Heart, Lung and Circulation (2015) 24, 327–334 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2014.10.013
REVIEW
Target-Vessel Versus Multivessel Revascularisation in ST-Elevation Myocardial Infarction: A Meta-Analysis of Randomised Trials Kiran Sarathy, MBBS a, Vinayak Nagaraja, MBBS a,c, Amit Kapur, Bsc, PhD, MBBS a, Richard Szirt, MBBS a, Jwalant Raval, MBBS, FRACP b*, Guy D. Eslick, PhD, MMedSc (Clin Epi), MMedStat c, David Burgess, BMed, MBBS MPH, PhD b, A. Robert Denniss, MBBS, MD, MSc, FRACP, FACC, FESC, FAHA, FCSANZ b a
Prince of Wales Hospital, University of New South Wales, Sydney Department of Cardiology, Blacktown Hospital, Sydney c The Whiteley-Martin Research Centre, University of Sydney, Nepean Hospital, Sydney b
Received 19 October 2013; received in revised form 10 September 2014; accepted 15 October 2014; online published-ahead-of-print 5 December 2014
Introduction
In acute ST-segment elevation myocardial infarction (STEMI), coronary reperfusion with percutaneous coronary intervention (PCI) to treat the culprit lesion responsible for infarction improves clinical outcomes in nearly all patients. The concurrent treatment of non-infarct vessels with significant stenoses during initial angiography remains an area of controversy.
Methods
A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane Library, Google Scholar, Science Direct, and Web of Science. Original data were abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI).
Results
Only four randomised trials comprising 775 patients met full criteria for analysis. The incidence of non-fatal MI (3.25% vs 8.51%, OR: 0.376, 95% CI: 0.192-0.763), refractory angina (4.01% vs 9.57%, OR: 0.400, 95% CI: 0.241-0.741) and repeat revascularisation (10.52% vs 24.20%, OR: 0.336, 95% CI: 0.202-0.661) was lower in the multivessel revascularisation cohort. Death from cardiac causes or refractory angina or non-fatal MI (11.78% vs 28.86%, OR: 0.336, 95% CI: 0.223-0.505) and death from cardiac causes or non-fatal MI (5.26% vs 12.76%, OR: 0.420, 95% CI: 0.245-0.722) were significantly lower in the multivessel revascularisation cohort. The Median Contrast Volume and Procedure Length were similar in both cohorts.
Conclusions
In patients with acute STEMI who undergo primary PCI, a strategy of treatment of significant non-infarct stenosis (preventive PCI) in addition to the culprit lesion responsible for infarction may result in improved cardiovascular outcomes and reduced overall mortality; however there is insufficient data to fully validate this from currently published literature.
Keywords
Acute ST-segment elevation myocardial infarction Randomised trials Multivessel revascularisation Two-stage revascularisation Meta-analysis
*Corresponding author at: Department of Cardiology, Blacktown Hospital. Tel.: +029881800., Email: [email protected] © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
328
Introduction In patients with acute ST-segment elevation myocardial infarction (STEMI), coronary reperfusion with percutaneous coronary intervention (PCI) to treat the culprit lesion responsible for infarction is considered the treatment of choice [1,2]. In this setting, up to 40-65% of patients may also be found to have multivessel disease with significant coronary stenoses that are not responsible for the acute infarction [3,4]. The recommendation for concurrent treatment of non-infarct vessels with significant stenosis to achieve complete revascularisation during initial angiography is reserved for patients with haemodynamic compromise [5]. Nonetheless, the optimal management of multivessel disease in this setting remains controversial as the aforementioned recommendation is based on nonrandomised data. To date, there remains a class III recommendation with Grade C evidence for a staged approach to non-culprit lesions at a later date [6]. Recently, the Preventative Angioplasty in Acute Myocardial Infarction (PRAMI) trial evaluated the role of preventive PCI and its impact on the outcomes including cardiac death, non-fatal myocardial infarction, and refractory angina, and found this strategy conferred significant benefits [7]. We synthesised the available evidence from this randomised trial, as well as the other three previous randomised trials in the literature on preventive PCI in patients with STEMI and focussed on a comparison of outcomes of this strategy against the standard treatment strategy of PCI to the culprit lesion only.
