Author, date journal and country

Study type (level of evidence)

Patient group

Outcomes

Key results

Comments/weaknesses

Kourliouros et al. (2011), J Thorac Cardiovasc Surg, United Kingdom [13]

Single-centre prospective randomised trial

(level 1b)

Patients on routine statin treatment.

Atorvastatin given for 7 days before and 14 days after surgery, or until discharge.

Atorvastatin 10 mg: n = 53

Atorvastatin 80 mg: n = 49

Atrial fibrillation (AF)

AF occurred in 19 of 53 (36%) in the 10 mg group vs 14 of 49 (29%) in the 80 mg group (p = 0.43)

Single-blinded

Elective first-time coronary artery bypass graft (CABG) or aortic valve replacement (AVR) by a single surgeon

Usual statin dose: atorvastatin 10 or 20 mg; simvastatin 10, 20 or 40 mg

Usual statin discontinued during intervention period

Ludman et al. (2011), Basic Res Cardiol, United Kingdom [14]

Single-centre prospective randomised trial

(level 1b)

Patients on >4 weeks statin treatment.

Study 1:

Atorvastatin 160 mg 2 hours prior to surgery and 24 hours after: n = 23

Control (standard chronic statin therapy): n = 22

Study 2:

Atorvastatin 160 mg 12 hours prior to surgery and 24 hours after: n = 30

Control (standard chronic statin therapy): n = 26

Myocardial injury (Troponin T (TnT) and creatine kinase (CK) prior to surgery and at 6, 12, 24, 48 and 72 hours)

AF

Duration of intensive care unit (ICU) stay

Hours on mechanical ventilation

Need for re-operation

No significant difference between groups in all outcomes

Single-blinded

Elective on-pump CABG

Usual statin therapy continued in both groups

Not adequately powered for clinical endpoints

Castaño et al. (2015), J Cardiovasc Surg (Torino), Spain [15]

Single-centre prospective randomised trial

(level 1b)

Patients with dyslipidaemia on >15 days statin treatment.

2 hours prior to induction of anaesthesia:

Pravastatin 80 mg: n = 10

Pravastatin 40 mg: n = 10

Placebo control: n = 10

AF

Mortality (30 day)

Duration of hospital stay

Duration of ICU stay

Myocardial injury (Troponin I (TnI) and CK-MB on ICU admission and 4, 8, 16, 24, 32, 40, 48, 96 hours and at 30 days)

CK, AST, ALT and creatinine at the same time points

Proinflammatory cytokines TNF-α and IFN-γ at baseline, 30 minutes after cross-clamp removal and at 24 hours and 5 days after surgery

No significant difference between groups in clinical outcomes or markers of myocardial, renal and hepatic injury

Statin reloading  reduced postoperative serum concentrations of proinflammatory cytokines:

At 24 hours TNF-α and IFN-γ was lower in 80 mg pravastatin group compared with 40 mg and placebo groups (p < 0.05)

After 5 days both 40 mg and 80 mg pravastatin groups had lower TNF-α and IFN-γ than placebo control (p < 0.05)

Double-blinded placebo-controlled

Elective on-pump CABG under aortic cross-clamping

Usual statin dose omitted night before surgery

Usual statin dose: atorvastatin 20, 40 or 80 mg; simvastatin 20 or 40 mg; fluvastatin 40 or 80 mg

Billings et al. (2016), JAMA, USA [16]

Single-centre prospective randomised trial

(level 1b)

Patients on routine statin treatment

Atorvastatin 80 mg given on the morning of surgery and 40 mg the morning after

Intervention: n = 206

Placebo control: n = 210

Acute kidney injury (AKI)

Creatinine peak at 48 hours

Delirium

Myocardial injury (Day 1 CK-MB)

AF

Stroke

Pneumonia

Time to extubation

Duration of ICU stay

Hospital mortality

No significant difference between groups in all outcomes

Double-blinded placebo-controlled

Elective CABG, valve surgery or ascending aorta repair

Usual statin was discontinued on day of surgery and resumed on postoperative day 2

AKI defined as an increase of 0.3 mg dL^-1 in serum creatinine within 48 hours of surgery

Chee et al. (2017), J Cardiothorac Surg, Ireland [17]

Single-centre prospective randomised trial

(level 1b)

Patients on routine simvastatin or atorvastatin treatment with dose ≤40 mg

Atorvastatin 80 mg for 2 weeks before surgery

Intervention: n = 15

Control: n = 15

Serum IL-8 and MMP-9 levels at baseline, 5 minutes and 4 hours after cross-clamp removal

High sensitivity TnI at baseline and 4 hours after cross-clamp removal

Urine neutrophil gelatinase-associated lipocalin (NGAL) at 4 hours after cross-clamp removal

Creatinine on admission and daily to postoperative day 5

Duration of ICU stay

Duration of hospital stay

Transient ischaemic attack

Hours on mechanical ventilation

No significant difference between groups in clinical end points or MMP-9 levels at all time points

Trend towards lower creatinine in the treatment group which did not reach significance

Urine NGAL 75.9 ± 35.9 ng ml^-1 in control vs 48.4 ± 102.8 ng ml^-1 in treatment (p = 0.002)

Serum IL-8 was 8.6 ± 1.0 pg ml^-1 at baseline in control vs 11.2 ± 1.8 pg ml^-1 in treatment (p = 0.036). No significant difference at 5 minutes. At 4 hours, 28.3 ± 4.3 pg ml^-1 vs 44.3 ± 8.5 pg ml^-1 (p = 0.035).

High sensitivity TnI similar at baseline.  At 4 hours, 3516.1 ± 465.2 pg ml^-1 in control vs 6380.6 ± 1672.5 pg ml^-1 in treatment (p = 0.002).

Study not blinded

Elective on-pump cardiac surgery (including CABG, valve and combined surgery)

Study was not powered to detect a difference in clinical end points