Comparative effects of angiotensin receptor blockade and ACE inhibition on the fibrinolytic and inflammatory responses to cardiopulmonary bypass

Clin Pharmacol Ther. 2012 Jun;91(6):1065-73. doi: 10.1038/clpt.2011.356.

Abstract

The effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor blockade (ARB) on fibrinolysis and inflammation after cardiopulmonary bypass (CPB) are uncertain. This study tested the hypothesis that ACE inhibition enhances fibrinolysis and inflammation to a greater extent than ARB in patients undergoing CPB. One week to 5 days before surgery, patients were randomized to ramipril 5 mg/day, candesartan 16 mg/day, or placebo. ACE inhibition increased intraoperative bradykinin and tissue-type plasminogen activator (t-PA ) concentrations as compared to AR B. Both ACE inhibition and AR B decreased the need for plasma transfusion relative to placebo, but only ACE inhibition decreased the duration of hospital stay. Neither ACE inhibition nor AR B significantly affected concentrations of plasminogen activator inhibitor-1 (PAI -1), interleukin (IL )-6, IL -8, or IL -10. ACE inhibition enhanced intraoperative fibrinolysis without increasing the likelihood of red-cell transfusion. By contrast, neither ACE inhibition nor ARB affected the inflammatory response. ACE inhibitors and ARBs may be safely continued until the day of surgery.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Biphenyl Compounds
  • Blood Transfusion
  • Bradykinin / metabolism
  • Cardiopulmonary Bypass / adverse effects*
  • Endpoint Determination
  • Female
  • Fibrinolysis / drug effects*
  • Hematocrit
  • Hospital Mortality
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Interleukins / metabolism
  • Length of Stay
  • Male
  • Middle Aged
  • Monitoring, Intraoperative
  • Perioperative Care
  • Postoperative Complications / epidemiology
  • Ramipril / therapeutic use*
  • Tetrazoles / therapeutic use*
  • Treatment Outcome

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Biphenyl Compounds
  • Interleukins
  • Tetrazoles
  • Ramipril
  • candesartan
  • Bradykinin