• Multivessel disease in patients over 75 years old with ST elevated myocardial infarction. Current management strategies and related clinical outcomes in the ESTROFA MI + 75 nation-wide registry

    Abstract

    Background

    In elderly patients with ST elevated myocardial infarction (STEMI) and multivessel disease (MVD the outcomes related with different revascularization strategies are not well known.

    Methods

    Subgroup-analysis of a nation-wide registry of primary angioplasty in the elderly (ESTROFA MI + 75) with 3576 patients over 75 years old from 31 centers. Patients with MVD were analyzed to describe treatment approaches and 2 years outcomes.

    Results

    Of 1830 (51%) with MVD, 847 (46%) underwent multivessel revascularization either in acute (51%), staged (44%) or both procedures (5%). Patients with previous myocardial infarction and those receiving drug-eluting stents or IIb–IIIa inhibitors were more prone to be revascularized, whereas older patients, females and those with Killip III–IV, renal failure and higher ejection fraction were less likely. Survival free of cardiac death and infarction at 2 years was better for those undergoing multivessel PCI (85.8% vs. 80.4%, p < 0.0008), regardless of Killip class. Multivessel PCI was protective of cardiac death and infarction (HR 0.60, 95% CI 0.40–0.89; p = 0.011). Complete revascularization made no difference in outcomes among those patients undergoing multivessel PCI. The best prognosis corresponded to those undergoing multivessel PCI in staged procedures (p < 0.001). A propensity score matching analysis (514 patients in each group) yielded similar results.

    Conclusions

    In elderly patients with STEMI and MVD, multivessel PCI was related with better outcomes especially after staged procedures. Among those undergoing multivessel PCI, anatomically defined completeness of revascularization had not prognostic influence.

    Summary

    We sought to investigate the revascularization strategies applied and their prognostic implications in patients aged over 75 years with ST elevated myocardial infarction showing multivessel disease. Of 1830 patients, 847 (46%) underwent multivessel PCI either in acute (51%), staged (44%) or both procedures (5%). Multivessel PCI was independent predictor of cardiac death and infarction with the best prognosis corresponding to those undergoing staged procedures.

    Highlights

     

    •  

      Half of patients over 75 years old with STEMI undergoing pPCI present with MVD

    •  

      Nearly half of them underwent multivessel revascularization, with a similar rate of acute or staged procedures

    •  

      Multivessel PCI is related with better 2 years outcomes but the benefit seems to be greater for staged PCI procedures

    •  

      No harm was found for multivessel PCI during acute procedures

    •  

      Among those undergoing multivessel PCI, the achievement of complete revascularization did not have influence on outcomes.

     

    Introduction

    Primary percutaneous coronary intervention (pPCI) is the first line treatment for ST elevated myocardial infarction (STEMI). Up to 50% of these patients present multivessel disease (MVD) which portends a worse prognosis  . The appropriate therapeutic strategy for patients with MVD in this setting has been addressed in multiple trials and observational studies. Observational studies and their meta-analyses concluded that culprit-only PCI, as opposed to multivessel-PCI, at the time of initial reperfusion led to better outcomes. However, when patients who were treated with staged PCI during the hospitalization were analyzed separately, short- and long-term outcomes favored multivessel revascularization compared with only-culprit PCI strategy  . More recently, randomized trials and the corresponding pooled analysis have shown a clinical benefit for multivessel revascularization approach mostly through a reduction in repeat revascularization and recurrent infarction and with a non-significant trend toward reduced cardiovascular mortality  . However, there is not enough evidence to support a specific timing to accomplish it, if at the time of the pPCI or in a staged procedure. In this regard, staged revascularization before discharge could be related to better outcomes according to some registries  .

    The proportion of patients older than 75 years is progressively growing and now reach up to 30% of patients presenting with STEMI.  These patients show higher mortality, higher procedural risks, lower reinfarction and revascularization rates in follow up and shortened life expectancy  .

    As for many clinical conditions, there is paucity of data comparing the different therapeutic alternatives in this growing subpopulation. Patients over 75–80 years old have been systematically excluded from STEMI trials or have been only minimally represented in those trials with no age restrictions for inclusion. In accordance with this, the current management of patients over 75 years undergoing pPCI and showing multivessel disease is not well characterize and the prognostic implications for the different therapeutic alternatives remain largely unknown.

