beting on the evidence

2007 EACTS guidelines

Guideline methodology Guideline methodology Every topic is supported by a structured reviewEvery topic is supported by a structured review Review is published as a ‘Best Evidence Topic‘ in the Review is published as a ‘Best Evidence Topic‘ in the

ICVTS ICVTS A summary recommendation is given in the guidelineA summary recommendation is given in the guideline Each recommendation is graded, based on the Each recommendation is graded, based on the

strength of evidence to support that recommendation strength of evidence to support that recommendation


Best Evidence Topics Best Evidence Topics Follows a structured protocol Follows a structured protocol Answers a single narrowly phrased clinical questionAnswers a single narrowly phrased clinical question Performed by Clinicians throughout EuropePerformed by Clinicians throughout Europe Evidence supported by : Evidence supported by :

Second author check Second author check Information scientist search checkInformation scientist search check Journal Club evidence check Journal Club evidence check Web-based comments on ICVTS website Web-based comments on ICVTS website

Then publicationThen publication


Perioperative management of anticoagulation Perioperative management of anticoagulation and anti-platelet therapy in cardiac surgeryand anti-platelet therapy in cardiac surgery

Dose of aspirin after coronary arterial bypass Dose of aspirin after coronary arterial bypass graftinggrafting

Timing of aspirin after coronary arterial bypass Timing of aspirin after coronary arterial bypass graftinggrafting

Clopidogrel for the optimisation of graft patency.Clopidogrel for the optimisation of graft patency.

Clopidogrel cessation prior to urgent coronary Clopidogrel cessation prior to urgent coronary bypass grafting.bypass grafting.


Anticoagulation after mechanical valve Anticoagulation after mechanical valve replacementreplacement

Warfarin after bioprosthetic valve replacementWarfarin after bioprosthetic valve replacement

Aspirin in addition to warfarin for patients with a Aspirin in addition to warfarin for patients with a mechanical valve replacementmechanical valve replacement

Warfarin and mitral valve repairWarfarin and mitral valve repair

Anticoagulation for patients with de novo AF after Anticoagulation for patients with de novo AF after cardiac cardiac surgerysurgery




Aprotinin to reduce perioperative bleedingAprotinin to reduce perioperative bleedingAprotinin and stroke risk for cardiothoracic surgeryAprotinin and stroke risk for cardiothoracic surgeryTranexamic acid to reduce perioperative bleedingTranexamic acid to reduce perioperative bleedingTopical tranexamic acid to reduce perioperative Topical tranexamic acid to reduce perioperative bleedingbleedingProtamine administration post cardiac surgeryProtamine administration post cardiac surgeryHepcon for minimisation of blood and blood Hepcon for minimisation of blood and blood product usageproduct usageThromboelastography to guide blood and blood Thromboelastography to guide blood and blood product usage.product usage.Recombinant Factor VIIa for intractable bleeding Recombinant Factor VIIa for intractable bleeding after cardiac surgeryafter cardiac surgeryLow molecular weight heparin for deep vein Low molecular weight heparin for deep vein thrombosis prophylaxisthrombosis prophylaxis


Aspirin should be given post-operatively to all patients without Aspirin should be given post-operatively to all patients without contra-indications after coronary artery bypass grafting in order contra-indications after coronary artery bypass grafting in order to improve the long term patency of venous grafts. to improve the long term patency of venous grafts.

The dose given should be 150-325mg.The dose given should be 150-325mg.

(Grade A recommendation based on Level 1a and 1b studies)(Grade A recommendation based on Level 1a and 1b studies)

There is no evidence to promote the use of aspirin after There is no evidence to promote the use of aspirin after coronary arterial bypass grafts to improve the patency of coronary arterial bypass grafts to improve the patency of arterial grafts. However aspirin may be recommended on the arterial grafts. However aspirin may be recommended on the basis of improved survival of patients in general who have basis of improved survival of patients in general who have atherosclerotic disease.atherosclerotic disease.

(Grade E recommendation based on expert consensus)(Grade E recommendation based on expert consensus)

Dose of aspirin after CABG :Dose of aspirin after CABG :Recommendation Recommendation


Fremes(1993) meta-analysis of 12 studies showing benefit of low or Fremes(1993) meta-analysis of 12 studies showing benefit of low or

medium dose aspirin over high dose aspirinmedium dose aspirin over high dose aspirin Veterans and antiplatelet trialists meta-analyses unable to differentiate Veterans and antiplatelet trialists meta-analyses unable to differentiate

between doses of aspirin.between doses of aspirin.

Mangano(2002) in 5065 CABG pts showed mortality benefit for aspirin, NNT Mangano(2002) in 5065 CABG pts showed mortality benefit for aspirin, NNT 3030

Lim(2003) comparative meta-analysis showed highest risk reduction with Lim(2003) comparative meta-analysis showed highest risk reduction with 300-325mg compared to 75-150mg of aspirin (P=NS)300-325mg compared to 75-150mg of aspirin (P=NS)

ACCP 6ACCP 6thth consensus conference(2001) recommended 325mg of aspirin consensus conference(2001) recommended 325mg of aspirin ACCP 7ACCP 7thth consensus conference(2004) recommended 75mg-162mg per day consensus conference(2004) recommended 75mg-162mg per day

(both graded as level 1a evidence) (both graded as level 1a evidence) ACC/AHA 2004 Dosing regimes from 100mg to 325mg seem efficacious ACC/AHA 2004 Dosing regimes from 100mg to 325mg seem efficacious

Dose of aspirin after CABG :Dose of aspirin after CABG :

Evidence Evidence

Dunning J, Das S. What is the optimal dose of aspirin after discharge following Dunning J, Das S. What is the optimal dose of aspirin after discharge following coronary bypass surgery. ICVTS 2003;(4):427-30coronary bypass surgery. ICVTS 2003;(4):427-30.


Aspirin should be commenced within 24 hours after Aspirin should be commenced within 24 hours after coronary artery bypass grafting.coronary artery bypass grafting.

(Grade A recommendation based on Level 1a and 1b studies)(Grade A recommendation based on Level 1a and 1b studies)

There is a trend towards maximal benefit of aspirin the sooner There is a trend towards maximal benefit of aspirin the sooner it is given post-operatively. Giving aspirin at 6 hours or when it is given post-operatively. Giving aspirin at 6 hours or when bleeding has ceased may therefore be the optimal strategy.bleeding has ceased may therefore be the optimal strategy.

(Grade B recommendation based on individual Level 1a and (Grade B recommendation based on individual Level 1a and 1b studies)1b studies)

Timing of aspirin after CABG :Timing of aspirin after CABG :Recommendation Recommendation


Fremes(1993) 12 study meta-analysis showed maximal risk reduction if Fremes(1993) 12 study meta-analysis showed maximal risk reduction if

aspirin given <6hrs (p=NS)aspirin given <6hrs (p=NS)

Gavaghan(1991) 237pts showed largest risk reduction with aspirin at Gavaghan(1991) 237pts showed largest risk reduction with aspirin at 1hr but increased re-operation rate1hr but increased re-operation rate

Sharma(1983) showed no benefit if aspirin started at 48hrsSharma(1983) showed no benefit if aspirin started at 48hrs

ACCP 7ACCP 7thth consensus conference recommend aspirin at 6 hrs post- consensus conference recommend aspirin at 6 hrs post-operatively (grade 1a evidence).operatively (grade 1a evidence).

ACC/AHA guidelines 2004 : Prospective controlled trials have ACC/AHA guidelines 2004 : Prospective controlled trials have demonstrated a graft patency benefit when aspirin was started 1, 7, or demonstrated a graft patency benefit when aspirin was started 1, 7, or 24 hours after operation24 hours after operation

Timing of aspirin after CABG :Timing of aspirin after CABG :

Evidence Evidence

Musleh G, Dunning J. Does aspirin 6 h after coronary artery bypass grafting Musleh G, Dunning J. Does aspirin 6 h after coronary artery bypass grafting optimise graft patency? ICVTS 2003;(4):413-5optimise graft patency? ICVTS 2003;(4):413-5


Clopidogrel (75mg) is an acceptable alternative to aspirin for the Clopidogrel (75mg) is an acceptable alternative to aspirin for the optimisation of graft patency post coronary arterial bypass optimisation of graft patency post coronary arterial bypass grafting.grafting.

(Grade B recommendation based on individual Level 1b studies)(Grade B recommendation based on individual Level 1b studies)

The superiority of clopidogrel over aspirin for optimising graft The superiority of clopidogrel over aspirin for optimising graft patency after coronary arterial bypass grafting has not yet been patency after coronary arterial bypass grafting has not yet been established and thus aspirin should be regarded as the first drug established and thus aspirin should be regarded as the first drug of choice. of choice.

(Grade B recommendation based on individual Level 1b studies) (Grade B recommendation based on individual Level 1b studies)

Clopidogrel in addition to Clopidogrel in addition to aspirin :aspirin :

Recommendation 1 Recommendation 1


In patients having cardiac surgery for acute coronary syndrome, In patients having cardiac surgery for acute coronary syndrome, clopidogrel should be considered for 9-12 months in addition to clopidogrel should be considered for 9-12 months in addition to aspirin. aspirin.

( Grade B recommendation based on sub-analyses of level 1b studies)( Grade B recommendation based on sub-analyses of level 1b studies)

Clopidogrel may further improve the patency of saphenous vein grafts Clopidogrel may further improve the patency of saphenous vein grafts when given in addition to aspirin, but this will be at the expense of an when given in addition to aspirin, but this will be at the expense of an increase in bleeding complicationsincrease in bleeding complications

(Grade B recommendation based on individual level 1a and 1b (Grade B recommendation based on individual level 1a and 1b studies)studies)

In patients having coronary bypass surgery with a coronary stent in In patients having coronary bypass surgery with a coronary stent in situ, clopidogrel should be continued if the stent has not been covered situ, clopidogrel should be continued if the stent has not been covered by a graft.by a graft.

