uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
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)
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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 36
Molecular medicine, pharmacogenomics, irbesartan, atenolol, hypertension, digoxin, RIKS-HIA, atrial fibrillation, heart failure, Molekylärmedicin
National Category
Medical Genetics
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)
Available from: 2005-05-04 Created: 2005-05-04 Last updated: 2009-08-14Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Medical Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 161 hits
ReferencesLink to record
Permanent link

Direct link