Phase 3
N=458
Renin-angiotensin-aldosterone System (RAAS), Inflammation, and Post-Operative Atrial Fibrillation (AF)
Atrial Fibrillation
Bottom Line
View on ClinicalTrials.gov: NCT00141778 ↗Enrolled (actual)
458
Serious AEs
4.3%
Results posted
Mar 2013
Primary outcome: Primary: Postoperative Atrial Fibrillation — 27.2; 27.8; 25.9 percentage of patients — p=0.95
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Placebo (Drug); Ramipril (Drug); Spironolactone (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Vanderbilt University
- Primary completion
- Jul 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Postoperative Atrial Fibrillation |
27.2; 27.8; 25.9 | 0.95 |
| SECONDARY Acute Renal Failure |
5.4; 0.7; 0.7 | 0.006 sig |
| SECONDARY Hypotension |
5.4; 10.6; 10.2 | 0.15 |
| SECONDARY Hypokalemia |
11.6; 13.8; 6.8 | 0.14 |
| SECONDARY Time to Tracheal Extubation |
1091.3; 970.1; 576.4 | 0.56 |
| SECONDARY Length of Hospital Stay (Days) |
6.8; 5.7; 5.8 | 0.15 |
| SECONDARY Death |
1.4; 2.0; 0 | 0.38 |
| SECONDARY Stroke |
2.7; 1.3; 2.0 | 0.65 |
| SECONDARY Perioperative Interleukin(IL)-6 Concentrations |
4.7; 4.6; 6.6; 12.0; 20.5; 11.3 | — |
| SECONDARY Perioperative Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations |
19.6; 16.2; 17.3; 19.2; 19.7; 17.3 | — |
| SECONDARY Perioperative C-reactive Protein (CRP) Concentrations |
4.1; 4.3; 3.9; 51.4; 49.9; 64.3 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Undergoing elective valvular heart surgery, coronary artery bypass grafting
- If female, must be postmenopausal for at least 1 year, status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and willing to undergo urine beta-hcg testing prior to drug treatment and throughout the study
Exclusion Criteria
- History of AF other than remote paroxysmal AF
- Ejection fraction less than 30%
- Evidence of coagulopathy (INR greater than 1.7 without warfarin therapy)
- Emergency surgery
- History of ACE inhibitor-induced angioedema
- Low blood pressure (systolic blood pressure less than 100 mmHg and evidence of hypoperfusion)
- Hyperkalemia (potassium level greater than 5.0 milliequivalents (mEq)/L at study entry)
- Impaired kidney function (serum creatinine level greater than 1.6 mg/dl)
- Any underlying or acute disease requiring regular medication that could possibly cause complications or make implementation of the study or interpretation of the study results difficult
- Inability to discontinue current ACE inhibitor, AT1 receptor antagonist, or aldosterone receptor antagonist therapy
- History of alcohol or drug abuse
- Treatment with any investigational drug in the month prior to study entry
- Mental condition that makes it impossible to understand the nature, scope and possible consequences of the study
- Inability to comply with the study procedures (e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study)
- Pregnant or breastfeeding
Data sourced from ClinicalTrials.gov (NCT00141778). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.