( Grade E recommendation based on expert consensus)( Grade E recommendation based on expert consensus)


Recommendation 2 Recommendation 2


ACCP 7ACCP 7thth consensus conference 2004 : Grade 1C recommendation consensus conference 2004 : Grade 1C recommendation

For patients who undergo CABG for non–ST segment elevation acute For patients who undergo CABG for non–ST segment elevation acute coronary syndrome(ACS), Clopidogrel, 75 mg/d should be given for 9 to 12 coronary syndrome(ACS), Clopidogrel, 75 mg/d should be given for 9 to 12 months following the procedure in addition to treatment with aspirin.months following the procedure in addition to treatment with aspirin.

CAPRIE CAPRIE ( Aspirin vs Clopidogrel 19,185pts) 1480 pts had CABG, ( Aspirin vs Clopidogrel 19,185pts) 1480 pts had CABG, RRR 39% death, 38% MI. RRR 39% death, 38% MI.

CURECURE ( Clopidogrel plus aspirin, 12,562pts) 2072pts had subsequent CABG, ( Clopidogrel plus aspirin, 12,562pts) 2072pts had subsequent CABG, 11% RRR in MACE , 18% if CABG was same admission 11% RRR in MACE , 18% if CABG was same admission

CREDOCREDO (Clopidogrel plus aspirin after PCI, 2116pts) 320 CABG - RRR 17% (Clopidogrel plus aspirin after PCI, 2116pts) 320 CABG - RRR 17% CASCADECASCADE(Clopidogrel After Surgery for Coronary Artery DiseasE) – 100pt (Clopidogrel After Surgery for Coronary Artery DiseasE) – 100pt

RCTRCT


Evidence Evidence

Kunadian B, Babu N, Dunning J. Should High Risk Patients Receive Kunadian B, Babu N, Dunning J. Should High Risk Patients Receive Clopidogrel as well Clopidogrel as well as Aspirin post Coronary Arterial Bypass Grafting? ICVTS as Aspirin post Coronary Arterial Bypass Grafting? ICVTS 2006 – web prepublication2006 – web prepublication

Nagarajan DV, Lewis PS, Dunning J. Is clopidogrel beneficial following Nagarajan DV, Lewis PS, Dunning J. Is clopidogrel beneficial following coronary bypass coronary bypass surgery? ICVTS 2004;(2):311-3.surgery? ICVTS 2004;(2):311-3.


Patients requiring urgent coronary arterial bypass grafting Patients requiring urgent coronary arterial bypass grafting should have their clopidogrel omitted for 5-7 days prior to should have their clopidogrel omitted for 5-7 days prior to their surgery if their clinical condition allows. their surgery if their clinical condition allows.

The benefits in terms of the reduction in perioperative blood The benefits in terms of the reduction in perioperative blood loss, reduced risk of re-exploration and reduction of blood loss, reduced risk of re-exploration and reduction of blood product usage is at the expense of a 1% increase in the risk product usage is at the expense of a 1% increase in the risk of MI while awaiting surgeryof MI while awaiting surgery(Grade B recommendation based on individual Level 1a and (Grade B recommendation based on individual Level 1a and 1b studies)1b studies)

Clopidogrel cessation pre-Clopidogrel cessation pre-CABG:CABG:

Recommendation Recommendation


Clopidogrel cessation pre-Clopidogrel cessation pre-CABG :CABG :

Evidence Evidence

Kunadian B, Thornley AR, Tanos M, Dunning J. Should Clopidogrel be stopped Kunadian B, Thornley AR, Tanos M, Dunning J. Should Clopidogrel be stopped prior to prior to urgent cardiac surgery? ICVTS 2006 web prepublication. urgent cardiac surgery? ICVTS 2006 web prepublication.

Purkayastha (2006) 11 study meta-analysis: Mean increase in blood Purkayastha (2006) 11 study meta-analysis: Mean increase in blood loss of 323mls, a 6-fold increase in the odds of re-exploration, an loss of 323mls, a 6-fold increase in the odds of re-exploration, an increase in adverse events and ventilation time,no difference in increase in adverse events and ventilation time,no difference in hospital length-of-stay or mortalityhospital length-of-stay or mortality

PCI-CURE study(2001) 2,658pts having clopidogrel or placebo prior to PCI-CURE study(2001) 2,658pts having clopidogrel or placebo prior to PCI at day 6, 5.1% MI without clopidogrel , vs 3.6% with clopidogrel PCI at day 6, 5.1% MI without clopidogrel , vs 3.6% with clopidogrel while waiting for PCI while waiting for PCI

ACC/AHA guideline : stop clopidogrel 5-7 days prior to CABG (grade B) ACC/AHA guideline : stop clopidogrel 5-7 days prior to CABG (grade B) ACCP guideline : stop clopidogrel 5-7 days prior to CABG (grade 2A) ACCP guideline : stop clopidogrel 5-7 days prior to CABG (grade 2A)


We recommend that European Cardiothoracic Surgeons We recommend that European Cardiothoracic Surgeons follow the guidelines provided by the European Society of follow the guidelines provided by the European Society of Cardiology. Cardiology. These guidelines are both up to date, detailed and will be These guidelines are both up to date, detailed and will be kept up to date by the European Society of Cardiology in the kept up to date by the European Society of Cardiology in the future.future.

