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Abstract

Background: The incidence of multivessel disease (MVD) among patients presenting with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is very high, and the optimum revascularization strategy is debatable. The aim of this study was to evaluate the different patterns of percutaneous revascularisation (PCI) for NSTE-ACS patients with MVD and to determine the long-term outcomes in terms of major adverse cardiac and cerebrovascular events (MACCE).

Methods: This study included 490 patients who presented at our hospital for NSTE-ACS with MVD, from January 2008 to June 2016. Based on revascularization patterns, the patients were divided into 3 groups: Group I: 211 patients underwent incomplete revascularisation (IR) for the culprit vessel only, Group II: 249 patients underwent complete revascularization (CR) for both, culprit and non-culprit vessels in the same setting and Group IIΙ: 30 patients underwent complete revascularisation for both culprit and non-culprit vessels in different settings. The primary study endpoint was the incidence of MACCE, which was defined as a composite of cardiac death, all cause death, re-infarction, re-hospitalisation for unstable angina, need for repeat coronary revascularization, and stroke in-hospital and at a minimum period of 6 months.

Results: There was no statistically significant difference between the 3 groups in terms of the in-hospital outcomes. The composite MACCE endpoint at 6 months (death, re-infarction, need for revascularization and stroke) was higher in group Ӏ than in the other 2 groups. The overall MACCE were 50% higher in group 1 compared to the other 2 groups (P<0.001). The composite MACCE endpoint at 6 months was higher in group ӀӀӀ than in group ӀӀ (16% vs. 12.8% respectively), but without statistical significance. Cardiac death occurred in 11 patients (6.3%) in group Ӏ, and in 4 patients (1.9%) in group ӀӀ; however, there was no cardiac death in group ӀӀӀ (P=0.045). Stroke occurred only in 1 patient (0.6%) in group Ӏ. There was no statistically significant difference in the incidence of stroke between the 3 groups (P=0.485). Re-infarction occurred in 19 patients (10.8%) in group Ӏ, 12 patients (5.7%) in group ӀӀ, and 4 patients (16%) in group ӀӀӀ (P=0.081). The need for revascularization procedures was very high in group Ӏ (76 patients; 43.2%) compared to both group ӀӀ (17 patients; 8.1%), and group ӀӀӀ (4 patients; 16%) (P<0.001). In group Ӏ we also calculated the RSS (RSS) and there was a higher incidence of MACE with RSS >8 compared to RSS ≤ 8 (61% vs. 41.4% respectively) (P=0.010)

Conclusion: In patients of NSTE-ACS with MVD, complete revascularisation either in the same setting or in a staged manner is better compared to only culprit vessel PCI in terms of long term total MACCE, cardiac death and the need for revascularisation. There was no difference in MACCE outcomes between revascularisation in the same setting and staged revascularisation. In case of incomplete revascularisation, RSS is a good and reliable predictor of total MACCE.

Key words

 multivessel disease, revascularization, coronary artery disease.

Introduction

Cardiovascular diseases are currently the leading cause of death in industrialised countries, and a similar situation is expected to occur in the developing countries by 2020. Among these, coronary artery disease (CAD) is the most prevalent manifestation and is associated with high mortality and morbidity [1]. Registry data consistently show that NSTE-ACS is more frequent than ST segment elevation (STE)-ACS [2]. The annual incidence is 3 per 1000 inhabitants but varies between countries [3]. Long term follow-up has shown that death rates are higher among patients with NSTE-ACS than in those with STE-ACS, with a two-fold difference at 4 years [4]. This difference in the death rates at mid and long-term follow up might be due to different patient profiles since NSTE-ACS patients tend to be older, with higher number of co-morbidities, especially diabetes and renal failure. Outcomes from epidemiological observations suggest that treatment strategies for NSTE-ACS need to focus not only on the acute phase, but also provide equal emphasis on longer term management [5].

