Perioperative statin therapy in cardiac and non-cardiac surgery: a systematic review and meta-analysis of randomized controlled trials

Putzu, Alessandro; de Carvalho e Silva, Carolina Maria Pinto Domingues; de Almeida, Juliano Pinheiro; Belletti, Alessandro; Cassina, Tiziano; Landoni, Giovanni; Hajjar, Ludhmila Abrahao

doi:10.1186/s13613-018-0441-3

Annals of Intensive Care

Table 1 Characteristics of the trials included in the analysis

From: Perioperative statin therapy in cardiac and non-cardiac surgery: a systematic review and meta-analysis of randomized controlled trials

Trial	Journal	Surgical procedure	Number of patients	Statin	Statin regimen	Control	Patients naïve to statin therapy (%)	Outcomes for meta-analysis	Risk of bias
Cardiac surgery
Almansob 2012	Arterioscler Thromb Vasc Biol	Non-coronary cardiac surgery	132	Simvastatin 20 mg	5–7 days pre-op and post-op day 2	No treatment	nr	MI, S, M	High
Aydin 2015	Anatol J Cardiol	On-pump CABG	60	Atorvastatin	7 h post-op and 30 days post-op	No treatment	100	MI, M	High
Baran 2011	Stem Cell Rev and Rep	On-pump CABG	60	Atorvastatin 40 mg	14 days pre-op and post-op (no day 0)	Placebo	100	AKI, MI, S, M, RRT	High
Berkan 2008	Thorac Cardiov Surg	On-pump CABG	46	Fluvastatin 80 mg	3 weeks pre-op	Placebo	100	MI	High
Billings 2016	JAMA	On-/Off-pump cardiac surgery	615	Atorvastatin 40 mg	Bid day 1, qd day 0, and qd post-op^°	Placebo	32	AKI, MI, S, M, RRT	Low
Carrascal 2016	Journal of Arrhythmia	Valvular surgery	90	Atorvastatin 40 mg	7 days pre-op and 7 days post-op	No treatment	100	AKI, MI, S, M, RRT	High
Castaño 2015	J Cardiovasc Surg	On-pump CABG	30	Pravastatin 40 or 80 mg	2 h pre-op	Placebo	0	AKI, MI, S, M, RRT	Low
Chello 2006	Crit Care Med	On-pump CABG	40	Atorvastatin 20 mg	3 weeks pre-op	Placebo	100	AKI, MI, S, M	Unclear
Christenson 1998	Eur J Cardiothorac Surg	On-pump CABG	77	Simvastatin 20 mg	4 weeks pre-op	No treatment	nr	AKI, MI, M	High
Dehghani 2014	J Cardiovasc Pharmacol Ther	Valvular surgery	58	Atorvastatin 40 mg	3 days pre-op and 5 days post-op	Placebo	100	MI, S, M	High
Hua 2017	Biomed Res Int	Valvular surgery	130	Simvastatin 20 mg	5–7 days pre-op and 7 days post-op (no days 0–1).	Placebo	100	M	High
Ji 2009	Circ J	Off-pump CABG	140	Atorvastatin 20 mg	7 days pre-op	Placebo	100	MI, S, M	High
Mannacio 2008	J Thorac Cardiovasc Surg	On-pump CABG	200	Rosuvastatin 20 mg	7 days pre-op	Placebo	100	AKI, MI, S, M	High
Mansour 2016	Int J Adv Biomed	Cardiac surgery	50	Atorvastatin 40 mg	7 days pre-op and post-op	No treatment	100	MI, S, M	High
Nakamura 2006	Cytokine	On-/Off-pump CABG	31	Atorvastatin 10 mg	Unclear	No treatment	32	M	Unclear
Park 2016	Intensive Care Med	Valvular surgery	200	Atorvastatin 40 mg	Bid day − 1 and qd days 0–1–2	Placebo	100	AKI, MI, S, M, RRT	Low
Patti 2006	Circulation	On-pump cardiac surgery	200	Atorvastatin 40 mg	7 days pre-op and post-op until discharge (no day 0)	Placebo	100	MI, M	High
Prowle 2012	Nephrology	On-pump cardiac surgery	100	Atorvastatin 40 mg	Days 0–1–2–3	Placebo	30	AKI, M, RRT	Low
Song 2008	Am Heart J	Off-pump CABG	124	Atorvastatin 20 mg	3 days pre-op and continued for 30 days post-op	No treatment	100	MI, S	High
Spadaccio 2010	J Cardiovasc Pharmacol	On-pump CABG	50	Atorvastatin 20 mg	3 weeks pre-op	Placebo	100	AKI, MI, S, M	Unclear
Sun 2011	Int Heart J	On-pump CABG	100	Atorvastatin 20 mg	7 days pre-op	Placebo	100	MI	High
