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Three Part Question

In [patients following coronary arterial bypass grafting] is [aspirin commenced 6-hours post surgery compared to 24-hours post surgery] the best treatment to [optimise graft patency]?

Clinical Scenario

You are asked to review a 65-year-old patient who had a coronary artery bypass grafting (CABG) 6 hours ago. Preoperatively he had triple vessel disease and good ventricular function. 600mls has been recorded in the drain bottles and 40mls drained in the last hour. The nurse asks you if the first dose of aspirin should be omitted. You are tempted to omit this first dose of aspirin but you wonder what implication this may have on the long-term patency of this man's grafts.

Search Strategy

Medline 1966-07/03 using the OVID interface.
[exp Coronary Artery Bypass OR coronary art$ bypass.mp OR CABG.mp OR exp Thoracic surgery OR cardiopulmonary bypass.mp OR exp Cardiovascular Surgical Procedures OR exp Thoracic surgical procedures] AND [exp Aspirin OR aspirin.mp] AND [exp vascular patency OR exp Graft occlusion, Vascular OR exp Graft survival OR graft patency.mp] AND [maximally sensitive RCT filter] LIMIT to human AND English

Search Outcome

201 papers were found of which 6 were deemed to be relevant. In addition the American Heart Association guideline for CABG surgery provided a recent systematic review and was added.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Sharma GV et al, 1983, USA	176 patients randomised to aspirin 975mg/day, or aspirin and dipyridamole 225mg/day, or placebo Therapy started at day 3 to 5 post operation Follow up angiography at 1 year	PRCT double blind (1b)	Graft patency at 1 year	Aspirin 78% aspirin-dipyrid 83% Placebo 80% P=NS	80% angiography rate No power calculations presented
			Subanalysis of those with small vein grafts	Still no significant difference
Lorenz RL et al, 1984, Germany	60 patients given aspirin 100mg 24 hrs after operation or placebo	PRCT double blind (1b)	Angiographic graft patency at 4 months	Aspirin 90% Placebo 68% P=0.012	18 lost to the trial after offered entry 3 died Blood loss and reoperations not recorded
			Bleeding time	Aspirin 98 secs Placebo 68 secs P<0.05
Chesebro JH et al, 1984, USA	202 patients randomised to receive Aspirin 325mg 7 hours after surgery and Dipyridamole 100mg qds, 2 days pre-operatively and post-operatively. 205 patients received placebo Angiography performed at 1 year	PRCT Double blind (1b)	Patients with at least 1 occlusion at 1 year	Aspirin 22% Placebo 47%	4 deaths Mean no. of grafts in all patients was 2 Control group was no treatment rather than aspirin given 24 hrs after operation
			Occluded grafts at 1 year	Aspirin 11% Placebo 25%
			Blood loss	No data given
Sanz G, 1990, Spain	927 consecutive patients randomised to either placebo, Aspirin 50mg tds or Aspirin 50mg tds and Dypiridamole 75my tds First Dose was given 7 hours after operation. All patients received pre-op Dipyridamole 100mg qds for 2 days and 1 dose 1 hr after surgery. All patients had angiography at 10 days post surgery	PRCT Double blind (1b)	Occluded distal anastomoses	Aspirin 14% asp + Dipyrid 13% Placebo 18% P=0.058 for Aspirin	185 lost to follow up (27 deaths) Randomisation method not described Data not fully described in this paper Control group was no treatment rather than aspirin given 24 hrs after operation
			Patients with at least 1 occlusion	Aspirin 27%% asp + Dipyrid 24% Placebo 33% P=0.01 for Asp+dyp
			Blood loss	No figures given but stated that no significant between group difference in blood loss or reoperation
Gavaghan TP et al, 1991, Australia	127 patients assigned to receive 324mg of Aspirin, 1 hour after leaving theatre (via an NG tube on the 1st day) and daily thereafter 110 patients received placebo, in a similar pattern Angiography perfomed 7 days and 363 days after surgery. 97% and 92% angiography rate achieved	PRCT Double blind (1b)	Angiographic early vein graft occlusion rate	Aspirin 1.6% Placebo 6.2% P=0.004	3 early deaths and 3 late deaths well conducted study
			Angiographic late vein graft occlusion rate	Aspirin 5.8% Placebo 11.6% P=0.01
			Blood loss in 24 hrs	Aspirin 571ml Placebo 563ml
			Reoperation rate	Aspirin 4.8% Placebo 1% P=0.1
Fremes SE et al, 1993, Canada	12 studies that evaluated, occlusion rates of saphenous vein grafts after CABG Aspirin in various regimes of 50mg to 975mg +/- Dipyridamole vs control N=3224 patients in the 12 trials	Meta-analysis (1a)	Timing of aspirin dosage and odds of graft occlusion (calculated by logistic regression)	Preop OR 1.0 (CI 0.8-1.3) <6hrs post-op OR 0.59 (CI 0.47-0.73) >6hrs post-op OR 0.76 (CI 0.57-1.00) >24hrs post-op OR 0.91 (CI 0.68-1.22)	Saphenous veins only Significant heterogeneity demonstrated amongst studies Studies are from July 1991 or earlier
Eagle KA et al, 1999, USA	Systematic review of a wide range of issues in Coronary arterial Bypass grafting This review updated a previous review conducted in 1991	Systematic review (1a)	Antiplatelet therapy for SVG patency	Aspirin significantly reduces occlusion if given at 1, 7 or 24 hours but not at 48 hrs. Dypiridamole has no additional benefits but ticlopidine or clopidogrel are alternatives to aspirin. This is a grade 1 recommendation	Search strategies not given

Comment(s)

Fremes et al in their Meta-analysis of 12 studies found that the benefit of aspirin was optimal if given at 6 hrs. In the individual studies, Gavaghan showed the largest risk reduction, when aspirin was given at 1-hour post operation, but there was a non-significant increased rate of re-operation in this group. The study by Sharma et al showed that there was no benefit in giving aspirin if starting more than 48hrs post-operatively. No significant increases in bleeding were shown in any studies here.

Clinical Bottom Line

There is good evidence that aspirin given <6 hours post surgery optimally reduces graft occlusion, without an increase in bleeding.

References

1. Sharma GV, Khuri SF, Josa M, et al. The effect of antiplatelet therapy on saphenous vein coronary artery bypass graft patency. Circulation 1983;68(3 Pt 2):II218-221.
2. Lorenz RL, Schacky CV, Weber M, et al. Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily). Lancet 1984;1(8389):1261-4.
3. Chesebro JH, Fuster V, Elveback LR, et al. Effect of dipyridamole and aspirin on late vein-graft patency after coronary bypass operations. N Eng J Med 1984;310(4):209-14.
4. Sanz G. Does low-dose aspirin prevent aortocoronary vein bypass graft occlusion? The Spanish Group for Aortocoronary Bypass Follow-up (GESIC Study). Thromb Res 1990;12:23-6.
5. Gavaghan TP, Gebski V, Baron DW. Immediate postoperative aspirin improves vein graft patency early and late after coronary artery bypass graft surgery. A placebo-controlled, randomized study. Circulation 1991;83(5):1526-33.
6. Fremes SE, Levinton C, Naylor CD, et al. Optimal antithrombotic therapy following aortocoronary bypass: a meta-analysis. Eur J Cardiothorac Surg 1993;7(4):169-80.
7. Eagle KA, Guyton RA, Davidoff R, American College of Cardiology. Guidelines for Coronary Artery Bypass Graft Surgery. J Am Coll Cardiol 1999;34(4):1262-347.