*6.4.1. The synergy between PCI with taxus and cardiac surgery (SYNTAX) score*

The SYNTAX score was designed as a comprehensive tool to classify the anatomic complexity and functional severity of a patients' coronary anatomy [57]. It is in fact an amalgamation of five different scoring/classification systems which can be distilled into three basic guiding principles: the first which describes the segments of the coronary artery tree; the second which describes the relative importance of the lesion based on the location and vascular territory to which the lesion impedes flow; the third which describes the complexity of the lesion [Table 1]. The 3-year follow-up for this study more definitively demonstrated that PCI and CABG tended to have similar cardiovascular outcomes in patients with lower complexity while at higher levels of anatomical complexity, patients that underwent CABG faired better [Figure 5] [59]. At three-year follow-up, patients with 3VD in the CABG group versus the PCI group with intermediate complexity (SYNTAX Score 23-32) had overall **decrease in MI with an ARR of 5.8**% and those with the highest complexity (SYNTAX Score >33) had a decrease in **all cause mortality (ARR of 6.6%) and a decrease in MI (ARR of 5.3%)** [51, 59]. This was also reflected in an *overall lower all-cause death* in the 3VD patients treated with CABG versus PCI with an *ARR of 3.8% (p=0.02)* and a *lower rate of cardiac death* in those treated with CABG versus PCI *ARR 3.3% (p=0.01) [59].* Interestingly, there was no significant difference for all-cause death or cardiac death between the CABG group versus the PCI group among patients with LM disease [59]. In contrast to those with 3VD, there were only significantly lower MACCE rates among patients with LM disease treated with CABG compared with PCI at the highest SYNTAX scores (>33) [59]. Although it is difficult to make precise conclusions regarding the subgroup analyses,

e. Presence or absence of heavy calcification f. Presence or absence of Thrombus g. Presence or absence of diffuse disease

1. The coronary tree can be divided into 16 major segments

the percentage of the left ventricle to which it supplies. For example the left main supplies 5 times the vascular territory compared to that of a dominant RCA; hence the

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LM will be given a score of 5 whereas the RCA will be given a score of 1.

a. Degree of involvement of side branches, anatomic configuration of lesions b. Presence or absence of a total occlusions and presence of collaterals

Functional significance 2. Functional importance of the particular epicardial vessel is weighted according to

Lesion Complexity 3. The complexity of the lesion itself can be described in terms of

c. Lesion length d. Tortuousity of vessel

**Table 1.** Principles underlying the development of the SYNTAX score

The recent SYNTAX trial has heralded a new era in revascularization. The recent European Guidelines have responded to the findings by giving a **IIa recommendation (level B evi‐ dence)** to PCI for revascularization in 3VD with low angiographic complexity (SYNTAX score ≤22) while giving a **class III recommendation (level A evidence)** for revascularization of such patients moderate to high angiographic complexity (SYNTAX score >22) [26]. The most recent ACC/AHA PCI guidelines state that in patients with 3VD with or without proximal LAD, revascularization with PCI for the purposes of prognosis is of **uncertain benefit (IIb recom‐ mendation, level B evidence)** [14]. In these populations, CABG is still given **Class I recom‐**

the overall trends are certainly compelling.

**Principle Description**

Definition and segmentation of the coronary artery tree

**mendation (level B evidence)** [Table 2 and 3] [14, 26].

### *6.4.2. The SYNTAX trial*

As techniques and technology for percutaneous coronary intervention have evolved, there has been an increasing number of patients with multivessel disease treated with percutaneous intervention [58].The SYNTAXtrial has evaluatedthePCI versus CABGinpatients with highly complex disease in the contemporary context of paclitaxel drug eluting stenting [51]. At 12 months there was a significantly lower incidence of the primary outcome of major cardiac and cerebrovascular events (MACCE) (ie. all cause death, stroke myocardial infarction or repeat revascularization) CABG group compared than the PCI group with an **ARR of 5.4% or NNT 19** [51]. This was largely driven by an increase need for repeat revascularization as the rates of *all cause death, MI or stroke was similar between the two groups* [51]. In the initial subgroup analysis at 12 months, while there was a trend towards lower MACCE in the CABG group compared to thePCIgroupas theSYNTAXscores increased,asignificantlylowerrateoftheprimaryoutcome could only be demonstrated at the highest SYNTAX scores (>33) [Figure 4] [51].


