© 2014, Wiley Periodicals, Inc. DOI: 10.1111/joic.12167
ACUTE CORONARY SYNDROME Preventive versus Culprit-Only Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction Patients with Multivessel Disease: A Meta-Analysis YEO-JEONG SONG, M.D., HO-CHEOL SHIN, M.D., JOO-II YANG, HO-YOUNG LEE, HAN-YOUNG JIN, M.D., JEONG-SOOK SEO, M.D., P H .D., TAE-HYUN YANG, M.D., P H .D., DAE-KYEONG KIM, M.D., P H .D., DONG-SOO KIM, M.D., P H .D., and JAE-SIK JANG, M.D., P H .D. From the Department of Cardiology, Inje University Busan Paik Hospital, Busan, Korea
Background: Although previous studies have suggested clinical benefits of complete revascularization in patients with multivessel coronary artery disease, it is still controversial whether preventive percutaneous coronary intervention (PCI) leads to better clinical outcomes in the clinical setting of ST-segment elevation myocardial infarction (STEMI). Methods: Relevant studies through September 2014 were searched and identified in the electronic databases. Primary endpoint was all-cause mortality at the longest follow-up. Secondary endpoints included myocardial infarction (MI), repeat revascularization, and major adverse cardiac events (MACE). Results: From 836 initial citations, 7 randomized trials, and 23 observational studies with 44,256 patients (8,087 preventive and 36,169 culprit-only) were included in this study. Preventive PCI was associated with a significant reduction in repeat revascularization (odds ratios [OR]: 0.71; 95% CI: 0.51–0.99) with no differences in all-cause mortality (OR: 0.99; 95% CI: 0.76–1.29) or MI (OR: 1.08; 95% CI: 0.62–1.87) as compared with culprit-only PCI. Comparison of preventive PCI to the culprit-only PCI group revealed OR for MACE of 0.80 (95% CI: 0.57–1.12). Stratified analysis according to revascularization strategy demonstrated a significant survival benefit of culprit-only PCI over multivessel PCI during the index procedure and a significantly lower incidence of all-cause mortality with staged PCI as compared with culprit-only or multivessel PCI during the index procedure. Conclusions: Preventive PCI strategy appears to be effective in reducing the risk of repeat revascularization without significant benefits for mortality or MI when compared with culprit-only revascularization in STEMI patients with multivessel disease. (J Interven Cardiol 2015;28:1–13)
Introduction About 40–65% of patients with ST-elevation myocardial infarction (STEMI) have one or more significant stenosis in non-culprit vessels as well as the culprit lesion.1 Non-culprit lesions found during primary percutaneous coronary intervention (PCI) could be
Grant sponsor: National Research Foundation of Korea; Grant sponsor: Korea government (MSIP); Grant number: R132007-023-00000-0. Address for reprints: Jae-Sik Jang, Department of Cardiology, Inje University Busan Paik Hospital, Busan, Korea. Fax: þ82-51-8920273; e-mail: [email protected]
Vol. 28, No. 1, 2015
managed with three different strategies. After successful restoration of blood flow to culprit vessel, the physicians might complete revascularization of nonculprit vessels during index PCI, plan staged procedure during or after hospitalization period, or decide to treat medically unless they are hemodynamically compromised. Current STEMI guidelines recommend only culprit vessel to be treated during index PCI unless hemodynamically unstable condition.2,3 Recently, several observational studies have been published with conflicting results, while the large, randomized trials Preventive Angioplasty in Acute Myocardial Infarction (PRAMI)4 and Complete versus Lesion-only Primary PCI Trial (CvLPRIT) study5 report better outcomes in
Journal of Interventional Cardiology
1
SONG, ET AL.
STEMI patients treated with preventive strategy. Therefore, we performed a systematic review of literature and meta-analyses to compare preventive PCI to culpritonly PCI in patients with STEMI and multivessel disease.
Methods We followed the PRISMA statement for metaanalysis in health care interventions6 and performed the analysis in accordance with the Meta-Analysis of Observational Studies in Epidemiology guidelines in describing all stages design, implementation, and reporting of this meta-analysis.7 Data Sources and Searches. We identified relevant studies through electronic searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from January 2001 through September 2014. In addition, we hand-searched the content pages of the 2013–2014 issues of the American College of Cardiology, the European Society of Cardiology, and the Transcatheter Cardiovascular Therapeutics to retrieve further potential publications. Medical subject headings and keyword searches included “multivessel”, “complete”, “staged”, “culprit”, “revascularization”, “angioplasty”, “PCI”, “revascularization”, and “myocardial infarction.” Study Selection. Two investigators (J.-S.J. and Y.J.S.) independently conducted the literature search, data extraction, and quality assessment by using a standardized approach. Selected publications were reviewed by the same investigators to assess whether or not studies met the inclusion criteria: comparison of preventive PCI strategies of both simultaneous multivessel PCI at index procedure or staged procedure either during or after index hospitalization and culpritonly revascularization at the time of index procedure in patients with STEMI. Exclusion criteria were: 1 studies comparing PCI with surgical revascularization; 2 studies with lack of control group. Data Extraction and Quality Assessment. Two reviewers (Y.-J.S. and J.-I.Y.) extracted relevant information from the articles including study design, follow-up duration, patient characteristics, primary end point, and exclusion criteria. To reduce the effect of treatment-selection bias and potential confounding in non-randomized observational studies, we also abstracted adjusted risk estimates from observational studies.
2
End Points. The primary end point of this study was all-cause mortality at the longest follow-up. Secondary end points were myocardial infarction (MI), repeat revascularization, and major adverse cardiac events (MACE). Definition of MACE was slightly different across studies, and we used the trial specific definitions of MACE. Data Synthesis and Analysis. We calculated odds ratios (ORs) for each outcome using the DerSimonian and Laird random-effects model.8 Crude OR with 95% confidence interval (CI) was used to assess the efficacy of each revascularization strategy on adverse clinical events in study populations. All p values were 2-tailed, with statistical significance set at 0.05. We assessed statistical heterogeneity between trials with I2 statistic, which is derived from Cochran’s Q and the degree of freedom [100 (Q—df)/Q)].9 I2 values greater than 25%, 50%, and 75% were considered evidence of low, moderate, and severe statistical heterogeneity, respectively. Sensitivity analyses were conducted to examine the heterogeneity on the basis of the study design, inclusion of cardiogenic shock, and the revascularization strategy. Publication bias was examined by visual inspection of constructed funnel plot for the all-cause mortality and mathematically by means of Egger’s test and trim-and-fill method.10,11 All statistical analyses were performed using the Review Manager Version 5.1 (The Nordic Cochrane Center, Copenhagen, Denmark) and MIX version 2.0 (BiostatXL, Sunnyvale, CA, USA).
Results A total of 836 publications were reviewed and 30 studies (7 randomized, 23 non-randomized) were selected for inclusion and further evaluated (Supplementary Figure S1). Twenty-nine studies had been published in peer-reviewed literature, whereas the CvLPRIT trial is as yet unpublished but was presented at a scientific meeting.5 Characteristics of the included studies are summarized in Table 1. Of the 44,256 patients, 8,087 patients underwent multivessel PCI at index procedure or staged PCI during or after hospitalization and 36,169 underwent culprit-only revascularization at the time of index procedure. Six studies were prospective, randomized trials with 1,384 patients that compared the clinical outcomes of multivessel PCI versus culprit-only PCI in patients with STEMI.4,5,12–15 One randomized study including 92
Journal of Interventional Cardiology
Vol. 28, No. 1, 2015
Vol. 28, No. 1, 2015
2005
2006
2007
2008
Chen et al.21
Kong et al.28
Kalarus et al.26
Rigattieri et al.35
2004
Ochala et al.16
2004
2004
Corpus et al.22
Ijsselmuiden et al.13
2003
Poyen et al.33
2004
2001
Roe et al.36
HELP AMI12
Year
Study
Journal of Interventional Cardiology 2004–2006
1999–2003
2000–2001
1997–2002
1995–1998
NA
NA
1998–2002
NA
1995–1999
Study period
Retrospective observational Retrospective observational
Retrospective observational Retrospective observational
RCT
RCT
RCT
Retrospective observational
Retrospective observational Retrospective observational
Design
/64/46
193/–/605
632/–/1350
239/–/1145
108/–/111
52/–/17
48/44/–
26/126/354
86/–/81
79/–/79
PCI strategies (multivessel/ staged/ culprit-only)
MACE-cardiac or noncardiac death, MI, need for CABG, repeat PCI Cumulative survival at 6, 12, and 36 months. MACE, death, emergency CABG, acute occlusion or stent thrombosis, stroke, renal failure, length of stay Any-cause mortality rate and MACE In-Hospital MACE; death, stroke, major bleedings, stent thrombosis, periprocedural MI, vascular complications. Outpatient MACE; death, stroke, stent thrombosis, CABG, PCI, rehospitalization for ACS
12-month repeat revascularization (any revascularization, IRA as well as non-IRA), In Hospital MACEs
Absolute improvement of LVEF
Composite of death, reinfarction, repeat PCI, or bypass surgery Presence of symptom, deaths, new infarctions, residual ischemia, cardiac failure, angioplasties, or bypass surgery Death, re-infarction, TVR, need for CABG, MACEs
Primary endpoint
Table 1. Characteristics of Included Studies
Shock, LM, previous CABG, and severe VHD
CABG during hospitalization.
Previous MI/angioplasty/bypass surgery, shock, CPR, LM
Graft vessel, LM, PCI for acute occlusion, staged PCI after discharge LM, shock, non-IRA not suitable for PCI, renal insufficiency or single kidney, contraindications for antiplatelet therapy, previous CABG, VHD requiring surgery, pregnancy Previous CABG, previous PCI, thrombolysis 2.0 mm Life expectancy 1 year, graft stenosis, participation in another clinical trial, noncompliance or living abroad Shock, thrombolysis before PCI
Shock
branch vessels, LM
Exclusion criteria
392 236 days.
29.7 months
6, 12, 36 months In-hospital
1 year
1 year
6 months
1 year
2.5 years
6 months
Follow-up
PREVENTIVE PCI IN STEMI PATIENTS
3
4
38
Journal of Interventional Cardiology 2002–2006
2010
2010
2011
Dambrink et al.15
EUROTRANSFER23 Mohamad et al.31
2011
2005–2007
2010
Politi et al.14
HORIZONSAMI29
2004–2007
2010
Hannan et al.25
2005–2007
2003–2007
2003–2006
NA
2010
2004–2007
2004–2005
APEX-AMI37
2008
Khattab et al.27
2001–2004
2009
2008
Qarawani et al.34
NA
2004–2007
Study period
Cavender et al.19
2008
2008
Year
Han et al.24
Varani et al.
Study
TABLE 1. Continued
Retrospective observational
Retrospective observational Retrospective observational
RCT
RCT
Retrospective observational
Retrospective observational Retrospective observational
Prospective observational
Retrospective observational Retrospective observational Retrospective observational
Design
/393/275
33/–/30
70/–/707
80/–/41
65/65/84
503/259/259
217/–/1,984
3,134/–/25,802
28/–/45
95/–/25
/93/149
147/96/156
PCI strategies (multivessel/ staged/ culprit-only)
All-cause mortality, MACE, including all-cause death, acute coronary syndrome, acute CHF, or TVR MACE, including death, reinfarction, ischemia-driven TVR, and stroke
All-cause mortality
Ejection fraction assessed by radionuclide ventriculography
MACEs
Mortality
Mortality, composite of death, CHF, shock
In-hospital mortality
Death for any cause and any coronary revascularization MACE, including cardiac death, recurrent MI, and TLR Reischemia, reinfarction, recatheterization, acute heart failure, hospitalization MACE, including death, MI, TVR
Primary endpoint
Use of fibrinolysis, bivalirudin, GPI, LMWH, or fondaparinux, current use of warfarin, bleeding diathesis, hemoglobin
ACUTE CORONARY SYNDROME Preventive versus Culprit-Only Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction Patients with Multivessel Disease: A Meta-Analysis YEO-JEONG SONG, M.D., HO-CHEOL SHIN, M.D., JOO-II YANG, HO-YOUNG LEE, HAN-YOUNG JIN, M.D., JEONG-SOOK SEO, M.D., P H .D., TAE-HYUN YANG, M.D., P H .D., DAE-KYEONG KIM, M.D., P H .D., DONG-SOO KIM, M.D., P H .D., and JAE-SIK JANG, M.D., P H .D. From the Department of Cardiology, Inje University Busan Paik Hospital, Busan, Korea
Background: Although previous studies have suggested clinical benefits of complete revascularization in patients with multivessel coronary artery disease, it is still controversial whether preventive percutaneous coronary intervention (PCI) leads to better clinical outcomes in the clinical setting of ST-segment elevation myocardial infarction (STEMI). Methods: Relevant studies through September 2014 were searched and identified in the electronic databases. Primary endpoint was all-cause mortality at the longest follow-up. Secondary endpoints included myocardial infarction (MI), repeat revascularization, and major adverse cardiac events (MACE). Results: From 836 initial citations, 7 randomized trials, and 23 observational studies with 44,256 patients (8,087 preventive and 36,169 culprit-only) were included in this study. Preventive PCI was associated with a significant reduction in repeat revascularization (odds ratios [OR]: 0.71; 95% CI: 0.51–0.99) with no differences in all-cause mortality (OR: 0.99; 95% CI: 0.76–1.29) or MI (OR: 1.08; 95% CI: 0.62–1.87) as compared with culprit-only PCI. Comparison of preventive PCI to the culprit-only PCI group revealed OR for MACE of 0.80 (95% CI: 0.57–1.12). Stratified analysis according to revascularization strategy demonstrated a significant survival benefit of culprit-only PCI over multivessel PCI during the index procedure and a significantly lower incidence of all-cause mortality with staged PCI as compared with culprit-only or multivessel PCI during the index procedure. Conclusions: Preventive PCI strategy appears to be effective in reducing the risk of repeat revascularization without significant benefits for mortality or MI when compared with culprit-only revascularization in STEMI patients with multivessel disease. (J Interven Cardiol 2015;28:1–13)
Introduction About 40–65% of patients with ST-elevation myocardial infarction (STEMI) have one or more significant stenosis in non-culprit vessels as well as the culprit lesion.1 Non-culprit lesions found during primary percutaneous coronary intervention (PCI) could be
Grant sponsor: National Research Foundation of Korea; Grant sponsor: Korea government (MSIP); Grant number: R132007-023-00000-0. Address for reprints: Jae-Sik Jang, Department of Cardiology, Inje University Busan Paik Hospital, Busan, Korea. Fax: þ82-51-8920273; e-mail: [email protected]
Vol. 28, No. 1, 2015
managed with three different strategies. After successful restoration of blood flow to culprit vessel, the physicians might complete revascularization of nonculprit vessels during index PCI, plan staged procedure during or after hospitalization period, or decide to treat medically unless they are hemodynamically compromised. Current STEMI guidelines recommend only culprit vessel to be treated during index PCI unless hemodynamically unstable condition.2,3 Recently, several observational studies have been published with conflicting results, while the large, randomized trials Preventive Angioplasty in Acute Myocardial Infarction (PRAMI)4 and Complete versus Lesion-only Primary PCI Trial (CvLPRIT) study5 report better outcomes in
Journal of Interventional Cardiology
1
SONG, ET AL.
STEMI patients treated with preventive strategy. Therefore, we performed a systematic review of literature and meta-analyses to compare preventive PCI to culpritonly PCI in patients with STEMI and multivessel disease.
Methods We followed the PRISMA statement for metaanalysis in health care interventions6 and performed the analysis in accordance with the Meta-Analysis of Observational Studies in Epidemiology guidelines in describing all stages design, implementation, and reporting of this meta-analysis.7 Data Sources and Searches. We identified relevant studies through electronic searches of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from January 2001 through September 2014. In addition, we hand-searched the content pages of the 2013–2014 issues of the American College of Cardiology, the European Society of Cardiology, and the Transcatheter Cardiovascular Therapeutics to retrieve further potential publications. Medical subject headings and keyword searches included “multivessel”, “complete”, “staged”, “culprit”, “revascularization”, “angioplasty”, “PCI”, “revascularization”, and “myocardial infarction.” Study Selection. Two investigators (J.-S.J. and Y.J.S.) independently conducted the literature search, data extraction, and quality assessment by using a standardized approach. Selected publications were reviewed by the same investigators to assess whether or not studies met the inclusion criteria: comparison of preventive PCI strategies of both simultaneous multivessel PCI at index procedure or staged procedure either during or after index hospitalization and culpritonly revascularization at the time of index procedure in patients with STEMI. Exclusion criteria were: 1 studies comparing PCI with surgical revascularization; 2 studies with lack of control group. Data Extraction and Quality Assessment. Two reviewers (Y.-J.S. and J.-I.Y.) extracted relevant information from the articles including study design, follow-up duration, patient characteristics, primary end point, and exclusion criteria. To reduce the effect of treatment-selection bias and potential confounding in non-randomized observational studies, we also abstracted adjusted risk estimates from observational studies.
2
End Points. The primary end point of this study was all-cause mortality at the longest follow-up. Secondary end points were myocardial infarction (MI), repeat revascularization, and major adverse cardiac events (MACE). Definition of MACE was slightly different across studies, and we used the trial specific definitions of MACE. Data Synthesis and Analysis. We calculated odds ratios (ORs) for each outcome using the DerSimonian and Laird random-effects model.8 Crude OR with 95% confidence interval (CI) was used to assess the efficacy of each revascularization strategy on adverse clinical events in study populations. All p values were 2-tailed, with statistical significance set at 0.05. We assessed statistical heterogeneity between trials with I2 statistic, which is derived from Cochran’s Q and the degree of freedom [100 (Q—df)/Q)].9 I2 values greater than 25%, 50%, and 75% were considered evidence of low, moderate, and severe statistical heterogeneity, respectively. Sensitivity analyses were conducted to examine the heterogeneity on the basis of the study design, inclusion of cardiogenic shock, and the revascularization strategy. Publication bias was examined by visual inspection of constructed funnel plot for the all-cause mortality and mathematically by means of Egger’s test and trim-and-fill method.10,11 All statistical analyses were performed using the Review Manager Version 5.1 (The Nordic Cochrane Center, Copenhagen, Denmark) and MIX version 2.0 (BiostatXL, Sunnyvale, CA, USA).
Results A total of 836 publications were reviewed and 30 studies (7 randomized, 23 non-randomized) were selected for inclusion and further evaluated (Supplementary Figure S1). Twenty-nine studies had been published in peer-reviewed literature, whereas the CvLPRIT trial is as yet unpublished but was presented at a scientific meeting.5 Characteristics of the included studies are summarized in Table 1. Of the 44,256 patients, 8,087 patients underwent multivessel PCI at index procedure or staged PCI during or after hospitalization and 36,169 underwent culprit-only revascularization at the time of index procedure. Six studies were prospective, randomized trials with 1,384 patients that compared the clinical outcomes of multivessel PCI versus culprit-only PCI in patients with STEMI.4,5,12–15 One randomized study including 92
Journal of Interventional Cardiology
Vol. 28, No. 1, 2015
Vol. 28, No. 1, 2015
2005
2006
2007
2008
Chen et al.21
Kong et al.28
Kalarus et al.26
Rigattieri et al.35
2004
Ochala et al.16
2004
2004
Corpus et al.22
Ijsselmuiden et al.13
2003
Poyen et al.33
2004
2001
Roe et al.36
HELP AMI12
Year
Study
Journal of Interventional Cardiology 2004–2006
1999–2003
2000–2001
1997–2002
1995–1998
NA
NA
1998–2002
NA
1995–1999
Study period
Retrospective observational Retrospective observational
Retrospective observational Retrospective observational
RCT
RCT
RCT
Retrospective observational
Retrospective observational Retrospective observational
Design
/64/46
193/–/605
632/–/1350
239/–/1145
108/–/111
52/–/17
48/44/–
26/126/354
86/–/81
79/–/79
PCI strategies (multivessel/ staged/ culprit-only)
MACE-cardiac or noncardiac death, MI, need for CABG, repeat PCI Cumulative survival at 6, 12, and 36 months. MACE, death, emergency CABG, acute occlusion or stent thrombosis, stroke, renal failure, length of stay Any-cause mortality rate and MACE In-Hospital MACE; death, stroke, major bleedings, stent thrombosis, periprocedural MI, vascular complications. Outpatient MACE; death, stroke, stent thrombosis, CABG, PCI, rehospitalization for ACS
12-month repeat revascularization (any revascularization, IRA as well as non-IRA), In Hospital MACEs
Absolute improvement of LVEF
Composite of death, reinfarction, repeat PCI, or bypass surgery Presence of symptom, deaths, new infarctions, residual ischemia, cardiac failure, angioplasties, or bypass surgery Death, re-infarction, TVR, need for CABG, MACEs
Primary endpoint
Table 1. Characteristics of Included Studies
Shock, LM, previous CABG, and severe VHD
CABG during hospitalization.
Previous MI/angioplasty/bypass surgery, shock, CPR, LM
Graft vessel, LM, PCI for acute occlusion, staged PCI after discharge LM, shock, non-IRA not suitable for PCI, renal insufficiency or single kidney, contraindications for antiplatelet therapy, previous CABG, VHD requiring surgery, pregnancy Previous CABG, previous PCI, thrombolysis 2.0 mm Life expectancy 1 year, graft stenosis, participation in another clinical trial, noncompliance or living abroad Shock, thrombolysis before PCI
Shock
branch vessels, LM
Exclusion criteria
392 236 days.
29.7 months
6, 12, 36 months In-hospital
1 year
1 year
6 months
1 year
2.5 years
6 months
Follow-up
PREVENTIVE PCI IN STEMI PATIENTS
3
4
38
Journal of Interventional Cardiology 2002–2006
2010
2010
2011
Dambrink et al.15
EUROTRANSFER23 Mohamad et al.31
2011
2005–2007
2010
Politi et al.14
HORIZONSAMI29
2004–2007
2010
Hannan et al.25
2005–2007
2003–2007
2003–2006
NA
2010
2004–2007
2004–2005
APEX-AMI37
2008
Khattab et al.27
2001–2004
2009
2008
Qarawani et al.34
NA
2004–2007
Study period
Cavender et al.19
2008
2008
Year
Han et al.24
Varani et al.
Study
TABLE 1. Continued
Retrospective observational
Retrospective observational Retrospective observational
RCT
RCT
Retrospective observational
Retrospective observational Retrospective observational
Prospective observational
Retrospective observational Retrospective observational Retrospective observational
Design
/393/275
33/–/30
70/–/707
80/–/41
65/65/84
503/259/259
217/–/1,984
3,134/–/25,802
28/–/45
95/–/25
/93/149
147/96/156
PCI strategies (multivessel/ staged/ culprit-only)
All-cause mortality, MACE, including all-cause death, acute coronary syndrome, acute CHF, or TVR MACE, including death, reinfarction, ischemia-driven TVR, and stroke
All-cause mortality
Ejection fraction assessed by radionuclide ventriculography
MACEs
Mortality
Mortality, composite of death, CHF, shock
In-hospital mortality
Death for any cause and any coronary revascularization MACE, including cardiac death, recurrent MI, and TLR Reischemia, reinfarction, recatheterization, acute heart failure, hospitalization MACE, including death, MI, TVR
Primary endpoint
Use of fibrinolysis, bivalirudin, GPI, LMWH, or fondaparinux, current use of warfarin, bleeding diathesis, hemoglobin
