**9. Results**

Figure 3. Statistical analysis and cost-benefit report calculation

type of the antiagregant regimen

Clopidogrel (controls). The confounders were controlled by stratification.

Data interpretation was performed taking into account the following hypothesis:

being appreciated on case to case basis, depending on the risk and benefit for each patient;

The main conclusion of our study was that using Clopidogrel single or associated with Aspirin for antiplatelet treatment in the immediate postoperative period in CABG patients is more effective than Aspirin alone, with a better cost-benefit report. The cost benefit report associated with using Aspirin plus Clopidogrel was almost two times higher than with Aspirin alone (Figure 4) **9. Results** The main conclusion of our study was that using Clopidogrel single or associated with Aspirin for antiplatelet treatment in the immediate postoperative period in CABG patients is more effective than Aspirin alone, with a better cost-benefit report. The cost benefit report associated with using Aspirin plus Clopidogrel was almost two times higher than with Aspirin alone (Figure 4)

Using the above mentioned parameters, the special programme calculated a risk score per patient on types of treatment and the cost of routinely use clopidogrel in cabg patients, which was used then for estimation of the cost-benefit ratio associated with the

Data were grouped on types of surgical interventions according to the exposure level to the risk factors. For each exposure level there were introduced the number of patients taking Clopidogrel (cases) and the number of patients who have not taken




different depending on the patients age, NYHA class, LVEF, the severity of associated MR , but, in all cases were lower among

Conventional statistical testing for Clopidogrel plus Aspirin versus Clopidogrel alone versus Aspirin alone resulted in p values of

different depending on the patients age, NYHA class, LVEF, the severity of associated MR , but, in all cases were lower among

The Antiagregant Treatment After Coronary Artery Surgery Depending on Cost – Benefit Report

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303

Conventional statistical testing for Clopidogrel plus Aspirin versus Clopidogrel alone versus Aspirin alone resulted in p values of

At hospital discharge and at 30 days, the combined efficacy and safety outcome endpoints were smaller in Clopidogrel plus

At hospital discharge and at 30 days, the combined efficacy and safety outcome endpoints

**Figure 5.** Relative risks and 95% Confidence Indexes for primary efficacy composite endpoints in the study groups

For the primary efficacy plus safety endpoint (30 day mortality, inhospital graft oclusion or inhospital major bleeding), the rates

In-hospital graft oclusion and myocardial infarction occurred rarely in patients treated with Clopidogrel plus Aspirin compared with the patients treated with Aspirin alone. Major hemorrhagic events were similar in the study groups. Concerning the duration

For the primary efficacy plus safety endpoint (30 day mortality, inhospital graft oclusion or inhospital major bleeding), the rates were smaller for Clopidogrel plus Aspirin group, as the

In-hospital graft oclusion and myocardial infarction occurred rarely in patients treated with Clopidogrel plus Aspirin compared with the patients treated with Aspirin alone. Major hemor‐ rhagic events were similar in the study groups. Concerning the duration of the hospitalisation and imobilisation, there were a little bit smaller in Clopidogrel plus Aspirin group. (Figure 6)

At hospital discharge and at 30 days, the combined efficacy and safety outcome endpoints were smaller in Clopidogrel plus

For the primary efficacy plus safety endpoint (30 day mortality, inhospital graft oclusion or inhospital major bleeding), the rates

In-hospital graft oclusion and myocardial infarction occurred rarely in patients treated with Clopidogrel plus Aspirin compared with the patients treated with Aspirin alone. Major hemorrhagic events were similar in the study groups. Concerning the duration

On long term, the incidence of death, myocardial infarction, and revascularization occurring at one year following CABG was greater in Aspirin group compared with Clopidogrel and Clopidogrel plus Aspirin groups (15% versus 12% versus 10%)

The Kaplan Meier curves for primary efficacy and safety endpoints showed a smaller probability for death, myocardial infarction

On long term, the incidence of death, myocardial infarction, and revascularization occurring at one year following CABG was