Tamayo 2009	J Thorac Cardiovasc Surg	On-pump CABG	44	Simvastatin 20 mg	3 weeks pre-op	No treatment	100	M	High
Vukovic 2010	Perfusion	On-pump CABG	57	Atorvastatin 20 mg	3 weeks pre-op	Placebo	100	MI, M	High
Youn 2011	Korean J Thorac Cardiovasc Surg	Off-pump CABG	142	Rosuvastatin 40 mg	Bid day 1, qd day 0	No treatment	45	MI, M	High
Zheng 2016	N Engl J Med	On–/Off-pump CABG/AVR/CABG + AVR	1922	Rosuvastatin 20 mg	1–8 days pre-op and 5 days post-op	Placebo	66	AKI, MI, S, M, RRT	Low
Non-cardiac surgery
Amar 2015	J Thorac Cardiovasc Surg	Pulmonary resection	88	Atorvastatin 40 mg	7 days pre-op and 7 days post-op	Placebo	100	MI, M	High
Bass 2018	HSSJ	Hip fracture and total hip/knee replacement surgery	20	Atorvastatin 40 mg	4 days pre-op and 45 days post-op	Placebo	100	AKI, MI, S, M	High
Berwanger 2017	Am Heart J	Non-cardiac surgery in high-risk patients^a	642	Atorvastatin 80 mg	1 day pre-op and seven days post-op	Placebo	100	AKI, MI, S, M	High
Durazzo 2004	J Vasc Surg	Aortic, femoropopliteal, and carotid vascular surgery	100	Atorvastatin 20 mg	At least 14 days pre-op and up to 4 weeks post-op	Placebo	100	MI, S, M	Low
Neilipovitz 2012	Can J Anaesth	Non-cardiac surgery in high-risk patients^b	76	Atorvastatin 80 mg	7 days pre-op and 7 days post-op or day 0 and 7 days post-op	Placebo	100	MI, S, M	High
Parepa 2017	Farmacia	Elective non-cardiac, non- vascular surgery without known cardiac disease	1380	Rosuvastatin 10 mg	10 days pre-op and 20 days post-op	Placebo	100	MI, M	High
Shyamsundar 2014	Annals of Surgery	Esophagectomy	31	Simvastatin 80 mg	4 days pre-op and 7 days post-op	Placebo	100	AKI, MI, S, M	Unclear
Singh 2016	J Am Coll Surg	Colorectal resection or reversal of Hartmann’s procedure surgery	132	Simvastatin 40 mg	3–7 days pre-op and 14 days post-op	Placebo	100	M	Low
Xia 2014	Cardiology	Urgent abdominal surgery^c in patients with stable CAD	500	Atorvastatin 80 mg	2 h before surgery	Placebo	0	MI, M	Low
Xia 2015	Cardiology	Urgent abdominal surgery^c in patients with stable CAD	550	Rosuvastatin 20 mg	2 h before surgery	Placebo	0	MI, S, M	Unclear

AKI, acute kidney injury; AVR, aortic valve replacement; CABG, coronary artery bypass grafting; CAD, coronary artery disease; M, mortality; MI, myocardial infarction; RRT, renal replacement therapy; nr, not reported; pre-op, pre-operatively; post-op, post-operatively; day 0, the morning of the day of surgery; qd, once a day; bid, twice a day; °, patients on chronic statin therapy received study drug only on day 0 and day 1, resuming chronic statin therapy on postoperative day 2
^aDefined as: history of CAD, peripheral vascular disease, stroke, major vascular surgery, or any 3 of 7 risk factors criteria (intrathoracic or intraperitoneal surgery, congestive heart failure, transient ischemic attack, diabetes, renal failure, age > 70 years, or emergent/urgent surgery)
^bDefined as: history of CAD, peripheral vascular disease, stroke, or congestive heart failure, or three of six risk factor (high-risk surgery, previous congestive heart failure, diabetes, renal failure, age > 70 years, previous transient ischemic attack)
^cAcute suppurative appendicitis, acute cholecystitis, acute cholangitis, acute pancreatitis, peptic ulcer perforation or urinary calculi

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