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The International Journal of Angiology : Official Publication of the International College of Angiology, Inc logoLink to The International Journal of Angiology : Official Publication of the International College of Angiology, Inc
. 2022 Mar 3;31(4):273–283. doi: 10.1055/s-0042-1742610

Association of Admission Time and Mortality in STEMI Patients: A Systematic Review and Meta-analysis

Surya Dharma 1,2,✉, William Kamarullah 3, Adelia Putri Sabrina 3
PMCID: PMC9803553  PMID: 36588865

Abstract

This systematic review and meta-analysis aimed to evaluate patients with acute ST-segment elevation myocardial infarction (STEMI) who were admitted during off-hours and treated with primary angioplasty associated with an increased risk of mortality compared with those admitted during regular working hours. We performed a systematic literature search using PubMed, SCOPUS, Europe PMC, and Cochrane CENTRAL databases that was finalized on March 15, 2021. The primary outcome was mortality comprising early (in-hospital), midterm (30 days to 1 year), and long-term mortality (>1 year). A total of 384,452 patients from 56 studies were included. The overall mortality of acute STEMI patients admitted during off-hours and regular hours were 6.1 and 6.7%, respectively. Patients admitted during off-hours had similar risk of early, midterm, and long-term mortality compared to those admitted during regular working hours ([relative risk or RR = 1.07, 95% confidence interval or CI, 1.00–1.14, p  = 0.06; I 2  = 45%, p  = 0.0009], [RR = 1.00, 95% CI, 0.95–1.05, p  = 0.92; I 2  = 13%, p  = 0.26], and [RR = 0.95, 95% CI, 0.86–1.04, p  = 0.26; I 2  = 0%, p  = 0.76], respectively). Subgroup analyses indicated that the results were consistent across all subgroups ([women vs. men], [age >65 years vs. ≤65 years], and [Killip classification II to IV vs. Killip I]). Funnel plot was asymmetrical. However, Egger's test suggests no significance of small-study effects ( p  = 0.19). This meta-analysis showed that patients with acute STEMI who were admitted during off-hours and treated with primary angioplasty had similar risk of early, midterm, and long-term mortality compared with those admitted during regular working hours.

Keywords: STEMI, admission time, primary angioplasty, mortality, off-hours, working hours

It is still unclear whether timing of admission (off-hours or regular working hours) associates with mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Previous meta-analysis showed that off-hours presentation is associated with short-term mortality but not with long-term mortality in patients with STEMI. 1 However, several recent studies found no differences in short and long-term mortality among patients with STEMI admitted during off-hours and regular hours. 2 3 4 5 6 7 8 9 10 We therefore conducted a systematic review and meta-analysis to evaluate whether patients with acute STEMI admitted during off-hours and treated with primary PCI were associated with an increased risk of early, midterm, and long-term mortality compared with those admitted during regular working hours.

Methods

Eligibility Criteria

We included both prospective and retrospective research articles of adult patients diagnosed with STEMI and treated with primary PCI with information on mortality events. The study has to evaluate the mortality outcomes for patients admitted during off-hours and regular working hours. We excluded review articles, non-research letters, commentaries, case reports and series, animal studies, meta-analyses, and studies of pregnant populations.

Search Strategy and Study Selection

We systematically searched PubMed, SCOPUS, Europe PMC, and Cochrane CENTRAL databases with the search terms (STEMI) AND (“primary PCI”) AND ([weekend] OR [weekday] OR [“after hour”] OR [“off hour”] OR [“out of hour”] OR [“regular hour”] OR [“working hour”]) AND (mortality). After initial search, duplicates were excluded. Two independent authors (S.D. and W.K.) screened the title and abstracts for potentially relevant articles. The full text of the potential articles were assessed by applying the inclusion and exclusion criteria. The literature search was finalized on March 15, 2021. To find additional citations, the reference lists of the included studies and recent review articles were screened when necessary. We adapted the search terms to fit the requirements of each database. Our search was in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 11 12 and the flowchart in Fig. 1 portrays the search and screening processes. The study protocol was registered in the International Prospective Registry of Systematic Reviews (registration number CRD42021241314).

Fig. 1.

Fig. 1

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PRISMA flowchart of study selection. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Data Extraction

Data extraction was performed independently by two authors (W.K. and A.P.S.). We used standardized forms that included author, year, country, study design, total subjects, gender, off-hours definition, hypertension, diabetes mellitus, dyslipidemia, smoking, family history of coronary artery disease, previous myocardial infarction (MI), previous PCI or coronary artery bypass graft, anterior wall MI, Killip classification II to IV, use of aspirin, clopidogrel, β-blocker, angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and statin. The primary outcome was mortality rate. We divided mortality into early (in-hospital period), midterm (30 days until 1-year follow-up), and long-term (>1-year follow-up). We extracted mortality data as the number of deaths within the studies. Disagreements regarding study selection and data extraction were resolved through consensus or by a third party reviewer.

Statistical Analysis

The meta-analysis of studies was performed using Review Manager 5.4 (Cochrane Collaboration). To pool continuous variables, Mantel-Haenszel formula was used to calculate dichotomous variables to obtain the risk ratios (RRs) and 95% confidence intervals (CIs). Random-effects models were used to pool analysis regardless of heterogeneity. Univariable subgroup analyses were conducted to adjust the RRs to several potential confounders which were categorized based on a median split. Publication bias was estimated using Egger's test and a funnel plot in qualitative and quantitative ways. All p -values were two-tailed and statistical significance was set at <0.05.

Results

Baseline Characteristics and Study Selection

We found a total of 1,100 records of which 1,021 remained after the removal of duplicates. A total of 884 records were excluded after screening the title/abstracts. After assessing 137 articles for eligibility, we excluded 81 studies due to several reasons presented in Fig. 1 . Thereby, 56 studies remained for qualitative synthesis and meta-analysis. A total of 384,452 patients from 56 studies were included. 2 3 4 5 6 7 8 9 10 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Baseline characteristics are presented in Table 1 .