The Kaplan Meier curves for primary efficacy and safety endpoints showed a smaller probability for death, myocardial infarction

greater in Aspirin group compared with Clopidogrel and Clopidogrel plus Aspirin groups (15% versus 12% versus 10%)

**Figure 6.** Frequency of composite and single endpoints at hospital discharge and at 30 days

of the hospitalisation and imobilisation, there were a little bit smaller in Clopidogrel plus Aspirin group. (Figure 6)

of the hospitalisation and imobilisation, there were a little bit smaller in Clopidogrel plus Aspirin group. (Figure 6)

Also, there were different depending on the patients age, NYHA class, LVEF and associated severe mitral regurgitation.

Also, there were different depending on the patients age, NYHA class, LVEF and associated severe mitral regurgitation.

patients treated with Clopidogrel associated with Aspirin than among those treated with Aspirin alone

patients treated with Clopidogrel associated with Aspirin than among those treated with Aspirin alone

Figure 5. Relative risks and 95% Confidence Indexes for primary efficacy composite endpoints in the study groups

Figure 5. Relative risks and 95% Confidence Indexes for primary efficacy composite endpoints in the study groups

were smaller for Clopidogrel plus Aspirin group, as the rates of in-hospital death

were smaller for Clopidogrel plus Aspirin group, as the rates of in-hospital death

were smaller in Clopidogrel plus Aspirin group.

Figure 6. Frequency of composite and single endpoints at hospital discharge and at 30 days

Figure 6. Frequency of composite and single endpoints at hospital discharge and at 30 days

or graft oclusion in Clopidogrel plus Aspirin group (Figure 7).

or graft oclusion in Clopidogrel plus Aspirin group (Figure 7).

Aspirin group.

Aspirin group.

rates of in-hospital death

0,0002 and 0,0003 respectively for the primary efficacy plus safety composite endpoints.

0,0002 and 0,0003 respectively for the primary efficacy plus safety composite endpoints.

Clopidogrel as antiplatelet therapy after coronary artery bypass surgery was considered as having uncertain indication;

The incidence of myocardial infarction and death following graft thrombosis was 21% in Aspirin group,12% in Clopidogrel group and respectively 7% in aspirin plus Clopi‐ dogel group. The incidence of myocardial infarction and death following graft thrombosis was 21% in Aspirin group,12% in Clopidogrel group and respectively 7% in aspirin plus Clopidogel group.

**Figure 4.** Cost-benefit report depending on the type of antiplatelet treatment in CABG patients

Figure 4. Cost-benefit report depending on the type of antiplatelet treatment in CABG patients Relative risks and 95% confidence indexes for primary efficacy composite endpoints (30 days mortality, myocardial infarction, inhospital graft oclusion, hospital stay and immobilization (days), Intensive Care Unit length of stay and cost, quality of life) were Relative risks and 95% confidence indexes for primary efficacy composite endpoints (30 days mortality, myocardial infarction, inhospital graft oclusion, hospital stay and immobilization (days), Intensive Care Unit length of stay and cost, quality of life) were different depending on the patients age, NYHA class, LVEF, the severity of associated MR, but, in all cases were lower among patients treated with Clopidogrel associated with Aspirin than among those treated with Aspirin alone

Also, there were different depending on the patients age, NYHA class, LVEF and associated severe mitral regurgitation.

Conventional statistical testing for Clopidogrel plus Aspirin versus Clopidogrel alone versus Aspirin alone resulted in p values of 0,0002 and 0,0003 respectively for the primary efficacy plus safety composite endpoints.

Also, there were different depending on the patients age, NYHA class, LVEF and associated severe mitral regurgitation. Conventional statistical testing for Clopidogrel plus Aspirin versus Clopidogrel alone versus Aspirin alone resulted in p values of The Antiagregant Treatment After Coronary Artery Surgery Depending on Cost – Benefit Report http://dx.doi.org/10.5772/54467 303

different depending on the patients age, NYHA class, LVEF, the severity of associated MR , but, in all cases were lower among

different depending on the patients age, NYHA class, LVEF, the severity of associated MR , but, in all cases were lower among

patients treated with Clopidogrel associated with Aspirin than among those treated with Aspirin alone

patients treated with Clopidogrel associated with Aspirin than among those treated with Aspirin alone

0,0002 and 0,0003 respectively for the primary efficacy plus safety composite endpoints.