The recent guidelines for the management of patients presenting with NSTE-ACS, indicate that there are no prospective randomised trials comparing complete versus staged revascularization (i.e. complete vs. incomplete) and the timing (i.e. simultaneous vs. staged) of revascularization in such patients [6,7]. A complete revascularisation strategy for significant lesions in patients of NSTE-ACS with multivessel disease (MVD) is based on two considerations. One, several studies showing the benefit of early intervention compared to the conservative approach in patients with NSTE-ACS, mandated a complete revascularization strategy, irrespective of the identification and/or treatment of the culprit lesion [8-10]. Secondly, multiple PCI and NSTE-ACS trials have shown poor prognostic outcomes of incomplete revascularization. Accordingly, an RSS >8 has been shown to be independently associated with a poor 30-day and 1-year prognosis, including higher mortality after PCI in patients with moderate and high-risk. [11,12].  

Aim of the study

The aim of the study was to compare the different patterns of PCI in NSTE-ACS patients with MVD, and to determine the outcomes in terms of the major adverse cardiac and cerebrovascular events (MACCE) like cardiac death, re-infarction, stroke, the need for revascularisation, and major bleeding.

Methods

This study included 490 patients of NSTE-ACS with MVD who presented at our hospital from January 2008 until June 2016. Based on the revascularization strategies, the patients were divided into 3 groups: Group I: 211 patients underwent incomplete revascularization (IR) for the culprit vessel only; Group II: 249 patients underwent complete revascularization (CR) for both culprit and non-culprit vessels in the same setting; and Group IIΙ: 30 patients underwent complete revascularization for both culprit and non-culprit vessels in different settings. Coronary angiography and the PCI procedure including pre-procedural preparation, PCI procedure details, materials used, intra-procedure complications, and post-PCI management were documented. Baseline SYNTAX score and RSS were also calculated. The primary endpoint of the study was the incidence of MACCE, which was defined as a composite of cardiac death, any cause death, re-infarction, re-hospitalisation for unstable angina, the need for repeat coronary revascularization, and stroke while in hospital and at a minimum of 6 months follow up.

Results

Patient Characteristics: All groups were well matched with respect to the demographic and clinical characteristics; the baseline characteristics of all groups are presented in Table 1. 

Table 1. Baseline Characteristics of the Studied Populations. *statistically significant at p <.05, Using F test. a,b: similar letters mean no significant difference between groups , different letters means significant difference between groups using post hoc test. MCP: Monte carlo significance test.

	Group Ӏ Culprit only PCI (n=211)	Group ӀӀ Total Revascularisation (n=249)	Group ӀӀӀ Staged Revascularisation (n=30)	P Value
Age, yrs     Mean ± SD.	64.6 ± 10.42a	63.02 ± 9.9a,b	58.73 ± 8.96 b	0.008*
Sex     Male     Female	160(75.8%) 51(24.2%)	195(78.3%) 54(21.7%)	28(93.3%) 2(6.7%)	0.094
Medical history      DM      HTN      Hypercholesterolaemia      Current smoker      Previous MI      Previous PCI	118(55.9%) 139(65.9%) 72(34.1%) 28(13.3%) 16(7.6%) 44(20.9%)	133(53.4%) 149(59.8%) 80(32.1%) 36(14.5%) 11(4.4%) 42(16.9%)	17(56.7%) 19(63.3%) 10(33.3%) 7(23.3%) 2(6.7%) 5(16.7%)	0.843 0.410 0.902 0.342 0.352 0.528
Risk stratification      GRACE score Mean ± SD.      CRUSADE score Mean ± SD.	127.5 ± 31a   26.7 ± 13a	121.6 ± 30a,b   25.5 ± 13a,b	113.3 ± 24b   20.9 ± 11 b	0.02*   0.04*
Lab investigation     Positive Troponin        Creatinine     Normal RFT     CKD     CKD on HD	127(60.2%)   177(83.9%) 33(15.6%) 1(0.47%)	155(62.2%)   212(85.1%) 34(13.7%) 3(1.2%)	21(70%)   25(83.3%) 5(16.7%) 0(0%)	0.575   MCP=0.834
LV EF%	58.8 ± 11.36a	61.72 ± 8.87b	60.8 ± 11.15a,b	0.016*
MR	211	249	30
No	164(77.7%)a	218(87.6%)b	21(70.0%)a	0.004*
Mild	25(11.8%)a	23(9.2%)a	9(30.0%)b	0.004*
Moderate	12(5.7%)a	5(2.0%)b	0(0.0%)b	0.056
Severe	10(4.7%)a	3(1.2%)b	0(0.0%)b	0.041*

