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- 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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| 2. |
- Herlitz, Johan, 1949, et al.
(författare)
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Low-dose aspirin therapy for cardiovascular prevention: quantification and consequences of poor compliance or discontinuation.
- 2010
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Ingår i: American journal of cardiovascular drugs : drugs, devices, and other interventions. - : Springer Science and Business Media LLC. - 1175-3277 .- 1179-187X. ; 10:2, s. 125-41
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Tidskriftsartikel (refereegranskat)abstract
- Long-term therapy with low-dose aspirin (acetylsalicylic acid; ASA), 75-325 mg, is highly effective for the secondary prevention of cardiovascular (CV) events. For high-CV-risk patients to attain the full benefits of this therapy, it is important that treatment is continuous and that good compliance is maintained over the long term. We aimed to quantify the level of, and investigate the reasons for, patient-driven non-compliance and treatment discontinuation among patients taking low-dose ASA for the prevention of CV events. We therefore performed a systematic search of the PubMed, Embase, and Cochrane databases using the terms 'aspirin' AND 'patient compliance' OR 'withdrawal', with no restrictions on the start date and up to July 2008. A total of 32 studies, summarizing >144 800 patients, were selected from over 400 results for inclusion. Poor compliance (defined differently among the studies included) with low-dose ASA therapy ranged from approximately 10% to over 50%, and patient-initiated discontinuation of therapy occurred in up to 30% of patients. Common predictors of both non-compliance and treatment discontinuation were lower education level, female sex, or a history of depression, diabetes mellitus, or cigarette smoking. Adverse events were cited as the reason for low-dose ASA discontinuation in almost 50% of patients. The findings of this review suggest that poor compliance is common among patients receiving low-dose ASA therapy, placing them at substantial risk of CV events. By addressing barriers to compliance with low-dose ASA therapy, healthcare professionals can improve CV risk management for such patients.
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