**3. Patients with STEMI and MVD**

#### **3.1 Introduction**

About half of the patients who enter with acute myocardial infarction with ST segment elevation (STEMI) have MVD [46]. Although it seems logical that patients with MVD have a worse prognosis, due to the extent of coronary lesions manifested by higher scores, this remains controversial. There are elements that determine that lesions at multiple sites of the coronary arteries can be complicated, and there are studies in which the multivessel PCI shows a better evolution compared to patients in whom they only receive treatment of the culprit vessel, although there are other studies they don't confirm it and consider them innocent [47], and therefore these arteries warrant treatment in much the same way one would approach any unstable lesion. An update on primary PCI for patients with STEMI (class IIb) [20, 48] by the guidelines recommends intervention of the non-culprit at the time of primary PCI if the patient is hemodynamically stable before the discharge. Subsequently, two randomized trials showed that treatment of non-culprit lesions in the acute phase reduced the risk of future adverse events. The PRAMI trial [49], CvlPRIT trial [50], and recently DANAMI-3-PRIMULTI trial [51] studied the clinical outcomes by comparing the FFR guided by CR with culprit-only PCI in STEMI and found that the composite rate of all-cause mortality, nonfatal reinfarction, and repeat revascularization was significantly lower in the CR group, which was mainly driven by a reduction in repeat revascularization. More recently, another randomized trial (COMPARE ACUTE) [52] revealed that FFR-guided complete revascularization of non-culprit arteries in an acute setting was associated with a lower risk of the composite cardiovascular outcome. We emphasized the importance of individualizing care for each patient, balancing the anticipated benefits from multivessel PCI against the potential risks.

#### **3.2 Complete vs. incomplete revascularization**

Data derived from more than 150,000 patients undergoing PCI suggest that less than 50% of all patients with MVD have CR after they have undergone percutaneous revascularization. It was observed that CR is associated with a fall in the incidence of mortality, MI, and MACCE, regardless of whether an anatomical or functional definition was used for the evaluation of IR, and perhaps the degree CR is associated with the magnitude of the risk. The association between IR and adverse clinical outcomes suggests that in patients with MVD, the degree of CR that can be achieved by PCI should be considered when discussing the choice of revascularization modality with the heart team, in addition to considering the complexity of the injury, functional significance, patient characteristics, and ERACI score [9, 53].

#### **3.3 Randomized trials**

The preventive angioplasty in acute myocardial infarction (PRAMI) study [49] was performed in five centers in the United Kingdom in patients with STEMI and MVD, where they were randomized to preventive angioplasty of non-culprit vessels vs. only PCI of the culprit vessel. It was the first of the trials that incorporated a new concept on complete revascularization in STEMI and MVD. At practically 2 years of follow-up, a reduction of more than 50% was observed on the primary end point that was the combined event of cardiac death, nonfatal MI, and refractory angina, of the patients of the preventive PCI group vs. PCI only of the culprit vessel. The study was designed to include 600 patients but was stopped early with 465 patients because the data was conclusive by the data security committee. CvLPRIT [50] (trial of primary PCI vs. complete primary injury) compared a multivessel PCI strategy in patients with STEMI (performed at the time of primary PCI or revascularization in stages before discharge) to revascularization of culprit-vessel only. In this trial, 7 centers in the United Kingdom participated, where 296 patients were included, randomization was performed by stratification between previous or non-previous infarction, and according to the time ≤3 or >3 h. The primary end point of the study was the combined events of all-cause mortality, recurrent MI, heart failure, or revascularization driven by 12-month ischemia. The result produced a reduction of primary events to more than half in the CR group (10 vs. 21%; hazard ratio (HR), 0.45; 95% CI, 0.24–0.84; p = 0.009). There were no differences in individual events. In the compare acute study [52] (multivessel angioplasty guided by fractional flow reserve in myocardial infarction), they included 885 patients in 24 centers in Asia and Europe, where patients with STEMI and MVD, after a primary PCI stable, were randomized to complete revascularization guided by FFR of the artery not culprit of all lesions greater than 50% vs. angioplasty only of the culprit vessel. The FFR was performed in both groups, but its results were blind to operators and patients in the culprit vessel group only. The primary end point of the study was the MACCE at 1 year, which was significantly better in the FFR-guided group (7.8% vs. 20.5%) than in the culprit vessel only (HR, 0.35; 95% CI, 0.22–0.55; p < 0.001). This was at the expense of revascularization without changes in mortality or MI. The DANAMI-3- PRIMULTI [51] (The Third Danish Study of Optimal Acute Treatment of Patients With STEMI: Primary PCI in Multivessel Disease) was conducted at two university centers in Denmark, where they randomized 627 patients with STEMI and MVD after a successful primary PCI of the culprit vessel to a complete revascularization guided by FFR compared to conservative treatment. The primary end point was MACCE, which was composed of death, nonfatal MI, and revascularization driven by ischemia. After an average follow-up of 27 months, it was observed that the FFR group presented a MACCE of 13% vs. 22% in conservative treatment (HR, 0.56; 95%

**17**

**Figure 2** [59].

**3.7 Guidelines**

*Current Status, Perspectives, and Future Directions of Multivessel Disease and Left Main…*

CI, 0.38–0.83; p = 0.004). This result was due to an excess of revascularization driven by ischemia in the conservative group. In the PRAGUE-13 trial [54], Ota Hlinomaz et al. in a university hospital in the Czech Republic randomized 214 patients with STEMI and MVD, who had an obstruction of at least ≥70%, to a group with CR day 3–40 after primary PCI compared with conservative treatment, where the primary end point was MACCE that was composed of death from all causes, nonfatal MI, and stroke, and after a mean of 38 months showed no significant differences in both groups, (16% in CR vs. 13.9 in conservative treatment; HR, 1.35; 95% CI, 0.66–2.74; p = 0.407). CULPRIT-SHOCK [55] was a study that surprised in terms of results and gave new directives in the treatment that we had been doing in this pathology, this multicenter study was carried out in 83 centers in Europe that included 706 patients with cardiogenic shock, with SETEMI and NSTEMI, at CR compared to the treatment of the culprit vessel only (CVO), whose primary end point was mortality and renal failure with dialysis at 30 days. The combined event occurred in 55.4 in the CR vs. 45.9% in the treatment of the CVO, (relative risk, 0.83; 95% CI, 0.71–0.96; p = 0.01). A significant difference in mortality between the two groups was also observed (CR 51.5 vs. CVO 43.3%; relative risk, 0.84; 95% CI, 0.72–0.98; p = 0.03).

Hae Chang Jeong et al., developed a new Score to predict combined events in patients with AMI and MVD, the CONVERSE score, based on the PCI registry of nine centers in universities in Korea, in a registry of 5025 patients, evaluated 2630 patients who AMI and MVD had presented, and they were divided into two groups those who were treated CVO that were 1029 patients vs. those with PCI of MVD 1601, for this they used 8 variables that had been predictors of events in a previous study [56]. The variables were patients with arterial hypertension, diabetes, age over 65 years, deterioration of EF, heart failure in presentation, chronic renal failure, elevated CRP plasmatic, anterior descending or LMCA as culprit vessel, each variable awarded a point, the elevation above 3 points in these patients were in

In this meta-analysis of 10 trials with 2285 patients. Among the three complete revascularization strategies, that is, during the procedure index, during hospitalization or after discharge vs. treatment of the culprit vessel only, it was associated with MACCE reduction (reference rate ratio [RR], 0.57; 95% CI, 0.42–0.77), due to a lower rate of emergency revascularization. Mortality of all causes and spontaneous reinfarction was similar between the two groups. There were no differences between the different types of strategies at the time of revascularization in patients with CR [58].

MVD PCI treatment during STEMI is considered strongly indicated when there

are critical lesions or associated thrombotic lesions when the culprit vessel has already been treated if there is persistent ischemia. When there is cardiogenic shock, the only treatment of the culprit vessel is the treatment of choice [20]. Patients with stable STEMI and MVD after a primary PCI the recommendation of multivessel PCI

**3.6 An algorithm for the management of STEMI patients with MVD**

*DOI: http://dx.doi.org/10.5772/intechopen.89419*

**3.4 Score to evaluate the treatment in MVD with MI**

linear relationship with the elevation of the MACCE [57].

**3.5 Meta-analysis of MVD in STEMI**

*Current Status, Perspectives, and Future Directions of Multivessel Disease and Left Main… DOI: http://dx.doi.org/10.5772/intechopen.89419*

CI, 0.38–0.83; p = 0.004). This result was due to an excess of revascularization driven by ischemia in the conservative group. In the PRAGUE-13 trial [54], Ota Hlinomaz et al. in a university hospital in the Czech Republic randomized 214 patients with STEMI and MVD, who had an obstruction of at least ≥70%, to a group with CR day 3–40 after primary PCI compared with conservative treatment, where the primary end point was MACCE that was composed of death from all causes, nonfatal MI, and stroke, and after a mean of 38 months showed no significant differences in both groups, (16% in CR vs. 13.9 in conservative treatment; HR, 1.35; 95% CI, 0.66–2.74; p = 0.407). CULPRIT-SHOCK [55] was a study that surprised in terms of results and gave new directives in the treatment that we had been doing in this pathology, this multicenter study was carried out in 83 centers in Europe that included 706 patients with cardiogenic shock, with SETEMI and NSTEMI, at CR compared to the treatment of the culprit vessel only (CVO), whose primary end point was mortality and renal failure with dialysis at 30 days. The combined event occurred in 55.4 in the CR vs. 45.9% in the treatment of the CVO, (relative risk, 0.83; 95% CI, 0.71–0.96; p = 0.01). A significant difference in mortality between the two groups was also observed (CR 51.5 vs. CVO 43.3%; relative risk, 0.84; 95% CI, 0.72–0.98; p = 0.03).

### **3.4 Score to evaluate the treatment in MVD with MI**

Hae Chang Jeong et al., developed a new Score to predict combined events in patients with AMI and MVD, the CONVERSE score, based on the PCI registry of nine centers in universities in Korea, in a registry of 5025 patients, evaluated 2630 patients who AMI and MVD had presented, and they were divided into two groups those who were treated CVO that were 1029 patients vs. those with PCI of MVD 1601, for this they used 8 variables that had been predictors of events in a previous study [56]. The variables were patients with arterial hypertension, diabetes, age over 65 years, deterioration of EF, heart failure in presentation, chronic renal failure, elevated CRP plasmatic, anterior descending or LMCA as culprit vessel, each variable awarded a point, the elevation above 3 points in these patients were in linear relationship with the elevation of the MACCE [57].

#### **3.5 Meta-analysis of MVD in STEMI**

In this meta-analysis of 10 trials with 2285 patients. Among the three complete revascularization strategies, that is, during the procedure index, during hospitalization or after discharge vs. treatment of the culprit vessel only, it was associated with MACCE reduction (reference rate ratio [RR], 0.57; 95% CI, 0.42–0.77), due to a lower rate of emergency revascularization. Mortality of all causes and spontaneous reinfarction was similar between the two groups. There were no differences between the different types of strategies at the time of revascularization in patients with CR [58].

#### **3.6 An algorithm for the management of STEMI patients with MVD**

**Figure 2** [59].

#### **3.7 Guidelines**

MVD PCI treatment during STEMI is considered strongly indicated when there are critical lesions or associated thrombotic lesions when the culprit vessel has already been treated if there is persistent ischemia. When there is cardiogenic shock, the only treatment of the culprit vessel is the treatment of choice [20]. Patients with stable STEMI and MVD after a primary PCI the recommendation of multivessel PCI

*The Current Perspectives on Coronary Artery Bypass Grafting*

**3.2 Complete vs. incomplete revascularization**

**3.3 Randomized trials**

Data derived from more than 150,000 patients undergoing PCI suggest that less than 50% of all patients with MVD have CR after they have undergone percutaneous revascularization. It was observed that CR is associated with a fall in the incidence of mortality, MI, and MACCE, regardless of whether an anatomical or functional definition was used for the evaluation of IR, and perhaps the degree CR is associated with the magnitude of the risk. The association between IR and adverse clinical outcomes suggests that in patients with MVD, the degree of CR that can be achieved by PCI should be considered when discussing the choice of revascularization modality with the heart team, in addition to considering the complexity of the injury, functional significance, patient characteristics, and ERACI score [9, 53].