INR after mechanical valve INR after mechanical valve replacement: Recommendation replacement: Recommendation


Mechanical aortic

valve Mechanical aortic valve

with risk factors Higher risk valve

types

ESC Guidelines INR target 2.5 (Low risk valves : Medtronic

Hall, St Jude Medical (without Silzone), Carbomedics)

INR Target 3.0 Low risk valve,3.5 Medium risk valve, 4.0 High risk valveRisk factors : AF, LA>50mm, Mitral valve

gradient, EF<35%, spontaneous echo contrast, additional valve replacements, hypercoagulability, history of Thromboembolism

INR Target 3.0 (For medium risk valves Bileaflet

valves with insufficient data, Bjork–Shiley valves.)

INR Target 3.5 ( for high risk valves Lillehei Kaster, Omniscience, Starr Edwards)

AHA/ACC guidelines

INR 2.0-3.0 (INR 2.5-3.5 for first 3

months)

INR 2.5-3.5Atrial fibrillation, LVdysfunction, previous thromboembolism,

and hypercoagulable condition.

INR 2.5-3.5Aortic disk valves and Starr-

Edwards valves

ACCP guidelines

INR 2.0-3.0 INR 2.5-3.5 INR 2.5-3.5 Caged ball or caged disk valve

BSH guidelines INR Target 2.5(Bileaflet valves)

No additional guidance INR Target 3.0(tilting disc) INR Target 3.5 (Caged ball or caged disc)

SIGN guidelines INR Target 3.0 (range 2.5-3.5)

For second generation valves such as St. Jude,

Medtronic, Monostrut

No additional guidance Target INR 3.5 (Range 3.0-4.5)

Starr-Edwards, Bjork Shiley standard).


Mechanical mitral

valve Mechanical mitral

valve with risk factors

Higher risk valve types

ESC Guidelines INR target 3.0 (Low risk valves : Medtronic Hall, St Jude Medical (without Silzone), Carbomedics)

INR Target 3.0 ( For low risk valves)

INR Target 3.5 (For medium risk valves Bileaflet valves with insufficient data, Bjork–Shiley valves.)

INR Target 4.0 ( for high risk valves

AHA/ACC guidelines INR 2.5-3.5 INR 2.5-3.5Atrial fibrillation, LVdysfunction, previous

thromboembolism, and hypercoagulable condition.

INR 2.5-3.5

ACCP guidelines INR 2.5-3.5(For tilting disc and bileaflet

valves)

INR 2.5-3.5AF, myocardial infarction, left

atrial enlargement, endocardial damage, systemic embolism and low ejection fraction

INR 2.5-3.5 Caged ball or caged disk valve

BSH guidelines INR Target 3.0(Bileaflet valves)

No additional guidance

INR Target 3.0(tilting disc) INR Target 3.5 ( Caged ball

or caged disc)

SIGN guidelines INR Target 3.0 (range 2.5-3.5) For second generation valves such as St. Jude,

Medtronic, Monostrut

No additional guidance

Target INR 3.5 (Range 3.0-4.5)

Starr-Edwards, Bjork Shiley standard).


Patients post-mitral bioprosthesis should have Patients post-mitral bioprosthesis should have heparinisation and warfarin for 3 months with an INR heparinisation and warfarin for 3 months with an INR of 2-3. of 2-3.

For patients post-aortic bioprosthesis without For patients post-aortic bioprosthesis without additional risk factors, antiplatelet therapy alone is additional risk factors, antiplatelet therapy alone is adequate.adequate.

(Grade B recommendation based on Level 2b and 3b studies)(Grade B recommendation based on Level 2b and 3b studies)

Warfarin after bioprosthesis:Warfarin after bioprosthesis:Recommendation Recommendation


Warfarin after bioprosthesis :Warfarin after bioprosthesis :

Evidence Evidence

El-Husseiny M, Salhiyyah K, Raja SG, Dunning J. Should warfarin be routinely El-Husseiny M, Salhiyyah K, Raja SG, Dunning J. Should warfarin be routinely prescribed for the first three months after a biprosthetic valve replacement? ICVTS prescribed for the first three months after a biprosthetic valve replacement? ICVTS 2006 web prepublication2006 web prepublication

ESC(2005) due to the absence of studies that demonstrate the safety of omitting ESC(2005) due to the absence of studies that demonstrate the safety of omitting anticoagulation for 3-months post-bioprosthesis, warfarinisation with a target INR of 2.5 or anticoagulation for 3-months post-bioprosthesis, warfarinisation with a target INR of 2.5 or 3.0 in higher risk patients should be given.3.0 in higher risk patients should be given.