Procedural characteristics of the studied population: There was no statistically significant difference between the 3 groups in terms of the percentages of LM, LAD and RAMUS as the target vessel. Group Ӏ and group ӀӀӀ had a greater number of patients with significantly diseased LCX and RCA, than group ӀӀ and this difference was statistically significant (P=0.027 for LCX) and (P<0.001 for RCA). GP ӀӀb/ӀӀӀa inhibitors were administered to 72 (34.1%) patients in group Ӏ, 74 (29.7%) in group ӀӀ, and 13 (43.3%) patients in group ӀӀӀ and there was no statistically significant difference in the percentages between the 3 groups (P=0.52). Chronic total occlusion (CTO) lesions were found in 107 (50.7%) patients in group Ӏ, 55 (22.1%) patients in group ӀӀ, and 10 (33.3%) patients in group ӀӀӀ. The difference in percentage of CTO lesions between group Ӏ and group ӀӀ was statistically significant (P<0.001). Long lesions were found in 67 (31.7%) patients in group Ӏ, 73 (29.3%) patients in group ӀӀ, and 13 (43.3%) patients in group ӀӀӀ; however, there was no statistically significant difference between the 3 groups (P=0.153). The mean syntax score was higher in group Ӏ (16.9; range 4-50) than in group ӀӀ (13.8; range 4-39) and the difference was statistically significant (P<0.001). In group ӀӀӀ, the mean syntax score was 15 (range 4-30) without statistical significance with the other 2 groups. The number of stents inserted was lowest in group Ӏ with a mean of 2 (range 1-5), followed by group ӀӀ with a mean of 2 (range 1-6), and highest in group ӀӀӀ with a mean of 3.5 (range 2-7). There was a significant statistical difference between the 3 groups with respect to the number of stents used per patient (P<0.001). In group Ӏ patients, 87 bare metal stents (BMS) (23.6%) and 282 drug eluting stents (DES) (76.4%) were used; in group ӀӀ patients, 112 BMS (18.2%) and 502 DES (81.8%) were used; while in group ӀӀӀ patients 8 BMS (7%) and 107 (93%) were used. There was no statistically significant difference between the 3 groups with respect to the use of BMS (P=0.923). More number of DES were used in group ӀӀ than in group Ӏ (P=0.006).

Syntax score post-procedure (RSS): The mean RSS in group Ӏ was 7 (range 1-30), which was significantly higher than that of the other 2 groups. In group ӀӀ the mean RSS was 0 (range 0-17), and in group ӀӀӀ the mean RSS was 1.5 (range 0-15). The difference in RSS between group Ӏ and group ӀӀ was statistically significant (P<0.001). All data of the procedural characteristics of the studied population are summarised in Table 2. 

Table 2. Procedural Characteristics According to randomised allocation. *statistically significant at p<0.05 using Kruskal Wallis test (H). **statistically significant at p<0.05 using Pearson Chi square test. a,b,c :similar letters mean no significant difference between groups , different letters means significant difference between groups using post hoc test

	Group Ӏ Culprit only PCI (n=211)	Group ӀӀ Total Revascularisation (n=249)	Group ӀӀӀ Staged Revascularisation (n=30)	P Value
Target vessels     Left Main     LAD     RAMUS     LCX     RCA	13(6.2%) 185(87.7%) 22(10.4%) 147(69.7%)a 166(78.7%)a	7(2.8%) 205(82.3%) 28(11.2%) 155(62.2%)b 108(43.4%)b	1(3.3%) 24(80%) 2(6.7%) 25(83.3%)a 24(80%)a	0.202 0.193 0.778 0.027* <0.001*
Total no of Stent/patient Stent type     BMS     DES	2(1-5) a   87(23.6%) 282(76.4%)a	2(1-6)b   112(18.2%) 502(81.8%)b	3.5(2-7) c   8(7%) 107(93%)a,b	<0.001*   0.923 0.006**
Presence of CTO Presence of long lesions	107(50.7%)a 67(31.7%)	55(22.1%)b 73(29.3%)	10(33.3%)a,b 13(43.3%)	<0.001** 0.153
Use of GP IIb/IIIa	72(34.1%)	74(29.7%)	13(43.3%)	0.52
Syntax score (pre-procedural) Syntax score (post-procedural)	16.9(4-50)a   7(1-30)a	13.8(4-39)b   0(0-17)b	15(4-30)a,b   1.5(0-15)a,b	<0.001*   <0.001*

In-hospital outcomes: In group Ӏ, 0.5% of the patients required revascularization (TVR), 0.5% developed heart failure, 0.5% developed cardiogenic shock (due to post-PCI pericardial effusion, and pericardiocentesis was performed), and 1.9% developed arrhythmia (AF in 2 patients, ventricular tachycardia in 1 patient and ventricular bigeminy in 1 patient). Additionally, 0.5% of the patients developed major bleeding, 0.9% patients developed minor bleeding, and 2.8% patients developed contrast induced nephropathy CIN. In group ӀӀ, 0.4% of the patients developed a re-infarct, 0.4% patients required revascularization (TVR), 0.8% patients developed heart failure (2 patients, of which 1 required mechanical ventilation), 1.6% patients developed cardiogenic shock, 1.2% patients developed major bleeding, 0.4% patients developed minor bleeding and 3.2% patients developed CIN (8 patients, 2 of them needed HDF). There was no in-hospital complication in group III. However, there was no statistically significant difference between the 3 groups with respect to the in-hospital complications. The data of in-hospital outcomes are summarised in Table 3.

Table 3. In hospital outcomes. MCP: Monte carlo significance test

	Group Ӏ Culprit only PCI (n=211)	Group ӀӀ Total Revascularisation (n=249)	Group ӀӀӀ Staged Revascularisation (n=30)	P Value
Cardiac death Re-infarction Need for revascularisation (TVR) Heart failure Cardiogenic shock Arrhythmia Major bleeding Minor bleeding CIN	0(0%) 0(0%) 1(0.5%)   1(0.5%) 1(0.5%) 4(1.9%) 1(0.5%) 2(0.9%) 6(2.8%)	0(0%) 1(0.4%) 1(0.4%)   2(0.8%) 4(1.6%) 0(0%) 3(1.2%) 1(0.4%) 8(3.2%)	0(0%) 0(0%) 0(0%)   0(0%) 0(0%) 0(0%) 0(0%) 0(0%) 0(0%)	- MCP=1 MCP=1   MCP=1 MCP=0.79 MCP=0.07 MCP=0.71 MCP=0.67 MCP=0.61

Follow-up (at least 6 months follow-up): The composite MACCE (Major Adverse Cardiac and Cerebrovascular Events) endpoint at 6 months (death, re-infarction, need for revascularization and stroke) was higher in group Ӏ than in the other 2 groups, the overall MACCE were 50% higher in group 1 compared to the other 2 groups (P<0.001). The composite MACCE endpoint at 6 months was higher in group ӀӀӀ than in group ӀӀ 16% vs. 12.8% respectively, but no statistical significance was found.

Cardiac death occurred in 11 patients (6.3%) in group Ӏ, and in 4 patients (1.9%) in group ӀӀ, but none in group ӀӀӀ. The difference in cardiac death between group Ӏ and group ӀӀ was statistically significant (P=0.045). Stroke occurred only in 1 patient (0.6%) in group Ӏ. No statistical significance was seen between the 3 groups with respect to stroke (P=0.485). Re-infarction occurred in 19 patients (10.8%) in group Ӏ, 12 (5.7%) in group ӀӀ, and 4 patients (16%) in group ӀӀӀ. No statistical significance was seen between the 3 groups with respect to re-infarction (P=0.081). Revascularization was required in 76 patients (43.2%) in group Ӏ, 17 patients (8.1%) in group ӀӀ, and 4 patients (16%) in group ӀӀӀ. The differences were statistically significant (P<0.001). The need for either TVR OR non-TVR was much higher in group Ӏ than in the 2 other groups and the difference was statistically significant (P<0.001). Group Ӏ required earlier revascularization compared to the 2 other groups. The mean time for revascularization was 35.8 ± 20.1 months in group Ӏ, 41.2 ± 21.2 months in group ӀӀ, and 42.1 ± 24.4 months in group ӀӀӀ (P=0.03).

Heart failure occurred in 10 patients (5.7%) in group Ӏ, 6 patients (2.9%) in group ӀӀ and 0 in group ӀӀӀ. There was no statistically significant difference between the 3 groups (P=0.216). Arrhythmia occurred in 3 patients (1.7%) in group Ӏ, 4 patients (1.9%) in group ӀӀ, but in none in group ӀӀӀ. No statistically significant difference was seen between the 3 groups (MCP=1). Major bleeding occurred in 2 patients (1.1%) in group Ӏ, 2 patients (1%) in group ӀӀ, but in none in group ӀӀӀ. No statistically significant difference was seen between the 3 groups (MCP=1). Minor bleeding occurred in 2 patients (1%) in group ӀӀ, and in none in the other 2 groups. No statistically significant difference was seen between the 3 groups in terms of minor bleeding (MCP=0.57). All the follow up data are summarized in Table 4 and Figures 1 and 2.

Figure 1. Kaplan-Meier survival curve for MACCE

Figure 2. Kaplan-Meier survival curve for Cardiac death

Table 4. 6 months at least Clinical Events according to randomised allocation. *statistically significant at p <.05 using F test. **statistically significant at p <.05 using Pearson Chi square test. -a,b: similar letters mean no significant difference between groups , different letters mean significant difference between groups using post hoc test. -MCP: Monte Carlo significance test

	Group Ӏ Culprit only PCI (n=176) Missed=35	Group ӀӀ Total Revascularisation (n=211) Missed=38	Group ӀӀӀ Staged Revascularisation (n=25) Missed=5	P Value
Total MACCE	88(50.0%)a	27(12.8%)b	4(16%)b	<0.001*
Cardiac death	11(6.3%)a	4 (1.9%)b	0(0%)a,b	0.045*
Reinfarction	19(10.8%)	12(5.7%)	4(16%)	0.081
Stroke	1(0.6%)	0(0%)	0(0%)	0.485
Need for Revascularisation	76(43.2%)a	17(8.1%)b	4(16%)b	<0.001*
TVR	27(15.3%)a	8(3.8%)b	3(12%)a,b	<0.001*
TLR	18(10.2%)a	6(2.8%)b	2(8%)a,b	0.011*
NON-TLR	9(5.1%)	3(1.4%)	1(4%)	0.125
NON TVR	42(23.9%)a	12(5.7%)b	2(8%)a,b	<0.001*
Time till revascularisation	35.8±20.1a	41.2±21.2b	42.1±24.4a,b	0.03*
Heart Failure Arrhythmia Major bleeding Minor bleeding	10(5.7%) 3(1.7%) 2(1.1%) 0(0%)	6(2.9%) 4(1.9%) 2(1%) 2(1%)	0(0%) 0(0%) 0(0%) 0(0%)	0.216 MCP=1 MCP=1 MCP=0.57

Relationship between the RSS and MACCE, cardiac death, re-infarction, stroke, need for revascularization in the only culprit vessel PCI group: We classified the only culprit vessel PCI group according to the RSS into 2 subgroups, the first subgroup comprising 99 patients with an RSS ≤8 and the second subgroup comprising 77 patients with an RSS>8. We compared the groups for incidence of total MAACE, cardiac death, re-infarction, stroke and the need for revascularization either TVR or Non-TVR after 6 months. We found a statistically significant relationship between the RSS and total MAACE after 6 months. The incidence of total MACCE was higher in the second subgroup than in the first subgroup with a statistical significance (61% and 41.4% respectively, P=0.010).

We found a statistically significant relationship between RSS and the rate of re-infarction after 6 months; the incidence of re-infarction was higher in the second subgroup compared to the first (19.5% and 4% respectively, P=0.001). We found a statistically significant relationship between the RSS and the need for revascularization after 6 months. The need for revascularization was higher in the second subgroup than in the first (54.5% and 34.3% respectively, P=0.007). We found a statistically significant relationship between the RSS and Non-TVR after 6 months; the incidence of Non-TVR was higher in the second subgroup than in the first with statistical significance (31.2% and 18.2% respectively, P=0.045).

Thus, there was a statistically significant trend towards a higher rate of MACCE, re-infarction, the need for revascularization and non-TVR in the only culprit vessel PCI subgroup of patients with RSS>8. Considering only the (death/re-infarction), the outcomes were in favor of patients with RSS ≤8 with statistical significance (24.7% and 10.1% respectively, P=0.010). All data are summarised in Table 5.

Table 5. Relation between RSS with different parameters in group I. c², p:  c² and p values for Chi square test to compare the two groups. FE: Fisher Exact for Chi square test to compare the two groups *: Statistically significant at P ≤ 0.05. #: Patient number 308 had a Cardiac death and re-infarction in the RSS>8 subgroup

	RSS		c2	P
	≤8 (n=99)	>8 (n=77)
Total MACCE	41(41.4%)	47(61.0%)	6.672*	0.010*
Cardiac death	6(6.1%)	5(6.5%)	0.014	FEp=1.00
re-infarction	4(4.0%)	15(19.5%)	10.722*	0.001*
Cardiac death + re-infarction	10(10.1%)	19(24.7%) #	6.685*	0.010*
Stroke	0(0.0%)	1(1.3%)	1.293	FEp=0.438
Need for revascularisation	34(34.3%)	42(54.5%)	7.205*	0.007*
TVR	17(17.2%)	10(13.0%)	0.584	0.445
TLR	10(10.1%)	8(10.4%)	0.004	0.950
Non TLR	7(7.1%)	2(2.6%)	1.786	0.302
Non TVR	18(18.2%)	24(31.2%)	4.021*	0.045*

Discussion

In recent times, PCI has become one of the most frequently performed therapeutic interventions in medicine, and the progress in technology has resulted in a steady decline of periprocedural adverse events, coupled with excellent outcomes [13]. A consensus on the best possible revascularization approach, taking into consideration the social and cultural context, and frequent interactions between cardiologists and cardiac surgeons, referring physicians, or other specialists as appropriate, is necessary [14]. Ultimately, risk stratification can be used as a guide, while clinical judgement and multidisciplinary dialogue (The Heart Team) continue to remain essential [15]. The distribution of PCI vs. CABG in patients with multivessel disease suitable for revascularization is approximately 80% vs. 20% [16]. The revascularization strategy in patients with multivessel CAD should be determined early by the Heart Team, based on the patient’s clinical status as well as the severity and distribution of the CAD and the characteristics of the lesion [17].

The SYNTAX score has proven to be strongly predictive of death, myocardial infarction and TVR [17]. The 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation have mentioned [18], that there is a lack of prospective randomized trials about complete versus staged revascularization, addressing the type (i.e. complete vs. incomplete) and timing (i.e. simultaneous vs. staged) of revascularization in NSTE-ACS.

