Related Experiment Video

Updated: Jul 4, 2026

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice
08:15

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice

Published on: September 17, 2015

Effects of AGTR1 A1166C gene polymorphism in patients with heart failure treated with candesartan

Simon de Denus1, Marcin Zakrzewski-Jakubiak, Marie-Pierre Dubé

  • 1Faculty of Pharmacy, University of Montreal, Montreal Heart Institute, Montreal, QC, Canada.

The Annals of Pharmacotherapy
|July 3, 2008
PubMed

Insights

Genetic variations in the AGTR1 gene may predict how well heart failure patients respond to candesartan, an angiotensin II receptor blocker (ARB). This finding could help personalize ARB therapy for better outcomes.

Area of Science:

  • Cardiology
  • Pharmacogenomics
  • Genetics

Background:

  • Angiotensin II receptor blockers (ARBs) benefit heart failure patients on standard therapy, but predicting individual response is challenging.
  • Previous trials established ARB efficacy, yet patient-specific factors influencing treatment response remain unclear.

Purpose of the Study:

  • To investigate the influence of specific genetic polymorphisms on the hemodynamic, neurohormonal, and anti-inflammatory effects of candesartan.
  • To determine if candidate genes impact treatment response in heart failure patients already receiving an angiotensin-converting enzyme (ACE) inhibitor.

Main Methods:

  • Examined 10 candidate genetic polymorphisms in 31 heart failure patients on ACE inhibitors.
  • Assessed acute (2 weeks) and long-term (24 weeks) changes in blood pressure, NT-proBNP, and hsCRP during candesartan treatment.
  • Utilized analysis of variance (ANOVA) for statistical analysis, adjusting for drug dosage.

Main Results:

  • Patients with the AGTR1 A1166 allele showed significantly greater reductions in systolic and diastolic blood pressure after 2 weeks of candesartan.
  • After 6 months, C1166 allele carriers exhibited a more pronounced decrease in NT-proBNP and hsCRP compared to AA1166 genotype patients.
  • No other significant genetic associations were identified for the evaluated polymorphisms.

Conclusions:

  • The AGTR1 A1166C polymorphism may influence patient response to candesartan in heart failure patients treated with ACE inhibitors.
  • These preliminary findings suggest potential for genotype-guided ARB therapy.
  • Larger population studies are necessary to validate these exploratory results for clinical application.
Abstract

Related Concept Videos

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Heart Failure Drugs: β-Blockers01:22

Heart Failure Drugs: β-Blockers

β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation, vasodilation, and...
Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
Heart Failure V: Medical Management01:30

Heart Failure V: Medical Management

Medical Management of Acute Decompensated Heart Failure (ADHF)The primary goals of therapy for patients hospitalized with acute decompensated heart failure (ADHF) include:Relieving symptomsOptimizing volume statusSupporting oxygenation and ventilationMaintaining cardiac output (CO) and end-organ perfusionIdentifying and addressing the cause of ADHFPreventing complicationsProviding patient education on factors precipitating HF exacerbationPlanning for dischargeOngoing monitoring and assessment...