    We sought to evaluate first, how is in real practice the management of elderly patients with STEMI and multivessel disease and second, the clinical implications for the different strategies applied.

    Methods

    This is a retrospective registry in 31 centers distributed throughout Spain. This registry is supported by the Interventional Cardiology Working Group of the Spanish Society of Cardiology and is part of the ESTROFA (Estudio Español Sobre Trombosis de Stents Farmacoactivos [Spanish Thrombosis in Drug-eluting Stents Study]) study group.

    Population

    Each participating center enrolled retrospectively a strictly consecutive series of patients aged > 75 years who underwent pPCI due to STEMI. The sample sizes of the series of each center depended on the number of admissions to that center of patients with STEMI but included only patients with at least 1 year of follow-up from the start date of the study. The inclusion period ran from 2006 (at the earliest) to 2013, although most patients were enrolled in the most recent period (2010–2013). Additionally, this study also included those patients older than 75 years from the EXAMINATION trial  .

    We did not apply any kind of clinical or angiographic exclusion criteria. The procedures were performed according to the preferences of each operator and each institution. The clinical, angiographic, procedural, and follow-up information was collected in a specifically designed study database. Ejection fraction was collected from the echocardioagraphy performed at admission before the interventional procedure.

    The overall results of this registry have been already published.  For the purpose of the present analysis we selected those patients presenting multivessel disease (MVD) defined as the presence of angiographically significant non-culprit lesions in vessels other than the infarct related. These lesions should meet all the following criteria: a) Located in a different vessel than the clearly identified culprit lesion; b) Reference vessel diameter > 2 mm; c) Diameter stenosis > 50%.

    Patients were followed up by reviewing local databases, hospital or unit registries, and medical records, as well as through personal or familial phone contact if deemed necessary. The database was analyzed by 2 researchers in the coordinating center (H. U. Marques de Valdecilla, Santander, Spain).

    Event analysis and definitions

    The primary endpoint was the combination of cardiac death and myocardial infarction at 2 years. Secondary endpoints were definite or probable stent thrombosis at 2 years, any new revascularization at 2 years and in-hospital bleeding BARC > 1.

    Major adverse cardiac events were defined as follows: a) cardiac death, as death due to cardiovascular causes, including unexplained sudden death; b) myocardial infarction if the event fulfilled certain criteria meeting the third definition of infarction of the European Society of Cardiology and the American College of Cardiology;  c) repeat revascularization, including any revascularization procedure done during follow up; d) definite and probable stent thrombosis, according to the Academic Research Consortium;  e) bleeding, scored according to the classification of the Bleeding Academic Research Consortium (BARC)  .

    The events identified by the researchers were adjusted to the definitions provided; nonetheless, to guarantee their homogeneous application, the final event adjudication performed by investigators was reviewed at the coordinating center and additional information was requested when necessary.

    Complete revascularization was defined as the treatment of all angiographically significant lesions, as defined previously.

    Statistical analysis

    Continuous variables are presented as mean ± standard deviation. Categorical variables are expressed as percentages. Continuous variables were compared with the -test if they followed a normal distribution or with Wilcoxon test when not normally distributed (distribution type was assessed with the Kolmogorov-Smirnov test). Categorical variables were compared with the chi-square test or the Fischer's exact test as required. Kaplan-Meier curves of event-free survival were obtained for each pre specified group or subgroup and were compared using the log-rank test. A logistic regression analysis was conducted to establish clinical, angiographic and procedural predictors for performing different revascularization strategies. We used Cox proportional-hazards regression to determine hazard ratios for selected outcomes in the analyzed subgroups and to identify independent predictors of death, cardiac death and infarction. All variables showing an association with the incidence of major cardiac adverse events in the univariate analysis (p < 0.1) were included in the model. An additional analysis was conducted by means of a propensity score matching, pairing patients with MVD disease with and without multivessel PCI. The propensity score matching process was conducted with all baseline variables (clinical and angiographic) listed in Table 1 and the center entered as covariates for deriving the propensity scores. This procedure involved three stages: 1) The propensity scores were estimated using logistic regression in which PCI of non-culprit lesion was used as the outcome variable and all the covariates as predictors. 2) Patients were matched using simple 1.1 nearest neighbor matching. In order to exclude bad matches we imposed a caliper of 0.2 of the standard deviation of the logit of the propensity score. 3) A series of model adequacy checks were performed to check whether balance on the covariates was achieved through the matching procedure. Standardized differences were calculated for all covariates before and after matching to assess balance after matching. A standardized difference < 10% for a given covariate indicates a relatively low imbalance. The “psmatching” custom dialogue was used in conjunction with SPSS version 19 (IBM, Armonk, New York). The psmatching program performs all analyses in R (R Foundation for Statistical Computing, Vienna, Austria) through the SPSS R-Plugin (version 2.10.1). A p value < 0.05 was considered as statistically significant. All statistical analyses were performed using SPSS version 19 for windows. 