Methods Study Protocol We followed the Preferred Reporting Items for Systematic reviews and MetaAnalyses PRISMA guidelines where possible in performing our systematic review [8]. We performed a systematic search through MEDLINE (from 1950), PubMed (from 1946), EMBASE (from 1949), Current Contents Connect (from 1998), Cochrane Library, Google Scholar, Science Direct, and Web of Science to November 2014. The search terms included ‘‘complete revascularization,’’ ‘‘multivessel revascularization,’’ ‘‘culprit revascularization,’’ ‘‘culprit-only revascularization,’’ and ‘‘myocardial infarction’’ which was searched as text word and as exploded medical subject headings where possible. No language restrictions were used in either the search or study selection. The reference lists of relevant articles were also searched for appropriate studies. A search for unpublished literature was not performed.
Study Selection We included studies that met the following inclusion criteria: Studies identifying the population of patients with ST
elevation myocardial infarction
K. Sarathy et al.
Randomised trials comparing complete versus culprit-
only revascularisation.
Data Extraction We performed the data extraction using a standardised data extraction form, collecting information on the publication year, study design, number of cases, total sample size, population type, country, continent, mean age and clinical data. The event rate and confidence intervals were calculated.
Statistical Analysis Pooled event rate and 95% confidence intervals were using a random effects model [9]. We tested heterogeneity with Cochran’s Q statistic, with P70%
Infarction (AMI),
time of emergency
diameter stenosis
70%)
PCI, infarct artery
of two or more
symptoms onset,
non-IRA stenosis
treated
epicardial coronary
undergoing
for PCI, successful
successfully, stenosis of 50%
arteries or their major branches by
primary angioplasty, with
PCI of IRA
or more in one or
visual estimation),
documented
more coronary
Chest Pain between
multivessel
arteries other than
30min-12 hrs, ECG
disease and both
infarct artery and
criteria for STEMI
culprit lesion
the stenosis was
and 1 to 3 other
deemed to be
lesions suitable
treatable by PCI
for stent implantation
147
135
5
10
NA
NA
NA
NA
165
NA
NA
NA
NA
NA
NA
NA
300
200
NA
NA
242
341
315.6
243.9
Median Procedure Length (minutes) IQR
63
45
4.8
5.3
53
69
65.8
84.1
Hospital Stay
NA
NA
NA
NA
NA
NA
4.7 days
7.6 days
culprit Drug Eluting Stent in non-culprit Median Contrast Volume (mL) IQR
331
Table 2 Overall odds ratio and 95% CI. I2
Primary outcome
Absolute event rates
OR
95% CI
P value
Death from cardiac causes, non-fatal MI, refractory angina
11.78% vs 28.86%
0.336
0.223-0.505
0.00
0.783
Death from cardiac causes or
5.26% vs 12.76%
0.42
0.245-0.722
0.00
0.86
Death from cardiac outcomes
2.25% vs 5.31%
0.454
0.201-1.027
0.00
0.85
Death from non-cardiac outcomes
2.50% vs 2.39%
1.185
0.47-2.99
0.00
0.68
Non-fatal MI
3.25% vs 8.51%
0.376
0.192-0.763
0.00
0.89
Refractory angina
4.01% vs 9.57%
0.4
0.241-0.741
0.00
0.55
Repeat revascularisation
10.52% vs 24.20%
0.336
0.202-0.661
42.64
0.16
non-fatal MI
finding was that patients who underwent one stage revascularisation had improved LVEF recovery at 30 days. However, this study was not powered to assess MACE outcomes. Nonetheless, they observed no significant differences in outcomes between the two groups. Two-stage revascularisation was associated with longer hospital stay, fluoroscopy time, and total contrast use. The HELP-AMI (Results of the multicentre randomised HEpacaoat for cuLPrit or multivessel stenting for Acute Myocardial Infarction) [18] study was a European trial which enrolled 69 patients with STEMI within 12 hours of symptom onset undergoing primary PCI with multivessel disease (between one and three non-culprit stenosis) suitable for PCI. The study had unbalanced randomisation between the two arms (17 patients in the culprit lesion only group and 52 in the multivessel group). Multivessel PCI was found to be safe without an increased rate of adverse clinical outcomes. Contrast usage and procedural time were only slightly higher in the multivessel arm. In our study, the Median Contrast Volume and Procedure Length were similar in both cohorts. In terms of revascularisation, HELP-AMI [18] found there was no reduction in the need for repeat
Table 3 Median contrast volume and procedure length. Preventive
No
PCI
preventive PCI
Median contrast volume (ml)
Mean
285.87
261.63
SD
38.78
72.15
SEM
22.39
41.66
