None listed
Conditions
Brief summary
In patients undergoing urgent orthopaedic surgery , Heart muscle damage around the time of surgery(perioperative myocardial Injury-PMI) can occure in 52.9% of patients shown in a study conducted in the northern hospital. The majority of these patients were asymptomatic, with only 9.8% of patients meeting the universal definition criteria for myocardial infarction (heart attack). One year mortality was dramatically increased across the board in those with any troponin(a blood test showing heart muscle damage) elevation (37% versus 2.1%)after the surgery. The exact mechanisms of PMI are not well understood, however two broad theories are postulated; myocardial(heart muscle) stress and cholestrol plaque rupture. Prevention of myocardial stress and/or plaque rupture may reduce the incidence of PMI and have been the subject of multiple studies. This study is going to assess if Ivabradine(a medication lowers the heart rate without affecting the blood pressure) will reduce the rate and magnitude of PMI following emergent lower limb orthopaedic surgery by reducing heart rate and attenuating catecholamine(stress hormons) induced tachycardia(fast heart rate) after operation and to assess if it will correlate with a reduction in biomarkers of cardiovascular stress(blood tests) as measured by NT-proBNP, MR-proANP, MR-proADM and CT-proET-1 and if it will reduce the incidence and burden of atrial fibrillation after the surgery. Also this study is going to assess if Atorvastatin(a medication lowers the cholestrol and inflamatiom) will reduce the rate and magnitude of PMI following emergent lower limb orthopaedic surgery and if it will correlate with a reduction in sPLA2 and Lp-PLA2 mass and activity(markers of cholesterol plaque burden and inflammation ). Also we will assess if that patients with higher measures of platelet function(aggregation and reactivity) before and after surgery will have an increased incidence and magnitude of PMI and if patients with a higher burden of atherosclerotic(chorestrol plaque) disease as measured by CT coronary calcium scores( a ct scan messuring amount of calcium in arteries supplying blood to the heart) will have a higher incidence and magnitidue of PMI. And finally to assess if that the benefit from reduction in the incidence and magnitude of PMI by Ivabradine and Atorvastatin is derived primarily in patients with greater atherosclerotic (cholesterol Plaque) burden as measured by higher CT coronary calcium scores.
Interventions
Patients will be randomised using a computerised block randomisation method with blocks of variable sizes to ensure ‘true’ randomisation and equal numbers in each treatment group. Patients will be randomized to one of four groups in a 1:1:1:1 ratio.
1) No treatment (control group)
2) Atorvastatin orally 80 mg daily till discharge from acute hospital care (to home / rehab)
3) Ivabradine 5mg orally twice daily till discharge from acute hospital care (to home / rehab)
4) Ivabradine 5 mg orally
Patients will be randomised using a computerised block randomisation method with blocks of variable sizes to ensure ‘true’ randomisation and equal numbers in each treatment group. Patients will be randomized to one of four groups in a 1:1:1:1 ratio. 1) No treatment (control group) 2) Atorvastatin orally 80 mg daily till discharge from acute hospital care (to home / rehab) 3) Ivabradine 5mg orally twice daily till discharge from acute hospital care (to home / rehab) 4) Ivabradine 5 mg orally twice daily and atorvastatin orally 80 mg daily till discharge from acute hospital care (to home / rehab) Treatment would start on randomization prior to surgery which would be as soon as practicable after admission.
Sponsors
Northern hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Factorial
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Age greater than 60 years 2) Neck of femur fracture with planned surgical treatment within 48 hours
Exclusion criteria
1) Current ivabradine use 2) Patients who do not undergo surgical treatment for lower limb fracture for any reason. If such patients were initially enrolled they will be excluded from the analysis, i.e per protocol analysis. 3) Heart rate < 65bpm prior to randomisation 4) Known liver disease or liver enzymes > 3 times the higher limits of normal 5) Pre-operative troponin elevation 6) Artificial pacemakers, sick sinus syndrome or complete heart block 7) Concomittant CYP3A4 inhibitors – ketoconazole, macrolides, cyclosporin, gestodene, antiretrovirals
Outcome results
None listed