Dataset Information

The Pharmacogenomic and Metabolomic Predictors of ACE Inhibitor and Angiotensin II Receptor Blocker Effectiveness and Safety.

ABSTRACT: Hypertension (HTN) is the most common chronic disease in the USA. Hypertensive patients frequently require repeat primary care visits to find an effective drug or drug combination to control their disease. Currently, patients are prescribed drugs for HTN based on race, age, and comorbidities and although the current guidelines are reasonable starting points for prescribing, 50% of hypertensive patients still fail to achieve target blood pressures. Despite numerous strategies to improve compliance, drug effectiveness, and optimization of initial drug choice, effectiveness has remained largely unchanged over the past two decades. Therefore, it is important to pursue alternative strategies to more effectively treat patients and to decrease medical costs. Additional precision medicine work is needed to identify factors associated with effectiveness of commonly used antihypertensive medications. The objective of this manuscript is to present a comprehensive review of the pharmacogenomic and metabolomic factors associated with ACEI and ARB effectiveness and safety.

SUBMITTER: Flaten HK

PROVIDER: S-EPMC5727913 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Pharmacogenomic and Metabolomic Predictors of ACE Inhibitor and Angiotensin II Receptor Blocker Effectiveness and Safety.

Flaten Hania K HK Monte Andrew A AA

Cardiovascular drugs and therapy 20170801 4

Hypertension (HTN) is the most common chronic disease in the USA. Hypertensive patients frequently require repeat primary care visits to find an effective drug or drug combination to control their disease. Currently, patients are prescribed drugs for HTN based on race, age, and comorbidities and although the current guidelines are reasonable starting points for prescribing, 50% of hypertensive patients still fail to achieve target blood pressures. Despite numerous strategies to improve complianc ...[more]

PMID: 28741243

Similar Datasets

Project description:Background:Angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACE-I/ARB) improve outcomes in patients with heart failure and reduced left-ventricular (LV) systolic function. However, these medications can cause a rise in serum creatinine and their benefits in patients with HF accompanied by kidney disease are less certain. Objective:To characterize associations between estimated glomerular filtration rate (eGFR), patterns of ACE-Is and ARBs use, and 1-year survival following hospitalization for heart failure (HF). Design:We formed a retrospective cohort study of patients admitted with HF and followed HF medication prescriptions using the pharmaceutical information network, stratified by discharge eGFR. Setting:Cardiology services in 3 centers in Southern Alberta, Canada. Patients:The study cohort included patients admitted to hospital with a clinical diagnosis of HF. Measurements:eGFR was determined from inpatient laboratory data prior to discharge. Outpatient prescription data prior to and following the index hospitalization was obtained using the Pharmaceutical Information Network of Alberta and survival was determined from provincial vital statistics. Methods:Characteristics of the HF cohort were obtained from the Admissions Module of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. Multivariable Cox proportional hazards models were used to evaluate the association between time-varying ACE-I/ARB use, and mortality, and to test whether eGFR modified this association. Results:Totally, 1404 patients were included. Within the first 3 months following discharge, ACE-I/ARBs were used in 71%, 67%, 62%, and 52% for those with eGFR > 90, 45-89, 30-44, and < 30 mL/min/1.73 m2, respectively, with differences in use persisting after 1 year of follow-up. Patients with eGFR < 45 mL/min/1.73 m2 had significantly lower rates of ACE-I/ARB use following hospitalization. In adjusted models, ACE-I/ARB use following discharge was associated with 25% lower risk of mortality (Hazard Ratio [HR]: 0.75, 95% confidence interval [CI]: 0.61-0.92; P < 0.01), without evidence that this association differed by eGFR (P = 0.75). Limitations:LV function measurements were not available for the cohort. Due to the observation design of the study, treatment-selection bias may be present. Conclusion:Patients with HF and reduced eGFR at time of hospital discharge were less likely to receive ACE-I/ARB despite these medications being associated with lower mortality independent of eGFR. These findings demonstrate the need for further research on strategies for safe use of ACE-I and ARB in patients with HF and kidney disease.

Project description:BackgroundAngiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses.Methods and findingsIn this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs. non-ARB/ACEI (excluding Veterans with compelling indications to reduce confounding by indication) and (B) ARB vs. ACEI among (1) SARS-CoV-2+ outpatients and (2) COVID-19 hospitalized inpatients. The primary outcome was all-cause hospitalization or mortality (outpatients) and all-cause mortality (inpatients). We estimated hazard ratios (HR) using propensity score-weighted Cox regression. Baseline characteristics were well-balanced between exposure groups after weighting. Among outpatients, there were 5.0 and 6.0 primary outcomes per 100 person-months for ARB/ACEI (n = 2,482) vs. non-ARB/ACEI (n = 2,487) users (HR 0.85, 95% confidence interval [CI] 0.73-0.99, median follow-up 87 days). Among outpatients who were ARB (n = 4,877) vs. ACEI (n = 8,704) users, there were 13.2 and 14.8 primary outcomes per 100 person-months (HR 0.91, 95%CI 0.86-0.97, median follow-up 85 days). Among inpatients who were ARB/ACEI (n = 210) vs. non-ARB/ACEI (n = 275) users, there were 3.4 and 2.0 all-cause deaths per 100 person months (HR 1.25, 95%CI 0.30-5.13, median follow-up 30 days). Among inpatients, ARB (n = 1,164) and ACEI (n = 2,014) users had 21.0 vs. 17.7 all-cause deaths, per 100 person-months (HR 1.13, 95%CI 0.93-1.38, median follow-up 30 days).ConclusionsThis observational analysis supports continued ARB or ACEI use for patients already using these medications before SARS-CoV-2 infection. The novel beneficial association observed among outpatients between users of ARBs vs. ACEIs on hospitalization or mortality should be confirmed with randomized trials.

Project description:Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARB-induced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes via systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAE-associated genes (SERPING1, F12, PLG, ANGPT1, and KNG1) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest p-value for an individual variant was found in PLG (rs4252129, p.R523W, p = 0.057, p.adjust > 0.999, Fisher's exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phred-scaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the F12 gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants.

Dataset Information

The Pharmacogenomic and Metabolomic Predictors of ACE Inhibitor and Angiotensin II Receptor Blocker Effectiveness and Safety.

Publications

The Pharmacogenomic and Metabolomic Predictors of ACE Inhibitor and Angiotensin II Receptor Blocker Effectiveness and Safety.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets