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      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


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          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.


          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.


          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.

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              Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.

              Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results. This randomised controlled trial, done in 190 hospitals in 23 countries, was designed to investigate the effects of perioperative beta blockers. We randomly assigned 8351 patients with, or at risk of, atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate (n=4174) or placebo (n=4177), by a computerised randomisation phone service. Study treatment was started 2-4 h before surgery and continued for 30 days. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00182039. All 8351 patients were included in analyses; 8331 (99.8%) patients completed the 30-day follow-up. Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint (244 [5.8%] patients in the metoprolol group vs 290 [6.9%] in the placebo group; hazard ratio 0.84, 95% CI 0.70-0.99; p=0.0399). Fewer patients in the metoprolol group than in the placebo group had a myocardial infarction (176 [4.2%] vs 239 [5.7%] patients; 0.73, 0.60-0.89; p=0.0017). However, there were more deaths in the metoprolol group than in the placebo group (129 [3.1%] vs 97 [2.3%] patients; 1.33, 1.03-1.74; p=0.0317). More patients in the metoprolol group than in the placebo group had a stroke (41 [1.0%] vs 19 [0.5%] patients; 2.17, 1.26-3.74; p=0.0053). Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm, and the importance and need for large randomised trials in the perioperative setting. Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol.

                Author and article information

                BioMed Central (London )
                7 September 2014
                7 September 2014
                : 15
                : 1
                [ ]Department of Cardiology, The Northern Hospital, 185 Cooper Street, Epping, 3076 VIC Australia
                [ ]Department of Medicine, University of Melbourne, Grattan St, Melbourne, 2010 VIC Australia
                © Rudd et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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