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The effect of digoxin on mortality – a cohort study of patients with atrial fibrillation, heart failure or both
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-93020OAI: oai:DiVA.org:uu-93020DiVA: diva2:166368
Available from: 2005-05-04 Created: 2005-05-04 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Pharmacogenomics of Antihypertensive Treatment & Clinical Pharmacological Studies of Digoxin Treatment
Open this publication in new window or tab >>Pharmacogenomics of Antihypertensive Treatment & Clinical Pharmacological Studies of Digoxin Treatment
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In Part I we found that the CYP2C9 genotype appears to influence the diastolic blood pressure response to the angiotensin II-receptor antagonist irbesartan in patients with hypertension and left ventricular hypertrophy. Those with the *1/*2 genotype (slower metabolism) responded better than those with the *1/*1 genotype (normal metabolism), likely due to a slower elimination of the drug. We further found that a +9/-9 exon 1 polymorphism of the B2 bradykinin receptor gene – shown to affect mRNA expression - appears to influence the regression of left ventricular mass during therapy with irbesartan or the beta-blocker atenolol in the same patients. Subjects with the -9/-9 genotype (higher mRNA expression) had a greater regression than carriers of the +9 allele.

In Part II we found that women on digoxin therapeutic drug monitoring have higher serum digoxin concentrations (SDCs) as compared to men (1.54±0.04 [nmol/L±SE] vs 1.20±0.05 [nmol/L±SE], p<0.001), which could be of importance since an SDC >1.4 nmol/L has been associated with increased mortality. We further found that coadministration of P-glycoprotein inhibitors with digoxin was common (47%) among the same patients, and that the SDC increased in a stepwise fashion with the number of P-glycoprotein inhibitors (20-60%). Lastly, we found that patients admitted to Swedish coronary care units with atrial fibrillation without heart failure and who had been given digoxin had a higher 1-year mortality than those not given digoxin (RR 1.44 [95% CI 1.29-1.60], adjustment made for potential confounders).

In conclusion, Part I represents a further step in the pharmacogenomic prospect of tailoring antihypertensive therapy. Part II indicates that heightened attention to the digoxin-dose is warranted in women, that there is a need for awareness about P-glycoprotein interactions with digoxin, and that long-term therapy with digoxin is an independent risk factor for death among patients with atrial fibrillation without heart failure.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 107 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 36
Keyword
Molecular medicine, pharmacogenomics, irbesartan, atenolol, hypertension, digoxin, RIKS-HIA, atrial fibrillation, heart failure, Molekylärmedicin
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-5782 (URN)91-554-6241-3 (ISBN)
Public defence
2005-05-25, Enghoffsalen, Entrance 50, Uppsala University Hospital, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2005-05-04 Created: 2005-05-04 Last updated: 2009-08-14Bibliographically approved

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