A complete revascularization strategy for significant lesions should be pursued in multivessel disease patients with NSTE-ACS based on two considerations. First, several studies proving the benefit of early intervention compared to the conservative approach in patients with NSTE-ACS mandated a complete revascularization strategy, irrespective of the identification and/or treatment of the culprit lesion [8-10]. Second, multiple PCI and NSTE-ACS trials have shown a poor prognosis following incomplete revascularization. Accordingly, an RSS >8 has been shown to be independently associated with a poor 30-day and 1-year prognosis, including higher mortality after PCI in patients with moderate and high-risk ACS. The decision to treat all significant lesions in the same setting or in a staged manner should be based on clinical presentation, comorbidities, complexity of the coronary anatomy, ventricular function, revascularization modality, and patient preference [11,12].

In our study the mean age of the patients was 61.6 years, which was not very different from that in other studies published in the literature in the developed countries. An exception was the SMILE trial [19], where the mean age was 72.5 years. This indicates an earlier occurrence of coronary artery disease in our country due to the higher prevalence of some CAD risk factors like diabetes and hypertension in our country, reaffirming the urgent need for strict control of these risk factors.

In our study the mean age in group Ӏ was higher than that in group ӀӀ and ӀӀӀ with statistical significance; the same was found in the study by M.G. Bourassa, et al. [20], where patients with incomplete revascularization were older. This difference might be explained by a higher prevalence of risk factors, co-morbidities, and a higher risk of bleeding in group Ӏ patients. Hence, in this subgroup of older patients only the culprit vessel stenting might be a better strategy.

We also found a higher prevalence of diabetes in our study (56.7%) compared to other studies like the SMILE trial Gennaro Saradella, et al. [19] (39.5%) and those by Corrado Tamburino, et al. [21] (35%), Giuseppe Mariani, et al. [22] (26%), Shubrooks Jr, et al. [23] (22%). This indicates the significant impact of diabetes mellitus as a CAD risk factor in our study. The prevalence of hypertension in our study was similar to that in the other studies, ranging from 42% to 73% and reaffirming the impact of hypertension as CAD risk factor worldwide. The mean GRACE risk score in our study was (120.8), which was lower than that in the SMILE trial [19] (175.5). This can be explained by a higher mean age in the SMILE trial; [19] in our study as well, the GRACE risk score and CRUSADE risk score for bleeding were higher in group Ӏ where the mean age was higher than that of group ӀӀӀ.

In the present study, the mean syntax score was found to be higher in group Ӏ (16.9; range 4-50) than in group ӀӀ (13.8; range 4-39); this was due to more complex coronary lesions in group Ӏ. Higher the complexity of lesions, better the strategy of targeting only the culprit lesion. In the SMILE Trial Gennaro Saradella, et al. [19] in one-stage PCI group, the mean syntax score was 16 (ranging from 14 to 18), while in the multi-stage PCI group, the mean syntax score was 15 (ranging from 14 to 18) without any statistical significance.

In our study there was no statistically significant difference in the in-hospital outcomes between the groups, which might be due to the lower GRACE risk score in our patients compared to that in other studies. This finding was similar to that in studies by Corrado Tamburino, et al. [21]. Edward L. Hannan, et al. [24] and Giuseppe Mariani, et al. [22] However, our findings were in contrast with those of M. G. Bourassa, et al. [20] who reported a higher incidence of emergency and elective CABG in the incomplete revascularization group and Hawranek M, et al. [25] who reported a lower in-hospital mortality in the complete revascularization group. Our study findings were also in contrast to that of Ljsselmuiden, et al. [26] who reported that the success rate was higher in the culprit vessel PCI group than in the complete revascularization group. Shubrooks, et al. [23] reported a lower frequency of vascular complications (thrombosis or pseudoaneurysm requiring surgery or bleeding requiring transfusion) with ad hoc procedures, although in our study no statistically significant difference between the groups was seen with respect to major or minor bleeding.

