Evaluation of the effect of crocin on prevention of atrial fibrillation after coronary artery bypass grafting or heart valve replacement: A double-blind, randomized, placebo-controlled trial

Document Type : Original Research Article


1 Department of Clinical pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Anesthesia, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Cardiac Surgeon, Department of Cardiac Surgery, Mashhad University of Medical Sciences, Mashhad, Iran

4 Vascular and Endovascular Surgery Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Cardiovascular Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

6 Department of Biostatistics, Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran


Objective: The aim of this study was to evaluate the effect of crocin on the prevention of atrial fibrillation after coronary artery bypass grafting (CABG) and heart valve replacement.
Materials and Methods: 100 patients who were scheduled for CABG or heart valve replacement surgeries were randomly assigned into two groups of treatment and placebo. In the treatment group, patients received crocin tablets from three days prior to surgery and on the first three postoperative days (for a total of six days). During the first three days after surgery, postoperative atrial fibrillation (POAF) was assessed by electrocardiogram monitoring. Prooxidant–antioxidant balance (PAB) and c-reactive protein (CRP) levels were also assessed.
Results: POAF developed in 7 patients in the treatment group versus 18 patients in the control (p=0.02). PAB levels were significantly lower in the crocin group (p<0.001), while differences in CRP levels were insignificant (p=0.39).
Conclusion: It seems that prophylactic use of crocin is effective in reducing the incidence of POAF in patients undergoing heart surgeries.


Al-Shawabkeh Z, Al-Nawaesah K, Anzeh RA,
Al-Odwan H, Al-Rawashdeh WA,
Altaani H. 2017. Use of short-term
steroids in the prophylaxis of atrial
fibrillation after cardiac surgery. J Saudi
Heart Assoc, 29: 23-29.
Alamdari DH, Ghayour-Mobarhan M,
Tavallaie S, Parizadeh MR, Moohebati
M, Ghafoori F, Kazemi-Bajestani SM,
Paletas K, Pegiou T, Koliakos G. 2008.
Prooxidant–antioxidant balance as a new
risk factor in patients with
angiographically defined coronary artery
disease. Clin Biochem, 41: 375-380.
Alavizadeh SH, Hosseinzadeh H. 2014.
Bioactivity assessment and toxicity of
crocin: a comprehensive review. Food
Chem Toxicol, 64: 65-80.
Barangi S, Hayes AW, Karimi G. 2018. The
more effective treatment of atrial
fibrillation applying the natural
compounds; as NADPH oxidase and ion
channel inhibitors. Crit Rev Food Sci
Nutr, 58: 1230-1241.
Baysan O, Ocaklı EP, Altuner TK, Kocaman
SA. 2017. Atria: A comprehensive
evaluation with echocardiography. Heart,
Vessels and Transplantation, 1: 11-19.
Bierman EL. 1992. George Lyman Duff
Memorial Lecture. Atherogenesis in
diabetes. Arterioscler Thromb Vasc Biol,
12: 647-656.
Bockeria OL, Shvartz VA, Akhobekov AA,
Glushko LA, Le TG, Kiselev AR,
Prokhorov MD, Bockeria LA. 2017.
Statin therapy in the prevention of atrial
fibrillation in the early postoperative
period after coronary artery bypass
grafting: A meta-analysis. Cor et Vasa,
59: e266-e271.
Dastan F, Talasaz AH, Mojtahedzadeh M,
Karimi A, Salehiomran A, Bina P, Jalali
A. 2018. Randomized trial of carnitine for
the prevention of perioperative atrial
fibrillation. In Seminars in thoracic and
cardiovascular surgery, 7-13. Elsevier.
Del Campo A, Roldán J, Verdejo HE,
Zalaquett R, Becerra E, Navarro-Marquez
M, Mellado R, Lavandero S, Corbalán R,
García L, Chiong M. 2017. Increased Creactive protein plasma levels are not
involved in the onset of post-operative
atrial fibrillation. J Cardiol, 70: 578-583.
Elahi MM, Flatman S, Matata BM. 2008.
Tracing the origins of postoperative atrial
fibrillation: the concept of oxidative
stress-mediated myocardial injury
phenomenon. Eur J Cardiovasc Prev
Rehabil, 15: 735-741.
Galea R, Cardillo MT, Caroli A, Marini MG,
Sonnino C, Narducci ML, Biasucci LM.
2014. Inflammation and C-reactive
protein in atrial fibrillation: cause or
effect? Tex Heart Inst J, 41: 461-468.
Ghazizadeh H, Saberi-Karimian M,
Aghasizadeh M, Sahebi R, Ghazavi H,
Khedmatgozar H, Timar A, Rohban M,
Javandoost A, Ghayour-Mobarhan M.
2020. Pro-oxidant–antioxidant balance
(PAB) as a prognostic index in assessing
the cardiovascular risk factors: a narrative
review. Obes Med, 19: 100272.
Goli SA, Mokhtari F, Rahimmalek M. 2012.
Phenolic compounds and antioxidant
activity from saffron (Crocus sativus L.)
petal. J Agric Sci, 4: 175-181.
Haghjoo M. 2018. Postoperative rhythm
disorders after adult cardiac surgery. in,
Postoperative Critical Care for Adult
Cardiac Surgical Patients (Springer).
Hashemzaei M, Mamoulakis C, Tsarouhas K,
Georgiadis G, Lazopoulos G, Tsatsakis A,
Asrami ES, Rezaee R. 2020. Crocin: A
fighter against inflammation and pain.
Food Chem Toxicol, 143: 111521.
Hashemi Shahri et al.
AJP, Vol. 12, No. 6, Nov-Dec 2022 600
Huang Z, Xu J, Huang X, Sun G, Jiang R, Wu
H, Shan X, Bao K, Wu Q, Wu H, Tao W.
2019. Crocin induces anti-ischemia in
middle cerebral artery occlusion rats and
inhibits autophagy by regulating the
mammalian target of rapamycin. Eur J
Pharmacol, 857: 172424.
Joss JD, Hernan J, Collier R, Cardenas A.
2017. Perioperative supplementation of
polyunsaturated omega-3 fatty acid for
the prevention of atrial fibrillation after
cardiothoracic surgery. Am J Health Syst
Pharm, 74: e17-e23.
Khori V, Alizadeh AM, Yazdi H, Rakhshan E,
Mirabbasi A, Changizi S, Mazandarani
M, Nayebpour M. 2012. Frequencydependent electrophysiological
remodeling of the AV node by
hydroalcohol extract of Crocus sativus L.
(saffron) during experimental atrial
fibrillation: the role of endogenous nitric
oxide. Phytother Res, 26: 826-832.
Kocaman G, Altinoz EY, Erdemli ME, Gul M,
Erdemli Z, Gul SE, Bag HG. 2019.
Protective effects of crocin on
biochemistry and histopathology of
experimental periodontitis in rats. Biotch
Histochem, 94: 366-373.
Korani S, Korani M, Sathyapalan T, Sahebkar
A. 2019. Therapeutic effects of Crocin in
autoimmune diseases: A review.
BioFactors, 45: 835-843.
Korkmaz GG, Altınoglu E, Civelek S, Sozer
V, Erdenen F, Tabak O, Uzun H. 2013.
The association of oxidative stress
markers with conventional risk factors in
the metabolic syndrome. Metabolism, 62:
Li J, Solus J, Chen Q, Rho YH, Milne G, Stein
