Renin-angiotensin-aldosterone System (RAAS), Inflammation, and Post-Operative Atrial Fibrillation (AF)
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation; Inflammation
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Atrial fibrillation (AF) is the most prevalent, sustained type of irregular heartbeat and
      affects over 2 million Americans. Post-operative AF, which leads to significant morbidity and
      a prolonged hospital stay, complicates 20% to 40% of cardiopulmonary bypass (CPB) surgical
      procedures. While recent studies indicate that interruption of the
      renin-angiotensin-aldosterone system by either angiotensin-converting enzyme (ACE) inhibition
      or AT1 receptor antagonism decreases the incidence of AF following a heart attack or
      cardioversion (electric shock to the heart), its effect on the incidence of post-operative AF
      has not been throughly studied. Studies in both animals and humans suggest that
      inflammation-induced atrial remodeling plays an important role in the cause of AF. Recent
      studies also provide evidence that activation of the renin-angiotensin-aldosterone system
      induces inflammation, myocyte injury, proarrhythmic electrical remodeling, and fibrosis
      through aldosterone.
    

Detailed description: 
      AF is the most prevalent, sustained type of irregular heartbeat and affects over 2 million
      Americans. Post-operative atrial fibrillation(AF), which leads to significant morbidity and a
      prolonged hospital stay, complicates 20% to 40% of CPB surgical procedures. While recent
      studies indicate that interruption of the renin-angiotensin-aldosterone system by either
      angiotensin-converting enzyme(ACE) inhibition or angiotensin II subtype 1 (AT1) receptor
      antagonism decreases the incidence of AF following a heart attack or cardioversion (electric
      shock to the heart), its effect on the incidence of post-operative AF has not been throughly
      studied. Studies in both animals and humans suggest that inflammation-induced atrial
      remodeling plays an important role in the cause of AF. Recent studies also provide evidence
      that activation of the renin-angiotensin-aldosterone system induces inflammation, myocyte
      injury, proarrhythmic electrical remodeling, and fibrosis through aldosterone.

      This study will evaluate the effectiveness of ACE inhibition and aldosterone receptor
      antagonism at decreasing inflammation and AF following cardiopulmonary bypass (CPB) surgery.
    

Intervention name(s): Placebo; Ramipril; Spironolactone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Matching placebo taken once a day; Taken orally, once a day; Taken orally, once a day
Other intervention name(s): Placebo tablet; Angiotensin-converting enzyme inhibitor; Mineralocorticoid Receptor Antagonist
Intervention MeSH terms: Ramipril; Spironolactone; Mineralocorticoid Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Enzyme Inhibitors; Mineralocorticoids
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: atrial fibrillation; cardiac surgery