The preventive angioplasty in acute myocardial infarction (PRAMI) study [49] was performed in five centers in the United Kingdom in patients with STEMI and MVD, where they were randomized to preventive angioplasty of non-culprit vessels vs. only PCI of the culprit vessel. It was the first of the trials that incorporated a new concept on complete revascularization in STEMI and MVD. At practically 2 years of follow-up, a reduction of more than 50% was observed on the primary end point that was the combined event of cardiac death, nonfatal MI, and refractory angina, of the patients of the preventive PCI group vs. PCI only of the culprit vessel. The study was designed to include 600 patients but was stopped early with 465 patients because the data was conclusive by the data security committee. CvLPRIT [50] (trial of primary PCI vs. complete primary injury) compared a multivessel PCI strategy in patients with STEMI (performed at the time of primary PCI or revascularization in stages before discharge) to revascularization of culprit-vessel only. In this trial, 7 centers in the United Kingdom participated, where 296 patients were included, randomization was performed by stratification between previous or non-previous infarction, and according to the time ≤3 or >3 h. The primary end point of the study was the combined events of all-cause mortality, recurrent MI, heart failure, or revascularization driven by 12-month ischemia. The result produced a reduction of primary events to more than half in the CR group (10 vs. 21%; hazard ratio (HR), 0.45; 95% CI, 0.24–0.84; p = 0.009). There were no differences in individual events. In the compare acute study [52] (multivessel angioplasty guided by fractional flow reserve in myocardial infarction), they included 885 patients in 24 centers in Asia and Europe, where patients with STEMI and MVD, after a primary PCI stable, were randomized to complete revascularization guided by FFR of the artery not culprit of all lesions greater than 50% vs. angioplasty only of the culprit vessel. The FFR was performed in both groups, but its results were blind to operators and patients in the culprit vessel group only. The primary end point of the study was the MACCE at 1 year, which was significantly better in the FFR-guided group (7.8% vs. 20.5%) than in the culprit vessel only (HR, 0.35; 95% CI, 0.22–0.55; p < 0.001). This was at the expense of revascularization without changes in mortality or MI. The DANAMI-3- PRIMULTI [51] (The Third Danish Study of Optimal Acute Treatment of Patients With STEMI: Primary PCI in Multivessel Disease) was conducted at two university centers in Denmark, where they randomized 627 patients with STEMI and MVD after a successful primary PCI of the culprit vessel to a complete revascularization guided by FFR compared to conservative treatment. The primary end point was MACCE, which was composed of death, nonfatal MI, and revascularization driven by ischemia. After an average follow-up of 27 months, it was observed that the FFR group presented a MACCE of 13% vs. 22% in conservative treatment (HR, 0.56; 95%

**16**

#### *The Current Perspectives on Coronary Artery Bypass Grafting*

**Figure 2.**

*Algorithm for the Management of STEMI Patients With MVD. Modified from "The Management of MVD in STEMI: The Science and Art of Decision-Making in STEMI" (Feb 07, 2018) (Jacqueline E. Tamis-Holland, MD, FACC; Addi Suleiman, MBBS).*

has been updated to a Class IIB, this could be done at the time of the primary index or in stages during hospitalization or after discharge [48].

#### **3.8 Ongoing trials**

The COMPLETE [60] (Complete vs. Culprit-only Revascularization to Treat Multi-vessel Disease After Primary PCI for STEMI) trial will compare the outcomes of approximately 3900 patients randomized to a strategy of staged multivessel PCI or culprit-only revascularization. The FULL REVASC [61] (FFR-Guidance for Complete Non-Culprit Revascularization) This trial intends to evaluate the CR in about 4000 patients with STEMI or not with very high risk in patients of MVD guided by FFR during the same hospitalization of the index procedure, to evaluate clinical results.

#### **3.9 Our experience**

We were the precursors in the treatment of primary PCI in acute infarction as revealed by one of the first randomized trials with stent in acute myocardial infarction, our trial GRAMI [62]. In our daily practice we try to identify culprit vessel. If we have a territory where we find two vessels with critical lesions, we treat them. If the patient presents a critical lesion in another territory, we defer to perform it pre-discharge. We also consider the amount of territory that this vessel irrigates as well as its renal function when making the decision with the heart team.