ACCP(2004) Bioprosthetic valves in the mitral position should receive warfarin for the first 3 ACCP(2004) Bioprosthetic valves in the mitral position should receive warfarin for the first 3 months ( Grade 1C+) and also in the aortic position( grade 2C) months ( Grade 1C+) and also in the aortic position( grade 2C)

ACC/AHA (1998) warfarin is recommended although in several centres only aspirin is used. ACC/AHA (1998) warfarin is recommended although in several centres only aspirin is used. SIGN(1999) 3 months of warfarin in the aortic position( grade C) and the mitral position SIGN(1999) 3 months of warfarin in the aortic position( grade C) and the mitral position

(grade A) (grade A) BSH (1998, 2005) warfarin in the aortic position is not required although many centres BSH (1998, 2005) warfarin in the aortic position is not required although many centres

anticoagulate for 3-6 months. Mitral bioprosthesis should receive warfarin for 3-6 months anticoagulate for 3-6 months. Mitral bioprosthesis should receive warfarin for 3-6 months (grade A)(grade A)

Surveys in UK and USA show that 60% of surgeons do not anticoagulate aortic Surveys in UK and USA show that 60% of surgeons do not anticoagulate aortic bioprosthesesbioprostheses

No primary studies show convincing evidence in favour of anticoagulating aortic valves.No primary studies show convincing evidence in favour of anticoagulating aortic valves.


Low dose aspirin (80-100 mg daily) in addition to warfarin in Low dose aspirin (80-100 mg daily) in addition to warfarin in patients with prosthetic heart valves reduces all cause patients with prosthetic heart valves reduces all cause mortality (NNT=19), with significant reductions in mortality (NNT=19), with significant reductions in thromboembolism despite an increase in bleeding.thromboembolism despite an increase in bleeding.

(Grade A recommendation based on Level 1a and 1b (Grade A recommendation based on Level 1a and 1b

studies)studies)

Aspirin in addition to warfarin for Aspirin in addition to warfarin for mechanical valves: mechanical valves: Recommendation Recommendation


Aspirin in addition to warfarin Aspirin in addition to warfarin for mechanical valves: for mechanical valves:

Evidence Evidence

Nagarajan DV, Lewis PS, Botha P, Dunning J. Is addition of anti-platelet therapy to Nagarajan DV, Lewis PS, Botha P, Dunning J. Is addition of anti-platelet therapy to warfarin beneficial to patients with prosthetic heart valves? ICVTS 2004;(3):450-5warfarin beneficial to patients with prosthetic heart valves? ICVTS 2004;(3):450-5

11 trials found and 12 meta-analyses or guidelines 11 trials found and 12 meta-analyses or guidelines Massel (2001) meta-analysis of 11 studies 2428 patients.Massel (2001) meta-analysis of 11 studies 2428 patients.

significant reduction of all cause mortality from 9% to 5.2%significant reduction of all cause mortality from 9% to 5.2%significant increase in major bleeding of 5.4% to 8.5%significant increase in major bleeding of 5.4% to 8.5%

ACC/AHA (1998) 80mg-100mg aspirin in addition to warfarin ACC/AHA (1998) 80mg-100mg aspirin in addition to warfarin (Grade 2A) (Grade 2A)

ACCP(2004) patients who suffer systemic embolism despite ACCP(2004) patients who suffer systemic embolism despite warfarin aspirin should be added ( Grade 1C) warfarin aspirin should be added ( Grade 1C)

ESC (2005) Aspirin in addition to warfarin only for patients with ESC (2005) Aspirin in addition to warfarin only for patients with arterial disease, systemic embolisation or stenting. arterial disease, systemic embolisation or stenting.


There is an absence of studies demonstrating the safety of There is an absence of studies demonstrating the safety of omitting warfarin for patients undergoing mitral valve omitting warfarin for patients undergoing mitral valve repair. repair. In addition, due to higher atrial fibrillation and In addition, due to higher atrial fibrillation and thromboembolic episodes in the early postoperative period thromboembolic episodes in the early postoperative period a period of 6 weeks to 3 months of anticoagulation may be a period of 6 weeks to 3 months of anticoagulation may be regarded as current best practise.regarded as current best practise.

(Grade C recommendation based on an absence of studies (Grade C recommendation based on an absence of studies demonstrating the safety of omission and level 2b and 3b demonstrating the safety of omission and level 2b and 3b studies )studies )

Warfarin for mitral valve repair: Warfarin for mitral valve repair: Recommendation Recommendation


Warfarin for mitral valve Warfarin for mitral valve

repair: Evidence repair: Evidence

Asopa S, Patel A, Dunning J. Is short term anticoagulation necessary after mitral valve Asopa S, Patel A, Dunning J. Is short term anticoagulation necessary after mitral valve repair? ICVTS 2006;Accepted for publication. repair? ICVTS 2006;Accepted for publication.

