidence interval (CI) 1.31-11.64]; the corresponding hazard ratio was 1.45 (95% CI 1.13-1.85). Adjusted 30-day survival was 4.7% for patients with COVID-19, 9.8% for patients without COVID-19, and 7.6% in the pre-pandemic period. With regards to IHCA during the pandemic, the odds ratio for COVID-19-positive cases, compared with COVID-19-negative cases, was 2.27 (95% CI 1.27-4.24); the corresponding hazard ratio was 1.48 (95% CI 1.09-2.01). Adjusted 30-day survival was 23.1% in COVID-19-positive cases, 39.5% in patients without COVID-19, and 36.4% in the pre-pandemic period.CONCLUSION: During the pandemic phase, COVID-19 was involved in at least 10% of all OHCAs and 16% of IHCAs, and, among COVID-19 cases, 30-day mortality was increased 3.4-fold in OHCA and 2.3-fold in IHCA.
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| 3. |
- Aunes-Jansson, Maria, et al.
(författare)
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Decrease of the atrial fibrillatory rate, increased organization of the atrial rhythm and termination of atrial fibrillation by AZD7009
- 2013
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Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 46:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Background: The atrial fibrillatory rate (APR), on AZD7009 as compared to placebo, was investigated as a potential biomarker for electrophysiological effect in early antiarrhythmic drug development. Methods: Patients with permanent AF received infusions of AZD7009 and placebo in an exploratory two-way, single-blind, randomized cross-over study. The ECG was continuously recorded, and following QRST cancellation the APR, its standard deviation (SD), the exponential decay and the atrial electrogram amplitude were determined as 3-min averages. Results: The mean APR rapidly decreased by 43% from baseline (394 +/- 38 to 225 +/- 61 fibrillations/min, p = 0.0003) on AZD7009, but not on placebo. The SD of the AFR and the exponential decay decreased in parallel. In 2 of 8 patients, termination of AF occurred after the APR had decreased by 58% and 53%, respectively. Conclusions: The APR may potentially serve as a biomarker of electrophysiological effects in early evaluation of rhythm control agents. (C) 2013 Elsevier Inc. All rights reserved.
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| 6. |
- Johansson, Susanne, et al.
(författare)
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In Silico Predictions and In Vivo Results of Drug-Drug Interactions by Ketoconazole and Verapamil on AZD1305, a Combined Ion Channel Blocker and a Sensitive CYP3A4 Substrate.
- 2016
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Ingår i: Clinical pharmacology in drug development. - : Wiley. - 2160-7648 .- 2160-763X. ; 5:5, s. 364-73
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Tidskriftsartikel (refereegranskat)abstract
- The objectives were to estimate and compare, in silico and in vivo, the effects of a strong and a moderate CYP3A4 inhibitor on AZD1305 pharmacokinetics. In silico, simulations were performed with the computer software Simcyp, and the predicted outcome was compared with the results observed in healthy male subjects. In silico, the geometric mean plasma exposure of AZD1305 + ketoconazole showed a 7.1-fold higher AUC and a 4.4-fold higher Cmax compared with AZD1305 alone. Coadministration with verapamil gave a 1.9-fold higher AUC and a 1.7-fold higher Cmax compared with AZD1305 alone. In vivo, the plasma exposure of AZD1305 + ketoconazole showed a 7.7-fold higher AUC and a 4.8 -fold higher Cmax compared with AZD1305 alone. Coadministration with verapamil gave a 2.2-fold higher AUC and a 2.0-fold higher Cmax compared with AZD1305 alone. The mean maximum QTcF increase from baseline was 407, 487, and 437 milliseconds for AZD1305, alone and in combination with verapamil or ketoconazole, respectively. Simcyp predicted the effects of ketoconazole and verapamil on the sensitive CYP3A4 substrate AZD1305 pharmacokinetics well. Both the in vivo study and the Simcyp predictions suggest a contraindication for strong CYP3A4 inhibitors and AZD1305 when given in combination.
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| 7. |
- Johnston, S. Claiborne, et al.
