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Pharmacogenetic Risk Stratification in Angiotensin-Converting Enzyme Inhibitor-Treated Patients with Congestive Heart
Karl Emil Nelveg-Kristensen1, Majbritt Busk Madsen2, Christian Torp-Pedersen3
1Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark.
Insights
This study found no link between specific genetic markers and outcomes in patients with heart failure treated with angiotensin-converting enzyme inhibitors (ACEIs). Further research is needed to identify effective pharmacogenetic strategies for ACEI therapy.
Area of Science:
- Cardiovascular Medicine
- Pharmacogenetics
- Genomics
Background:
- Limited evidence exists for pharmacogenetic risk stratification in angiotensin-converting enzyme inhibitor (ACEI) treatment.
- Investigated two pharmacogenetic scores (Score A and Score B) in ACEI-treated congestive heart failure (CHF) patients.
- Scores previously predicted ACEI efficacy in ischemic heart disease and hypertension.
Purpose of the Study:
- To assess the predictive value of two pharmacogenetic scores for fatal outcomes in ACEI-treated CHF patients.
- To determine if genetic variations influence treatment response and prognosis in CHF.
Main Methods:
- Included 667 Danish patients with CHF from the Echocardiography and Heart Outcome Study.
- Genotyped patients and categorized them based on pharmacogenetic scores A and B.
- Followed patients for up to 10 years, assessing cardiovascular and all-cause death using cumulative incidence and Cox proportional hazard analyses.
Main Results:
- 80% of the 667 included patients were treated with ACEIs.
- No significant differences in cumulative incidences of cardiovascular death or all-cause death were observed for Score A or Score B.
- Cox proportional hazard analyses showed no significant difference in the risk of cardiovascular or all-cause death between different score categories for both Score A and Score B.
Conclusions:
- No association was found between the analyzed pharmacogenetic scores (Score A and Score B) and fatal outcomes in ACEI-treated patients with CHF.
- The studied genetic markers do not appear to predict outcomes in this patient population.
- Further investigation into other genetic factors or biomarkers may be necessary for personalized ACEI therapy in CHF.
Background:
Evidence for pharmacogenetic risk stratification of angiotensin-converting enzyme inhibitor (ACEI) treatment is limited. Therefore, in a cohort of ACEI-treated patients with congestive heart failure (CHF), we investigated the predictive value of two pharmacogenetic scores that previously were found to predict ACEI efficacy in patients with ischemic heart disease and hypertension, respectively. Score A combined single nucleotide polymorphisms (SNPs) of the angiotensin II receptor type 1 gene (rs275651 and rs5182) and the bradykinin receptor B1 gene (rs12050217). Score B combined SNPs of the angiotensin-converting enzyme gene (rs4343) and ABO blood group genes (rs495828 and rs8176746).
Methods:
Danish patients with CHF enrolled in the previously reported Echocardiography and Heart Outcome Study were included. Subjects were genotyped and categorized according to pharmacogenetic scores A and B of ≤1, 2 and ≥3 each, and followed for up to 10 years. Difference in cumulative incidences of cardiovascular death and all-cause death were assessed by the cumulative incidence estimator. Survival was modeled by Cox proportional hazard analyses.
Results:
We included 667 patients, of whom 80% were treated with ACEIs. Differences in cumulative incidences of cardiovascular death (P = 0.346 and P = 0.486) and all-cause death (P = 0.515 and P = 0.486) were not significant for score A and B, respectively. There was no difference in risk of cardiovascular death or all-cause death between subjects with score A ≤1 vs. 2 (HR 1.03 [95% CI 0.79-1.34] and HR 1.11 [95% CI 0.88-1.42]), score A ≤1 vs. ≥3 (HR 0.80 [95% CI 0.59-1.08] and HR 0.91 [95% CI 0.70-1.20]), score B ≤1 vs. 2 (HR 1.02 [95% CI 0.78-1.32] and HR 0.98 [95% CI 0.77-1.24]), and score B ≤1 vs. ≥3 (HR 1.03 [95% CI 0.75-1.41] and HR 1.05 [95% CI 0.79-1.40]), respectively.
Conclusions:
We found no association between either of the analyzed pharmacogenetic scores and fatal outcomes in ACEI-treated patients with CHF.
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