SecondarY Prevention and maNagement of Myocardial Injury aftER Noncardiac surGerY (SYNERGY) Pilot Trial

Average number of patients recruited per month. Feasibility is defined as average recruitment rate ≥3 patients/month/site as "trial feasible", between 1-2 patients/month/site as "potentially feasible with protocol modifications", and <1 patient/month/site as "unlikely feasible".

Defined as the proportion of patients allocated to the intervention group with referral to internal medicine or cardiology within 6 weeks of MINS. The adherence feasibility outcome is defined as follows: ≥70% as "trial feasible", between 40-69% "potentially feasible with protocol modifications", and <40% "unlikely feasible".

Defined as the proportion of patients allocated to the control group with referral to internal medicine or cardiology within 6 weeks of MINS. The crossover feasibility outcome is defined as follows: <30% as "trial feasible", between 30-49% "potentially feasible with protocol modifications", and >50% "unlikely feasible".

Proportion of patients who are prescribed an antiplatelet, statin, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blockers (ARB) (all three) at 6 months.

Proportion of patients who are prescribed an antiplatelet therapy.

Proportion of patients who are prescribed a statin.

Proportion of patients who are prescribed an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB).

Proportion of eligible patients which consented to participate in the trial

Proportion of patients enrolled in the trial that completed the 6-month follow-up

Difference in physical activity score (i.e., the short form of the International Physical Activity Questionnaire (IPAQ-SF) score in metabolic equivalents (METs) minute per week) between baseline and 6 months, expressed as a continuous outcome, with higher values meaning a larger increase in physical activity level.

Difference between the Mediterranean Diet Adherence Screener (MEDAS) questionnaire score at baseline and 6 months (score between 0 and 14, with high score reflecting higher adherence).

Proportion of patients who experience any of the following composite of cardiovascular death, non-fatal cardiac arrest, myocardial infarction, stroke, heart failure, and coronary revascularization.

Proportion of patients with a cardiovascular death is defined as any death with a cardiovascular cause and includes those deaths following a myocardial infarction, sudden cardiac arrest, stroke, cardiac revascularization procedure (i.e., percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery), and heart failure.

Proportion of patients with a myocardial infarction as defined according to the Fourth Universal Definition of Myocardial Infarction.

Proportion of patients with a nonfatal cardiac arrest defined as successful resuscitation from either documented or presumed ventricular fibrillation, sustained ventricular tachycardia, asystole, or pulseless electrical activity requiring cardiopulmonary resuscitation, pharmacological therapy, or cardiac defibrillation.

Proportion of patients with a cardiac revascularization procedures including percutaneous coronary intervention (PCI) and coronary arterial bypass grafting (CABG).

Proportion of patients with a stroke defined as either:

• a new focal neurological deficit thought to be vascular in origin with signs or symptoms lasting more than 24 hours or leading to death, OR
• a new focal neurological deficit thought to be vascular in origin with signs or symptoms lasting less 24 hours with a positive neuroimaging consistent with a stroke.

Proportion of patients with a transient ischemic attack defined as rapidly developed and transient clinical signs of focal or global disturbance of cerebral function, lasting less than 24 hours, with either 1) direct weighted magnetic resonance findings of acute brain ischemic lesions, or 2) high risk neurologic features (i.e., lateralizing weakness and/or speech disruption lasting >5 min).

Proportion of patients with a diagnosis of heart fialure, as defined by (criteria A and B required):

A. New or worsening symptoms due to heart failure (HF), including at least ONE of the following:

• Shortness of breath (dyspnea with exertion, dyspnea at rest, orthopnea, paroxysmal nocturnal dyspnea), 2. Decreased exercise tolerance, or 3. Fatigue.

B. Signs of new or worsening HF, consisting of at least TWO physical examination findings OR one physical examination finding and at least ONE laboratory (i.e., natriuretic peptide elevation) or radiological imaging.

Proportion of patients who died of any cause.

Proportion of patients with a new significant arrythmia defined as new supraventricular or ventricular arrythmia that results in angina, congestive heart failure, symptomatic hypotension, or that requires oral or intravenous treatment with a rate controlling drug, antiarrhythmic drug, electrical cardioversion, implantation of a pacemaker or implantable cardioverter defibrillator.

Proportion of patients with a major bleeding defined according to the criteria of International Society on Thrombosis and Haemostasis (ISTH) as clinically overt bleeding which was fatal or associated with any of the following:

• a fall in hemoglobin level of 2 g/dL or more or documented transfusion of at least 2 units of packed red blood cells,
• involvement of a critical anatomical site (intracranial, spinal, ocular, pericardial, articular, intramuscular with compartment syndrome, retroperitoneal).

Proportion of patients with a clinically relevant non-major bleeding defined as any sign or symptom of hemorrhage (e.g., more bleeding than would be expected for a clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria:

• requiring medical intervention by a healthcare professional
• leading to hospitalization or increased level of care
• prompting a face to face (i.e., not just a telephone or electronic communication) evaluation

Proportion of patients with a kidney Injury defined by the Acute Kidney Injury Network (AKIN) definition and classified according to the following stage:

Stage 1: Serum creatinine increase ≥26.5 μmol/l or increase to 1.5-2.0-fold from baseline Stage 2: Serum creatinine increase >2.0-3.0-fold from baseline Stage 3: Serum creatinine increase >3.0-fold from baseline or serum creatinine ≥354 μmol/l with an acute increase of at least 44 μmol/l or need for new renal replacement therapy.

Proportion of patients with a liver injury defined by elevation of ALT and/or AST ≥3 times the upper limit of normal.

Proportion of patients with a rhabdomyolysis defined as muscle symptoms with serum creatinine kinase ≥10 times the upper limit of normal.