P value Median procedure
0.73
Mean
46.65
50.85
SD
28.44
34.37
SEM P value
14.22 0.65
17.19
length (minutes)
revascularisation in the multivessel group with the need for revascularisation in the culprit only group remaining low. The small sample size of the study was a significant limitation, compounded by imbalanced randomisation such that the primary endpoint of difference in new revascularisation procedures did not reach statistical significance. However, in our meta-analysis, we found the rate of refractory angina (OR: 0.400, 95% CI: 0.241-0.741) and the need for repeat revascularisation (OR: 0.336, 95% CI: 0.202-0.661) was lower in the multivessel revascularisation cohort. Politi et al [19] examined the outcomes of 214 consecutive patients with STEMI and multivessel disease. They found an increased rate of death, repeat revascularisation, and rehospitalisation in the culprit vessel angioplasty only group. They also compared staged revascularisation against complete revascularisation with multivessel PCI and found a similar rate of MACE in these two arms. The largest and most recent trial is the PRAMI trial [7], a single-blind randomised study designed to assess whether multivessel (preventive) PCI would reduce the incidence of cardiac death, non-fatal myocardial infarction, or refractory angina. 465 patients from five UK centres were enrolled into the trial which was eventually stopped early due to a highly significant difference in the incidence of the primary outcome in favour of multivessel PCI. In our meta-analysis of all four randomised trials, the incidence of non-fatal MI (OR: 0.376, 95% CI: 0.192-0.763) was lower in the multivessel cohort. Death from cardiac causes or non-fatal MI (OR: 0.336, 95% CI: 0.223-0.505) and from non-cardiac outcomes (OR: 0.420, 95% CI: 0.245-0.722) was significantly lower in the multivessel revascularisation cohort. There was no heterogeneity among the trials and the multivessel PCI approach appears to be safe based on the current literature. Several limitations can be identified in our meta-analysis. Of note is the significant influence of the PRAMI trial which heavily influenced the statistical analysis as the largest of the trials. It is also worth noting that all the included trials were conducted in Europe. HELP-AMI [18] as well as the Politi study [19] included a significantly higher proportion of males compared to females (86.4% and 77.7%).
332
K. Sarathy et al.
Refractory Angina Study name
Statistics for each study
Odds ratio and 95% CI
Odds Lower Upper ratio limit limit Z-Value p-Value Wald et al Ochala et al
0.362 0.576 0.400
0.181 0.151 0.216
0.726 2.193 0.741
-2.860 -0.809 -2.910
0.004 0.419 0.004 0.01
0.1
1
10
100
Figure 2 Refractory angina.
In order to address the issue of limited power, a sufficiently large trial is clearly required with appropriate clinical endpoints including overall mortality, cardiac death, and nonfatal myocardial infarction. When thrombolytic treatment was initially trialled, population sizes in the order of 10,000 patients [20–22] were utilised to demonstrate statistically significant improvements in outcomes with novel strategies. Based on this, as well as the confidence intervals we have demonstrated, our meta-analysis demonstrates a statistically significant result. However, significantly large study populations will be required to inform decision making around multivessel PCI in the future. The limited numbers of patients involved in the studies we have analysed resulted in a limited number of end points that we have assessed, such as total cardiac mortality limited to less than 30 patients and cardiac death and infarction to less than 70 patients in the entire cohort. The final limitation of our analysis lies in the significantly higher incidence of non-culprit artery MI that was found in the included trials compared to rates reported from previous trials of larger populations elsewhere in the literature, such as retrospective analyses of the HERO2 trial [23]. HERO2 itself was initially conducted to investigate the benefit of Bivalirudin in STEMI in combination with thrombolysis. However, further analysis of the patients who suffered reinfarction using biomarker analysis and electrocardiograms
revealed ST elevation in a new territory occurred in 21 patients (3.8%) with confirmed reinfarction (2.3% and 0.12% of all HERO2 enrollees, respectively). This suggests that reinfarction does not occur commonly from non-culprit unstable plaques in STEMI patients and contrasts with the rate of non-culprit myocardial infarction that is suggested by the PRAMI data (hazard ratio in preventive-PCI group 0.35, 95% confidence interval, 0.21 to 0.58; P
REVIEW
Target-Vessel Versus Multivessel Revascularisation in ST-Elevation Myocardial Infarction: A Meta-Analysis of Randomised Trials Kiran Sarathy, MBBS a, Vinayak Nagaraja, MBBS a,c, Amit Kapur, Bsc, PhD, MBBS a, Richard Szirt, MBBS a, Jwalant Raval, MBBS, FRACP b*, Guy D. Eslick, PhD, MMedSc (Clin Epi), MMedStat c, David Burgess, BMed, MBBS MPH, PhD b, A. Robert Denniss, MBBS, MD, MSc, FRACP, FACC, FESC, FAHA, FCSANZ b a
Prince of Wales Hospital, University of New South Wales, Sydney Department of Cardiology, Blacktown Hospital, Sydney c The Whiteley-Martin Research Centre, University of Sydney, Nepean Hospital, Sydney b
Received 19 October 2013; received in revised form 10 September 2014; accepted 15 October 2014; online published-ahead-of-print 5 December 2014
Introduction
In acute ST-segment elevation myocardial infarction (STEMI), coronary reperfusion with percutaneous coronary intervention (PCI) to treat the culprit lesion responsible for infarction improves clinical outcomes in nearly all patients. The concurrent treatment of non-infarct vessels with significant stenoses during initial angiography remains an area of controversy.
Methods
A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane Library, Google Scholar, Science Direct, and Web of Science. Original data were abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI).
Results
Only four randomised trials comprising 775 patients met full criteria for analysis. The incidence of non-fatal MI (3.25% vs 8.51%, OR: 0.376, 95% CI: 0.192-0.763), refractory angina (4.01% vs 9.57%, OR: 0.400, 95% CI: 0.241-0.741) and repeat revascularisation (10.52% vs 24.20%, OR: 0.336, 95% CI: 0.202-0.661) was lower in the multivessel revascularisation cohort. Death from cardiac causes or refractory angina or non-fatal MI (11.78% vs 28.86%, OR: 0.336, 95% CI: 0.223-0.505) and death from cardiac causes or non-fatal MI (5.26% vs 12.76%, OR: 0.420, 95% CI: 0.245-0.722) were significantly lower in the multivessel revascularisation cohort. The Median Contrast Volume and Procedure Length were similar in both cohorts.
Conclusions
In patients with acute STEMI who undergo primary PCI, a strategy of treatment of significant non-infarct stenosis (preventive PCI) in addition to the culprit lesion responsible for infarction may result in improved cardiovascular outcomes and reduced overall mortality; however there is insufficient data to fully validate this from currently published literature.
Keywords
Acute ST-segment elevation myocardial infarction Randomised trials Multivessel revascularisation Two-stage revascularisation Meta-analysis
*Corresponding author at: Department of Cardiology, Blacktown Hospital. Tel.: +029881800., Email: [email protected] © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
328
Introduction In patients with acute ST-segment elevation myocardial infarction (STEMI), coronary reperfusion with percutaneous coronary intervention (PCI) to treat the culprit lesion responsible for infarction is considered the treatment of choice [1,2]. In this setting, up to 40-65% of patients may also be found to have multivessel disease with significant coronary stenoses that are not responsible for the acute infarction [3,4]. The recommendation for concurrent treatment of non-infarct vessels with significant stenosis to achieve complete revascularisation during initial angiography is reserved for patients with haemodynamic compromise [5]. Nonetheless, the optimal management of multivessel disease in this setting remains controversial as the aforementioned recommendation is based on nonrandomised data. To date, there remains a class III recommendation with Grade C evidence for a staged approach to non-culprit lesions at a later date [6]. Recently, the Preventative Angioplasty in Acute Myocardial Infarction (PRAMI) trial evaluated the role of preventive PCI and its impact on the outcomes including cardiac death, non-fatal myocardial infarction, and refractory angina, and found this strategy conferred significant benefits [7]. We synthesised the available evidence from this randomised trial, as well as the other three previous randomised trials in the literature on preventive PCI in patients with STEMI and focussed on a comparison of outcomes of this strategy against the standard treatment strategy of PCI to the culprit lesion only.
Methods Study Protocol We followed the Preferred Reporting Items for Systematic reviews and MetaAnalyses PRISMA guidelines where possible in performing our systematic review [8]. We performed a systematic search through MEDLINE (from 1950), PubMed (from 1946), EMBASE (from 1949), Current Contents Connect (from 1998), Cochrane Library, Google Scholar, Science Direct, and Web of Science to November 2014. The search terms included ‘‘complete revascularization,’’ ‘‘multivessel revascularization,’’ ‘‘culprit revascularization,’’ ‘‘culprit-only revascularization,’’ and ‘‘myocardial infarction’’ which was searched as text word and as exploded medical subject headings where possible. No language restrictions were used in either the search or study selection. The reference lists of relevant articles were also searched for appropriate studies. A search for unpublished literature was not performed.
Study Selection We included studies that met the following inclusion criteria: Studies identifying the population of patients with ST
elevation myocardial infarction
K. Sarathy et al.
Randomised trials comparing complete versus culprit-
only revascularisation.
Data Extraction We performed the data extraction using a standardised data extraction form, collecting information on the publication year, study design, number of cases, total sample size, population type, country, continent, mean age and clinical data. The event rate and confidence intervals were calculated.
Statistical Analysis Pooled event rate and 95% confidence intervals were using a random effects model [9]. We tested heterogeneity with Cochran’s Q statistic, with P70%
Infarction (AMI),
time of emergency
diameter stenosis
70%)
PCI, infarct artery
of two or more
symptoms onset,
non-IRA stenosis
treated
epicardial coronary
undergoing
for PCI, successful
successfully, stenosis of 50%
arteries or their major branches by
primary angioplasty, with
PCI of IRA
or more in one or
visual estimation),
documented
more coronary
Chest Pain between
multivessel
arteries other than
30min-12 hrs, ECG
disease and both
infarct artery and
criteria for STEMI
culprit lesion
the stenosis was
and 1 to 3 other
deemed to be
lesions suitable
treatable by PCI
for stent implantation
147
135
5
10
NA
NA
NA
NA
165
NA
NA
NA
NA
NA
NA
NA
300
200
NA
NA
242
341
315.6
243.9
Median Procedure Length (minutes) IQR
63
45
4.8
5.3
53
69
65.8
84.1
Hospital Stay
NA
NA
NA
NA
NA
NA
4.7 days
7.6 days
culprit Drug Eluting Stent in non-culprit Median Contrast Volume (mL) IQR
331
Table 2 Overall odds ratio and 95% CI. I2
Primary outcome
Absolute event rates
OR
95% CI
P value
Death from cardiac causes, non-fatal MI, refractory angina
11.78% vs 28.86%
0.336
0.223-0.505
0.00
0.783
Death from cardiac causes or
5.26% vs 12.76%
0.42
0.245-0.722
0.00
0.86
Death from cardiac outcomes
2.25% vs 5.31%
0.454
0.201-1.027
0.00
0.85
Death from non-cardiac outcomes
2.50% vs 2.39%
1.185
0.47-2.99
0.00
0.68
Non-fatal MI
3.25% vs 8.51%
0.376
0.192-0.763
0.00
0.89
Refractory angina
4.01% vs 9.57%
0.4
0.241-0.741
0.00
0.55
Repeat revascularisation
10.52% vs 24.20%
0.336
0.202-0.661
42.64
0.16
non-fatal MI
finding was that patients who underwent one stage revascularisation had improved LVEF recovery at 30 days. However, this study was not powered to assess MACE outcomes. Nonetheless, they observed no significant differences in outcomes between the two groups. Two-stage revascularisation was associated with longer hospital stay, fluoroscopy time, and total contrast use. The HELP-AMI (Results of the multicentre randomised HEpacaoat for cuLPrit or multivessel stenting for Acute Myocardial Infarction) [18] study was a European trial which enrolled 69 patients with STEMI within 12 hours of symptom onset undergoing primary PCI with multivessel disease (between one and three non-culprit stenosis) suitable for PCI. The study had unbalanced randomisation between the two arms (17 patients in the culprit lesion only group and 52 in the multivessel group). Multivessel PCI was found to be safe without an increased rate of adverse clinical outcomes. Contrast usage and procedural time were only slightly higher in the multivessel arm. In our study, the Median Contrast Volume and Procedure Length were similar in both cohorts. In terms of revascularisation, HELP-AMI [18] found there was no reduction in the need for repeat
Table 3 Median contrast volume and procedure length. Preventive
No
PCI
preventive PCI
Median contrast volume (ml)
Mean
285.87
261.63
SD
38.78
72.15
SEM
22.39
41.66
P value Median procedure
0.73
Mean
46.65
50.85
SD
28.44
34.37
SEM P value
14.22 0.65
17.19