**9. Results**

302 Artery Bypass

**9. Results**

recommended in each case.

Figure 2. Statistic methodology

type of the antiagregant regimen

Clopidogrel (controls). The confounders were controlled by stratification.

Data interpretation was performed taking into account the following hypothesis:

being appreciated on case to case basis, depending on the risk and benefit for each patient;

dogel group.

treated with Aspirin alone

severe mitral regurgitation.

plus safety composite endpoints.

higher than with Aspirin alone (Figure 4)

and respectively 7% in aspirin plus Clopidogel group.

Figure 3. Statistical analysis and cost-benefit report calculation

The main conclusion of our study was that using Clopidogrel single or associated with Aspirin for antiplatelet treatment in the immediate postoperative period in CABG patients is more effective than Aspirin alone, with a better cost-benefit report. The cost benefit report associated with using Aspirin plus Clopidogrel was almost two times

Using the above mentioned parameters, the special programme calculated a risk score per patient on types of treatment and the cost of routinely use clopidogrel in cabg patients, which was used then for estimation of the cost-benefit ratio associated with the

Data were grouped on types of surgical interventions according to the exposure level to the risk factors. For each exposure level there were introduced the number of patients taking Clopidogrel (cases) and the number of patients who have not taken




Clopidogrel as antiplatelet therapy after coronary artery bypass surgery was considered as having uncertain indication;

The incidence of myocardial infarction and death following graft thrombosis was 21% in Aspirin group,12% in Clopidogrel group and respectively 7% in aspirin plus Clopi‐

Figure 4. Cost-benefit report depending on the type of antiplatelet treatment in CABG patients

Relative risks and 95% confidence indexes for primary efficacy composite endpoints (30 days mortality, myocardial infarction, inhospital graft oclusion, hospital stay and immobilization (days), Intensive Care Unit length of stay and cost, quality of life) were different depending on the patients age, NYHA class, LVEF, the severity of associated MR, but, in all cases were lower among patients treated with Clopidogrel associated with Aspirin than among those

Also, there were different depending on the patients age, NYHA class, LVEF and associated

Conventional statistical testing for Clopidogrel plus Aspirin versus Clopidogrel alone versus Aspirin alone resulted in p values of 0,0002 and 0,0003 respectively for the primary efficacy

**Figure 4.** Cost-benefit report depending on the type of antiplatelet treatment in CABG patients

Figure 5. Relative risks and 95% Confidence Indexes for primary efficacy composite endpoints in the study groups **Figure 5.** Relative risks and 95% Confidence Indexes for primary efficacy composite endpoints in the study groups

At hospital discharge and at 30 days, the combined efficacy and safety outcome endpoints were smaller in Clopidogrel plus Aspirin group. For the primary efficacy plus safety endpoint (30 day mortality, inhospital graft oclusion or inhospital major bleeding), the rates were smaller for Clopidogrel plus Aspirin group, as the rates of in-hospital death At hospital discharge and at 30 days, the combined efficacy and safety outcome endpoints were smaller in Clopidogrel plus Aspirin group.

In-hospital graft oclusion and myocardial infarction occurred rarely in patients treated with Clopidogrel plus Aspirin compared with the patients treated with Aspirin alone. Major hemorrhagic events were similar in the study groups. Concerning the duration of the hospitalisation and imobilisation, there were a little bit smaller in Clopidogrel plus Aspirin group. (Figure 6) For the primary efficacy plus safety endpoint (30 day mortality, inhospital graft oclusion or inhospital major bleeding), the rates were smaller for Clopidogrel plus Aspirin group, as the rates of in-hospital death Figure 5. Relative risks and 95% Confidence Indexes for primary efficacy composite endpoints in the study groups

In-hospital graft oclusion and myocardial infarction occurred rarely in patients treated with Clopidogrel plus Aspirin compared with the patients treated with Aspirin alone. Major hemor‐ rhagic events were similar in the study groups. Concerning the duration of the hospitalisation and imobilisation, there were a little bit smaller in Clopidogrel plus Aspirin group. (Figure 6) At hospital discharge and at 30 days, the combined efficacy and safety outcome endpoints were smaller in Clopidogrel plus Aspirin group. For the primary efficacy plus safety endpoint (30 day mortality, inhospital graft oclusion or inhospital major bleeding), the rates were smaller for Clopidogrel plus Aspirin group, as the rates of in-hospital death In-hospital graft oclusion and myocardial infarction occurred rarely in patients treated with Clopidogrel plus Aspirin compared

with the patients treated with Aspirin alone. Major hemorrhagic events were similar in the study groups. Concerning the duration

of the hospitalisation and imobilisation, there were a little bit smaller in Clopidogrel plus Aspirin group. (Figure 6)

On long term, the incidence of death, myocardial infarction, and revascularization occurring at one year following CABG was

The Kaplan Meier curves for primary efficacy and safety endpoints showed a smaller probability for death, myocardial infarction

greater in Aspirin group compared with Clopidogrel and Clopidogrel plus Aspirin groups (15% versus 12% versus 10%)

Figure 6. Frequency of composite and single endpoints at hospital discharge and at 30 days **Figure 6.** Frequency of composite and single endpoints at hospital discharge and at 30 days

or graft oclusion in Clopidogrel plus Aspirin group (Figure 7).

On long term, the incidence of death, myocardial infarction, and revascularization occurring at one year following CABG was greater in Aspirin group compared with Clopidogrel and Clopidogrel plus Aspirin groups (15% versus 12% versus 10%)

Early after treatment, the curves for Clopidogel associated or not with Aspirin started to separate from the one of Aspirin alone. At

Until the end of the follow up, for the primary efficacy endpoint and for the primary efficacy plus safety endpoint, event rates were abut two times higher for Aspirin group compared with Clopidogrel plus Aspirin group with log rank tests highly significant and

> **Clopidogrel plus Aspirin versus Clopidogrel versus Aspirin - Kaplan-Meier curves for primary efficacy plus safety endpoint**

30 days, differences in the primary endpoints between the three groups were already present.

Figure 7. The Kaplan Meier curves for primary efficacy and safety endpoints

clopidogrel alone group, although these differences were not significant.

Figure 8. Hemorhagic and ischemic postoperative complications in the study groups.

hemoragic stroke were similar in the three study groups

Figure 9. Relative risk for early graft thrombosis, acute myocardial infarction or hemorrhagic stroke

**-2,2**

**-5 -4 -3 -2 -1 0 1 2**

**Relative risk**

**-3,8**

**Clopidogrel plus Aspirin**

associated with rare risk of haematological adverse events.

risk of perioperative bleeding and a need for transfusion [22- 26].

clopidogrel for at least 5 days before CABG surgery (27).

National Quality Improvement Initiative [15, 28- 29].

demonstrated a reduction in the frequency of major cardiac events[2-14].

aspirin for use following coronary stenting.

**Figure 8.** Hemorhagic and ischemic postoperative complications in the study groups.

**1,8**

factors for these perioperative complications. (Figure 9)

perative complications. (Figure 9)

three study groups

**10. Discussions**

Concerning antiagregany therapy complications, the dates on in-hospital strokes are summarized in Figure 8.

There were no significant differences between the three groups regarding major hemorrhage and thrombocytopenia. Minor hemorrhage occurs more frequently in patients taking Aspirin. Total stroke and ischemic stroke rates were similar in the three groups. A few hemorrhagic conversions were seen in each of the tthree treatment groups. More minor or major bleeding complications and blood transfusions were also seen in the aspirin alone or associated with clopidogrel groups compared with

**Days to death or revascularisation**

**Clopidogrel plus Aspirin Clopidogrel Aspirin**

Significantly more major bleeding complications (p=0,0001), more transfusions (p=0,002) and a higher rate of thrombocytopenia (p=0,001) were seen in patients with associated treatment with anticoagulants, in patients older than 75 years and in diabetics, the rate of major bleeding complications was three times higher in those with associated anticoagulant therapy (4%versus 14% and 2%

The Antiagregant Treatment After Coronary Artery Surgery Depending on Cost – Benefit Report

The probability of early graft oclusion and perioperative myocardial infarction was smaller with Clopidogrel alone or associated with Aspirin versus Aspirin alone, the associated relative risks being negative because the studied drugs worked as protection

The probability of early graft oclusion and perioperative myocardial infarction was smaller with Clopidogrel alone or associated with Aspirin versus Aspirin alone, the associated relative risks being negative because the studied drugs worked as protection factors for these perio‐

As we seen before, the relative risks for the most severe antiagregant therapy complications,

As we seen before, the relative risks for the most severe antiagregant therapy complications, hemoragic stroke were similar in the

**Clopidogrel plus Aspirin versus Clopidogrel versus Aspirin – relative risk for early graft thrombosis, acute myocardial infarction or hemorrhagic stroke** 

**-1,8**

**-3,1**

**Early graft oclusion Acute myocardial infarction Hemorrhagic stroke**

**1,81**

**Clopidogrel Aspirin**

**-0,92**

**-1,7**

**1,81**

http://dx.doi.org/10.5772/54467

305

Multiple clinical trials showed the favorable effects of Clopidogrel alone or combined with Aspirin extending the indication for using Clopidogrel in a wide range of at risk patients and in long-term prevention in various manifestations of atherosclerosis.

**Figure 9.** Relative risk for early graft thrombosis, acute myocardial infarction or hemorrhagic stroke

In recent years, enormous growth in the use of coronary stenting procedures has resulted in a significant decrease in restenosis rates, while acute and sub-acute stent thrombosis remain a significant potential complication. It has been shown, however, that the risk of acute and sub-acute stent thrombosis is greatly reduced by the administration of antiplatelet therapies following stenting. Much clinical experience with combination of aspirin and ticlopidine has been gained, however ticlopidine has been shown to be

The CLASSICS study demonstrated the safety and efficacy of clopidogrel (with or without loading dose) in combination with

A large randomized trial has demonstrated that the acute administration of clopidogrel—a long-acting antiplatelet therapy—to patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS) can reduce subsequent risk for death, myocardial infarction, or stroke by 20% when continued for a mean duration of nine months [21]. However, single-center case series have demonstrated that, in patients requiring coronary artery bypass graft surgery, the use of Clopidogrel is associated with increased

This risk appears to be time dependent. For example, post-hoc data analysis from the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial revealed that bleeding risks were increased when patients had CABG surgery within 5 days of

These findings are reflected in the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the acute management of patients with NSTE ACS, which endorse the acute use of clopidogrel but also recommend withholding

Adherence in community practice to this guidelines recommendation is very unclear. has not been characterized previously. There are studies trying to characterize patterns of Clopidogrel use before CABG and to examine the time-dependent risks for postoperative transfusion among NSTE ACS patients treated at 264 hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines)

Combined antiplatelet therapy was also studied in a lot of trials and most of them showed good safety and efficacy profiles. Antiplatelet therapy and antithrombin therapy have been demonstrated to reduce the risk of cardiac events in patients presenting with acute coronary syndrome, yet all effective therapies also increase the risk of bleeding. Antiplatelet therapy and antithrombotic therapy have been demonstrated to favorably modify clinical outcome, and recent trials of revascularization in ACSs have

clopidogrel treatment but not when surgery was delayed for >5 days after treatment with clopidogrel [21]

significant p values (p<0,0001).

**Probability (%)**

versus 7% respectively

The Kaplan Meier curves for primary efficacy and safety endpoints showed a smaller proba‐ bility for death, myocardial infarction or graft oclusion in Clopidogrel plus Aspirin group (Figure 7).

Early after treatment, the curves for Clopidogel associated or not with Aspirin started to separate from the one of Aspirin alone. At 30 days, differences in the primary endpoints between the three groups were already present. Early after treatment, the curves for Clopidogel associated or not with Aspirin started to separate from the one of Aspirin alone. At 30 days, differences in the primary endpoints between the three groups were already present.

Until the end of the follow up, for the primary efficacy endpoint and for the primary efficacy plus safety endpoint, event rates were abut two times higher for Aspirin group compared with Clopidogrel plus Aspirin group with log rank tests highly significant and significant p values (p<0,0001). Until the end of the follow up, for the primary efficacy endpoint and for the primary efficacy plus safety endpoint, event rates were abut two times higher for Aspirin group compared with Clopidogrel plus Aspirin group with log rank tests highly significant and significant p values (p<0,0001).

**Figure 7.** The Kaplan Meier curves for primary efficacy and safety endpoints

Figure 8. Hemorhagic and ischemic postoperative complications in the study groups.

factors for these perioperative complications. (Figure 9)

Figure 7. The Kaplan Meier curves for primary efficacy and safety endpoints Concerning antiagregany therapy complications, the dates on in-hospital strokes are summarized in Figure 8. Concerning antiagregany therapy complications, the dates on in-hospital strokes are sum‐ marized in Figure 8.

There were no significant differences between the three groups regarding major hemorrhage and thrombocytopenia. Minor hemorrhage occurs more frequently in patients taking Aspirin. Total stroke and ischemic stroke rates were similar in the three groups. A few hemorrhagic conversions were seen in each of the tthree treatment groups. More minor or major bleeding complications and blood transfusions were also seen in the aspirin alone or associated with clopidogrel groups compared with clopidogrel alone group, although these differences were not significant. Significantly more major bleeding complications (p=0,0001), more transfusions (p=0,002) and a higher rate of thrombocytopenia (p=0,001) were seen in patients with associated treatment with anticoagulants, in patients older than 75 years and in diabetics, the There were no significant differences between the three groups regarding major hemorrhage and thrombocytopenia. Minor hemorrhage occurs more frequently in patients taking Aspirin. Total stroke and ischemic stroke rates were similar in the three groups. A few hemorrhagic conversions were seen in each of the tthree treatment groups. More minor or major bleeding complications and blood transfusions were also seen in the aspirin alone or associated with clopidogrel groups compared with clopidogrel alone group, although these differences were not significant.

versus 7% respectively Significantly more major bleeding complications (p=0,0001), more transfusions (p=0,002) and a higher rate of thrombocytopenia (p=0,001) were seen in patients with associated treatment with anticoagulants, in patients older than 75 years and in diabetics, the rate of major bleeding complications was three times higher in those with associated anticoagulant therapy (4%ver‐ sus 14% and 2% versus 7% respectively

The probability of early graft oclusion and perioperative myocardial infarction was smaller with Clopidogrel alone or associated with Aspirin versus Aspirin alone, the associated relative risks being negative because the studied drugs worked as protection

rate of major bleeding complications was three times higher in those with associated anticoagulant therapy (4%versus 14% and 2%

Concerning antiagregany therapy complications, the dates on in-hospital strokes are summarized in Figure 8.

There were no significant differences between the three groups regarding major hemorrhage and thrombocytopenia. Minor hemorrhage occurs more frequently in patients taking Aspirin. Total stroke and ischemic stroke rates were similar in the three groups. A few hemorrhagic conversions were seen in each of the tthree treatment groups. More minor or major bleeding complications and blood transfusions were also seen in the aspirin alone or associated with clopidogrel groups compared with

**Days to death or revascularisation**

**Clopidogrel plus Aspirin Clopidogrel Aspirin**

Early after treatment, the curves for Clopidogel associated or not with Aspirin started to separate from the one of Aspirin alone. At

Until the end of the follow up, for the primary efficacy endpoint and for the primary efficacy plus safety endpoint, event rates were abut two times higher for Aspirin group compared with Clopidogrel plus Aspirin group with log rank tests highly significant and

> **Clopidogrel plus Aspirin versus Clopidogrel versus Aspirin - Kaplan-Meier curves for primary efficacy plus safety endpoint**

30 days, differences in the primary endpoints between the three groups were already present.

Figure 7. The Kaplan Meier curves for primary efficacy and safety endpoints

clopidogrel alone group, although these differences were not significant.

significant p values (p<0,0001).

**Probability (%)**

versus 7% respectively

three study groups

**10. Discussions**

associated with rare risk of haematological adverse events.

risk of perioperative bleeding and a need for transfusion [22- 26].

clopidogrel for at least 5 days before CABG surgery (27).

National Quality Improvement Initiative [15, 28- 29].

demonstrated a reduction in the frequency of major cardiac events[2-14].

aspirin for use following coronary stenting.

Figure 8. Hemorhagic and ischemic postoperative complications in the study groups. **Figure 8.** Hemorhagic and ischemic postoperative complications in the study groups.

On long term, the incidence of death, myocardial infarction, and revascularization occurring at one year following CABG was greater in Aspirin group compared with Clopidogrel and

The Kaplan Meier curves for primary efficacy and safety endpoints showed a smaller proba‐ bility for death, myocardial infarction or graft oclusion in Clopidogrel plus Aspirin group

Early after treatment, the curves for Clopidogel associated or not with Aspirin started to separate from the one of Aspirin alone. At 30 days, differences in the primary endpoints

Early after treatment, the curves for Clopidogel associated or not with Aspirin started to separate from the one of Aspirin alone. At

Until the end of the follow up, for the primary efficacy endpoint and for the primary efficacy plus safety endpoint, event rates were abut two times higher for Aspirin group compared with Clopidogrel plus Aspirin group with log rank tests highly significant and significant p values

Until the end of the follow up, for the primary efficacy endpoint and for the primary efficacy plus safety endpoint, event rates were abut two times higher for Aspirin group compared with Clopidogrel plus Aspirin group with log rank tests highly significant and

> **Clopidogrel plus Aspirin versus Clopidogrel versus Aspirin - Kaplan-Meier curves for primary efficacy plus safety endpoint**

Clopidogrel plus Aspirin groups (15% versus 12% versus 10%)

30 days, differences in the primary endpoints between the three groups were already present.

between the three groups were already present.

Figure 7. The Kaplan Meier curves for primary efficacy and safety endpoints

**Figure 7.** The Kaplan Meier curves for primary efficacy and safety endpoints

clopidogrel alone group, although these differences were not significant.

sus 14% and 2% versus 7% respectively

Figure 8. Hemorhagic and ischemic postoperative complications in the study groups.

factors for these perioperative complications. (Figure 9)

Concerning antiagregany therapy complications, the dates on in-hospital strokes are summarized in Figure 8.

There were no significant differences between the three groups regarding major hemorrhage and thrombocytopenia. Minor hemorrhage occurs more frequently in patients taking Aspirin. Total stroke and ischemic stroke rates were similar in the three groups. A few hemorrhagic conversions were seen in each of the tthree treatment groups. More minor or major bleeding complications and blood transfusions were also seen in the aspirin alone or associated with clopidogrel groups compared with

There were no significant differences between the three groups regarding major hemorrhage and thrombocytopenia. Minor hemorrhage occurs more frequently in patients taking Aspirin. Total stroke and ischemic stroke rates were similar in the three groups. A few hemorrhagic conversions were seen in each of the tthree treatment groups. More minor or major bleeding complications and blood transfusions were also seen in the aspirin alone or associated with clopidogrel groups compared with clopidogrel alone group, although these differences were

Concerning antiagregany therapy complications, the dates on in-hospital strokes are sum‐

**Days to death or revascularisation**

**Clopidogrel plus Aspirin Clopidogrel Aspirin**

Significantly more major bleeding complications (p=0,0001), more transfusions (p=0,002) and a higher rate of thrombocytopenia (p=0,001) were seen in patients with associated treatment with anticoagulants, in patients older than 75 years and in diabetics, the rate of major bleeding complications was three times higher in those with associated anticoagulant therapy (4%versus 14% and 2%

Significantly more major bleeding complications (p=0,0001), more transfusions (p=0,002) and a higher rate of thrombocytopenia (p=0,001) were seen in patients with associated treatment with anticoagulants, in patients older than 75 years and in diabetics, the rate of major bleeding complications was three times higher in those with associated anticoagulant therapy (4%ver‐

The probability of early graft oclusion and perioperative myocardial infarction was smaller with Clopidogrel alone or associated with Aspirin versus Aspirin alone, the associated relative risks being negative because the studied drugs worked as protection

(Figure 7).

304 Artery Bypass

(p<0,0001).

**Probability (%)**

marized in Figure 8.

versus 7% respectively

not significant.

significant p values (p<0,0001).

The probability of early graft oclusion and perioperative myocardial infarction was smaller with Clopidogrel alone or associated with Aspirin versus Aspirin alone, the associated relative risks being negative because the studied drugs worked as protection factors for these perioperative complications. (Figure 9) The probability of early graft oclusion and perioperative myocardial infarction was smaller with Clopidogrel alone or associated with Aspirin versus Aspirin alone, the associated relative risks being negative because the studied drugs worked as protection factors for these perio‐ perative complications. (Figure 9)

As we seen before, the relative risks for the most severe antiagregant therapy complications, hemoragic stroke were similar in the three study groups As we seen before, the relative risks for the most severe antiagregant therapy complications, hemoragic stroke were similar in the

Figure 9. Relative risk for early graft thrombosis, acute myocardial infarction or hemorrhagic stroke **Figure 9.** Relative risk for early graft thrombosis, acute myocardial infarction or hemorrhagic stroke

Multiple clinical trials showed the favorable effects of Clopidogrel alone or combined with Aspirin extending the indication for using Clopidogrel in a wide range of at risk patients and in long-term prevention in various manifestations of atherosclerosis.

In recent years, enormous growth in the use of coronary stenting procedures has resulted in a significant decrease in restenosis rates, while acute and sub-acute stent thrombosis remain a significant potential complication. It has been shown, however, that the risk of acute and sub-acute stent thrombosis is greatly reduced by the administration of antiplatelet therapies following stenting. Much clinical experience with combination of aspirin and ticlopidine has been gained, however ticlopidine has been shown to be

The CLASSICS study demonstrated the safety and efficacy of clopidogrel (with or without loading dose) in combination with

A large randomized trial has demonstrated that the acute administration of clopidogrel—a long-acting antiplatelet therapy—to patients with non–ST-segment elevation acute coronary syndromes (NSTE ACS) can reduce subsequent risk for death, myocardial infarction, or stroke by 20% when continued for a mean duration of nine months [21]. However, single-center case series have demonstrated that, in patients requiring coronary artery bypass graft surgery, the use of Clopidogrel is associated with increased

This risk appears to be time dependent. For example, post-hoc data analysis from the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial revealed that bleeding risks were increased when patients had CABG surgery within 5 days of

These findings are reflected in the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the acute management of patients with NSTE ACS, which endorse the acute use of clopidogrel but also recommend withholding

Adherence in community practice to this guidelines recommendation is very unclear. has not been characterized previously. There are studies trying to characterize patterns of Clopidogrel use before CABG and to examine the time-dependent risks for postoperative transfusion among NSTE ACS patients treated at 264 hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines)

Combined antiplatelet therapy was also studied in a lot of trials and most of them showed good safety and efficacy profiles. Antiplatelet therapy and antithrombin therapy have been demonstrated to reduce the risk of cardiac events in patients presenting with acute coronary syndrome, yet all effective therapies also increase the risk of bleeding. Antiplatelet therapy and antithrombotic therapy have been demonstrated to favorably modify clinical outcome, and recent trials of revascularization in ACSs have

clopidogrel treatment but not when surgery was delayed for >5 days after treatment with clopidogrel [21]
