Coronary artery bypass surgery aspirin and clopidogrel


 * Associate Editors-in-Chief:, Mohammed A. Sbeih, M.D.[mailto:msbeih@perfuse.org],

Aspirin and clopidogrel
Aspirin is a simple cost effective therapy that has been associated with improved clinical outcomes among patients undergoing CABG. The optimal timing of aspirin administration appears to be in the 48 hours immediately after CABG.

Rigorous randomized trials have been required to document the benefits of aspirin, to determine the optimal timing of aspirin, and to overcome fears surrounding the risk of bleeding associated with administration of aspirin in the setting of CABG. There has been a hesitancy to recommend the administration of antiplatelet agents in the setting of CABG for several reasons:
 * Platelet counts and platelet concentration are reduced during the peri-operative period as a result of sequestration and hemodilution
 * Platelet function is impaired following CABG due to both hypothermia and/or mechanical filtering.

In so far as the focus of clinical care has at times been on reducing the risk of bleeding rather than on reducing the risk of thrombosis, there has likewise been a tendency to discontinue aspirin and reverse anticoagulant therapy before surgery, to administer platelet transfusions during surgery,  There is little randomized controlled data to support these practices adn non-randomized data suggest that these practices are associated with a significant increase in death and ischemic events.

Benefit of early post-operative aspirin administration
In one of the first studies in this field, Goldman et al compared the rate of SVG patency among CABG patients treated with a variety of antiplatelet regimens. All therapies except aspirin were started 48 hours before CABG. When aspirin was part of the regime, one 325 mg dose was given 12 hours pre-operatively, and the assigned therapy was maintained thereafter. The 60 day rates of angiographic patency (555 patients with 1,781 grafts) were: (P<0.05 for all aspirin regimens vs placebo)
 * Aspirin, 325 mg daily: 93.5%
 * Aspirin, 325 mg three times daily: 92.3%
 * Aspirin plus dipyridamole (325 mg and 75 mg, respectively, three times daily): 91.9%
 * Sulfinpyrazone (267 mg three times daily): 90.2%
 * Placebo (three times daily): 85.2%

Aspirin was associated with a greater median chest tube drainage within the first 35 hours post-operatively compared with placebo (p<0.02):
 * Aspirin daily (965 ml)
 * Aspirin three times daily (1175 ml)
 * Aspirin plus dipyridamole (1000 ml)
 * Sulfinpyrazone (775 ml)
 * Placebo (805 ml)

The rate of reoperation was higher (p<0.01) among patients treated with aspirin (6.5%) than among those patients not treated with aspirin (1.7%).

At one year of follow-up in the same cohort of patients (n=406 patients with 1,315 SVGs), the rate of SVG occlusion was 15.8% in all the aspirin groups combined vs 22.6% among those treated with placebo (p = 0.029). This benefit was signficant among those SVGs in which the target vessel was less than or equal to 2.0 mm in diameter (20.1% vs 32.3% for the placebo group (p = 0.008), while in those SVGs anastomosed to target vessels > 2.0 mm in diameter there was no difference in the rate of SVG occlusion (8.7% vs. 9.0%, p = 0.918).

While there were benefits in early patency and patency at one year in this cohort of patients, between years one and three, there was no benefit in the rate of occlusion. Among those SVGs that were patent at 1 year, the occlusion rate at 3 years was 4.8% for aspirin treated patients vs 4.2% for placebo treated patients (p=NS).

The benefits of early antiplatelet therapy were also documented by Chesebro et al who performed a double blind randomized trial evaluating the benefit of dipyridamole (administered two days before operation) plus aspirin (added seven hours after operation) in 407 patients. At one month, the angiographic rate of SVG occlusion on a per lesion basis was 3% vs 10% of grafts, and on a per patient basis the rate of having at least one SVG occluded was 8% vs 21% for treated vs untreated patients respectively. Likewise, at one year, the angiographic rate of SVG occlusion on a per lesion basis was 11% vs 25% of grafts, and on a per patient basis the rate of having at least  one SVG occluded was 22% vs 47% for treated vs untreated patients  respectively.

In a non-randomized retrospective analysis of 7,500 variables, Mangano et al evaluated the relationship between early aspirin use and clinical outcomes in 5,065 patients at 70 centers in 17 countries. Mortality was 1.3% among those patients treated with aspirin in the first 48 hours after CABG vs 4.0% among those who were not treated with aspirin (p<0.001). Likewise, aspirin therapy reduced the risk of MI from 5.4% to 2.8% (p<0.001), the risk of stroke from 2.6% to 1.3% (p=0.01), the risk of bowel infarction from 0.8% to 0.3% (p=0.01) and the risk of renal failure from 3.4% to 0.9%, p<0.001). Aspirin treatment was not associated with an increased risk of hemorrhage or impaired wound healing.

Pre-Operative vs Post-Operative Administration of Aspirin
Although the aforementioned studies demonstrated improved early and late patency with the pre-operative administration of aspirin, there was a higher rate of bleeding. Goldman et al conducted a prospective, randomized, double-blind, placebo-controlled trial to compare the safety and effectiveness of 325 mg of aspirin therapy initiated either the night before before CABG vs aspirin initiated via nasogastric tube 6 hours post-operatively. The rate of saphenous vein graft occlusion rate was 7.4% vs 7.8% for pre vs post-operative aspirin administration. Pre-operative aspirin was associated with a greater amount of blood volume transfused (900 versus 725 cc, p = 0.006), greater chest tube drainage at 6 hours (500 vs 448 cc, p=0.011) and a higher rate of re-operation for bleeding (6.3% vs 2.4%, p = 0.036).

Post-operative clopidogrel
There are no randomized controlled trials that demonstrate the benefit of clopidogrel in the post-operative management of CABG patients. Furthermore, retrospective subgroup analyses from large trials of acute coronary syndrome patients (1 trial) and stable coronary artery disease patients (3 trials) have not demonstrated a benefit of post-operative clopidogrel. They did, however, demonstrate a trend toward an increased risk of major and minor bleeding with the combined use of clopidogrel plus aspirin.

==ACCF/AHA Guidelines for Preoperative Antiplatelet Therapy == {{cquote|

Class I
1. Aspirin (100 mg to 325 mg daily) should be administered to CABG patients preoperatively. (Level of Evidence: B)

2. In patients referred for elective CABG, clopidogrel and ticagrelor should be discontinued for at least 5 days before surgery  (Level of Evidence: B) and prasugrel for at least 7 days (Level of Evidence: C) to limit blood transfusions.

3. In patients referred for urgent CABG, clopidogrel and ticagrelor should be discontinued for at least 24 hours to reduce major bleeding complications. (Level of Evidence: B)

4. In patients referred for CABG, short-acting intravenous glycoprotein IIb/IIIa inhibitors (eptifibatide or tirofiban) should be discontinued for at least 2 to 4 hours before surgery and abciximab for at least 12 hours beforehand to limit blood loss and transfusions. (Level of Evidence: B)

Class IIb
In patients referred for urgent CABG, it may be reasonable to perform surgery less than 5 days after clopidogrel or ticagrelor has been discontinued and less than 7 days after prasugrel has been discontinued. (Level of Evidence: C)}}

Guidelines Resources

 * 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery : A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines