title: The effect of door-to-balloon delay in primary percutaneous coronary intervention on clinical outcomes of STEMI: a systematic review and meta-analysis protocol.
abstract: Acute myocardial infarction (AMI) is a medical emergency in which sudden occlusion of coronary artery(ies) results in ischemia and necrosis of the cardiac tissues. Reperfusion therapies that aim at reopening the occluded artery remain the mainstay of treatment for AMI. Primary percutaneous coronary intervention (PCI), which enables the restoration of blood flow by reopening the occluded artery(ies) via a catheter with an inflatable balloon, is currently the preferred treatment for AMI with ST segment elevation (STEMI). The door-to-balloon (D2B) delay refers to the time interval counting from the arrival of a patient with STEMI at a hospital to the time of the balloon inflation (or stent deployment) that reopens the occluded artery(ies). Reducing this delay in primary PCI is thought to be an important strategy toward achieving better patient outcomes. Unfortunately, significant reduction of D2B delay in the USA over the last decade has not been shown to be associated with improved STEMI mortality. It has been suggested that the lack of impact could be due to the expanding use of primary PCI in STEMI as well as the survival cohort effect, leading to a shift toward a higher risk population receiving the procedure. Others have suggested that reduction in D2B delay may not be as impactful as expected, given that it only represents a small fraction of the total ischemic time. Although most existing evidence have pointed to the presence of a beneficial effect of shorter D2B delay, some inconsistencies however exist. This study aims to synthesize available evidence in order to answer the following questions: (1) what is the overall effect of D2B delay on clinical outcomes in patients with STEMI treated with primary PCI? (2) What factors explain the differences of the effect estimates among the studies? (3) What are the important strength and limitation of the existing body of evidence?
  
  
  
  We will search PubMed/MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry, CINAHL Database, and the Cochrane Library using a predefined search strategy. Other sources of literature will include proceedings from the European Society of Cardiology, the American College of Cardiology, the American Heart Association, the EUROPCR, and the ProQuest Dissertations and Theses Database. We will include data from observational studies (case-control and cohort study design) and randomized control trials (that have investigated the relationship of D2B time and clinical outcome(s) in an adult (older than 18) STEMI population). Mortality (cardiac related and all-cause) and incidence heart failure (HF) have been prioritized as the primary outcomes. All eligible studies will be assessed for risk of bias using the Risk Of Bias in Non-randomized Studies - of Interventions tool. The Grading of Recommendations, Assessment, and Evaluation (GRADE) framework will be used to report the quality of evidence and strength of recommendations. We will proceed to analyze the data quantitatively if the pre-specified conditions are satisfied.
  
  
  
  Recent discussion on the negative findings of improved D2B delay over time being unrelated to better STEMI outcomes at the population level has reminded us of an important knowledge gap we have on this domain. This systematic review will serve to address some of these key questions not previously examined. Answers to these questions could clarify the controversies and offer empirical support for or against the suggested hypotheses.
  
  
  
  PROSPERO CRD42015026069.
authors.affiliation: National Clinical Research Centre, Kuala Lumpur, Malaysia. foocheeyoong@gmail.com.|School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia. foocheeyoong@gmail.com.
authors.forename: Chee Yoong
authors.identifier: 0000-0002-1833-4290
authors.initials: CY
authors.lastname: Foo
authors.affiliation: Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Reidpath
authors.affiliation: School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia.|Center of Pharmaceutical Outcomes Research (CPOR), Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.|School of Pharmacy, University of Wisconsin, Madison, WI, USA.|School of Population Health, University of Queensland, Brisbane, Australia.
authors.forename: Nathorn
authors.initials: N
authors.lastname: Chaiyakunapruk
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D055317:Evidence-Based Practice; D006801:Humans; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D062645:Percutaneous Coronary Intervention; D000078202:Systematic Reviews as Topic; D013997:Time Factors; D016896:Treatment Outcome; D015201:Meta-Analysis as Topic
keywords: Door-to-balloon time; Percutaneous coronary intervention; Protocol; STEMI; Systematic review