Table 1. Study characteristics (off-hours vs. regular working hours).

No Authors (Year) Country Study design Subjects Age (Mean ± SD) Male (%) Off-hours definition Hypertension (%) Diabetes mellitus (%) Dyslipidemia (%) Smoking (%) Family history of CAD (%) Previous MI (%) Previous PCI/CABG (%) Anterior wall MI (%) Killip class lI-IV (%) Aspirin (%) Clopidogrel (%) β-blocker (%) ACEi/ARB (%) Statin (%)
1 Garot et al (1997) France Retrospective cohort 288 (175 vs. 113) 60 ± 14 vs. 60 ± 14) 79 vs. 79 Night (8 pm to 8 am ) and weekends 37 vs. 38 12 vs. 12 38 vs. 42 70 vs. 68 36 vs. 27 16 vs. 9 N/A 51 vs. 49 N/A N/A N/A N/A N/A N/A
2 Zahn et al (1999) Germany Retrospective cohort 491 (113 vs. 378) 60.8 ± 3.1 vs. 62 ± 2.7) 77 vs. 73 Night (8 pm to 8 am ) 41.4 vs. 36.6 13.5 vs. 16.4 N/A N/A N/A 2.8 vs. 2.5 N/A 50.5 vs. 47.2 N/A 95.6 vs. 97.1 N/A 70.8 vs. 63.2 76.1 vs. 61.4 N/A
3 Henriques et al (2003) Netherlands Prospective cohort 1,702 (793 vs. 909) 59.7 ± 11.8 vs. 60.5 ± 11.3 79.7 vs. 80.2 Night (6 pm to 8 am ) N/A 8.6 vs. 8.1 N/A N/A N/A 12.7 vs. 10.9 N/A 48 vs. 49.3 10.6 vs. 11.7 N/A N/A N/A N/A N/A
4 Sadeghi et al (2004) United States Prospective cohort 2,036 (989 vs. 1,047) 58.5 ± 2.6 vs. 60 ± 2.6 75 vs. 71.4 Night (8 pm to 8 am ) and weekends 46 vs. 49.7 15.5 vs. 17.6 37.3 vs. 38.3 43.5 vs. 43.6 N/A 13.7 vs. 13.6 1.7 vs. 1.9 39.4 vs. 34.1 10.2 vs. 11.3 N/A N/A N/A N/A N/A
5 Magid et al (2005) United States Retrospective cohort 68,439 (46,450 vs. 21,989) 61 ± 13 vs. 63 ± 13 69.7 vs. 69 Night (5 pm to 7 am ) and weekends 47.8 vs. 47.6 19.7 vs. 19 33.8 vs. 33 40.5 vs. 36 31.5 vs. 29.7 16.7 vs. 15.2 6.6 vs. 6.1 32.9 vs. 31.9 N/A N/A N/A N/A N/A N/A
6 Assali et al (2006) Israel Retrospective cohort 273 (113 vs. 160) 58.8 ± 13.4 vs. 61 ± 13.9 74 vs. 82 Night (6 pm to 8 am ) 44 vs. 44 25 vs. 33 40 vs. 42 50 vs. 43 N/A 12.4 vs. 11.3 1 vs. 2 N/A 28 vs. 24 92 vs. 96 N/A 25 vs. 21 26 vs. 32 26 vs. 35
7 Ahmar et al (2008) Australia Retrospective cohort 97 (59 vs. 38) 60.5 ± 12 vs. 60.6 ± 13 76.2 vs. 71 Night (6 pm to 7 am ) and weekends 47 vs. 43 25 vs. 23 39 vs. 36 46 vs. 43 16 vs. 19 N/A 5 vs. 3 8 vs. 14 N/A N/A N/A N/A N/A N/A
8 Dominguez-Rodriguez et al (2007) Spain Retrospective cohort 90 (39 vs. 51) 72 ± 10 vs. 69 ± 8 76.9 vs. 84.3 Night (6 pm to 8 am ) 58.9 vs. 62.7 64.1 vs. 58.8 56.4 vs. 70.5 66.6 vs. 68.6 N/A 17.9 vs. 11.7 N/A N/A 12.8 vs. 11.7 N/A N/A N/A N/A N/A
9 Garceau et al (2007) Canada Retrospective cohort 197 (121 vs. 76) 59 ± 3.9 vs. 60 ± 4.1 76 vs. 74 Night (5 pm to 8 am ) and weekends 31 vs. 52 15 vs. 19 54 vs. 51 38 vs. 39 34 vs. 39 N/A 5 vs. 20 36 vs. 22 N/A N/A N/A N/A N/A N/A
10 Khot et al (2007) United States Prospective cohort 146 (86 vs. 60) 60 ± 13 vs. 58 ± 13 70.9 vs. 71.7 Weekends 53.5 vs. 56.7 19.8 vs. 16.7 36.1 vs. 31.7 55.8 vs. 51.7 32.6 vs. 36.7 N/A 26.7 vs. 16.7 30.2 vs. 40 N/A 98.8 vs. 95 96.5 vs. 100 87.2 vs. 88.3 N/A N/A
11 Ortolani et al (2007) Italy Retrospective cohort 985 (603 vs. 382) 67.1 ± 13.8 vs. 68.5 ± 13.1 71.4 vs. 68.8 Night (07:30 pm to 07:59 am ) and weekends 58.4 vs. 59.4 17.9 vs. 18.1 41.5 vs. 41.4 63.1 vs. 65.7 36.9 vs. 33.5 16.9 vs. 14.6 9.6 vs. 5.8 51.9 vs. 54.2 19.9 vs. 20.6 N/A N/A 43.8 vs. 41.9 N/A N/A
12 Słonka et al (2007) Poland Retrospective cohort 1,778 (1,296 vs. 482) 57.6 ± 10.9 vs. 58.2 ± 10.9 73.5 vs. 73.9 Night (3 pm to 8 am ) and weekends 51.2 vs. 55.2 19.9 vs. 19.8 59.7 vs. 52.1 64.5 vs. 63.3 N/A 18.8 vs. 21.2 N/A 41 vs. 44 N/A N/A N/A N/A N/A N/A
13 Srimahachota et al (2007) Thailand Prospective cohort 256 (149 vs. 107) 60.6 ± 12.8 vs. 61.9 ± 12.2 73.2 vs. 73.8 Night and weekends 52.7 vs. 39.6 33.8 vs. 30.2 64.1 vs. 53.6 49 vs. 62.6 N/A N/A 14.2 vs. 15 51 vs. 55.1 N/A N/A N/A N/A N/A N/A
14 Berger et al (2008) Switzerland Retrospective cohort 12,480 (6,022 vs. 6,458) N/A 74 vs. 71.9 Night (7 pm to 7 am ) and weekends 52.2 vs. 52 19.6 vs. 18.7 56.2 vs. 55.1 43.5 vs. 40.1 N/A 34.5 vs. 31.5 N/A N/A 24.9 vs. 24.2 94.8 vs. 94.6 44.8 vs. 43.9 70.2 vs. 71.2 42.3 vs. 42.7 72.3 vs. 70.2
15 Glaser et al (2008) United States Retrospective cohort 685 (457 vs. 228) N/A 63.9 vs. 72.4 Weekends 55 vs. 57.5 21.7 vs. 25.7 50.5 vs. 55.9 73.2 vs. 69.6 N/A 18.5 vs. 18.5 15.8 vs. 14.4 45.4 vs. 44.3 N/A 82.9 vs. 87.7 N/A 86.3 vs. 87 63.5 vs. 59.5 N/A
16 Holmes et al (2008) United States Retrospective cohort 494 (296 vs. 198) 62.7 ± 13.7 vs. 64.3 ± 14 74 vs. 72 Night (5 pm to 7 am ) and weekends 59 vs. 59 20 vs. 12 63 vs. 59 38 vs. 33 N/A 3 vs. 3 N/A 33 vs. 38 N/A N/A N/A N/A N/A N/A
17 Krüth et al (2008) Germany Prospective cohort 7,972 (4,115 vs. 3,857) 65.1 ± 2.5 vs. 65.2 ± 2.5 71.4 vs. 69.8 Night (6 pm to 8 am ) and weekends 50.1 vs. 50.1 24.3 vs. 21.4 46.2 vs. 49.1 36.3 vs. 37 N/A 18.3 vs. 15.6 11.1 vs. 10.3 47.6 vs. 47.4 N/A 93.6 vs. 94.1 56.6 vs. 61.8 72.5 vs. 73.6 63.2 vs. 63.7 63.1 vs. 66
18 Albuquerque et al (2009) Brazil Retrospective cohort 212 (70 vs. 142) 61.1 vs. 64.7 79.5 vs. 76.3 Night 57.9 vs. 67.7 12.5 vs. 16.1 51.1 vs. 56.9 29.5 vs. 20.9 N/A N/A 7.9 vs. 12.9 37.5 vs. 38.7 21.6 vs. 19.9 N/A N/A N/A N/A N/A
19 Becker et al (2009) Hungary Prospective cohort 1,890 (1,219 vs. 671) 63.4 ± 13.5 vs. 64.1 ± 13.5 63.3 vs. 63.5 Night (6 pm to 8 am ) and weekends 54.8 vs. 51.1 21.8 vs. 21 N/A N/A N/A 13.6 vs. 12.7 5.3 vs. 4.5 1.7 vs. 2.1 N/A N/A N/A N/A N/A N/A
20 Lairez et al (2009) France Prospective cohort 1,708 (1,072 vs. 636) 61.9 ± 14.5 vs. 66.6 ± 13 78.7 vs. 76.4 Night (8 pm to 8 am ) and weekends N/A N/A N/A N/A N/A 2.9 vs. 8.2 13.7 vs. 22.8 37.8 vs. 34.5 N/A N/A N/A N/A N/A N/A
21 Abi Rafeh et al (2009) United States Prospective cohort 85 (31 vs. 54) 55 ± 9.6 vs. 58.9 ± 10.9 87.1 vs. 66.7 Weekends 67.7 vs. 64.8 19.4 vs. 38.9 61.3 vs. 77.8 77.4 vs. 70.4 41.9 vs. 40.7 N/A N/A N/A N/A N/A N/A N/A N/A N/A
22 Uyarel et al (2009) Turkey Retrospective cohort 2,644 (1,503 vs. 1,141) 56 ± 11.9 vs. 57.5 ± 11.9 84.6 vs. 80.3 Night (6 pm to 8 am ) 36.5 vs. 42.6 24.6 vs. 25 32.7 vs. 34.5 58 vs. 56.1 16 vs. 15.8 10.2 vs. 11.6 6.8 vs. 9.5 49.7 vs. 48.1 7.5 vs. 7.8 N/A N/A N/A N/A N/A
23 Gonzalez et al (2010) United States Prospective cohort 786 (554 vs. 232) 60.7 ± 14 vs. 60.7 ± 14 66.8 vs. 66.4 Night (5 pm to 8 am ) and weekends 84.8 vs. 85.7 28.7 vs. 29.3 84.6 vs. 88.4 41.7 vs. 39.7 N/A N/A N/A 40.3 vs. 36.9 N/A 97.1 vs. 98.1 97.5 vs. 98.1 91.8 vs. 92.5 79.7 vs. 85 93.8 vs. 94.8
24 Graham et al (2011) Canada Retrospective cohort 1,664 (906 vs. 758) 60.3 ± 13.2 vs. 61.5 ± 12.7 78 vs. 74 Night (6 pm to 7 am ) and weekends 50 vs. 47.9 15.9 vs. 15.7 45.8 vs. 45.4 N/A N/A 10.7 vs. 13.7 3.5 vs. 3.7 42.4 vs. 41 N/A N/A N/A N/A N/A N/A
25 Maier et al (2010) Germany Retrospective cohort 2,131 (1,302 vs. 829) 62.9 ± 12.8 vs. 63.9 ± 12.9 70.3 vs. 68.2 Night (4 pm to 07:30 am ) and weekends 72.2 vs. 71.7 24.3 vs. 23.2 49.4 vs. 48.6 50.4 vs. 47.4 N/A 16 vs. 15.4 N/A N/A N/A N/A N/A N/A N/A N/A
26 Casella et al (2011) Italy Retrospective cohort 3,072 (1,628 vs. 1,444) 66.2 ± 13 vs. 67.2 ± 13.4 71 vs. 71.5 Night (8 pm to 8 am ) and weekends 60.4 vs. 61.2 20.5 vs. 19.4 51 vs. 49.6 35.3 vs. 30.6 N/A 12.5 vs. 13.1 10 vs. 10.8 50.6 vs. 48.7 N/A N/A N/A N/A N/A N/A
27 Siudak et al (2011) Poland Retrospective cohort 1,650 (1,005 vs. 645) 61.9 ± 11.5 vs. 64.4 ± 12.5 73 vs. 70 Night (5 pm to 8 am ) and weekends N/A 15.9 vs. 15.8 N/A 37.7 vs. 33.6 N/A 11.6 vs. 14.1 6.1 vs. 9.3 N/A 5.7 vs. 4.8 94 vs. 95 32 vs. 32 N/A N/A N/A
28 Al Faleh et al (2012) Saudi Arabia Prospective cohort 2,825 (1,809 vs. 1,016) 57.6 ± 13.3 vs. 57.9 ± 13.2 78.2 vs. 78.9 Night (5 pm to 8 am ) and weekends 56.4 vs. 56.2 56.4 vs. 57.5 24.7 vs. 28.2 34.7 vs. 31.8 N/A 45.3 vs. 44.1 15.3 vs. 17.6 54.2 vs. 59.8 N/A 98.9 vs. 97.9 87.5 vs. 86.9 83.1 vs. 85.9 70.6 vs. 71.8 96.5 vs. 96.8
29 de Boer et al (2012) Netherlands Retrospective cohort 4,352 (2,760 vs. 1,592) 60.9 ± 12.8 vs. 61.5 ± 12.5 73.5 vs. 75.2 Night (6 pm to 8 am ) and weekends 40.1 vs. 38.6 13 vs. 10.4 72.4 vs. 71.4 41.8 vs. 36 28.6 vs. 27.6 12.1 vs. 13.1 9.2 vs. 7.9 46.6 vs. 44.9 N/A 90.1 vs. 90.2 N/A 51.6 vs. 54 41.7 vs. 39.9 71.6 vs. 71.2
30 Noman et al (2012) United Kingdom Retrospective cohort 2,571 (1,535 vs. 1,036) 62.5 ± 13.1 vs. 64.1 ± 13.7 71.1 vs. 69.3 Night (6 pm to 8 am ) and weekends 40.9 vs. 41.1 11.4 vs. 11.2 32.2 vs. 34 46.3 vs. 43.4 47 vs. 43.7 14.7 vs. 15.9 7.2 vs. 8.2 39.2 vs. 37.5 N/A N/A N/A N/A N/A N/A
31 Cubeddu et al (2013) United States Prospective cohort 2,440 (1,235 vs. 1,205) 60.1 ± 2.7 vs. 60.7 ± 2.6 77.5 vs. 75.8 Night (5 pm to 8 am ) and weekends 53.8 vs. 50.8 17.8 vs. 15.7 46.2 vs. 42.1 64.4 vs. 61.8 30.2 vs. 26.6 11.7 vs. 11.6 12.1 vs. 12.7 40.3 vs. 41.6 10 vs. 7 27.7 vs. 26.5 3.3 vs. 3.6 N/A N/A N/A
32 Rathod et al (2013) United Kingdom Retrospective cohort 3,347 (2,048 vs. 1,299) 63.2 ± 14.3 vs. 64.1 ± 14.2 77.1 vs. 74.2 Night (5 pm to 8 am ) and weekends 38.3 vs. 39.2 17.7 vs. 17.3 29.7 vs. 30.9 58 vs. 55.6 N/A 11.8 vs. 13.2 9.6 vs. 9.9 47.3 vs. 49.5 N/A N/A N/A N/A N/A N/A
33 Shavelle et al (2013) United States Retrospective cohort 2,246 (922 vs. 1,324) 63 ± 13 vs. 62 ± 13 72 vs. 74 Night (5 pm to 8 am ) and weekends N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
34 Ahmed and Pancholy (2014) United States Retrospective cohort 399 (148 vs. 251) 64 ± 12 vs. 65 ± 13 55 vs. 59 Night (4 pm to 7 am ) and weekends 77 vs. 75 28 vs. 29 N/A 39 vs. 27 N/A 19 vs. 20 22 vs. 20 N/A N/A N/A N/A N/A N/A N/A
35 Cockburn et al (2015) Australia Retrospective cohort 720 (261 vs. 459) 64.5 ± 14.9 vs. 65.3 ± 13.7 75.1 vs. 75.1 Night (6 pm to 8 am ) and weekends 48.1 vs. 47.6 12.7 vs. 12.1 47.7 vs. 48.9 30.5 vs. 25.5 35.8 vs. 43.7 17.4 vs. 18.2 13.1 vs. 16 38.2 vs. 41.6 N/A 90.5 vs. 93.2 87 vs. 88.3 81 vs. 78.5 78.3 vs. 79.5 91.8 vs. 90
36 Breuckmann et al (2016) Germany Retrospective cohort 1,107 (607 vs. 500) 61.7 vs. 63.1 73.8 vs. 72 Night and weekends 65.8 vs. 70 19.3 vs. 20.2 49.3 vs. 52.4 48.3 vs. 44.6 19.2 vs. 21.2 10.8 vs. 13.5 15.1 vs. 15.9 N/A 2.1 vs. 0.4 N/A N/A N/A N/A N/A
37 Dasari et al (2014) United States Retrospective cohort 43,242 (27,270 vs. 15,972) 59.5 ± 2.2 vs. 61.3 ± 2.4 71.6 vs. 71.7 Night (6 pm to 8 am ) and weekends 60.3 vs. 61.7 21.2 vs. 21.8 51.5 vs. 51.8 46.3 vs. 42 N/A 19.5 vs. 18.7 21.2 vs. 20.8 N/A N/A 90.4 vs. 90.7 94.8 vs. 93.8 73.1 vs. 72.7 N/A 78.6 vs. 78
38 Dharma et al (2015) Indonesia Retrospective cohort 1,126 (857 vs. 269) 55.4 ± 9.7 vs. 56.4 ± 9.9 87 vs. 83 Night (Monday to Thursday [4 pm to 07:30 am ] Friday [04:30 pm to 07:30 am ]) and weekends 55 vs. 57.2 29.8 vs. 27.5 44.9 vs. 48.3 66.5 vs. 60.6 22 vs. 21.2 N/A N/A 46 vs. 43.5 27.3 vs. 23 97 vs. 98 97 vs. 98 75 vs. 69 76 vs. 71 92 vs. 89
39 Langabeer et al (2015) United States Prospective cohort 1,247 (636 vs. 611) 58 ± 12 vs. 59 ± 12.4 74.5 vs. 74.3 Night (5 pm to 8 am ) and weekends N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
40 Rosende et al (2015) Argentina Retrospective cohort 4,237 (1,048 vs. 3,189) 60.7 vs. 60.5 76.8 vs. 77.2 Weekends N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
41 Geng et al (2016) China Retrospective cohort 1,594 (903 vs. 691) 64.1 ± 12.4 vs. 65.1 ± 12.3 81.3 vs. 76.9 Night (6 pm to 8 am ) and weekends 63.1 vs. 57.3 26.6 vs. 25.1 N/A 53.5 vs. 48.1 N/A 6.2 vs. 3.6 4.5 vs. 2.5 47.5 vs. 40.9 28.1 vs. 26.9 N/A N/A N/A N/A N/A
42 Selvaraj et al (2016) United States Prospective cohort 1,992 (786 vs. 1,206) 60 ± 12 vs. 61 ± 12 74.7 vs. 73.9 Night (7 pm to 7 am ) and weekends N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
43 Song et al (2016) China Retrospective cohort 289 (184 vs. 105) 62.1 ± 13.4 vs. 63.2 ± 13.1 75.5 vs. 74.3 Night (6 pm to 8 am ) and weekends 62.5 vs. 52.4 29.9 vs. 21.9 28.3 vs. 25.7 60.9 vs. 54.3 15.2 vs. 14.3 8.2 vs. 2.9 N/A 57.6 vs. 53.3 20.6 vs. 18.2 98.9 vs. 99 98.9 vs. 99 85.9 vs. 91.4 N/A 89.7 vs. 96.2
44 Li et al (2017) China Prospective cohort 7,456 (4,086 vs. 3,370) 63.3 ± 12.5 vs. 64 ± 12.3 71.7 vs. 69.5 Night (5 pm to 8 am ) and weekends 41.7 vs. 41.3 11.6 vs. 11.3 3.6 vs. 4.1 35.3 vs. 34.1 N/A 5.9 vs. 4.9 N/A N/A 35.8 vs. 34.6 94 vs. 95.6 86.7 vs. 88 50.4 vs. 54.2 N/A 90.7 vs. 92
45 Noad et al (2017) Ireland Prospective cohort 2,240 (649 vs. 1,591) 62.9 ± 13.9 vs. 62.9 ± 13 73.2 vs. 72.9 Weekends 36.2 vs. 33.9 12 vs. 11.7 38.2 vs. 35.6 39.6 vs. 38.7 N/A 12.1 vs. 11.2 N/A N/A N/A N/A N/A N/A N/A N/A
46 Tang et al (2017) China Retrospective cohort 441 (129 vs. 312) 61.2 ± 13.9 vs. 61.8 ± 12.2 73.6 vs. 80.1 National holidays and weekends 58.9 vs. 59.3 24.8 vs. 20.8 30.2 37.8 58.1 vs. 55.4 N/A 6.2 vs. 6.7 7 vs. 6.4 58.9 vs. 52.2 50.4 vs. 46.5 96.1 vs. 93.3 96.9 vs. 95.2 55.8 vs. 62.5 67.4 vs. 58.9 96.1 vs. 95.5
47 Tscharre et al (2017) Austria Prospective cohort 2,829 (683 vs. 2,146) 60.3 ± 13.3 vs. 61.3 ± 13.5 73.2 vs. 69.8 Night (3 pm to 07:30 am ) and weekends 49.1 vs. 51.2 19.7 vs. 18.5 33.8 vs. 40.6 41.6 vs. 39.1 16.9 vs. 22.1 15.8 vs. 19.4 93.9 vs. 87.9 N/A N/A N/A N/A N/A N/A N/A
48 Dharma et al (2018) Indonesia Retrospective cohort 1,126 (857 vs. 269) 55.4 ± 9.7 vs. 56.4 ± 9.9 87 vs. 83 Night (Monday to Thursday [4 pm to 07:30 am ] Friday [04:30 pm to 07:30 am ]) and weekends 55 vs. 57.2 29.8 vs. 27.5 44.9 vs. 48.3 66.5 vs. 60.6 22 vs. 21.2 N/A N/A 56.5 vs. 56 27.3 vs. 23 97 vs. 98 97 vs. 98 75 vs. 69 76 vs. 71 92 vs. 89
49 Eindhoven et al (2018) Netherlands Retrospective cohort 25,630 (7,180 vs. 18,450) 64 ± 13 vs. 65 ± 13 71 vs. 69 Weekends N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
50 Fiorentino et al (2018) Portugal Retrospective cohort 21,485 (6,233 vs. 15,252) 66.5 ± 14.6 vs. 67.1 ± 14.2 68.5 vs. 68.4 Weekends N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
51 Geraiely et al (2020) Iran Prospective cohort 1,791 (1,296 vs. 495) 60.1 ± 11.5 vs. 58.8 ± 12.3 78.4 vs. 78.8 Night (7 pm to 7 am ) and weekends 45 vs. 43 35.4 vs. 36.6 49.9 vs. 51.1 37.6 vs. 36 N/A N/A N/A 49.9 vs. 48.1 N/A N/A N/A N/A N/A N/A
52 Lattuca et al (2019) France Prospective cohort 2,167 (1,119 vs. 1,048) 62.5 ± 14 vs. 63 ± 14 74.3 vs. 78.1 Night (6 pm to 8 am ) and weekends 43.5 vs. 47.4 18.8 vs. 18.2 41.4 vs. 43.9 49.9 vs. 40.6 19.9 vs. 20.8 N/A N/A 55 vs. 51.1 13.6 vs. 13.4 94.5 vs. 93.5 89.8 vs. 90.7 76.3 vs. 75.9 76.8 vs. 78.3 78.9 vs. 82.5
53 Case et al (2020) United States Retrospective cohort 3,796 (1,718 vs. 2,078) 61.7 ± 13.1 vs. 65.6 ± 11.9 66.5 vs. 65.6 Night (7 pm to 7 am ) and weekends 78.6 vs. 88.3 30.8 vs. 38.6 70.4 vs. 85.3 56.7 vs. 50.5 35.9 vs. 42.7 13.5 vs. 20.8 16 vs. 27.6 N/A N/A N/A N/A N/A N/A N/A
54 Javanshir et al (2020) Iran Prospective cohort 300 (122 vs. 178) 57.5 ± 12.2 vs. 58.5 ± 11.9 85.2 vs. 84.8 Night (8 pm to 8 am ) and weekends 43.4 vs. 30.9 23.7 vs. 17.9 1.6 vs. 0.5 39.3 vs. 33.1 N/A 0.8 vs. 0.5 0.8 vs. 0 55 vs. 54.5 14.4 vs. 17.4 N/A N/A N/A N/A N/A
55 Rodríguez-Arias et al (2020) Spain Retrospective cohort 8,608 (4,813 vs. 3,795) 62.9 ± 13.3 vs. 64.3 ± 13.1 77.6 vs. 77.4 Night (8 pm to 8 am ) and weekends N/A 20.9 vs. 21.3 N/A N/A N/A 11.7 vs. 10.2 9 vs. 8.7 4.6 vs. 3.8 18.6 vs. 15.5 N/A N/A N/A N/A N/A
56 Tokarek et al (2021) Poland Retrospective cohort 99,783 (61,394 vs. 38,389) 65.1 ± 12.2 vs. 65.4 ± 12.1 67.6 vs. 67.7 Night (5 pm to 7 am ) and weekends 59.9 vs. 59.7 18.2 vs. 17.8 N/A 30.7 vs. 28.6 N/A 12.4 vs. 12.9 11.4 vs. 11.6 N/A 7.5 vs. 9.3 N/A 36.2 vs. 36.8 N/A N/A N/A
Overall 3884,452 (192,364 vs. 192,088) 61.4 ± 11.6 vs. 62.3 ± 11.5 74.5 vs. 73.6 53.1 vs. 53.4 22.2 vs. 22.1 58.1 vs. 46.2 48.9 vs. 45.7 28.3 vs. 28.8 13.7 vs. 13.6 12.6 vs. 13.4 42.3 vs. 41.6 18.9 vs. 17.7 90.7 vs. 91.2 75.2 vs. 75.9 69.7 vs. 69.5 64.4 vs. 62.7 80.9 vs. 81.9
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Abbreviations: ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass graft; CAD, coronary artery disease; CI, confidence interval; MI, myocardial infarction; N/A, not available; PCI, percutaneous coronary intervention.

