Can Dipyridamole Induce Protection Against Ischemia and Reperfusion Injury in Patients Undergoing Elective Coronary Artery Bypass Grafting (CABG)?

Radboud University Medical Center

Status and phase

Completed

Phase 4

Conditions

Ischemic Heart Disease

Cardiovascular Disease

Treatments

Drug: placebo

Drug: Dipyridamole

Study type

Interventional

Funder types

Other

Identifiers

NCT01295567

dipy-cabg

2009-014299-22 (EudraCT Number)

Details and patient eligibility

About

Rationale:

Due to western lifestyle human coronary arteries are prone to develop atherosclerotic plaques. Hence the heart is an important target organ for atherothrombotic complications: myocardial ischemia, arrhythmias, myocardial infarction and heart failure. To alleviate symptoms and decrease mortality in these patients, myocardial revascularisation is recommended. Coronary artery bypass grafting (CABG) is indicated in patients with severe atherosclerotic disease of all three coronary arteries or the left main stem coronary artery. Cardiac ischemia and reperfusion injury during CABG is inevitable and jointly accountable for complications that occur after CABG (e.g. death, myocardial infarction, arrhythmias, stroke, or renal complications). Dipyridamole has been shown to reduce ischemia reperfusion injury in healthy volunteers using an intermediate endpoint and may prevent cardiovascular death or event in secondary prevention after cerebrovascular disease. The investigators hypothesise that oral pre-treatment with dipyridamole can increase cardiac tissue tolerance against ischemia and reperfusion injury due to CABG. The investigators expect lower troponin-I release in patients who were pretreated with dipyridamole.

Objective: To study the effect of oral pretreatment with dipyridamole on high sensitivity (HS)-troponin-I release after CABG. Secondary objectives are whether oral pretreatment with dipyridamole reduces postoperative CABG arrhythmias, prolonged inotropic support, and duration of Intensive Care-stay. Further secondary endpoints are the effects of dipyridamole pretreatment on renal injury and post-ischemic recovery of contractile function (measured ex-vivo).

Hypothesis:

The investigators hypothesize that oral pre-treatment with dipyridamole can increase cardiac tissue tolerance against ischemia and reperfusion injury. The investigators expect lower HS-troponin-I release in patients who were pretreated with dipyridamole. Additionally the investigators expect the incidence of arrhythmias, need for prolonged inotropic support (longer than 24 hours postoperative) to be decreased in pretreated patients.

Enrollment

95 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Acceptation for CABG in RUNMC
Informed consent

Exclusion criteria

Recent myocardial infarction (STEMI or non-STEMI), during two weeks prior to inclusion
Asthma
Use of insulin
Use of sulfonylurea derivates (e.g. glibenclamide, tolbutamide, gliclazide, glimepiride)
Use of metformin
Use of oral corticosteroids
Use of dipyridamole
Use of clopidogrel within 8 days prior to scheduled CABG surgery
Chronic use of Non Steroid Anti-Inflammatory Drugs (NSAIDs)
Off-pump surgery