(författare)
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Ischemic Benefit and Hemorrhage Risk of Ticagrelor-Aspirin Versus Aspirin in Patients With Acute Ischemic Stroke or Transient Ischemic Attack
- 2021
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Ingår i: Stroke. - : Wolters Kluwer. - 0039-2499 .- 1524-4628. ; 52:11, s. 3482-3489
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack, the THALES trial (Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and Aspirin for Prevention of Stroke and Death) demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit. Methods: In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk transient ischemic attack, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or nonhemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these 2 end points. Results: In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19% [95% CI, 0.31%-2.07%]). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29% [95% CI, 0.10%-0.48%]). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97% [95% CI, 0.08%-1.87%]). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups. Conclusions: In patients with mild-moderate ischemic stroke or high-risk transient ischemic attack, ischemic benefits of 30-day treatment with ticagrelor-aspirin outweigh risks of hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03354429.
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| 9. |
- Lip, Gregory Y. H., et al.
(författare)
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Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: A Phase II study of AZD0837 in patients who are appropriate for but unable or unwilling to take vitamin K antagonist therapy
- 2011
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848. ; 127:2, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- Background: Some patients with atrial fibrillation (AF) cannot be treated with vitamin K antagonists (VKAs) and will therefore not receive effective thromboprophylaxis. The primary objective of the present Phase II trial (NCT00623779) was to assess the feasibility of conducting a study with a novel oral anticoagulant, the direct thrombin inhibitor AZD0837, in patients with AF unable or unwilling to take warfarin, by evaluation of dropout rates and compliance. Methods: Patients were randomised to receive AZD0837 extended-release tablets 150 mg (n = 43) or 300 mg (n = 42) once daily, or standard therapy (no treatment, aspirin 75-325 mg or clopidogrel 75 mg once daily; n = 46) for a median treatment duration of 6 weeks. Results: Reasons for patients not being treated with warfarin were: refusal or permanent cessation decided by the patient (64.8%), inability to keep international normalised ratio 2-3 over a 3-month period (23.2%), physician assessment that VKA was inappropriate (20.4%) and warfarin allergy (2.8%). Compliance with treatment (mean +/- SD) was 97.0 +/- 16.5% for AZD0837 150 mg and 99.8 +/- 11.4% for 300 mg. Compliance with study visits was high (mean 93-98%). The numbers of dropouts were four, six and three, whilst minor or clinically significant minor bleeds were reported in zero, five and two patients in the AZD0837 150 mg, 300 mg and standard-therapy groups, respectively. No major bleeds were reported. Both doses of AZD0837 reduced levels of fibrin D-dimer and prolonged activated partial thromboplastin time, ecarin clotting time and thrombin clotting time. Conclusions: AZD0837 had a good safety profile during this study, including a low incidence of bleeding events, with effective anticoagulation on pharmacodynamic parameters. A larger study in AF patients unable or unwilling to take warfarin is feasible, as judged by compliance and dropout rates. (C) 2010 Elsevier Ltd. All rights reserved.
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| 10. |
- Tjäderborn, Micaela, et al.
(författare)
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Prediction of drug-related morphological changes of the T wave.
- 2010
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Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 44:4, s. 215-22
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To describe the characteristics of patients presenting with morphological T wave changes that lead to measurement difficulties, and to identify possible predictors of such changes at baseline and early after start of treatment. DESIGN: ECGs from 145 patients receiving a combined potassium and sodium channel blocking agent for conversion of atrial fibrillation (AF), underwent semiautomatic analysis in a digitalized high-precision analysis program. In 15 patients, one or more ECGs were identified as difficult to interpret due to morphological T wave changes. They were compared with the 130 patients without such changes. RESULTS: A history of cardiac failure (p=0.027), a smaller left atrial area (p=0.010) and a longer QT(tang) minus QT(top) interval (p<0.001) at baseline was significantly more frequent as compared to the controls. Identified patients also had somewhat longer baseline QT interval duration (median QT(cB) 432 vs. 408 ms, N.S.) and a larger proportion of them were females (47% vs. 27%, N.S.). After start of infusion the QT(cB) became significantly longer in identified patients than in controls (p=0.012). CONCLUSIONS: Independent predictors of subsequent morphological changes were found at baseline and shortly after start of treatment, and may be of use to identify individuals with a reduced repolarization reserve.
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