**3.1. Multivessel stenting versus staged revascularization with second‐generation drug‐ eluting stents in ST‐elevation myocardial infarction patients: results of randomized trial**

#### *3.1.1. Study population*

stress‐testing); (2) multivessel primary stenting (MPS): IRA is opened with the further dilata‐ tion of other significantly narrowed arteries during the same PPCI procedure; (3) multivessel staged stenting (MSS): the IRA only is treated during the first PPCI procedure with subse‐ quent complete revascularization during the second intervention. In this chapter, we justify the use of personalized approach for the optimal revascularization strategy in patients with STEMI and MVCAD using the latest generation of drug‐eluting stents (DES) with choosing MPS or MSS according to our original calculator. The chapter includes theoretical rationale, original single‐center study, an original calculator for choosing optimal revascularization

Earlier results of trials comparing MPS and CO approaches were controversial [12–19], prob‐ ably due to the heterogeneity of patient samples, variable endpoints, distinct inclusion criteria and different study protocols. European and American Cardiology Societies for 2010–2013 [1–3] recommended limiting PPCI to the vessel with a culprit stenosis with the exception of cardiogenic shock and persistent ischemia after PCI. Moreover, performance of PPCI in a

However, randomized controlled trial (RCT) results [20–23] demonstrated usefulness and safety of multivessel stenting in patients with STEMI and MVCAD, both with MPS and MSS

MPS approach was tested in two randomized controlled trials: PRAMI (Preventive Angio‐ plasty in Acute Myocardial Infarction) [20] and CvLPRIT (Complete Versus Culprit‐Lesion Only Primary PCI) [21]. In PRAMI trial, combined endpoint defined as cardiac death, nonfatal recurrent myocardial infarction (MI), or refractory angina at mean follow‐up of 23 months occurred in 21 (9%) patients treated with MPS approach compared to 53 (22%) patients treated with CO approach (hazard ratio (HR): 0.35; 95% confidence interval (CI): 0.21–0.58) [20]. Authors concluded that MPS approach significantly reduces the risk of adverse car‐ diovascular events, as compared to PCI limited to IRA [20]. In the CvLPRIT trial, authors showed that major adverse cardiac events (MACE) including all‐cause mortality, recurrent MI, heart failure, and ischemic‐driven revascularization at 12 months follow‐up occurred in 15 (10%) patients treated with MPS approach compared to 31 (21%) patients treated with CO approach (HR: 0.45; 95% CI: 0.24–0.84) [21]. In concordance with the PRAMI trial, researchers concluded that complete revascularization is beneficial for patients with STEMI and MVCAD

The MSS approach was also tested in two randomized controlled trials: DANAMI 3 PRIMULTI (Third Danish Study of Optimal Acute Treatment of Patients With ST‐segment Elevation Myocardial Infarction) [22] and PRAGUE‐13 (Primary Angioplasty in Patients Transferred From General

**2. The evolution of treatment strategies and guidelines for revascularization in patients with STEMI and MVCAD.** 

approaches. The current guidelines were updated by this data [4–6].

**The current evidence base. What do we know?**

noninfarct artery was considered harmful [2].

in comparison with CO approach [21].

strategy, and a clinical case example.

18 Interventional Cardiology

The purpose of this open‐label safety/efficacy randomized clinical trial (NCT01781715) is to determine outcomes of 136 consecutive patients with STEMI and multiple coronary artery disease (CAD) undergoing multivessel stenting in primary PCI or staged PCI with second‐ generation DES (Resolute Integrity™ Stent, Medtronic). Primary endpoints of this study were: (1) all death (cardiac and noncardiac), (2) any MI (STEMI and non‐STEMI), (3) TVR. Secondary: (1) composite rate of all death, any MI and TVR, (2) stent thrombosis (ST).

