Impact of High-dose Pretreatment of Rosuvastatin in Patients With Acute Coronary Syndrome Following Off-pump Coronary Artery Bypass: Results From the HIROP-ACS (HIgh-dose Pretreatment of Rosuvastatin During Off-Pump Coronary Bypass in Acute Coronary Syndrome) Study

Periprocedural treatment with high-dose statins is known to have cardioprotective and pleiotropic effects, such as anti-thrombotic and anti-inflammatory actions.

-Objective: to determine whether preoperative rosuvastatin loading is independently associated with reduced myocardial ischemia and clinical outcomes in patients with stable angina undergoing isolated off-pump coronary bypass (OPCAB) in patients with acute coronary syndrome.

Study design

• Prospective, double-blinded, single-center study of each 117 subjects enrolled
• Subjects with acute coronary syndrome who meet all inclusion and exclusion criteria will be enrolled preoperatively.
• Eligible subjects will be randomized 1:1 to A) High-dose rosuvastatin (n=117) vs. B) Placebo (n=117).
• The amount of preoperative administration of high-dose rosuvastatin will be 60mg of a total
• All subjects will undergo OPCAB procedure. - The primary and secondary endpoints will be compared at 30 days and 2 years postoperatively between two groups

Study Overview

• Status: Completed
• Conditions: A Total of 234 Patients With Acute Coronary Syndrome Who Will Undergo OPCAB.
• Intervention / Treatment: Drug: Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Division of Cardiovascular Surgery, Severance Cardiovascular Hospital , Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The presence of acute coronary syndrome, including unstable angina, acute non-ST elevation myocardial infarction
• Age of 19 years or older
• A need for isolated surgical myocardial revascularization
• Patients with signed informed consent

Exclusion Criteria:

• Patients with combined surgery with coronary bypass grafting
• On-pump conversion
• Patients with any increase in liver enzymes
• Patients with history of liver or muscle disease.
• Patients with moderate renal dysfunction (creatinine>2.0mg/dl) or need for dialysis
• Re-do surgery
• Urgent/emergent surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin group	Drug: Rosuvastatin; Patients will be randomized in a ratio of 1:1 to A) High-dose rosuvastatin vs. B) Placebo. A) Rosuvastatin group : Administration of 40mg of rosuvastatin PO 12 hours before surgery and 20mg of rosuvastatin PO 2hours before surgery and 10mg of rosuvastatin PO daily at postoperative period. B) Placebo group : Administration of placebo at 12 hours and 2 hours before surgery and 10mg of rosuvastatin PO daily at postoperative period.
Placebo Comparator: Placebo group	Drug: Rosuvastatin; Patients will be randomized in a ratio of 1:1 to A) High-dose rosuvastatin vs. B) Placebo. A) Rosuvastatin group : Administration of 40mg of rosuvastatin PO 12 hours before surgery and 20mg of rosuvastatin PO 2hours before surgery and 10mg of rosuvastatin PO daily at postoperative period. B) Placebo group : Administration of placebo at 12 hours and 2 hours before surgery and 10mg of rosuvastatin PO daily at postoperative period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac events (MACEs)	Major adverse cardiac events (MACEs), which include the following: death from all causes, non-fatal myocardial infarction (MI), and repeat revascularization by percutaneous intervention or bypass surgery within 30 days after OPCAB.	30 days after OPCAB

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The degree of myocardial ischemia and inflammatory	The degree of myocardial ischemia and inflammatory changes assessed by blood sampling and specific tests (CK-MB, Troponin T, ESR, CRP, hs-CRP) at the early period after OPCAB.	immediate, 24 hours, 48 hours, 72 hours, 7 days after OPCAB

Other Outcome Measures

Outcome Measure	Time Frame
Incidence of postoperative atrial arrhythmia including atrial fibrillation and atrial flutter	30 days after OPCAB
Incidence of postoperative renal impairment or a need for dialysis	30 days after OPCAB
Late MACEs 2 years after OPCAB	2 years after OPCAB

Collaborators and Investigators

• Sponsor: Yonsei University

Publications and helpful links

General Publications

• Patti G, Pasceri V, Colonna G, Miglionico M, Fischetti D, Sardella G, Montinaro A, Di Sciascio G. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol. 2007 Mar 27;49(12):1272-8. doi: 10.1016/j.jacc.2007.02.025.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: October 23, 2013
• First Submitted That Met QC Criteria: October 28, 2013
• First Posted (Estimate): October 29, 2013

Study Record Updates

• Last Update Posted (Estimate): November 1, 2013
• Last Update Submitted That Met QC Criteria: October 31, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Statin, coronary artery bypass grafting, off-pump surgery, acute coronary syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: 4-2007-0253