    Table 1
    Clinical, angiographic and procedural characteristics.
     SVD 
    n = 1746
    MVD 
    n = 1830
     
    Age, years 81.3 ± 4.5 81.1 ± 4.4 0.18
    Women 715 (41) 693 (37.8) 0.06
    Hypertension 1221 (70) 1324 (72.3) 0.13
    Dyslipidemia 709 (40.6) 805 (44) 0.04
    Diabetes mellitus 474 (27) 630 (34.4) 0.0001
    Smokers 258 (14.8) 281 (15.3) 0.71
    Chronic renal failure a 783 (44.8) 952 (52) 0.0001
    Atrial fibrillation 264 (15) 245 (13.4) 0.18
    Previous infarction 163 (9.3) 253 (13.8) 0.0001
    Previous PCI 141 (8) 199 (10.8) 0.005
    Previous CABG 13 (0.7) 37 (2) 0.001
    Anterior infarction 859 (49.2) 727 (39.7) 0.0001
    Killip class 1.45 ± 0.93 1.55 ± 0.99 0.002
    LVEF, % 48.7 ± 12.0 47.2 ± 12.3 0.0002
    Chest pain onset to PCI > 6 h 494 (28.3) 574 (31.3) 0.05
    Radial access 1075 (61.5) 941 (51.4) < 0.001
    Baseline TIMI flow 0.59 ± 1.00 0.66 ± 0.99 0.03
    Diseased vessels 1.0 ± 0.0 2.4 ± 0.5 < 0.001
    Lesions treated 1.09 ± 0.30 1.30 ± 0.50 < 0.001
    Stent length, mm 21.2 ± 6.5 21.4 ± 6.4 0.35
    Stent diameter, mm 3.01 ± 0.49 2.98 ± 0.47 0.20
    UFH alone 1151 (65.9) 1165 (63.6) 0.09
    UFH + IIb/IIIa inhibitors 371 (21.2) 466 (25.4) 0.008
    Bivalirudin alone 222 (12.7) 194 (10.6) 0.05
    Bivalirudin + IIb/IIIa inhibitors 2 (0.1) 5 (0.3) 0.33
    Thromboaspiration 1080 (61.8) 920 (50.3) < 0.001
    Drug-eluting stents 406 (23.2) 546 (29.8) < 0.001
    Final TIMI flow 2.86 ± 0.47 2.84 ± 0.52 0.20
    DAPT > 6 months 1060 (60.7) 1267 (69.2) < 0.001
    Values are n (%) or mean ± standard deviation.
    DAPT: dual antiplatelet therapy; LVEF: left ventricular ejection fraction; MVD: multivessel disease; PCI: percutaneous coronary intervention; SVD: single vessel disease; TIMI: Thrombolysis in Myocardial Infarction; UFH: unfractionated heparin.

    a Defined as a glomerular filtration rate < 60 mL/min.

     

    Results

    A total of 3576 patients over 75 years old, undergoing pPCI for STEMI were finally included in this registry and among these, 1830 (51%) met the criteria for the presence of MVD. The clinical, angiographic and procedural characteristics of these patients compared to those with single vessel disease (SVD) are shown in Table 1 . There were significant differences for many variables between both groups.

