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Editorial - (2014) Volume 5, Issue 4
In patients admitted for ST-segment sus-elevation myocardial infarction (STEMI), revascularization is the corner stone of the management, completing the medical treatments [1,2]. Although it is widely accepted and strongly recommended that the culprit lesion has to be treated during the Primary Percutaneous Coronary Intervention (PPCI), the better option regarding the other lesions in case of multivessel disease remains controversial. On the one hand, treating only the culprit lesion allows a shorter procedure with less renal impairment and lower risk of acute stent thrombosis. On the other hand, treating all the stenoses allow to shorten the hospitalization, stabilize the unstable plaques (See Table 1 for a detailed description of the advantages/disadvantages imbalance of the two sides of the medal). Importantly, this dilemma is not at all rare but should represent 30% to half of the patients admitted for STEMI [1,2].
Advantages | Disadvantages | |
---|---|---|
Culprit lesion only revascularization | The culprit lesion is treated and the more unstable plaque is treated The procedure is shorter Less contrast agent Less renal impairment Staff discussion is possible later Reevaluation of the lesions (-often overestimated during the emergency procedure, especially because of coronary spasms) Easier to obtain an informed consent, easier to inform the patient on different options and to take into account his preferences. opportunity to prove myocardial ischemia by functional test or FFR |
Unstable plaques remaining are not treated Hemodynamic stenoses are not treated Longer hospitalization (in case of staged procedure) Requiring 2 arterial punctures |
Full revascularization | All the significant lesions are stabilized and treated Shorter hospitalization Only one arterial puncture enhance of the collateral blood flow greater myocardial salvage achievement of a complete revascularization, factor that is associated with a better prognosis |
peri-procedural complications More severe in case of stent thrombosis Longer procedure Hemodynamic instability during balloon inflations Vessel related complications (dissections, no-reflow) More contrast agent More renal impairment No staff discussion, no heart team |
Table 1: Comparison of the two different options in case of multivessel disease revealed by a STEMI
A recent systemic review and metanalysis on this topic has just been published as well as an original work published in the leading medical journal [3,4]. In this important metanalysis, 26 studies with a total of 38,438 patients admitted for STEMI have been finally included [3]. The vast majority of them are not randomized (23 on 26). (See Table 2 for schematic description of the main features of the four prospective randomized trials available on this topic). The first three randomized trials have included only 339 patients. Among these three randomized trials, the multi-vessels PCI has been reported to be better than the culprit-only PCI as regards in hospital mortality (OR=0.24 (0.06-0.91), but only two small studies) and not in long-term mortality. Interestingly, among the non-randomized trials, it seems that the ideal timing of the revascularization is of great importance. As regards in-hospital mortality, immediate full revascularization is associated with poor outcomes (OR=1.35 (1.19-1.54)) whereas staged revascularization during the index hospitalization is associated with better outcomes (OR=0.35 (0.21-0.59). Similarly concerning the long term outcomes, immediate full revascularization is not statistically different from the culprit-only revascularization, but staged in hospital or later full revascularization is associated with better outcomes. Briefly, this work corroborates first that full revascularization, but perhaps not immediately during the index PCI, should be better that the culprit-only revascularization. Secondly, this analysis underlines that prospective randomized trials are mandatory.