length (minutes)
revascularisation in the multivessel group with the need for revascularisation in the culprit only group remaining low. The small sample size of the study was a significant limitation, compounded by imbalanced randomisation such that the primary endpoint of difference in new revascularisation procedures did not reach statistical significance. However, in our meta-analysis, we found the rate of refractory angina (OR: 0.400, 95% CI: 0.241-0.741) and the need for repeat revascularisation (OR: 0.336, 95% CI: 0.202-0.661) was lower in the multivessel revascularisation cohort. Politi et al [19] examined the outcomes of 214 consecutive patients with STEMI and multivessel disease. They found an increased rate of death, repeat revascularisation, and rehospitalisation in the culprit vessel angioplasty only group. They also compared staged revascularisation against complete revascularisation with multivessel PCI and found a similar rate of MACE in these two arms. The largest and most recent trial is the PRAMI trial [7], a single-blind randomised study designed to assess whether multivessel (preventive) PCI would reduce the incidence of cardiac death, non-fatal myocardial infarction, or refractory angina. 465 patients from five UK centres were enrolled into the trial which was eventually stopped early due to a highly significant difference in the incidence of the primary outcome in favour of multivessel PCI. In our meta-analysis of all four randomised trials, the incidence of non-fatal MI (OR: 0.376, 95% CI: 0.192-0.763) was lower in the multivessel cohort. Death from cardiac causes or non-fatal MI (OR: 0.336, 95% CI: 0.223-0.505) and from non-cardiac outcomes (OR: 0.420, 95% CI: 0.245-0.722) was significantly lower in the multivessel revascularisation cohort. There was no heterogeneity among the trials and the multivessel PCI approach appears to be safe based on the current literature. Several limitations can be identified in our meta-analysis. Of note is the significant influence of the PRAMI trial which heavily influenced the statistical analysis as the largest of the trials. It is also worth noting that all the included trials were conducted in Europe. HELP-AMI [18] as well as the Politi study [19] included a significantly higher proportion of males compared to females (86.4% and 77.7%).
332
K. Sarathy et al.
Refractory Angina Study name
Statistics for each study
Odds ratio and 95% CI
Odds Lower Upper ratio limit limit Z-Value p-Value Wald et al Ochala et al
0.362 0.576 0.400
0.181 0.151 0.216
0.726 2.193 0.741
-2.860 -0.809 -2.910
0.004 0.419 0.004 0.01
0.1
1
10
100
Figure 2 Refractory angina.
In order to address the issue of limited power, a sufficiently large trial is clearly required with appropriate clinical endpoints including overall mortality, cardiac death, and nonfatal myocardial infarction. When thrombolytic treatment was initially trialled, population sizes in the order of 10,000 patients [20–22] were utilised to demonstrate statistically significant improvements in outcomes with novel strategies. Based on this, as well as the confidence intervals we have demonstrated, our meta-analysis demonstrates a statistically significant result. However, significantly large study populations will be required to inform decision making around multivessel PCI in the future. The limited numbers of patients involved in the studies we have analysed resulted in a limited number of end points that we have assessed, such as total cardiac mortality limited to less than 30 patients and cardiac death and infarction to less than 70 patients in the entire cohort. The final limitation of our analysis lies in the significantly higher incidence of non-culprit artery MI that was found in the included trials compared to rates reported from previous trials of larger populations elsewhere in the literature, such as retrospective analyses of the HERO2 trial [23]. HERO2 itself was initially conducted to investigate the benefit of Bivalirudin in STEMI in combination with thrombolysis. However, further analysis of the patients who suffered reinfarction using biomarker analysis and electrocardiograms
revealed ST elevation in a new territory occurred in 21 patients (3.8%) with confirmed reinfarction (2.3% and 0.12% of all HERO2 enrollees, respectively). This suggests that reinfarction does not occur commonly from non-culprit unstable plaques in STEMI patients and contrasts with the rate of non-culprit myocardial infarction that is suggested by the PRAMI data (hazard ratio in preventive-PCI group 0.35, 95% confidence interval, 0.21 to 0.58; P