    The management of the 1830 patients with MVD is shown in Fig. 1 . In 847 patients (46%) multivessel revascularization was done, either during pPCI (51%), in a staged procedure (44%) or in both procedures combined (5%). Among the 847 patients who underwent multivessel PCI, in 566 (67%) a complete revascularization was achieved. Therefore, at the time of discharge incomplete revascularization was observed in 1264 patients (69%), including the 983 patients with culprit-only PCI and the 281 not achieving complete revascularization after multivessel PCI. Noteworthy, we observed a non-significant trend for more multivessel PCI done in most recent years. 

    Fig. 1
    Study flow chart.
    This figure shows the management of patients with multivessel disease according with the revascularization strategies applied before discharge.

     

    We analyzed the independent predictors for performing multivessel revascularization ( Table 2 ). Less older patients, males, those with previous infarction, no chronic renal failure, lower ejection fraction, in Killip class I or II, treated with drug-eluting stents or treated with IIb-IIIa inhibitors were more prone to be revascularized. With regards to gender, women were older (81.7 ± 4.7 years vs. 80.8 ± 4.1 years, p < 0.001), but they were less likely to get multivessel PCI even after adjustment by age. Noteworthy, some of the predictors of multivessel revascularization infer reverse causality, for example IIb-IIIa inhibitors or drug-eluting stents may have been used because multivessel PCI was performed and not vice versa. 

    Table 2
    Independent predictors for performing multivessel PCI and for doing so in primary vs. staged procedure.
     OR95% CIp
    Performing multivessel PCI
    Lower age 1.03 (1.01–1.06) 0.017
    Male 1.61 (1.28–2.08) 0.0001
    No chronic renal failure 1.58 (1.11–2.22) 0.012
    Killip class I or II 1.47 (1.04–2.08) 0.032
    Lower ejection fraction 1.02 (1.01–1.03) 0.0095
    Previous infarction 1.43 (0.97–2.11) 0.064
    Drug-eluting stents 1.33 (1.03–1.72) 0.025
    IIb-IIIa inhibitors 1.51 (1.17–1.96) 0.0016
     
    Performing multivessel PCI in primary vs. staged procedure before discharge
    Previous infarction 1.93 (1.01–3.69) 0.044
    Time delay > 6 h 1.72 (1.14–2.93) 0.0086
    Killip class III or IV 3 (1.62–5.52) 0.0005
    Anterior infarction 1.69 (1.13–2.51) 0.0095
    No 3-vessel disease 3 (2.22–4.01) < 0.0001
    Femoral access 1.54 (1.05–2.27) 0.025
    Bare metal stents 2.08 (1.38–3.12) 0.0005

     

    In Table 2 are listed as well the independent predictors for the timing approaches for multivessel revascularization. Patients with previous myocardial infarction, anterior location of infarction, longer time delay, advanced Killip class, no 3-vesel disease, use of femoral access site and treated with bare metal stents were more preferentially treated in the pPCI procedure.

    The clinical outcomes for different subgroups are shown in the Figs. 2–4 . The follow up was completed in 97.4% of patients. The survival free of all cause death + infarction or cardiac death + infarction at 2 years was better for those undergoing multivessel PCI ( Fig. 2 ). This favorable difference was observed both in patients in Killip classes I–II and classes III–IV ( Fig. 3 ). The achievement of a complete revascularization status made no difference in outcomes among those patients undergoing multivessel PCI ( Fig. 4 A). In relation with timing of non-culprit lesions PCI, the best prognosis corresponded to those with staged procedures ( Fig. 4 B). 

    Fig. 2
    Survival free of death/cardiac death and infarction in patients with MVD.
    The survival free of death and infarction (A) and cardiac death and infarction (B) at 2 years was significantly better for those patients with MVD undergoing multivessel PCI.
    Fig. 3
    Survival free of cardiac death and infarction in patients with MVD according to Killip class.
    In this figure survival free of cardiac death and infarction is shown for those in Killip class I or II (A) and Killip class III or IV (B). Patients undergoing multivessel revascularization showed better prognosis in both subgroups.
    Fig. 4
    Survival free of cardiac death and infarction in patients with MVD according to completeness of revascularization and timing of non-culprit lesions PCI.
    A). The achievement of an angiographically defined complete revascularization status made no difference in outcomes among those patients undergoing multivessel PCI. B) The best prognosis corresponded to those patients undergoing non-culprit lesions PCI in staged procedures.