The European Society of Cardiology state that there are no randomized The European Society of Cardiology state that there are no randomized controlled trials to support the safety of omitting warfarin after mitral controlled trials to support the safety of omitting warfarin after mitral repair. They recommend 3 months of warfarin at a target INR of 2.5 or 3.0.repair. They recommend 3 months of warfarin at a target INR of 2.5 or 3.0.

No other guidelines make recommendationsNo other guidelines make recommendations Vaughan UK survey – 64% of consultants use warfarin post-mitral valve Vaughan UK survey – 64% of consultants use warfarin post-mitral valve

repairrepair

Carpentier 29 year follow up series demonstrate very low rates of Carpentier 29 year follow up series demonstrate very low rates of thromboembolism ( Warfarin for 2 months) thromboembolism ( Warfarin for 2 months)

Jovin – of 181 patients post-repair who were discharged in sinus rhythm, Jovin – of 181 patients post-repair who were discharged in sinus rhythm, 36% had an episode of AF post discharge. 36% had an episode of AF post discharge.


The incidence of thromboembolism after cardiac surgery is The incidence of thromboembolism after cardiac surgery is similar to the incidence in patients undergoing high risk similar to the incidence in patients undergoing high risk general surgery. general surgery.

(Grade B recommendation based on Level 2b studies) (Grade B recommendation based on Level 2b studies)

The ACCP guidelines recommend heparin prophylaxis for The ACCP guidelines recommend heparin prophylaxis for this risk group and we conclude that patients post-cardiac this risk group and we conclude that patients post-cardiac surgery should be treated equivalently, with prophylaxis surgery should be treated equivalently, with prophylaxis using heparin or LMWH starting on the first post-operative using heparin or LMWH starting on the first post-operative day. day.

(Grade B recommendation based on Level 1b and 2b (Grade B recommendation based on Level 1b and 2b studies)studies)

DVT prophylaxis for cardiac DVT prophylaxis for cardiac surgery: Recommendation surgery: Recommendation


DVT prophylaxis for cardiac DVT prophylaxis for cardiac surgery: surgery:

Evidence Evidence

Close V, Purohit M, Tanos M, Hunter S. Should patients post cardiac surgery be given Close V, Purohit M, Tanos M, Hunter S. Should patients post cardiac surgery be given low molecular weight heparin for deep vein thrombosis prophylaxis? ICVTS 2006;In low molecular weight heparin for deep vein thrombosis prophylaxis? ICVTS 2006;In press press

Shammas(2000) review of 8 studies including over 18,000 patients post cardiac Shammas(2000) review of 8 studies including over 18,000 patients post cardiac surgery. Incidence of proximal DVT was 18%, PE 0.8%, 29 fatal PEs identified. surgery. Incidence of proximal DVT was 18%, PE 0.8%, 29 fatal PEs identified.

Ramos(1996) PRCT of 2551 patients undergoing cardiac surgery using heparin Ramos(1996) PRCT of 2551 patients undergoing cardiac surgery using heparin 5000sc +/- TEDS. Incidence of PE was 3%5000sc +/- TEDS. Incidence of PE was 3%

Systematic reviews in many specialties demonstrate the efficacy of LMWH and Systematic reviews in many specialties demonstrate the efficacy of LMWH and the safety with regard to bleeding complicationsthe safety with regard to bleeding complications

Malouf et al – patients with immediate heparin and warfarinisation post surgery Malouf et al – patients with immediate heparin and warfarinisation post surgery had a 32% pericardial effusion rate with 12 delayed tamponades. had a 32% pericardial effusion rate with 12 delayed tamponades.

Kulik(2006) systematic reviews of anticoagulation strategies- 4% bleed rate with Kulik(2006) systematic reviews of anticoagulation strategies- 4% bleed rate with LMWH, 8% with full dose heparin. LMWH, 8% with full dose heparin.


Aprotinin clearly reduces blood loss, requirement for blood Aprotinin clearly reduces blood loss, requirement for blood transfusion, and the risk of reoperation for bleeding, but transfusion, and the risk of reoperation for bleeding, but probably does increase the risk of saphenous vein graft probably does increase the risk of saphenous vein graft occlusion.occlusion.

(Grade A recommendation based on Level 1a and 1b (Grade A recommendation based on Level 1a and 1b

studies)studies)

Aprotinin to reduce perioperative Aprotinin to reduce perioperative bleeding: Recommendation bleeding: Recommendation


Kalkat M, Levine A, Dunning J. Does use of aprotinin in coronary artery bypass graft Kalkat M, Levine A, Dunning J. Does use of aprotinin in coronary artery bypass graft surgery affect graft patency? ICVTS 2004;(1):124-8. surgery affect graft patency? ICVTS 2004;(1):124-8. Ronald A, Dunning J. Does use of Aprotinin decrease the incidence of stroke and Ronald A, Dunning J. Does use of Aprotinin decrease the incidence of stroke and neurological complications in adult patients undergoing Cardiac Surgery? ICVTS 2006 neurological complications in adult patients undergoing Cardiac Surgery? ICVTS 2006 web pre-publicationweb pre-publication

