title: Resolving the paradox of randomised controlled trials and observational studies comparing multi-vessel angioplasty and culprit only angioplasty at the time of STEMI.
abstract: BACKGROUND
  Patients presenting with ST-elevation myocardial infarction commonly have multi-vessel coronary artery disease. After the culprit artery is treated, the optimal treatment strategy for the residual disease is not yet defined. Large observational studies suggest that treatment of residual disease should be deferred but smaller randomised controlled trials (RCTs) suggest multi-vessel primary percutaneous coronary intervention (MV-PPCI) at the time of STEMI is safe. We examine if allocation bias of high-risk patients could explain the conflicting results between observational studies and RCTs and aim to resolve the paradox between the two.
  
  
  METHODS
  A meta-analysis of registries comparing culprit-only PPCI to MV-PPCI was performed. We then determined if high-risk patients were more likely to be allocated to MV-PPCI. A meta-regression was performed to determine if any allocation bias of high-risk patients could explain the difference in outcomes between therapies.
  
  
  RESULTS
  47,717 patients (19 studies) were eligible. MV-PPCI had higher mortality than culprit-only PPCI (OR 1.59, 95% CI 1.12 to 2.24, p=0.03). However, higher risk patients were more likely to be allocated to MV-PPCI (OR 1.45, 95% CI 1.18 to 1.78, p=0.0005). When this was accounted for, there was no difference in mortality between culprit-only PPCI and MV-PPCI (OR 0.99, 95% CI 0.69 to 1.41, p=0.94).
  
  
  CONCLUSIONS
  Clinicians preferentially allocate higher-risk patients to MV-PPCI at the time of STEMI, resulting in observational studies reporting higher mortality with this strategy. When this is accounted for, these large observational studies in 'real world' patients support the conclusion of the smaller RCTs in the field: MV-PPCI has equivalent mortality to a culprit-only approach.
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Yousif
authors.initials: Y
authors.lastname: Ahmad
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cook
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Matthew
authors.initials: M
authors.lastname: Shun-Shin
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Balu
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Daniel
authors.initials: D
authors.lastname: Keene
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Sukhjinder
authors.initials: S
authors.lastname: Nijjer
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Petraco
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Baker
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Iqbal S
authors.initials: IS
authors.lastname: Malik
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Bellamy
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Amarjit
authors.initials: A
authors.lastname: Sethi
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Ghada W
authors.initials: GW
authors.lastname: Mikhail
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Mahmud
authors.initials: M
authors.lastname: Al-Bustami
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Masood
authors.initials: M
authors.lastname: Khan
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Raffi
authors.initials: R
authors.lastname: Kaprielian
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Foale
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Jamil
authors.initials: J
authors.lastname: Mayet
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Justin E
authors.initials: JE
authors.lastname: Davies
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust.
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
authors.affiliation: Imperial College London and Imperial College Healthcare NHS Trust. Electronic address: sayan.sen@imperial.ac.uk.
authors.forename: Sayan
authors.initials: S
authors.lastname: Sen
mesh_terms: D017130:Angioplasty / Q000379:methods*; D015982:Bias; D003324:Coronary Artery Disease / Q000150:complications* / Q000175:diagnosis; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D064887:Observational Studies as Topic; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D000072657:ST Elevation Myocardial Infarction / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000628:therapy; D012720:Severity of Illness Index; D016019:Survival Analysis
keywords: Angioplasty; Meta-analysis; Multi-vessel disease; STEMI