**Table 1.** Principles underlying the development of the SYNTAX score

the low overall use of optimal medical therapy, which may overestimate the effect size of revascularization in some anatomic subgroups. The use of ASA, ACEi's and BB's were all 40%

In summary, patients with moderate to high-risk scans by myocardial perfusion have signif‐ icant survival advantage if treated with revascularization over medical therapy alone *even in the absence of symptoms* [54, 55]. This benefit has more convincingly been demonstrated in patients undergoing CABG [54, 55]. Although the current standard and use of optimal medical therapy has improved over time, this effect is likely still significant. This survival benefit in the high-risk scans has not been clearly demonstrated in patients treated with PCI in stable coronary disease. Recently, the COURAGE trial involving over 2000 patients, which compared optimal medical therapy plus PCI with optimal medical therapy alone in stable CAD included a high prevalence of MVD (over two thirds) associated with the same proportion of multiple reversible defects by myocardial perfusion imaging [56]. This study showed, after exclusion of patients with high-risk anatomy (LM) and markedly positive exercise stress testing (sub‐ stantial ST depression or hypotensive response in stage I Bruce protocol), no significant difference in all cause death and non-fatal myocardial infarction between the medical therapy

*6.4.1. The synergy between PCI with taxus and cardiac surgery (SYNTAX) score*

The SYNTAX score was designed as a comprehensive tool to classify the anatomic complexity and functional severity of a patients' coronary anatomy [57]. It is in fact an amalgamation of five different scoring/classification systems which can be distilled into three basic guiding principles: the first which describes the segments of the coronary artery tree; the second which describes the relative importance of the lesion based on the location and vascular territory to which the lesion impedes flow; the third which describes the complexity of the lesion [Table 1].

As techniques and technology for percutaneous coronary intervention have evolved, there has been an increasing number of patients with multivessel disease treated with percutaneous intervention [58].The SYNTAXtrial has evaluatedthePCI versus CABGinpatients with highly complex disease in the contemporary context of paclitaxel drug eluting stenting [51]. At 12 months there was a significantly lower incidence of the primary outcome of major cardiac and cerebrovascular events (MACCE) (ie. all cause death, stroke myocardial infarction or repeat revascularization) CABG group compared than the PCI group with an **ARR of 5.4% or NNT 19** [51]. This was largely driven by an increase need for repeat revascularization as the rates of *all cause death, MI or stroke was similar between the two groups* [51]. In the initial subgroup analysis at 12 months, while there was a trend towards lower MACCE in the CABG group compared to thePCIgroupas theSYNTAXscores increased,asignificantlylowerrateoftheprimaryoutcome

could only be demonstrated at the highest SYNTAX scores (>33) [Figure 4] [51].

or less with no mention of statin therapy [55].

and PCI groups [56].

328 Artery Bypass

*6.4.2. The SYNTAX trial*

**6.4. Impact of complexity of disease**

The 3-year follow-up for this study more definitively demonstrated that PCI and CABG tended to have similar cardiovascular outcomes in patients with lower complexity while at higher levels of anatomical complexity, patients that underwent CABG faired better [Figure 5] [59]. At three-year follow-up, patients with 3VD in the CABG group versus the PCI group with intermediate complexity (SYNTAX Score 23-32) had overall **decrease in MI with an ARR of 5.8**% and those with the highest complexity (SYNTAX Score >33) had a decrease in **all cause mortality (ARR of 6.6%) and a decrease in MI (ARR of 5.3%)** [51, 59]. This was also reflected in an *overall lower all-cause death* in the 3VD patients treated with CABG versus PCI with an *ARR of 3.8% (p=0.02)* and a *lower rate of cardiac death* in those treated with CABG versus PCI *ARR 3.3% (p=0.01) [59].* Interestingly, there was no significant difference for all-cause death or cardiac death between the CABG group versus the PCI group among patients with LM disease [59]. In contrast to those with 3VD, there were only significantly lower MACCE rates among patients with LM disease treated with CABG compared with PCI at the highest SYNTAX scores (>33) [59]. Although it is difficult to make precise conclusions regarding the subgroup analyses, the overall trends are certainly compelling.

The recent SYNTAX trial has heralded a new era in revascularization. The recent European Guidelines have responded to the findings by giving a **IIa recommendation (level B evi‐ dence)** to PCI for revascularization in 3VD with low angiographic complexity (SYNTAX score ≤22) while giving a **class III recommendation (level A evidence)** for revascularization of such patients moderate to high angiographic complexity (SYNTAX score >22) [26]. The most recent ACC/AHA PCI guidelines state that in patients with 3VD with or without proximal LAD, revascularization with PCI for the purposes of prognosis is of **uncertain benefit (IIb recom‐ mendation, level B evidence)** [14]. In these populations, CABG is still given **Class I recom‐ mendation (level B evidence)** [Table 2 and 3] [14, 26].

**Figure 4.** 12-month Subgroup analysis of the rates of (all cause death, stroke, myocardial infarction and repeat revas‐ cularization) between those treated by CABG versus PCI stratified by SYNTAX score. A significant difference in the overall rates was not significantly different at low (<22) and intermediate (23-32) SYNTAX scores. At the highest SYN‐ TAX score (>33), there was a significantly lower rate of major cardiac and cerebrovascular events. Reproduced with permission from Serruys PW et al. NEJM 2009. 360;10: 961-972.

**Figure 5.** 3-year subgroup analysis of the rates of MACCE (all cause death, stroke, myocardial infarction and repeat revascularization) between those treated by CABG (blue line) versus PCI (yellow line) stratified by SYNTAX score: Low SYNTAX Score (0-22), Intermediate SYNTAX Score (23-32), High SYNTAX Score (>33). Results are provided for overall group (A-C), 3VD patients (D-F) and LM patients (G–I). Reproduced with permission from Kappetein et al. European

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Heart Journal 2011. 32: 2125-2134.

**Figure 5.** 3-year subgroup analysis of the rates of MACCE (all cause death, stroke, myocardial infarction and repeat revascularization) between those treated by CABG (blue line) versus PCI (yellow line) stratified by SYNTAX score: Low SYNTAX Score (0-22), Intermediate SYNTAX Score (23-32), High SYNTAX Score (>33). Results are provided for overall group (A-C), 3VD patients (D-F) and LM patients (G–I). Reproduced with permission from Kappetein et al. European Heart Journal 2011. 32: 2125-2134.

**Figure 4.** 12-month Subgroup analysis of the rates of (all cause death, stroke, myocardial infarction and repeat revas‐ cularization) between those treated by CABG versus PCI stratified by SYNTAX score. A significant difference in the overall rates was not significantly different at low (<22) and intermediate (23-32) SYNTAX scores. At the highest SYN‐ TAX score (>33), there was a significantly lower rate of major cardiac and cerebrovascular events. Reproduced with

permission from Serruys PW et al. NEJM 2009. 360;10: 961-972.

330 Artery Bypass


**Table 2.** ESC Guidelines on revascularization for complex coronary disease. Indications for CABG and PCI are tabulated for stable patients with low predicted surgical mortality and lesions suitable for either modes of revascularization. CABG= coronary artery bypass grafting; CAD= coronary artery disease; LAD = left anterior descending; PCI= percutaneous coronary intervention; VD= vessel disease. Reproduced with permission from Wijns W et al. European Heart Journal 2010. 31: 2501-2555.

**Table 3.** ACC Guidelines on revascularization for complex coronary disease to improve survival. Indications for CABG and PCI are tabulated. CABG = coronary artery bypass grafting; COPD= chronic obstructive pulmonary disease; EF= ejection fraction; LAD=left anterior descending artery; LIMA= left internal mammary artery; LV =left ventricular; N/A= not applicable; PCI = percutaneous coronary intervention; SIHD = stable ischemic heart disease; STEMI= ST-elevation myocardial infarction; STS= Society of Thoracic Surgeons; SYNTAX = Synergy between percutaneous coronary intervention with TAXUS and Cardiac Surgery; TIMI= Thrombolysis in myocardial infarction; UA/NSTEMI =unstable angina/ non-ST elevation myocardial infarction; UPLM= unprotected left main disease; VT=ventricular tachycardia.