A higher incidence of total MACCE and the need for revascularization (TVR or Non-TVR) at 6 months follow-up were seen in the only culprit vessel stenting group than in the total or the staged revascularization groups, with statistical significance. This was in line with that reported in studies like the SMILE Trial Gennaro Saradella, et al. [19] and those by Corrado Tamburino, et al. [21], Van den Brand, et al. [27], M.G. Bourassa, et al. [20], Ljsselmuiden, et al. [27] and Nikolsky E, et al. [28] where total MACCE and/or the need for revascularization was more in the incomplete revascularization group with a statistical significance. However, our finding was in contrast with that of Yang HH, et al. [29] and Guiseppe Mariani, et al. [22] where the total MACCE and/or the need for revascularization were similar in the incomplete and complete revascularization groups. In our study there was a higher incidence of cardiac death in the culprit only stenting group than in the total or the staged revascularization groups, with a statistical significance, at 6 months follow-up.

This finding was in line with studies by Corrado Tamburino, et al. [21], Edward L.Hannan, et al. [24], and M.B.Iqbal, et al. [30], where a higher incidence of cardiac death was seen in the incomplete revascularization group with a statistical significance, but was in contrast with other studies as those by HH YANG, et al. [29], Guiseppe Mariani, et al. [22] and Hawranek M, et al. [25] where the incidence of cardiac death was similar in the incomplete and complete revascularization groups. In our study there was no statistically significant difference in the incidence of myocardial infarction between the groups at 6 months follow up; this could indicate good compliance to medical treatment in our patients.

This finding was in line with some studies like the SMILE Trial Gennaro Saradella, et al. [19] and those by Yang HH, et al. [29] and Guiseppe Mariani, et al. [22] but was in contrast with studies by Corrado Tamburino, et al. [21], and Palmer N. D, et al. [31] where a higher incidence of myocardial infarction was found in the incomplete revascularization group, with statistical significance. It was noted in two studies by Edward L. Hannan, et al. [24] and Goldstein CL, et al. [32] that complete revascularization had poorer clinical outcomes including mortality, in patients with congestive heart failure and CCS class IV; hence, complete revascularization was not recommended in this category of patients.

In our study, there was a higher rate of MACCE, re-infarction, need for revascularization and non-TVR in the only culprit vessel PCI subgroup of patients with an RSS>8. When considering only the (death/re-infarction), the outcomes were better in patients with an RSS ≤8 (24.7% in the second subgroup and 10.1% in the first subgroup, P=0.010).

Witberg, et al. [33] studied the incremental impact of RSS on long-term clinical outcomes in 148 consecutive patients with MVD treated by PCI with triple vessel/left main CVD. Clinical outcomes at 3 years were collected, and the SS and rSS were calculated. The rSS at a cutoff value determined according to ROC curve fitted for 3 years MACCE to determine which definition has the strongest correlation with long-term outcomes. Witberg, et al. [33] found that rSS ≤ 8 was associated with significant reductions in the 3-year MACCE (19.4 vs. 51.1%, P=0.014), death/MI/CVA (13.7 vs. 28.8%, P=0.030) and repeat revascularization (8.6 vs. 28.9%, P=0.033).

Farooq, et al. [11] found that the RSS is an objective measure of the degree and complexity of residual stenosis after PCI. The RSS was > 0 to 4 in 20.4% [n=184], > 4 to 8 in 18.5% [n=167], and >8 in 16.9% [n=153]. It was seen that an RSS >8 was associated with significantly increased all-cause mortality (35.3%, P<0.001), MACCE (59.5%, P<0.001), MI (17.0%, P<0.001), all-cause revascularization (32.0%, P<0.001), and definite/probable stent thrombosis (16.0%, P=0.005) at 5 years follow up.

Conclusion

In patients of NSTE-ACS with MVD, complete revascularization either in the same setting or in a staged manner is better compared to only culprit vessel PCI in terms of long term total MACCE, cardiac death and the need for revascularization. There was no difference in MACCE outcomes between revascularization in the same setting and staged revascularization. In case of incomplete revascularization, RSS is a good and reliable predictor of total MACCE.

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