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- 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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| 4. |
- Egstrup, Kenneth, et al.
(författare)
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QT Response after a Test Dose and during Maintenance Therapy with AZD1305 in Patients with Atrial Fibrillation: A Double-Blind, Randomized, Placebo-Controlled Trial.
- 2011
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Ingår i: American journal of cardiovascular drugs : drugs, devices, and other interventions. - : Springer Science and Business Media LLC. - 1179-187X. ; 11:3, s. 199-208
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective: AZD1305 is an investigational antiarrhythmic agent that prolongs refractoriness through combined potassium and sodium channel inhibition. This study aimed to explore the utility of a test dose in predicting QT interval corrected according to Fridericia's formula (QTcF) during subsequent maintenance treatment with AZD1305. Methods: This was a randomized, double-blind, parallel-group, placebo-controlled trial carried out at multiple hospital cardiac facilities in Denmark, Norway, Poland, Slovakia, and Sweden. Patients with documented atrial fibrillation (AF) but currently in stable sinus rhythm for ≥2 hours and ≤90 days were eligible for inclusion. Patients were randomized in a 1:1:1 ratio to receive AZD1305 extended-release or matching placebo tablets as follows: group A - test dose 250mg, evening dose 125mg on day 1, maintenance dose 125mg twice daily; group B - test dose 500mg, placebo evening dose, maintenance dose 125mg twice daily; placebo group - placebo test and maintenance dose. Maintenance dosing was for 9 days. QTcF >550ms at any time during the in-patient phase or >500ms after discharge (day 4) were predefined study drug discontinuation criteria. The main outcome measure was the relationship between QTcF following the test dose and during maintenance treatment. Results: Sixty-five patients were randomized (n=21, 22, and 22 in group A, group B, and the placebo group, respectively). AZD1305 dose-dependently increased QTcF. There was a positive, linear correlation between the change in QTcF during the first 6 hours after the test dose and during the maintenance phase. Three patients, all from group B, discontinued treatment on day 1 due to QTcF >550ms. All other patients completed the study without events related to QT prolongation. There was a trend for reduced AF recurrence with AZD1305 compared with placebo. Conclusion: In this exploratory study a test dose predicted the QT response during maintenance treatment with AZD1305 and may thus be employed in further studies. [ClinicalTrials.gov Identifier: NCT00643448].
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- 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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