**8. Statistics (Figure 2, 3)**

The data base was done using Visual Fox Pro programme. The main variables used were:

	- **◦** patient ID Data

**Group A –**

Digoxin 23,68% 23,94% 24,13%

ACE inhibitors 67,25% 68,58% 63,68%

Angiotensin II inhibitors 24,43% 23,69% 25,12%

Beta blockers 89,92% 89,28% 90,29%

Aspirin before surgery 61,46% 63,84% 65,17%

Calcium channel blockers 25,44% 25,93% 26,37%

Diuretics 19,90% 20,70% 20,39%

Aldactone 21,91% 21,94% 20,89%

Lipid lowering agents 89,92% 93,76% 94,28%

61,46% of patients received Aspirin before surgery in group A, respectively 63,84% in group

The primary efficacy and efficacy plus safety endpoints and their individual components in

The clinical diagnosis at the time of randomization was similar in the three treated arms of the

**•** Over half of the patients presented with unstable angina (49,62% in group A, 51,63% in

**•** Approximately one in five-six patients had experienced a recent myocardial infarction

**•** About a third presented with stable angina or another diagnosis requiring antiagregant regimen (aproximatively 33,6% in each treatment arm - 33.75% in group A, 33,66% in group

The data base was done using Visual Fox Pro programme. The main variables used were:

(16.37% in group A, 21,94% in group B and 22.39% respectively in group C).

**Table 2.** Number of patients who received concomitant medications during stay in hospital

B and 65,17% in group C.

B, 33,58% in group C).

**8. Statistics (Figure 2, 3)**

study:

298 Artery Bypass

the treatment groups are shown in Table 3.

group B and 53.48% respectively in group C).

**397 pts Group B- 401 pts Group C-**

**402 pts**

	- **◦** presence and type of postoperative complications
	- **◦** death and its causes.

The statistical analysis was performed using the SYSTAT and SPSS programmes for:

	- **◦** for qualitative variables: CHI square test or Fischer exact test
	- **◦** for quantitative variables: T test (Student test), ANOVA test or U test depending on samples volumes and Kruskal Wallis nonparametric tests or other methods of statistical correlation as analysis of simple linear and multivariate regression

The calculation of the cost-benefit ratio for each type of treatment and for routinely use clopidogrel in CABG was done taking into account the following parameters:

	- **◦** cost of the treatment for each patient
	- **◦** number of supplementary echographic and endoscopic examinations per patient
	- **◦** number of bleeding episodes and cost per patient
	- **◦** global cost/ patient
	- **◦** early postoperative mortality rates for surgical intervention (global and specific depend‐ ing on individual risk and type of the antiagregant regimen)

Beta blockers 89,92% 89,28% 90,29% Aspirin before surgery 61,46% 63,84% 65,17% Calcium channel blockers 25,44% 25,93% 26,37% Diuretics 19,90% 20,70% 20,39% Aldactone 21,91% 21,94% 20,89% Lipid lowering agents 89,92% 93,76% 94,28% Table 2: Number of patients who received concomitant medications during stay in hospital

The data base was done using Visual Fox Pro programme. The main variables used were:

preoperative diagnosis

type of surgical intervention

 *Outcomes variables:*  presence and type of postoperative complications death and its causes. The statistical analysis was performed using the SYSTAT and SPSS programmes for:

for qualitative variables: CHI square test or Fischer exact test

*Relative Risk* calculation and the 95% *confidence limits* for treatment groups

efficiency of different antiplatelet therapies following coronary artery surgery.

number of supplementary echographic and endoscopic examinations per patient

Data interpretation was performed taking into account the following hypothesis:

 **Surgical risk depending on preoperative parameters Comorbidities & associated risk factors & NYHA class type of surgical intervention** 

 *- Outcome variables –* Occurence and type of postoperative complications - Death and its causes

coronary artery bypass surgery was considered as having *uncertain indication*;

Study protocol–*Prediction variables–* **ID data & age of the patients Preoperative diagnosis** 

ICU duration and complications occured

methods of statistical correlation as *analysis of simple linear and multivariate regression* 

immediate and long term postoperative complications rates depending on the type of the antiagregant regimen

cabg patients, which was used then for estimation of the cost-benefit ratio associated with the type of the antiagregant regimen

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

 **specific variables related to the surgical performance:** 

 **Antiagregant regimen has modified the evolution and how?**

coronary artery bypass surgery was considered as having a *standard indication,* being recommended in each case.

**duration of surgical intervention, intraoperative complications** 

**Database in Visual Fox Pro** 

 **ICU duration and complications** 

C).

**Statistics**

A, 33,66% in group B, 33,58% in group C).

*Prediction variables* : patient ID Data

 parameters related to the type of the treatment cost of the treatment for each patient

parameters related to surgical intervention

global cost/ patient

 age gender co-morbidities associated risk factors.

benefit for each patient;

Figure 2. Statistic methodology

**Parameters related to**:

**>1 UNFAVOURABLE**

**Figure 2.** Statistic methodology

**TREATMENT** -cost of antiplatelet treatment/ patient -nr. of bleeding episodes&cost per patient and disease -global cost/ patient

**Results**

Clopidogel group.

Calculation of cost-benefit ratio

Statistical analysis: Systat, SPSS

Power of association between *prediction and outcomes variables* 


*Cost-benefit ratio c***alculation for routinely use Clopidogrel postCABG**

**SURGICAL INTERVENTION** -early postoperativ e mortality (global&specif ic depending on indiv idual


depending on treatment -ICU length of stay and cost - quality of life at 1 y ear postop.dep.on


**RISK SCORE per patient on types of treatment COST of Clopidogrel routinely use COST-BENEFIT RATIO**

> **=1 NEUTRAL**

f (benef .&risk for each case)

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

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

risk& treatment)

treatment

**UNCERTAIN INDICATION RELATIVE INDICATION**

Figure 3. Statistical analysis and cost-benefit report calculation

times higher than with Aspirin alone (Figure 4)

**Figure 3.** Statistical analysis and cost-benefit report calculation

primary efficacy plus safety composite endpoints.

efficacy composite endpoints in the study groups

group, as the rates of in-hospital death

plus Aspirin group. (Figure 6)

Calculation of *relativ risk* & CI *95%* the type of antiagregant regimen in CABG

ICU length of stay and cost

Parameters related to the patient

number of bleeding episodes and cost per patient

 **(Figure 2, 3)**

61,46% of patients received Aspirin before surgery in group A, respectively 63,84% in group B and 65,17% in group C.

cardiac lesions (NYHA class), type and duration of surgical intervention, associated risk factors)

The clinical diagnosis at the time of randomization was similar in the three treated arms of the study:

The primary efficacy and efficacy plus safety endpoints and their individual components in the treatment groups are shown in Table 3.

– Over half of the patients presented with unstable angina (49,62% in group A, 51,63% in group B and 53.48% respectively in group C).

– Approximately one in five-six patients had experienced a recent myocardial infarction (16.37% in group A, 21,94% in group B and 22.39% respectively in group

– About a third presented with stable angina or another diagnosis requiring antiagregant regimen (aproximatively 33,6% in each treatment arm - 33.75% in group

specific variables related to the surgical performance: duration of surgical intervention, intraoperative complications

for quantitative variables: T test (*Student test*), ANOVA test or *U test* depending on samples volumes and *Kruskal Wallis nonparametric tests* or other

 *Cost-benefit ratio* calculation for using different antiplatelets agents after coronary artery bypass grafting. It was determined using a special programme, which used the data from the database and different economic data from specialized departments from our Institute, in order to perform the assessment of the

The calculation of the cost-benefit ratio for each type of treatment and for routinely use clopidogrel in CABG was done taking into account the following parameters:

quality of life at 1 month and 1 year postoperatively on risk subgroups and on type of surgical interventions depending on the type of the antiagregant regimen

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

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




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

301

**PATIENT** -age -gender -comorbidities -associated risk f actors

**<1 FAVOURABLE**

**FIRM INDICATION ROUTINE USE OF Clopidogr**

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

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

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

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

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

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

Figure 5. Relative risks and 95% Confidence Indexes for primary

associated MR , but, in all cases *were* lower among patients treated with Clopidogrel associated with Aspirin than among those treated with Aspirin alone

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

*Measurement of the power of association between the prediction variables and outcomes* using different tests depending on the type of variables:

 early postoperative mortality rates for surgical intervention (global and specific depending on individual risk and type of the antiagregant regimen) in hospital and at 1 year graft occlusion/myocardial infarction/severe bleeding on subgroups of patients taking into account the individual risk

of patients taking Clopidogrel (cases) and the number of patients who have not taken Clopidogrel (controls). The confounders were controlled by stratification.

surgical risk (calculated using a scale from 1 to 10 taking into account different preoperative parameters: age, co-morbidities, severity of

	- **◦** age
	- **◦** gender
	- **◦** co-morbidities
	- **◦** associated risk factors.

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 type of the antiagre‐ gant regimen

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 (controls). The confounders were controlled by stratification.

Data interpretation was performed taking into account the following hypothesis:


coronary artery bypass surgery was considered as having a *standard indication,* being recommended in each case.

immediate and long term postoperative complications rates depending on the type of the antiagregant regimen

cabg patients, which was used then for estimation of the cost-benefit ratio associated with the type of the antiagregant regimen

Beta blockers 89,92% 89,28% 90,29% Aspirin before surgery 61,46% 63,84% 65,17% Calcium channel blockers 25,44% 25,93% 26,37% Diuretics 19,90% 20,70% 20,39% Aldactone 21,91% 21,94% 20,89% Lipid lowering agents 89,92% 93,76% 94,28% Table 2: Number of patients who received concomitant medications during stay in hospital

The data base was done using Visual Fox Pro programme. The main variables used were:

preoperative diagnosis

type of surgical intervention

 *Outcomes variables:*  presence and type of postoperative complications death and its causes. The statistical analysis was performed using the SYSTAT and SPSS programmes for:

for qualitative variables: CHI square test or Fischer exact test

*Relative Risk* calculation and the 95% *confidence limits* for treatment groups

efficiency of different antiplatelet therapies following coronary artery surgery.

number of supplementary echographic and endoscopic examinations per patient

Data interpretation was performed taking into account the following hypothesis:

coronary artery bypass surgery was considered as having *uncertain indication*;

ICU duration and complications occured

methods of statistical correlation as *analysis of simple linear and multivariate regression* 

61,46% of patients received Aspirin before surgery in group A, respectively 63,84% in group B and 65,17% in group C.

cardiac lesions (NYHA class), type and duration of surgical intervention, associated risk factors)

The clinical diagnosis at the time of randomization was similar in the three treated arms of the study:

The primary efficacy and efficacy plus safety endpoints and their individual components in the treatment groups are shown in Table 3.

– Over half of the patients presented with unstable angina (49,62% in group A, 51,63% in group B and 53.48% respectively in group C).

– Approximately one in five-six patients had experienced a recent myocardial infarction (16.37% in group A, 21,94% in group B and 22.39% respectively in group

– About a third presented with stable angina or another diagnosis requiring antiagregant regimen (aproximatively 33,6% in each treatment arm - 33.75% in group

specific variables related to the surgical performance: duration of surgical intervention, intraoperative complications

for quantitative variables: T test (*Student test*), ANOVA test or *U test* depending on samples volumes and *Kruskal Wallis nonparametric tests* or other

 *Cost-benefit ratio* calculation for using different antiplatelets agents after coronary artery bypass grafting. It was determined using a special programme, which used the data from the database and different economic data from specialized departments from our Institute, in order to perform the assessment of the

The calculation of the cost-benefit ratio for each type of treatment and for routinely use clopidogrel in CABG was done taking into account the following parameters:

quality of life at 1 month and 1 year postoperatively on risk subgroups and on type of surgical interventions depending on the type of the antiagregant regimen

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

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



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

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

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

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

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

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

Figure 5. Relative risks and 95% Confidence Indexes for primary

associated MR , but, in all cases *were* lower among patients treated with Clopidogrel associated with Aspirin than among those treated with Aspirin alone

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

*Measurement of the power of association between the prediction variables and outcomes* using different tests depending on the type of variables:

 early postoperative mortality rates for surgical intervention (global and specific depending on individual risk and type of the antiagregant regimen) in hospital and at 1 year graft occlusion/myocardial infarction/severe bleeding on subgroups of patients taking into account the individual risk

of patients taking Clopidogrel (cases) and the number of patients who have not taken Clopidogrel (controls). The confounders were controlled by stratification.

surgical risk (calculated using a scale from 1 to 10 taking into account different preoperative parameters: age, co-morbidities, severity of

**Figure 2.** Statistic methodology

Figure 2. Statistic methodology

C).

**Statistics**

A, 33,66% in group B, 33,58% in group C).

*Prediction variables* : patient ID Data

 parameters related to the type of the treatment cost of the treatment for each patient

parameters related to surgical intervention

global cost/ patient

 age gender co-morbidities associated risk factors.

ICU length of stay and cost

Parameters related to the patient

number of bleeding episodes and cost per patient

 **(Figure 2, 3)**

**•** parameters related to surgical intervention

antiagregant regimen

**◦** ICU length of stay and cost

**•** Parameters related to the patient

**◦** age

300 Artery Bypass

**◦** gender

gant regimen

**◦** co-morbidities

**◦** associated risk factors.

The confounders were controlled by stratification.

surgery was considered as having uncertain indication;

**◦** early postoperative mortality rates for surgical intervention (global and specific depend‐

**◦** in hospital and at 1 year graft occlusion/myocardial infarction/severe bleeding on

**◦** immediate and long term postoperative complications rates depending on the type of the

**◦** quality of life at 1 month and 1 year postoperatively on risk subgroups and on type of

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 type of the antiagre‐

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 (controls).

**•** a cost-benefit report >1 was considered unfavourable from economic point of view; for these patients the routine use of Clopidogrel as antiplatelet therapy after coronary artery bypass

**•** a cost-benefit report =1 was considered neutral and included the patients subgroups classified as relative indication for the routine use of clopidogrel as antiplatelet therapy after coronary artery bypass surgery, risks and benefits of using that therapy it being appreciated

**•** a cost-benefit report <1 was considered favourable from economic point of view; for these patients the routine use of Clopidogrel as antiplatelet therapy after coronary artery bypass surgery was considered as having a standard indication, being recommended in each case.

Data interpretation was performed taking into account the following hypothesis:

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

surgical interventions depending on the type of the antiagregant regimen

ing on individual risk and type of the antiagregant regimen)

subgroups of patients taking into account the individual risk

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

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

Figure 3. Statistical analysis and cost-benefit report calculation **ResultsFigure 3.** Statistical analysis and cost-benefit report calculation

Clopidogel group.

times higher than with Aspirin alone (Figure 4)

primary efficacy plus safety composite endpoints.

efficacy composite endpoints in the study groups

group, as the rates of in-hospital death

plus Aspirin group. (Figure 6)

recommended in each case.

Figure 2. Statistic methodology