     

    In the analysis of independent predictors for cardiovascular death and infarction at 2 years ( Table 3 ), multivessel PCI lowered the incidence of these adverse events (HR 0.60, 95% CI 0.40–0.89: p = 0.011). Entering separately the variables of multivessel PCI during pPCI or in staged procedure, only the latter remained predictor for better outcomes, with the former showing a slight positive trend. When entering the variable of complete revascularization instead of the one of multivessel PCI in the multivariant model, the former resulted an independent predictor of major adverse events, but it was no longer the case in the subgroup of patients undergoing multivessel revascularization ( Table 3 ). 

    Table 3
    Independent protective predictors of cardiac death and infarction at 2 years in the population with MVD.
     HR95% CIp
    Overall population with MVD
    Killip class I or II 0.2 (0.13–0.32) < 0.0001
    Time delay < 6 h 0.66 (0.45–0.99) 0.041
    No chronic renal failure 0.39 (0.24–0.61) < 0.0001
    Ejection fraction 0.95 (0.93–0.97) < 0.0001
    Bivalirudin 0.40 (0.18–0.86) 0.019
    Thrombus aspiration 0.57 (0.38–0.85) 0.0058
    Drug-eluting stent 0.59 (0.34–0.99) 0.045
    Final TIMI flow III 0.43 (0.24–0.79) 0.0061
    DAPT > 6 months 0.63 (0.34–0.95) 0.029
    Multivessel PCI 0.60 (0.40–0.89) 0.011
    Multivessel PCI entered according to timing      
    In primary procedure 0.77 (0.48–1.22) 0.27
    In staged procedure 0.47 (0.26–0.85) 0.012
     
    Complete revascularization included in model instead of multivessel PCI
    Killip class I or II 0.2 (0.12–0.31) < 0.0001
    Time delay < 6 h 0.67 (0.45–0.99) 0.049
    Ejection fraction 0.95 (0.93–0.97) < 0.0001
    No chronic renal failure 0.37 (0.24–0.59) < 0.0001
    Bivalirudin 0.40 (0.18–0.86) 0.019
    Thrombus aspiration 0.57 (0.38–0.85) 0.0061
    Drug-eluting stents 0.60 (0.35–0.99) 0.048
    Final TIMI flow III 0.43 (0.24–0.78) 0.0059
    DAPT > 6 months 0.63 (0.42–0.94) 0.027
    Complete revascularization 0.62 (0.42–0.98) 0.047
    Only in multivessel PCI group      
    Complete revascularization 0.83 (0.39–1.77) 0.64
    DAPT: dual antiplatelet therapy; MVD: multivessel disease; PCI: percutaneous coronary intervention; TIMI: Thrombolysis in Myocardial Infarction.

     

    Regarding bleeding events during admission, the rate of bleeding BARC > 1 in multivessel PCI group was 2.7% and in the culprit-only PCI group was 2% (p = 0.4). The incidence of definite or probable thrombosis in 2 years follow up was 3.8% in multivessel PCI group and 2.9% in the culprit-only PCI group (p = 0.35). The incidence of revascularization after discharge in 2 years follow was 9.3% and 8.4% respectively (p = 0.53).

    The propensity score matching analysis yielded two groups of 514 patients each showing well balanced in all features (standardized difference < 10%). The survival free of death and infarction for the same subgroups considered in the overall analysis is shown in Fig. 5 . Again, a significant survival advantage was seen in favor of those undergoing multivessel PCI, especially when staged, and without differences according to completeness of revascularization. 

    Fig. 5
    Survival free of death and infarction in matched groups.
    A significant survival advantage was seen in favor of those undergoing multivessel PCI (A), especially when staged (B) and without differences according to anatomically defined completeness of revascularization (C).

     

    Discussion

    The main results of this study could be summarized as follows: a) Half of elderly patients (> 75 years old) with STEMI undergoing pPCI present with MVD; b) Nearly half of them underwent multivessel revascularization, with a similar rate of acute or staged procedures and under factors clearly influencing those decisions; c) Multivessel PCI is related with better 2 years outcomes and the benefit was greater if done in staged procedures; d) No harm was found for multivessel PCI during acute procedures; e) Among those patients undergoing multivessel PCI, the achievement of anatomically defined complete revascularization did not have influence on 2 years outcomes.

    Routine revascularization of non-culprit lesions before hospital discharge has been supported by the recently published 2017 ESC guidelines in which a class IIa recommendation is given for this strategy  . The recommendation for this strategy was class IIb in the 2015 ACC/AHA guidelines  . These recommendations are based on the evidence from randomized trials.

    The first trial included only 214 patients and after a mean follow-up of 2.5 years, patients allocated to culprit lesion angioplasty-only had more major adverse cardiac events  . After this study, four larger randomized clinical trials have been published.  Multivessel PCI was done either during the index procedure  , staged during hospital admission  , or any time before discharge (immediate or staged)  . Indication of non-culprit PCI was angiography-guided in lesions with ≥ 50% stenosis  , > 70% stenosis  , or fractional flow reserve-guided  . Primary outcome (composite of different endpoints) was significantly reduced in the multivessel revascularization group in all four trials but mortality was not statistically different in any of these four trials. The pooled analysis of these trials shows that multivessel PCI at index or staged procedures is associated to reduction in MACE due to reduction in urgent revascularization.  being the risk of all-cause mortality and spontaneous reinfarction not different. As the optimal timing of revascularization (immediate vs. staged) has not been adequately investigated, no recommendation in favor of immediate vs. staged multivessel PCI can be formulated.

    In the particular case of patients with MVD and cardiogenic shock a IIa recommendation has been given for multivessel PCI during index procedure in the 2017 ESC guidelines based on a level C evidence  . A meta-analysis of nonrandomized studies suggests that there may be no significant benefit with single-stage multivessel-PCI compared with culprit only-PCI.  Furthermore, this recommendation has been definitely challenged by the recently published CULPRIT SHOCK trial.  In this trial immediate multivessel PCI increased the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy and the relative risk of death.

    In clinical practice there are several factors to consider for performing multivessel PCI at the time of primary PCI including patient stability, ability to accurately assess lesion significance in the setting of acute coronary syndromes, likelihood of procedural success, risk of the intervention, and the potential benefit of revascularization. Furthermore, the presence of unstable morphology in angiography or intracoronary imaging, the use of pressure wire in lesions with stenosis 50–75% and the location of the lesion (if proximal or in a vessel that subtends a significant area of myocardium) play an important role.

    Patients over 75 years present particular characteristics that limit the validity of the application of results derived from general population. Thus, evidence is lacking to support any recommendation specifically aimed to the elderly with STEMI and MVD. Advanced age could induce a more conservative approach. In our registry, the proportion of patients with multivessel disease that were revascularized in hospital was 46% and ageing decreased likelihood of non-culprit intervention independently. Female sex was indentified as well as a variable promoting a culprit-only lesion revascularization approach, regardless of the age. Patients in worse clinical condition (Killip class III or IV) were less likely to undergo multivessel revascularization. The lack of supporting evidences at that time and prior negative experiences made the operators less prone to perform multivesel PCI in this setting. This conservative strategy has been proven to be more adequate just recently.  In fact, the survival benefit seen in the subgroup of patients with shock undergoing multivessel PCI in this registry support a careful selective indication for multivessel PCI in this critical scenario.

    The timing of non-culprit interventions was associated as well with certain variables. Patients with history of previous infarction, anterior infarction, Killip class III–IV or later presentation underwent more frequently multivessel PCI in the pPCI procedure. On the other side, a more extensive disease (three vessel disease) and the use of radial access and drug-eluting stents favored staged procedures. The apparent discrepancy for the Killip class III-IV in both analysis can be explained by the very high mortality of these patients in the first 24–48 h of presentation, which made very difficult for them to be referred for staged procedures, which accounted for almost half of non-culprit PCI procedures. With respect to the higher use of drug-eluing stents in staged procedures this is explained because staged procedures were related with more complex lesions, 3-vessel disease and with patients with Killip class I or II (higher expectancy of long term survival).

    Regarding the prognostic implications of the different therapeutic approaches. In this registry, multivessel PCI was associated with an absolute risk reduction of 5% and was an independent predictor (reduction by 40%) over 2 years in the combined incidence of cardiac death and myocardial infarction. The prognostic advantage of multivessel PCI was observed across all the Killip classes. When comparing multivessel revascularization vs. culprit-only revascularization in STEMI, the value of revascularization as an outcome is to some extent questionable and definitely less relevant. That is why a combined endpoint of cardiac death and infarction could be in our view more adequate and so was selected for this study.