Association of Admission Time and Mortality

There were 192,364 patients (50%) who were admitted during off-hours, and 192,088 were admitted during regular working hours. Off-hours definition for each included study is described in Table 1 . The pooled results of all 56 studies suggest that patients admitted during off-hours have no significant difference in the risk of overall mortality compared with patients admitted during regular working hours (RR = 1.03, 95% CI, 0.99 to 1.07, p  = 0.17; I 2  = 34%, p  = 0.002). No significant heterogeneity between articles was found in this study ( Fig. 2 ).

Fig. 2.

Fig. 2

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Risk of early, midterm, and long-term mortality between off- versus regular working hours admission.

Based on the timing of mortality (early, midterm, and long-term), there were no statistically significant differences in the risk of mortality in patients admitted during off-hours compared to those admitted during regular working hours ([RR = 1.07, 95% CI, 1.00–1.14, p  = 0.06; I 2  = 45%, p  = 0.0009], [RR = 1.00, 95% CI, 0.95–1.05, p  = 0.92; I 2  = 13%, p  = 0.26], and [RR = 0.95, 95% CI, 0.86–1.04, p  = 0.26; I 2  = 0%, p  = 0.76]), respectively. There was no significant heterogeneity found that requires further exploration ( Fig. 2 ).

Subgroup Analyses

The subgroup analyses involving several potential confounders showed consistent results with respect to similar mortality risk between the two admission times across all subgroups ( Table 2 ).

Table 2. Results of subgroup analyses.

Subgroup(s) Overall mortality (95% CI) ( n  = 80) Heterogeneity p -Value Early mortality (95% CI) ( n  = 42) Heterogeneity p -Value Mid-term mortality (95% CI) ( n  = 33) Heterogeneity p -Value Long-term mortality (95% CI) ( n  = 5) Heterogeneity p -Value
Age
 Number of cohort 74 vs. 6 36 vs. 6 33 vs. 0 5 vs. 0
 ≤65 y old 1.02 (0.98–1.06) I2  = 19% ( p  = 0.09) 0.27 1.08 (0.99–1.15) I2  = 24% ( p  = 0.10) 0.06 1.00 (0.95–1.05) I2  = 13% ( p  = 0.26) 0.92 0.95 (0.86–1.04) I2  = 0% ( p  = 0.76) 0.26
 > 65 y old 1.01 (0.85–1.21) I2  = 82% (P = < 0.0001) 0.89 1.01 (0.85–1.21) I2  = 82% (P = < 0.0001) 0.89 N/A N/A N/A N/A N/A N/A
Male
 Number of cohort 37 vs. 43 19 vs. 23 16 vs. 17 2 vs. 3
 ≤Median (74%) 1.03 (0.97–1.08) I2  = 44% ( p  = 0.002) 0.33 1.06 (0.98–1.14) I2  = 58% ( p  = 0.0009) 0.13 0.99 (0.93–1.06) I2  = 16% ( p  = 0.28) 0.82 0.97 (0.83–1.14) I2  = 0% ( p  = 0.35) 0.72
 > Median (74%) 1.02 (0.96–1.09) I2  = 22% ( p  = 0.11) 0.49 1.11 (0.95–1.29) I2  = 32% ( p  = 0.07) 0.17 1.02 (0.94–1.10) I2  = 12% ( p  = 0.31) 0.65 0.93 (0.83–1.05) I2 =0% ( p  = 0.65) 0.26
Hypertension
 Number of cohort 27 vs. 43 13 vs. 22 12 vs. 18 2 vs. 3
 ≤Median (48.4%) 1.00 (0.95–1.06) I2  = 4% ( p  = 0.40) 0.91 1.03 (0.93–1.14) I2  = 17% ( p  = 0.27) 0.61 1.01 (0.92–1.11) I2  = 0% ( p  = 0.49) 0.81 0.93 (0.82–1.05) I2  = 0% ( p  = 0.79) 0.22
 > Median (48.4%) 1.04 (0.99–1.09) I2  = 43% ( p  = 0.0006) 0.12 1.09 (0.99–1.19) I2  = 54% ( p  = 0.0004) 0.06 1.00 (0.94–1.06) I2  = 23% ( p  = 0.17) 0.95 0.98 (0.83–1.15) I2  = 0% ( p  = 0.47) 0.82
Diabetes mellitus
 Number of cohort 33 vs. 38 13 vs. 23 17 vs. 13 3 vs. 2
 ≤Median (19.1%) 1.09 (0.97–1.16) I2  = 18% ( p  = 0.19) 0.21 0.97 (0.83–1.28) I2  = 5% ( p  = 0.39) 0.07 1.09 (1.00–1.19) I2  = 0% ( p  = 0.49) 0.07 0.95 (0.86–1.06) I2  = 0% ( p  = 0.61) 0.37
 > Median (19.1%) 0.99 (0.95–1.04) I2  = 34% ( p  = 0.01) 0.70 1.04 (0.96–1.12) I2  = 46% ( p  = 0.004) 0.36 0.97 (0.93–1.01) I2  = 0% ( p  = 0.45) 0.17 0.92 (0.74–1.15) I2  = 0% ( p  = 0.36) 0.46
Dyslipidemia
 Number of cohort 17 vs. 42 10 vs. 21 5 vs. 18 2 vs. 3
 ≤Median (37.7%) 1.01 (0.95–1.08) I2  = 0% ( p  = 0.45) 0.70 1.05 (0.96–1.16) I2  = 8% ( p  = 0.37) 0.28 0.92 (0.78–1.09) I2  = 0% ( p  = 0.51) 0.33 0.97 (0.83–1.14) I2  = 0% ( p  = 0.35) 0.72
 > Median (37.7%) 1.03 (0.99–1.08) I2  = 39% ( p  = 0009) 0.15 1.07 (0.99–1.16) I2  = 52% ( p  = 0.0003) 0.10 1.01 (0.96–1.07) I2  = 17% ( p  = 0.20) 0.66 0.93 (0.83–1.05) I2  = 0% ( p  = 0.65) 0.26
Smoking status
 Number of cohort 25 vs. 39 12 vs. 24 12 vs. 11 1 vs. 4
 ≤Median (39.8%) 1.05 (0.97–1.14) I2  = 46% ( p  = 0.007) 0.23 1.09 (0.94–1.25) I2  = 68% ( p  = 0.0003) 0.25 1.04 (0.94–1.15) I2  = 0% ( p  = 0.74) 0.50 0.94 (0.81–1.08) N/A 0.38
 > Median (39.8%) 1.02 (0.97–1.06) I2  = 27% ( p  = 0.04) 0.43 1.06 (0.98–1.14) I2  = 28% ( p  = 0.08) 0.12 1.00 (0.94–1.06) I2  = 29% ( p  = 0.10) 0.93 0.95 (0.84–1.09) I2  = 0% ( p  = 0.60) 0.47
Family history of CAD
 Number of cohort 19 vs. 10 5 vs. 8 10 vs. 1 4 vs. 1
 ≤Median (28.4%) 0.96 (0.90–1.02) I2  = 0% ( p  = 0.65) 0.21 0.97 (0.77–1.21) I2  = 29% ( p  = 0.23) 0.77 0.96 (0.88–1.06) I2  = 0% ( p  = 0.54) 0.43 0.96 (0.86–1.07) I2  = 0% ( p  = 0.64) 0.42
 > Median (28.4%) 1.01 (0.93–1.09) I2  = 0% ( p  = 0.89) 0.89 1.02 (0.94–1.11) I2  = 0% ( p  = 0.87) 0.60 0.88 (0.38–2.03) N/A 0.76 0.91 (0.73–1.12) N/A 0.37
Killip classification II-IV
 Number of cohort 19 vs. 13 7 vs. 9 11 vs. 3 1 vs. 1
 ≤Median (17.1%) 1.10 (0.99–1.19) I2  = 30% ( p  = 0.11) 0.06 1.11 (0.90–1.36) I2  = 51% ( p  = 0.05) 0.33 1.06 (0.98–1.16) I2  = 6% ( p  = 0.39) 0.15 1.01 (0.75–1.38) N/A 0.93
 > Median (17.1%) 1.08 (0.92–1.26) I2  = 51% ( p  = 0.02) 0.37 1.17 (0.99–1.38) I2  = 38% ( p  = 0.12) 0.07 1.01 (0.61–1.67) I2  = 68% ( p  = 0.04) 0.98 0.83 (0.60–1.14) N/A 0.24
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Abbreviations: CAD, coronary artery disease; CI, confidence interval; N/A, not available.