references | publication date | design and intervention | number of patients and randomisation | inclusion criteria | exclusion criteria | delay of revascularization | primary (1) and secondary (2) endpoints | main results |
---|---|---|---|---|---|---|---|---|
Dambrink et al. [5] |
2010 | Culprit PPCI + medical treatment (conservative group) vs culprit PPCI + FFR in vessels with a significant stenosis (PCI performed if FFR < 0.75 or directly for severe lesions >90%) (invasive group) |
121 patients : - 80 patients in invasive group - 41 patients in conservative group |
STEMI with >50% stenosis in ≥ 2 arteries | - > 80 years - CTO of non IRA - Prior CABG - Left main significant stenosis - In-stent restenosis - Chronic AF |
Invasive group : during index hospitalization or electively during the 3 weeks following (mean 7.5 days (5-20)) | 1) LVEF at 6 months 2) MACE at 6 months |
1) No LVEF difference : 59+/-9% in invasive group and 57+/-9% in conservative group : p=0.362 2) No difference in MACE : 21% in invasive group and 22% in conservative group : p=0.929 |
Di Mario et al. [6] |
2004 | Culprit PPCI with additional revascularization at the investigators discretion (need and timing decided according to clinical status, evidence of ischemia in non-invasive tests or angiographic severity) vs complete revascularization during index catheterization Study using only one or more heparin coated stents (HepaCoat stents) | 69 patients : - 17 patients in culprit lesion treatment only group - 52 patients in complete revascularization group |
STEMI < 12h with MVD with 1-3 lesions in non IRA | - Lesion in vein and arterial grafts - In-stent restenosis - Chronic Total Occlusion - Thrombolysis - Cardiogenic shock - Left main significant stenosis |
Not specified for culprit lesion treatment only group | 1) 12-month incidence of any repeat revascularization 2) (a) Composite with in hospital repeat revascularization, reinfarction and death (b) total 12-month cost |
1) No significant difference in the incidence of new revascularization at 12 months : 35.3% in the culprit treatment group vs 17.3% in complete revascularization group, p = 0.174) 2) (a) Similar incidence of in-hospital MACE in the 2 groups : 0 and 3.8% in culprit and multivessel treatment, p=0.164) (b)No difference in total cost at 12-months : Euro 22,330 +/- Euro 13,653 in culprit treatment group vs Euro 20,382 +/- Euro 11,671 in complete revascularization group, p = 0.323). |
Politi et al. [7] |
2010 | 3 strategies - Culprit PPCI only - Full revascularization during index catheterization - Full revascularization during staged procedure |
214 patients : - 84 patients in the culprit PPCI only group, - 65 patients in the complete revascularization group - 65 patients in the staged revascularization group |
STEMI < 12h with > 70% stenosis in ≥ 2 arteries | - Cardiogenic shock - Left main significant stenosis - Previous CABG - Severe valvular disease - Unsuccessful procedure |
56.9 ± 12.9 days after the primary PCI for the staged revascularization group | 1) MACE at 2.5 years 2) (a) Each event of MACE assessed individually (b) Survival free of MACE (c) Survival (d) Multivariate analyses |
1) MACE occurred in 42 patients (50%) in the culprit only revascularization group, in 13 patients (20%) in the staged revascularization group and in 15 patients (23.1%) in the complete revascularization group (p<0.001). 2) (a) The incidence of inhospital death, repeat revascularization and re-hospitalization was significantly higher in the culprit only revascularization group (all p<0.05). No significant difference in re-infarction among the three groups. (b) Survival free of MACE was worse in the culprit only revascularization group compared with both the complete revascularization group (p=0.002) and the staged revascularization group (p=0.001), No difference between the complete and staged revascularization groups (p=0.815). (c) Tendency for a worse overall survival in the culprit only revascularization group compared with the other two groups (p=0.151). |
Wald et al. [4] | 2013 | Complete revascularization vs culprit PPCI + subsequent PCI only for refractory angina with objective evidence of ischemia | 465 patients : - 234 patients in preventive PCI group (complete revascularization) - 231 patients in no preventive PCI group (culprit PPCI only) |
STEMI < 12h with Stenosis ≥ 50% in one or more coronary arteries other than the IRA and cardiologist consider that both infarct artery-only PCI and preventive PCI would be acceptable treatment options. |
- Cardiogenic shock - Previous CABG - Left main stenosis > 50% - Chronic Total Occlusion |
Number and timing of requiring subsequent PCI in no preventive PCI group were not specified | 1) composite endpoint of cardiac death, non fatal myocardial infarction and refractory angina at 36 months 2) (a)Each item of composite endpoint assessed individually (b) Non cardiac death (c) Repeat revascularization |
Trial prematurely stopped 1) Significant reduction of composite endpoint in preventive PCI group with 21 patients (9%) vs 53 patients (22.9%) in no preventive PCI group (p<0.001) 2) (a) No difference for death from cardiac causes : 4 patients in preventive PCI group and 10 in no preventive PCI group (p=0.07) but significant reduction for myocardial infarction (7 vs 20 patients, p=0;009) and refractory angina (12 vs 30 patients, p=0.002) respectively in preventive PCI group and no preventive PCI group (b) No difference between the 2 groups for non cardiac death (p=0.86) (c) Significant reduction of repeat revascularization in preventive PCI group (p<0.001) |
Table 2: Main features of the four available prospective randomized trials on various strategies for PCI in patients admitted with STEMI and multivessel disease.
PPCI : Primary Percutaneous Coronary Intervention; STEMI : ST segment sus-elevation myocardial infarction; FFR : Flow Fraction Reserve; CTO : Chronic Total Occlusion; IRA : Infarction Related Artery; CABG : Coronary Artery Bypass Graft; AF : Atrial Fibrillation; MVD : MultiVessel Disease; LVEF : Left Ventricular Ejection Fraction; MACE : Major Adverse Cardiac Events
Recently, the important PRAMI trial was published [4]. In this prospective randomized trial, 465 patients with STEMI were treated by PCI (culprit lesion) and then randomly assigned either to preventive PCI or no preventive PCI. This trial has been largely discussed (at least 8 comments following the publication) on several points. The main concern is the choice to revascularize all stenoses>50% (and not 70% as usually recommended, except as regards the main left trunk). This full revascularization was performed at one time. In spite of all the concerns mentioned, this trial established for the first time a large prospective trial corroborating that full revascularization could be safe and better than the culprit-lesion only revascularization (the primary endpoint was a clinical composite endpoint; hazard ratio 0.35 (0.21-0.58).
Here, Dahud et al. (paper to quote by the editorial office) report a retrospective trial including 491 patients admitted for STEMI and presenting a multiple vessel disease. 69.5% of the patients were treated with immediate full revascularization during the index PCI, whereas 30.5% were treated only on the culprit lesion and treated later for the other lesions. Importantly, these two different procedures don't evaluate the culprit only versus the full revascularization, but compare the ideal timing for the full revascularization: either immediate or staged full revascularization. This trial is a large retrospective study, corroborating that immediate full revascularization could be interesting, with a significantly shorter hospitalization, less MACEs, although by contrast, transient renal dysfunction was more frequent. Many limitations are to rise. Beyond the retrospective design, the long duration for inclusions (procedures have evolved and stents or antiplatelet agents have changed for instance), one important concern is how the patients had been allocated to each group? The more severe patients are likely to have been allocated to the more simple procedure first. If true, the results are a very good surprise. As regards methods, the regression models could be more detailed (especially the impact of the different operators). On ethical point of view, informed consent and preferences of the patients are obviously difficult to obtain in the onetime full revascularization procedures. As no surgical back-up is available in this centre, heart team discussion is difficult.
In spite of all these limitations, the authors provide interesting real-life data, underlining that this question is not solved. On contrary, several trials currently on going are precisely addressing this issue as briefly presented in Table 3.
Country | Endpoint | Number of patients Planned to enroll | Design Randomization between two distinct PCI strategies | Delay for the full revascularization | NCT number |
---|---|---|---|---|---|
Spain | Clinical composite endpoint | 400 | Randomization 1) Full revascularization in a staged procedure during the index admission 2) Stress echocardiography and revascularization if required |
1) During the initial hospitalization 2) Delayed (delay not provided) |
NCT01179126 |
Denmark | Clinical composite endpoint | 650 | Randomization 1) Full revascularization guided by Fractional Flow Reserve (FFR) in a separate procedure within the index hospitalization 2) Culprit lesion revascularization only |
1) During the initial hospitalization 2) Not applicable |
NCT01960933 |
Korea | target vessel related major adverse cardiac events | 646 | Randomization 1) Complete revascularization : one time 2) Culprit revascularization : PCI of only the culprit lesion and staged nonculprit PCI at a later date |
Immediate full revascularization versus later (delay not provided) | NCT01180218 |
Canada | Infarct size by CMR | 250 | Randomization 1) Full revascularization during the index PCI 2) IRA only PCI with planned staging for non-IRA lesions |
1) Immediate 2) Delayed (delay not detailed) |
NCT01818960 |
International | Clinical composite endpoint | 885 | Randomization 1) Full revascularization guided by FFR 2) Evaluation by FFR and referred to the cardiologist for further management |
1) Same procedure (or delayed if necessary) 2) Delayed if any (delay not provided) |
NCT01399736 |
Russia | Clinical composite endpoint | 120 | Randomized 1) one-time PCI of the culprit and nonculprit lesions 2) PCI of only the culprit lesion and staged nonculprit PCI at a later date (3-15 days) With Zotarolimus-eluting coronary stents |
1) One time 2) 3-15 days |
NCT01781715 |
Czech Republic | Clinical composite endpoint | 400 | Randomized 1) complete revascularization of significant stenoses of "non-infarct" coronary arteries (PCI or surgery; 3rd-40th day after primary PCI) 2) conservative management standard guideline-based medical therapy |
1) Day 3-40 2) Not applicable |
NCT01332591 |
Germany | 30-day mortality and/or severe renal failure (Only patients with cardiogenic shock are included) |
706 | Randomization 1) immediate full revascularization 2) culprit lesion only and other revascularization later following guidelines |
1) Immediate 2 ) Delayed (delay not provided) |
NCT01927549 |
Table 3: Prospective randomized clinical trials currently registered dealing with STEMI and various PCI strategies for the management of patients with multiple vessel disease.
In conclusion, a systematic approach is difficult to recommend. Two schematic situations are to be considered. On the one hand, a young patient with two critical stenoses on the RCA and on the LDA. The culprit lesion is clearly the LDA. In case the revascularization of the LDA should be easy and quick, it seems then reasonable to treat the other lesion during the same procedure (immediate full revascularization). On the other hand, an old patient, with severe multiple stenoses, unknown (but likely impaired) renal function. In case the revascularization of the LDA should be long and difficult, it is obviously preferable to propose the angioplasty of the RCA later (staged procedure). The ideal delay, how to evaluate the stenosis, remain under debate. An individually tailored strategy should be the best option, but the best parameters to take into account are to be defined through prospective randomized trials currently on going (See Table 4 for some propositions presently taken into consideration routinely).
The clinical presentation (including cardiogenic shock) |
The clinical background (including renal function and other comorbidities) |
The anatomy of the lesions (dedicated scores) |
The thrombotic context (thrombus, drugs…) |
The lesion severity: significant or critical? |
The initial result on the culprit lesion (opportunity to check the result later) |
ECG +/- echography parameters |
The arterial access (in case of difficult access, it seems reasonable to prefer one time full revascularization) |
The duration of the procedure |
The necessity for heart team /staff discussion |
The necessity for multiple operators procedure |
The local facilities |
Table 4: How could we decide to continue or to stop the procedure?
Only trials comparing full revascularization to culprit-only revascularization are compared, not trials comparing for instance two different stents. Research with the keyword "multivessel disease", March 19th, 2014 on the clinicaltrials.gov site
NCT: National Clinical Trial, FFR: Fractional Flow Reserve; PPCI: Primary Percutaneous Coronary Intervention; IRA: Infarct-Related Artery
This is an editorial on the article "Infarct related artery only versus multivessel revascularization during primary PCI for STEMI” published in the Journal of Clinical & Experimental Cardiology.
The authors would like to acknowledge Drs Jean-Christophe MACIA, Richard GERVASONI and Thien-Tri CUNG (Montpellier University Hospital, France) for their suggestions and improvement of this manuscript.