CM, Darbar D. 2010. Role of
inflammation and oxidative stress in atrial
fibrillation. Heart rhythm, 7: 438-444.
Mantovani A, Garlanda C, Doni A, Bottazzi B.
2008. Pentraxins in innate immunity:
from C-reactive protein to the long
pentraxin PTX3. J Clin Immunol, 28: 1-
McDonagh TA, Metra M, Adamo M, Gardner
RS, Baumbach A, Böhm M, Burri H,
Butler J, Čelutkienė J, Chioncel O,
Cleland JG. 2021. 2021 ESC Guidelines
for the diagnosis and treatment of acute
and chronic heart failure. Eur Heart J, 42:
Meyre PB, Sticherling C, Spies F,
Aeschbacher S, Blum S, Voellmin G,
Madaffari A, Conen D, Osswald S, Kühne
M, Knecht S. 2020. C-reactive protein for
prediction of atrial fibrillation recurrence
after catheter ablation. BMC Cardiovasc
Disord, 20: 427.
Nabatchican F, Einollahi N, Khaledi AK.
2014. Relationship between prooxidantantioxidant balance and severity of
coronary artery disease in patients of
Imam Khomeini Hospital of Tehran, Iran.
Acta Medica Iranica, 52: 116-121.
Nikbakht-Jam I, Khademi M, Nosrati M,
Eslami S, Foroutan-Tanha M, Sahebkar
A, Tavalaie S, Ghayour-Mobarhan M,
Ferns GA, Hadizadeh F, Tabassi SA.
2016. Effect of crocin extracted from
saffron on pro-oxidant–anti-oxidant
balance in subjects with metabolic
syndrome: A randomized, placebocontrolled clinical trial. Eur J Integr Med,
8: 307-312.
Nomani H, Mohammadpour AH, Moallem
SM, Sahebkar A. 2020. Antiinflammatory drugs in the prevention of
post-operative atrial fibrillation: a
literature review.
Inflammopharmacology, 28: 111-129.
Nomani H, Saei S, Johnston TP, Sahebkar A,
Mohammadpour AH. 2021. The efficacy
of anti-inflammatory agents in the
prevention of atrial fibrillation
recurrences. Curr Med Chem, 28: 137-
Pakfetrat A, Talebi M, Dalirsani Z, Mohajeri
A, Zamani R, Ghazi A. 2019. Evaluation
of the effectiveness of crocin isolated
from saffron in treatment of burning
mouth syndrome: A randomized
controlled trial. Avicenna J
Phytomedicine, 9: 505-516.
Pepys MB, Hirschfield GM. 2003. C-reactive
protein: a critical update. J Clin Investig,
111: 1805-1812.
Rodrigo R, Korantzopoulos P, Cereceda M,
Asenjo R, Zamorano J, Villalabeitia E,
Baeza C, Aguayo R, Castillo R, Carrasco
R, Gormaz JG. 2013. A randomized
controlled trial to prevent post-operative
atrial fibrillation by antioxidant
reinforcement. J Am Coll Cardiol, 62:
Royster RL, Deng H, Whalen SP. 2017.
Postoperative atrial fibrillation. Anesth
Analg, 125: 10-12.
Effect of crocin on postoperative atrial fibrillation
AJP, Vol. 12, No. 6, Nov-Dec 2022 601
Sefidgar SM, Ahmadi-Hamedani M, Javan AJ,
Sani RN, Vayghan AJ. 2019. Effect of
crocin on biochemical parameters,
oxidative/antioxidative profiles, sperm
characteristics and testicular
histopathology in streptozotocin-induced
diabetic rats. Avicenna J Phytomedicine,
9: 347-361.
Shahbazian H, Aleali AM, Amani R,
Namjooyan F, Cheraghian B, Latifi SM,
Bahrainian S, Ghadiri A. 2019. Effects of
saffron on homocysteine, and antioxidant
and inflammatory biomarkers levels in
patients with type 2 diabetes mellitus: a
randomized double-blind clinical trial.
Avicenna J Phytomed, 9: 436-445.
Soleimani A, Habibi MR, Kiabi FH, Alipour
A, Habibi V, Azizi S, Zeydi AE, Sohrabi
FB. 2018. The effect of intravenous Nacetylcysteine on prevention of atrial
fibrillation after coronary artery bypass
graft surgery: a double-blind, randomised,
placebo-controlled trial. Kardiol Pol
(Polish Heart Journal), 76: 99-106.
St-Onge S, Perrault LP, Demers P, Boyle EM,
Gillinov AM, Cox J, Melby S. 2018.
Pericardial blood as a trigger for
postoperative atrial fibrillation after
cardiac surgery. Ann Thorac Surg, 105:
Taghizadeh N, Sharifan P, Toosi MS, Doust
FN, Darroudi S, Afshari A, Rezaie M,
Safarian M, Vatanparast H, Eslami S,
Ghazizadeh H. 2021. The effects of
consuming a low-fat yogurt fortified with
nano encapsulated vitamin D on serum
pro-oxidant-antioxidant balance (PAB) in
adults with metabolic syndrome; a
randomized control trial. Diabetes Metab
Syndr, 15: 102332.
Thijs V, Lemmens R, Farouque O, Donnan G,
Heidbuchel H. 2017. Postoperative atrial
fibrillation: Target for stroke prevention?
Eur Stroke J, 2: 222-228.
Wang Y, Wang Q, Yu W, Du H. 2018. Crocin
attenuates oxidative stress and myocardial
infarction injury in rats. Int Heart J, 59:
Zakkar M, Ascione R, James AF, Angelini
GD, Suleiman MS. 2015. Inflammation,
oxidative stress and postoperative atrial
fibrillation in cardiac surgery. Pharmacol
Ther, 154: 13-20.
Zipes DP, Libby P, Bonow RO, Mann DL,
Tomaselli GF. 2019. Braunwald’s Heart
Disease (ELSEVIER: Philadelphia).