    With respect to the timing of intervention, the survival curves showed an early separation and this finding could justify a prompt non-culprit PCI. We found that staged PCI of non-culprit lesions was associated to better outcomes. Moreover, in survival curves it appears that patients having non-culprit PCI during pPCI showed a quite similar outcome than those with culprit lesion PCI alone. Nevertheless, though multivessel PCI in acute procedure was clearly associated to a worse patient profile, it was associated to a trend for better outcomes in multivariant analysis.

    Finally, completeness of revascularization emerged as an independent predictor of cardiac death and myocardial infarction in overall population with MVD. However, among those patients who underwent multivessel PCI, the achievement of anatomically defined complete revascularization did not appear to have influence on two years outcomes. These results suggest that not all lesions have the same prognostic impact on outcomes, and perhaps only the treatment of non-culprit lesions located in proximal or large segments of main coronary arteries is prognostically relevant. Furthermore, lesions with 50–75% stenosis left untreated could be functionally nonsignificant. In this regard, a combination of angiographic and functional criteria (based on fractional flow reserve) could be more adequate no define complete revascularization.

    Study limitations

    This is a retrospective multicenter registry and, although patients were strictly consecutively recruited from each center, data collection and follow-up were not as accurate and uniform as they would have been with a prospective design. Due to the retrospective design, it was not possible to record medical therapy adherence and its eventual relationship with ischemic and hemorrhagic events. Given the nature of the study and the large number of events in this population, event adjudication was decided by the local investigators using pre-defined criteria. In case of conflicting data, the clinical information was analyzed at the coordination site and adjudication was done accordingly by two investigators.

    Regarding the predictors for performing multivessel PCI, some of the predictors infer reverse causality, which means that these factors may have been used because multivessel PCI was performed and not vice versa. For the purpose of comparing outcomes between treatment groups, the registries entail limitations particularly the problem of bias secondary to known and unknown confusion factors not fully sorted out even after careful adjustments with multivariant analyses. Then, it still remains highly possible that some unmeasured confounders could favor the use of one therapeutic alternative over the other. Thus, the results of the multivariant analysis might have been somewhat affected by hidden biases, such as comorbidities omitted from the databases or biological frailty, which could in turn be linked to some therapeutic strategies more than others. These biases could be particularly relevant in the elderly population and could affect the results of the survival analysis for the different treatment groups. The steps taken in order to attenuate these limitations consisted in the use of a propensity score matching using a full set of baseline (clinical and angiographic) variables, and avoiding the inclusion of procedural factors that could bias the analysis (such as access site, stent type or antithrombotic therapy among others).

    Definition of significant lesion was based on angiographic findings. We realize that a certain proportion of these lesions could not be significant by means of a functional assessment with pressure wire. Data relative to the use and results of pressure wire within the procedures was not found to be reliably collected and is not provided. Regarding completeness of revascularization, the residual Syntax score would have been of value, but this information is not available. The use of drug-eluting stents was not high, but these results reflect the real practice in recent years. Although a higher penetration could be considered currently, the exclusion of revascularization from the primary outcome diminish the influence of this variable.

    Conclusions

    In this registry around half of patients showed significant multivessel disease and almost half of them underwent multivessel PCI with similar rate for acute or staged procedures and under factors clearly influencing those decisions. Multivessel PCI was related with better two years outcomes but the benefit seems to be greater for staged procedures. Of note, no harm was detected for multivessel intervention during pPCI. Angiographically defined complete revascularization had no influence among those undergoing multivessel PCI.

    Statements

    No conflicts of interest to disclose. None of the authors hold any kind of financial and personal relationships with other people or organizations that could inappropriately influence (bias) this work.

    This work has not been published previously (except in the form of an abstract) and it is not under consideration for publication elsewhere.

    The manuscript has been approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder.

    No funding was required for this study.

    Author bio

    Cardiovascular Revascularization Medicine, 2018-07-01, Volume 19, Issue 5, Pages 580-588, Copyright © 2017

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