#### **3.10 Conclusions**

Multivessel PCI both during the index procedure and in stages in stable patients is safe and could lead to better long-term results at the expense of reducing emergency

**19**

*Current Status, Perspectives, and Future Directions of Multivessel Disease and Left Main…*

define the opportunity of the treatment of the non-culprit critical lesions.

revascularization without altering mortality. The PCI of associated intermediate or very complex lesions at the time of STEMI is contraindicated. In cardiogenic shock and MVD, the treatment of the culprit vessel is only the indication. When one faces a patient with STEMI and MVD, the analysis of a heart team, where the scores are analyzed, the clinical status, the comorbidities, as well as the common sense should

DM is a global health problem; about 10% of adult patients will have the disease, and a quarter of all revascularized patients globally have DM [63]. However, patients with DM compared to nondiabetics have more MACCE and chronic heart failure. In addition, these patients have diffused and segmental disease, which puts them at greater risk of events regardless of the revascularization selected [64, 65]. PCI is limited by a higher rate of repeat revascularization and a worse clinical outcome in DM patients than with nondiabetic patients. CABG carries a greater morbidity, increased length of stay, and longer recovery times. However, both strategies have been improved during the last decade. In particular, the introduction of DES [66] has dramatically changed the landscape for PCI, with a significant reduction in the rate of restenosis especially the so-called second-generation stents that can reduce the gap [67]. The FREEDOM trial [68] demonstrated lower rates of major adverse cardiovascular events in patients with stable ischemic coronary disease who were assigned to CABG than with PCI using DES of first generation, at long-term followup. It is evident that this pathology carries a high atherogenic risk, and its current treatment is of surgical competence. Even so, we think that patients with a low ERACI score [17] are good candidates for PCI treatment, and the arrival of the new generation stents of Ultrathin-Strut DES [69] could reduce the gap that was created.

This trial [68] has become the most important among patients with diabetes and type of revascularization as well as follow-up, which was carried out worldwide in 140 centers that included 1900 patients with DM with MVD who were randomized to PCI with DES from first generation or CABG and its long-term follow-up of at least 5 years. The primary end point was the combined mortality events of all causes, nonfatal MI, and stroke, such as MACCE. The MACCE was significantly in favor of the CABG (18.7% vs. 26.6%, p < 0.005), there was also a decrease in the mortality of all causes (10.9% vs. 16.9%, p = 0.049), the stroke was lower in the PCI group (2.4% vs. 5.2%, p = 0.03), and the revascularization of the treated vessel was highly significant in favor of the CABG almost three more times on the first year of follow-up. The nonfatal MI was almost double with the PCI group [68]. When the quality of life was evaluated, it was although slightly significantly better with surgery than with PCI; this is due to the amount of repeated revascularization. So, this study showed strong data and full impact on revascularization guidelines [70]. Also with respect to FREEDOM, a study of hospital costs was carried out; it was

also favorable for surgical treatment vs. percutaneous treatment [71].

randomized to CABG (18.7%) than patients randomized to PCI (26.6%) (**Figure 3A**). A closer look at how these rates were derived is warranted. A total of 1900 patients (953 in the PCI group and 947 in the CABG group) were enrolled

The study showed that the outcomes were significantly lower among patients

*DOI: http://dx.doi.org/10.5772/intechopen.89419*

**4. Diabetes and multivessel disease**

**4.2 FREEDOM, critics, and main trials**

**4.1 Introduction**

*Current Status, Perspectives, and Future Directions of Multivessel Disease and Left Main… DOI: http://dx.doi.org/10.5772/intechopen.89419*

revascularization without altering mortality. The PCI of associated intermediate or very complex lesions at the time of STEMI is contraindicated. In cardiogenic shock and MVD, the treatment of the culprit vessel is only the indication. When one faces a patient with STEMI and MVD, the analysis of a heart team, where the scores are analyzed, the clinical status, the comorbidities, as well as the common sense should define the opportunity of the treatment of the non-culprit critical lesions.
