Do selective serotonin reuptake inhibitors increase the risk of bleeding or mortality following coronary artery bypass graft surgery? A meta-analysis of observational studies

Abstract

Introduction:

Depressive illness has a high prevalence in patients undergoing coronary artery bypass graft surgery (CABG). The first line treatment for depression are selective serotonin reuptake inhibitors (SSRIs) which inhibit serotonin reuptake in the presynaptic neuronal membrane and uptake by platelets, inhibiting subsequent serotonin-mediated platelet activation. This presents a theoretically increased risk of bleeding and subsequent postoperative mortality. This review aims to investigate the effects of SSRIs on postoperative bleeding, defined as the need for transfusions and re-operation for bleeding, as well as 30-day mortality in patients undergoing CABG.

Method:

Four hundred and thirty-seven papers were screened with seven meeting the full inclusion criteria.

Results:

Meta-analysis demonstrated that SSRI use increased the risk of red blood cell transfusion (odds ratio (OR) = 1.15; 95% confidence interval (CI): 1.06-1.26), but resulted in no difference in the rate of re-operation for bleeding (OR = 1.07; 95% CI: 0.66-1.74). SSRI use had no effect on the rates of platelet (OR = 0.93; 95% CI: 0.79-1.09) or fresh frozen plasma (OR = 0.96; 95% CI: 0.74-1.24) transfusion nor on the mortality rate (OR =1.03; 95 CI: 0.90-1.17).

Conclusion:

This review demonstrates that SSRIs are largely safe in cardiac surgery as no increase in mortality was observed. However, there is a significantly raised chance of red blood cell transfusion. The heterogeneous nature of the current evidence base highlights the need for further research into SSRIs and whether any effect on patient outcomes in cardiac surgery occurs.

Keywords

cardiac surgery coronary artery bypass graft surgery depression selective serotonin reuptake inhibitors bleeding outcomes

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References

King

Nazareth

Levy

et al . Prevalence of common mental disorders in general practice attendees across Europe. Br J Psychiatry 2008; 192: 362–367.

Organisation for Economic Co-operation and Develop-ment. Pharmaceutical consumption - Health at a Glance 2013: OECD Indicators Paris: OECD Publishing 2013.

Bridgewater

Keogh

Kinsman

et al . Sixth National Adult Cardiac Surgical Database Report. Society for Cardiothoracic Surgery in Great Britain and Ireland. 2008.

Joint Formulary Committee. British National Formulary.

Javors

Houston

Tekell

et al . Reduction of platelet serotonin content in depressed patients treated with either paroxetine or desipramine. Int J Neuropsychopharmacol 2000; 3: 229–235.

Mehta

Sheng

O’Brien

et al . Reoperation for bleeding in patients undergoing coronary artery bypass surgery: incidence, risk factors, time trends, and outcomes. Circ Cardiovasc Qual Outcomes 2009; 2: 583–590.

Meszaros

Fuehrer

Grogg

et al . Risk factors for sternal wound infection after open heart operations vary according to type of operation. Ann Thorac Surg 2016; 101: 1418–1425.

Kuduvalli

Newall

et al . Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery. Eur J Cardiothorac Surg 2005; 27: 592–598.

Moher

Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Ann Intern Med 2009;151: 264.

10.

Stroup

Berlin

Morton

et al . Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283: 2008–2012

11.

Andreasen

Riis

Hjortdal

et al . Effect of selective serotonin reuptake inhibitors on requirement for allogeneic red blood cell transfusion following coronary artery bypass surgery. Am J Cardiovasc Drugs 2006; 6: 243–250.

12.

Chocron

Vandel

Durst

et al . Antidepressant therapy in patients undergoing coronary artery bypass grafting: the MOTIV-CABG trial. Ann Thorac Surg 2013; 95: 1609–1618.

13.

Gagne

Polinski

Rassen

et al . Selective serotonin reuptake inhibitor use and perioperative bleeding and mortality in patients undergoing coronary artery bypass grafting: a cohort study. Drug Saf 2015; 38: 1075–1082.

14.

Kim

Daskalakis

Whellan

et al . Safety of selective serotonin reuptake inhibitor in adults undergoing coronary artery bypass grafting. Am J Cardiol 2009; 103: 1391–1395.

15.

Tully

Cardinal

Bennetts

et al . Selective serotonin reuptake inhibitors, venlafaxine and duloxetine are associated with in hospital morbidity, but not bleeding or late mortality after coronary artery bypass graft surgery. Heart Lung Circ 2012; 21: 206–204.

16.

Xiong

Jiang

Clare

et al . Safety of selective serotonin reuptake inhibitor use prior to coronary artery bypass grafting. Clin Cardiology 2010; 33: 94–98.

17.

Xiong

Jiang

Clare

et al . Prognosis of patients taking selective serotonin reuptake inhibitors before coronary artery bypass grafting. Am J Cardiol 2006; 98: 42–47.

18.

Singh

Achuthan

Chakrabarti

et al . Influence of pre-operative use of serotonergic antidepressants (SADs) on the risk of bleeding in patients undergoing different surgical interventions: a meta-analysis Pharmacoepidemiol Drug Saf 2015; 24: 237–245.

19.

Targownik

Bolton

Metge

et al . Selective serotonin reuptake inhibitors are associated with a modest increase in the risk of upper gastrointestinal bleeding. Am J Gastroenterol 2009; 104: 1475–2482.

20.

Movig

Janssen

de Waal Malefijt

et al . Relationship of serotonergic antidepressants and need for blood transfusion in orthopaedic surgical patients. Arch Intern Med 2003; 163: 2354–2358.

21.

Mahdanian

Looper

Bacon

et al . Serotonergic antidepressants and increased bleeding risk in patients undergoing breast biopsy. Ther Adv Psychopharmacol 2015; 5: 332–338.

22.

Serebruany

O’Connor

Gurbel

PA.

Effect of selective serotonin reuptake inhibitors on platelets in patients with coronary artery disease. Am J Cardiol 2001; 87: 1398–1400.

23.

Kuliczkowski

Sliwka

Kaczmarski

et al . Low platelet activity predicts 30-day mortality in patients undergoing heart surgery. Blood Coagul Fibrinolysis 2016; 27: 199–204.

24.

Blumenthal

Lett

Babyak

et al . Depression as a risk factor for mortality after coronary artery bypass surgery. Lancet 2003; 362: 604–609.

25.

DiMatteo

Lepper

Croghan

TW.

Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med 2000; 160: 2101–2107.

26.

Kronish

Rieckmann

Halm

et al . Persistent depression affects adherence to secondary prevention behaviours after acute coronary syndromes. J Gen Intern Med 2006; 21: 1178–1183.

27.

Stenman

Holzmann

Sartipy

Relation of major depression to survival after coronary artery bypass grafting. Am J Cardiol 2014; 114: 698–703.