Publication Bias

Funnel plot analysis showed relatively asymmetrical shape ( Fig. 3 ). However, Egger's test showed that the pooled analysis was not statistically significant for small-study effects ( p  = 0.19).

Fig. 3.

Fig. 3

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Begg's funnel plot for publication bias analysis.

Discussion

Primary PCI is preferred over fibrinolytic therapy as a method of acute reperfusion in patients with acute STEMI, 60 and it should be performed within the recommended time. 61 62 To ensure that all patients with acute STEMI received timely primary PCI, a regional STEMI network is introduced to organize the care between the referring center, ambulance, and PCI centers. 61 The system of care of STEMI minimizes the barriers for rapid reperfusion therapy in the community, 61 and when such a STEMI pathway exists, treatment disparities during off- and regular working hours should not occur. The results of the current meta-analysis support the concept.

The majority of studies included in this meta-analysis were performed in developed countries, of which the STEMI network of each developed country probably allows a timely primary PCI that contributes to similar mortality risk between the two admission times. In fact, several studies from developing countries 6 9 25 35 45 47 52 58 also found a similar early mortality risk between two admission times.

Five studies included in this meta-analysis found higher risk of early mortality in patients who were admitted during off-hours compared with regular hours. Several reasons have been described to explain the higher early mortality rate, including less angioplasty of non-culprit lesions, 18 longer door-to-balloon time, 10 32 46 worse clinical presentation at admission, and less use of evidence-based medications 49 in patients who were admitted during off-hours compared with those admitted during regular hours. Interestingly, a study of a developed country showed a higher risk of midterm mortality during off-hours due to longer ischemic time and lack of public awareness in seeking medical help. 15

The results of the subgroup analyses from this study found similar mortality risk across subgroup of patients who were admitted during off- and regular hours ( Table 2 ), and suggest no disparities of treatment between women and men, elderly patients, and Killip classification at presentation during off- and regular hours.

It should be noted that regional STEMI networks should provide a common protocol for treating patients with STEMI to ensure a similar performance of treatment during day and night. Each region should evaluate the availability of health care infrastructures to improve early reperfusion therapy. It is also important to perform registry-based studies which can be used as a performance measure of regional STEMI networks as part of the STEMI network program. 63

Clinical Implication

The results of this meta-analysis encourage similar performance when treating patients with acute STEMI during off- and regular working hours. The introduction of a regional STEMI network with 24/7 primary PCI service, along with application of a common STEMI protocol may increase the utilization of primary PCI and use of evidence-based medications when treating patients with STEMI. This network should be available during day and night, thus allowing a similar performance when treating patients with STEMI during regular and off-hours. Furthermore, to improve the PCI center performance during day and night, the number of interventional cardiologists who work in the PCI center should be increased to enable the cardiologist on duty to work within shifts and maintain their primary PCI skills. It is known that a number of cardiologists are associated with higher utilization of PCI. 64 It is also important to educate public to directly find a PCI center if a symptom of heart attack is suspected, as this may shorten the total ischemic time and lower 12-month mortality. 65

Study Limitation

There are several limitations found in this study. First, the definitions used to specify off-hours and regular working hours were different across studies. Second, we did not evaluate the ischemic time metrics between off-and regular hours since not all the studies reported the data. Finally, several retrospective studies included may have incomplete data.

Conclusion

This meta-analysis showed that patients with acute STEMI who were admitted during off-hours and treated with primary PCI had a similar risk of early, midterm, and long-term mortality compared with those admitted during regular working hours.

Acknowledgment

None.

Funding Statement

Funding None.

Conflict of Interest None declared.

Authors' Contribution

S.D. contributed to the study design and concept, data interpretation, drafting, and editing the manuscript. W.K. and A.P.S. contributed to data acquisition, data analysis, interpretation, statistical expertise, and editing the manuscript.

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