Use of ivabradine and atorvastatin in emergent orthopedic lower limb surgery and computed tomography coronary plaque imaging and novel biomarkers of cardiovascular stress and lipid metabolism for the study and prevention of perioperative myocardial infarction: study protocol for a randomized controlled trial.

Background: The incidence of perioperative myocardial infarction (PMI) globally is known to be around 2 to 3% and can prolong hospitalization, increased morbidity and mortality. Little is known about the pathophysiology and risk factors for PMI. We investigate the presence of elevated novel cardiac markers and preoperative coronary artery plaque through contemporary laboratory techniques to determine the correlation with PMI, as well as studying ivabradine and atorvastatin as protective pharmacotherapies against PMI in the context of orthopedic surgery.

Methods/design: We aim to enroll 200 patients aged above 60 years who suffer from neck of femur fracture requiring surgery. Patients will be randomized to four arms (no study drugs, atorvastatin only, ivabradine only and ivabradine and atorvastatin). Our primary outcome is incidence of PMI. All patients will receive an electrocardiogram, cardiac echocardiography, measurement of novel cardiac biomarkers and computed tomography (CT) coronary angiography. A telephone interview post discharge will be conducted at 30 days, 60 days and 1 year.

Discussion: We postulate that ivabradine and atorvastatin will reduce the rate and magnitude of PMI following surgery by reducing heart rate and attenuating catecholamine-induced tachycardia postoperatively. Secondly, we postulate that postoperative reduction in heart rate and catecholamine-induced tachycardia with ivabradine will correlate with a reduction in cardiovascular novel biomarkers which will reduce atrial stretch and postoperative incidence of arrhythmia. We aim to demonstrate that treatment with ivabradine and atorvastatin will cause a reduction in the incidence and magnitude of PMI, the benefit of which is derived primarily in patients with greater atherosclerotic burden as measured by higher CT coronary calcium scores.

Trial Registration: This study protocol has been listed in the Australia New Zealand Clinical Trial Registry (registration number: ACTRN12612000340831) on 23 March 2012.