Aprotinin to reduce perioperative Aprotinin to reduce perioperative bleeding: Evidence bleeding: Evidence

Odds ratio.004858 1 205.864

Study % Weight Odds ratio (95% CI)

1.61 (1.07,2.41) Alderman [3] 51.2

0.67 (0.11,4.22) Havel [4] 3.8

1.67 (0.68,4.10) Lemmer [5] 10.2

0.80 (0.35,1.82) Lass [6] 17.1

1.97 (0.18,21.99) Kalangos [7] 1.3

1.33 (0.35,5.06) Bidstrup [8] 5.0

1.88 (0.88,4.03) Van der Meer [9] 10.7

11.00 (0.59,205.86) Laub [10] 0.6

1.52 (1.14,2.03) Overall (95% CI)


Tranexamic acid reduces blood loss, requirement for blood Tranexamic acid reduces blood loss, requirement for blood transfusion, and the risk of reoperation for bleedingtransfusion, and the risk of reoperation for bleeding

(Grade A recommendation based on Level 1b studies)(Grade A recommendation based on Level 1b studies)

No study has yet looked directly at vein graft patency with No study has yet looked directly at vein graft patency with tranexamic acid, but equally no randomized studies have tranexamic acid, but equally no randomized studies have raised concerns over its safetyraised concerns over its safety

(Grade B recommendation based on individual Level 1b (Grade B recommendation based on individual Level 1b studies)studies)

Tranexamic acid to reduce Tranexamic acid to reduce perioperative bleeding: perioperative bleeding:



Thiagarajamurthy S, Levine A, Dunning J. Does prophylactic tranexamic acid safely Thiagarajamurthy S, Levine A, Dunning J. Does prophylactic tranexamic acid safely reduce bleeding without increasing thrombotic complications in patients undergoing reduce bleeding without increasing thrombotic complications in patients undergoing cardiac surgery? ICVTS 2004;(3):489-94cardiac surgery? ICVTS 2004;(3):489-94.

10 PRCTs and one meta-analysis found10 PRCTs and one meta-analysis found

5 PRCTS of Tranexamic acid versus placebo – 4/5 demonstrated 5 PRCTS of Tranexamic acid versus placebo – 4/5 demonstrated significant reductions in bleedingsignificant reductions in bleeding

Casati 2001 (Aprotinin vs Tranexamic acid) 1040 primary Casati 2001 (Aprotinin vs Tranexamic acid) 1040 primary elective CABG patients. No difference in bleeding, re-operation elective CABG patients. No difference in bleeding, re-operation for bleeding, transfusion or outcome. for bleeding, transfusion or outcome.

Tranexamic acid to reduce Tranexamic acid to reduce perioperative bleeding: Evidence perioperative bleeding: Evidence


Topical Tranexamic acid to reduce Topical Tranexamic acid to reduce perioperative bleeding: perioperative bleeding:


Only 1 RCT exists to answer this question, which Only 1 RCT exists to answer this question, which demonstrated a clinically small benefit in favour of demonstrated a clinically small benefit in favour of topical tranexamic acid in low risk patients. Further topical tranexamic acid in low risk patients. Further RCTs should be performed prior to any further use of RCTs should be performed prior to any further use of topical tranexamic acid as a strategy to reduce topical tranexamic acid as a strategy to reduce postoperative bleeding.postoperative bleeding.

(Grade B recommendation based on a single Level 1b (Grade B recommendation based on a single Level 1b study)study)


Hanif M, Nourei SM, Dunning J. Does the use of topical tranexamic acid in cardiac Hanif M, Nourei SM, Dunning J. Does the use of topical tranexamic acid in cardiac surgery reduce the incidence of post-operative mediastinal bleeding? ICVTS surgery reduce the incidence of post-operative mediastinal bleeding? ICVTS 2004;2004;(4):603-5(4):603-5

De Bonis (2001) 40 patients undergoing CABG. 36% reduction De Bonis (2001) 40 patients undergoing CABG. 36% reduction in bleeding at 2 hours, 25% at 24 hours. in bleeding at 2 hours, 25% at 24 hours.

NB new abstract presented at this meeting – to await full paperNB new abstract presented at this meeting – to await full paper

Topical Tranexamic acid to reduce Topical Tranexamic acid to reduce perioperative bleeding: Evidence perioperative bleeding: Evidence


High doses of protamine can cause increased bleeding and High doses of protamine can cause increased bleeding and impaired platelet function, but these effects have never impaired platelet function, but these effects have never been demonstrated below a ratio of 2.6:1 protamine to been demonstrated below a ratio of 2.6:1 protamine to heparin.heparin.