We examined patients with STEMI and multivessel CAD undergoing primary PCI. Between October 2011 and October 2014 in our 24 h catheterization laboratory randomized 136 patients with multivessel CAD (defined as ≥70% diameter stenosis of two or more epicardial coronary arteries or their major branches by visual estimation with diameter ≥2.5mm). Inclusion criteria were (1) Subject must be at least 18 years of age; (2) Subject is able to verbally confirm under‐ standings of risks and benefits of treatment of either multivessel stenting or staged PCI using the zotarolimus‐eluting stent (Resolute Integrity™ Stent, Medtronic) and he or she or his or her legally authorized representative provides written informed consent prior to any study‐related procedure; (3) Subject must have significant stenoses (≥70%) of two or more than two coronary arteries and requiring primary PCI for acute ST elevation myocardial infarction (STEMI) within 12 h; (4) Target lesions must be located in a native coronary artery with visually estimated diameter of less than 2.5 mm and more than 4.0 mm; (5) Target lesion(s) must be amenable for percutaneous coronary intervention.

Exclusion criteria were as follows: (1) Single lesions; (2) Acute heart failure Killip III‐IV; (3) ≥50% left main stenosis; (4) Small vessels' diameter (<2.5mm); (5) The patient has a known hypersen‐ sitivity or contraindication to any of the following medications: heparin, aspirin, clopidogrel or ticagrelor, zotarolimus. Included were patients with the presence of prolonged (more than30min) chest pain, started less than 12 h before hospital arrival and ST elevation of at least 1 mm in two or more contiguous limb electrocardiographic leads or 2 mm in precordial leads.

Procedure success was defined as the achievement of an angiographic residual stenosis of less than 20% and a thrombolysis in myocardial infarction (TIMI) flow grade 3 after treat‐ ment of the lesions. Before the procedure patients were treated with loading doses of aspirin, clopidogrel or ticagrelor, unfractioned heparin. Post‐PCI medical oral treatment included aspirin, statins, and clopidogrel or ticagrelor, which was recommended for 12 months in all cases after second‐generation zotarolimus‐eluting stent implantation. Signed informed con‐ sent for primary PCI and for the study was obtained from all patients before the procedure. Soon after every diagnostic angiography, the eligible patients were randomly allocated to two different strategies: 1. Multivessel stenting in primary PCI (MS primary): the IRA was opened followed by dilatation of other significantly narrowed arteries during the same pro‐ cedure. 2. Multivessel stenting in staged revascularization (MS staged): the IRA only was treated during the primary intervention while the complete revascularization was planned in a second procedure (10.1 ± 5.1 days). The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the institution's human research committee.

#### *3.1.2. Definitions and endpoints*

Clinical and procedural data were collected by reviewing hospital records and angiographic runs stored in DICOM CDs. The primary endpoint of the study was the incidence of major adverse cardiac events (MACE) defined as cardiac or noncardiac death, reinfarction, and repeat coronary revascularization. For repeat revascularization we included all PCI or CABG occur‐ ring after the baseline procedure and justified by recurrent symptoms, reinfarction, or objective evidence of significant ischemia on provocative testing. In the staged group we classified as repeat revascularization only unplanned procedures. Follow‐up was obtained by outpatient visits or phone interviews.

We estimated clinical and angiographic criteria of ST. The incidence of ST was assessed through‐ out the follow‐up period, according to the conventional ARC (Academic Research Consortium) classification [24]. Clinical criteria consisted of acute onset of chest pain persisting for >15 min and/or accompanied by ST‐segment elevation or depression of at least 1 mm in two contigu‐ ous leads in the distribution of the target vessel. All patients with the clinical suspicion of ST underwent immediate coronary angiography to confirm the diagnosis followed by PCI.

Angiographic criteria of stent thrombosis consisted of partial or complete occlusion within the previously implanted stent with evidence of fresh thrombus. Within the first 18 h after index MI, recurrent MI required recurrent symptoms of myocardial ischemia associated with recurrent ST‐segment elevation or depression of at least 1 mm in two contiguous limb electro‐ cardiographic leads or 2 mm in precordial leads lasting at least 30 min. After 18 h, recurrent MI was defined as appearance of new Q waves, new left bundle‐branch block, and/or enzyme evidence (level of creatine kinase MB fraction and/or troponin) of MI.