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Reproduced with permission from Levine GN et al. Circulation 2011. 124: e574-e651.


**Table 3.** ACC Guidelines on revascularization for complex coronary disease to improve survival. Indications for CABG and PCI are tabulated. CABG = coronary artery bypass grafting; COPD= chronic obstructive pulmonary disease; EF= ejection fraction; LAD=left anterior descending artery; LIMA= left internal mammary artery; LV =left ventricular; N/A= not applicable; PCI = percutaneous coronary intervention; SIHD = stable ischemic heart disease; STEMI= ST-elevation myocardial infarction; STS= Society of Thoracic Surgeons; SYNTAX = Synergy between percutaneous coronary intervention with TAXUS and Cardiac Surgery; TIMI= Thrombolysis in myocardial infarction; UA/NSTEMI =unstable angina/ non-ST elevation myocardial infarction; UPLM= unprotected left main disease; VT=ventricular tachycardia. Reproduced with permission from Levine GN et al. Circulation 2011. 124: e574-e651.

**Table 2.** ESC Guidelines on revascularization for complex coronary disease. Indications for CABG and PCI are tabulated for stable patients with low predicted surgical mortality and lesions suitable for either modes of revascularization. CABG= coronary artery bypass grafting; CAD= coronary artery disease; LAD = left anterior descending; PCI= percutaneous coronary intervention; VD= vessel disease. Reproduced with permission from Wijns W et al. European

Heart Journal 2010. 31: 2501-2555.

332 Artery Bypass

For those with unprotected left main disease (UPLM), both the ACC and ESC guidelines still give a **Class I** *recommendation for CABG in all cases* **(Classified as Grade A evidence for ESC and Grade B evidence for ACC)**[14, 26]. They have both also given a **IIa recommendation for PCI in Stable Ischemic Heart Disease (SIHD) in UPLM when the SYNTAX is 22 or less (eg isolated ostial or main trunk LM)** and **IIb recommendation for PCI for low or inter‐ mediate SYNTAX score (<33) (Level B evidence)** [14, 26]

**7.3 Cardiogenic shock**

attempt was 0.9 hour for PCI and 2.7 hours for CABG [64].

man JS. et al. JAMA 2006. 295;21: 2511-2515.

The optimal mode of revascularization in patients with multivessel disease and cardiogenic shock is still under debate due to lack of supporting evidence for or against either PCI or CABG. It has been previously shown in the **Should We Emergently Revascularize Occluded Arteries for Cardiogenic Shock (SHOCK) Trial** that urgent revascularization with PCI or CABG for cardiogenic shock in the setting of STEACS has *mortality benefit* with an **ARR of 13 percent** or **NNT of 8** at 6 months compared with medical management [64]. This difference continued out to one year and remained stable at long-term follow up [Figure 6] [65, 66]. In the revascu‐ larization group, 64 percent were treated with angioplasty whereas 36 percent were treated with CABG [64]. Interestingly, because the mode of revascularization was at the discretion of the treating physicians, patients treated with CABG compared with those that received PCI tended to more often have LM disease and 3VD [64]. Nevertheless, there was no significant difference between patients treated with PCI versus CABG at either 30 days or at 1 year [64]. Certainly the advantage of PCI for revascularization over CABG would be a reduced time required to achieve revascularization; the time of randomization to first revascularization

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**Figure 6.** Kaplan-Meier Survival Curves For Early Revascularization Versus Initial Medical Stabilization in Long Term Follow-Up. ERV= Early Revascularization; IMS =Initial Medical Stabilization. Reproduced with permission from Hoch‐

There is a lack of randomized data regarding the optimal mode of revascularization in cardiogenic shock for acute coronary syndromes [67]. Currently, both the ACC and ESC

It is recognized however, that some populations are not expected to derive prognostic benefit from revascularization. In such groups for the purposes of alleviating symptoms refractory to optimal medical therapy, CABG and PCI have equivalent **Class I recommendation (level A evidence)** unless **SYNTAX is >22 in which case CABG is still favored (Class IIa recommen‐ dation, level B evidence)** [14].