Protamine post-cardiac surgery: Protamine post-cardiac surgery: Recommendation Recommendation


Mclaughlin KE, Dunning J. In patients post cardiac surgery do high doses of protamine Mclaughlin KE, Dunning J. In patients post cardiac surgery do high doses of protamine cause increased bleeding? ICVTS 2003;(4):424-6cause increased bleeding? ICVTS 2003;(4):424-6

Carr (1994) and Moshizuki(1998) provide convincing evidence Carr (1994) and Moshizuki(1998) provide convincing evidence that at protamine to heparin ratios above 5:1 cause platelet that at protamine to heparin ratios above 5:1 cause platelet aggregation and function does become impaired. aggregation and function does become impaired.

Moshizuki - levels above 2.6:1 the ACT significantly increasesMoshizuki - levels above 2.6:1 the ACT significantly increases Butterworth(2002)– protamine half life is 7 mins and is fully Butterworth(2002)– protamine half life is 7 mins and is fully

eliminated in 20-30 minseliminated in 20-30 mins

Protamine post-cardiac surgery:Protamine post-cardiac surgery: Evidence Evidence


Hepcon monitoring is associated with higher heparin and Hepcon monitoring is associated with higher heparin and lower protamine doses and may decrease activation of the lower protamine doses and may decrease activation of the coagulation and inflammatory cascades. Some studies have coagulation and inflammatory cascades. Some studies have shown this may be associated with decreased postoperative shown this may be associated with decreased postoperative bleeding and blood component therapy requirement. Larger bleeding and blood component therapy requirement. Larger trials are required to investigate this further.trials are required to investigate this further.


Hepcon to reduce blood product Hepcon to reduce blood product usage: Recommendation usage: Recommendation

Aziz KAA, Masood O, Hoschtitzky A, Ronald A. Does use of the Hepcon decrease Aziz KAA, Masood O, Hoschtitzky A, Ronald A. Does use of the Hepcon decrease bleeding and blood and blood product requirements in patients undergoing cardiac bleeding and blood and blood product requirements in patients undergoing cardiac surgery? ICVTS 2006;5:469-82.surgery? ICVTS 2006;5:469-82.


Thromboelastography may be used to guide transfusion in Thromboelastography may be used to guide transfusion in the post-operative period and studies have demonstrated a the post-operative period and studies have demonstrated a reduction in blood and blood product usage if used in reduction in blood and blood product usage if used in conjunction with a treatment algorithm. conjunction with a treatment algorithm. Further studies are required before Thromboelastography Further studies are required before Thromboelastography can be recommended as the standard of care for post-can be recommended as the standard of care for post-operative transfusion management.operative transfusion management.

(Grade B recommendation based on Level 2b studies)(Grade B recommendation based on Level 2b studies)

TEG to guide blood product usage: TEG to guide blood product usage: Recommendation Recommendation

Ronald A, Dunning J. Can the use of thromboelastography predict and decrease Ronald A, Dunning J. Can the use of thromboelastography predict and decrease bleeding and blood and blood product requirements in adult patients undergoing bleeding and blood and blood product requirements in adult patients undergoing cardiac surgery? ICVTS 2005;(5):456-63.cardiac surgery? ICVTS 2005;(5):456-63.


FFor patients with intractable bleeding post cardiac surgery or patients with intractable bleeding post cardiac surgery refractory to conventional haemostatic interventions, factor refractory to conventional haemostatic interventions, factor VIIa is recommended and its complication rates are low.VIIa is recommended and its complication rates are low.

(Grade C recommendation based on Level 2b, 3b and level (Grade C recommendation based on Level 2b, 3b and level

4 studies)4 studies)

Factor VIIa for intractable Factor VIIa for intractable bleeding: Recommendation bleeding: Recommendation


Factor VIIa for intractable Factor VIIa for intractable bleeding: bleeding: Evidence Evidence

Tanos M, Dunning J. Is recombinant activated factor VII useful for intractable bleeding Tanos M, Dunning J. Is recombinant activated factor VII useful for intractable bleeding after cardiac surgery? ICVTS 2006;5:493-8.after cardiac surgery? ICVTS 2006;5:493-8.

Roberts(2004) over 400,000 usages of Factor VIIa across all specialties Roberts(2004) over 400,000 usages of Factor VIIa across all specialties recordedrecordedadverse event risk around 1%adverse event risk around 1%

Diprose – PRCT in cardiac surgery 20pts, halved blood lossDiprose – PRCT in cardiac surgery 20pts, halved blood loss At least 160 case reports of use in Cardiothoracic surgery, At least 160 case reports of use in Cardiothoracic surgery,

with a 1% risk of serious thrombosiswith a 1% risk of serious thrombosis


Future EACTS guidelines Future EACTS guidelines

2008 Guidelines : 2008 Guidelines : The Indications for The Indications for

Coronary Artery Bypass Coronary Artery Bypass Grafting Grafting


Any Questions ? Any Questions ? To get involved in writing the 2008 EACTS To get involved in writing the 2008 EACTS guidelines and Best Evidence Topics : guidelines and Best Evidence Topics :

www.icvts.orgwww.icvts.org

[email protected]@doctors.org.uk

beting on the evidence

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