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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Timing of early invasive intervention in patients with moderate to high risk acute coronary syndromes

M Jiang, B He, and Q Zhang.

Review published: 2012.

Link to full article: [Journal publisher]

CRD summary

This review found that early initiation of angiography in patients with moderate to high-risk acute coronary syndrome may reduce deaths and recurrent myocardial infarction. The results were consistent across the included study designs and are likely to be moderately reliable.

Authors' objectives

To determine the optimum time period for early invasive management with angiography in patients with acute coronary syndrome.


MEDLINE, EMBASE, Science Citation Index, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to September 2010; search terms were reported. Abstracts from cardiology conferences from 1970 to 2010 and Internet-based information sources were searched for additional studies. There were no language restrictions.

Study selection

Eligible for inclusion were published controlled trials that evaluated the timing of invasive interventions (angiography and revascularisation) after hospital admission or symptom onset in patients with moderate- or high-risk acute coronary syndrome. Trials were required to have early angiography performed within a mean of 72 hours, with the interventions used in combination with standard medical treatment in each group. Trials with fewer than two timing groups, lack of optimal medical treatment, or imbalances between groups for prior optimal medical treatment were excluded from the review. The primary endpoint was the rate of death or recurrent myocardial infarction.

The mean age of the included patients ranged from 58.9 years to 67.2 years; the proportion of men ranged from 58% to 72%. Some patients each of the included trials presented with diabetes mellitus (range 15% to 42%, where reported). In some trials, 55% to 63% of patients presented with hypertension.

Two reviewers independently performed the study selection.

Assessment of study quality

Methodological quality was assessed using the PRISMA criteria for the assessment of allocation concealment in the randomised controlled trials (RCTs). The quality of the trials were assessed for similarity of groups at baseline, blinding of patients and caregivers, blind measurement of outcome, percentages lost to follow-up, and the use of intention-to-treat analyses.

The quality of the observational studies was assessed using criteria from the Cochrane Handbook for the setting of the study (single- or multi-centre) and the presence of selection bias, attrition bias, performance bias, and detection bias.

The authors did not state how many reviewers performed the quality assessment.

Data extraction

Data were extracted to calculate odds ratios and 95% confidence intervals for the outcomes across multiple endpoints. The results were grouped according to the timing of angiography: less than three hours; less than 12 hours; 12 to 24 hours; 24 to 48 hours; and more than 48 hours. Recurrent myocardial infarction was defined as a new ischaemic event unrelated to the initial event. Study authors were contacted for additional information.

The authors did not state how many reviewers performed the data extraction.

Methods of synthesis

Pooled odds ratios and 95% confidence intervals were calculated using a random-effects model. The presence of statistical heterogeneity was evaluated using Ι². Given the variation in follow-up across the studies, the reviewers classified the results into two categories of follow-up: within one month of the symptom onset, and the longest follow-up. The potential for publication bias was assessed using the Egger's test and visual appraisals of funnel plots,

Results of the review

Ten studies (39,453 patients) were included in the review, comprising five RCTs (4,768 patients) and five observational studies (34,685 patients). Sample sizes ranged from 142 to 17,400 patients. All the RCTs reported adequate allocation concealment, blind assessment of outcomes zero or minimal losses to follow-up, and use of intention-to-treat analyses. There was no blinding of patients or caregivers in any of the studies. The quality assessment of the observational studies indicated that most of the studies had low to moderate risks of the biases evaluated; one study did not adequately report sufficient information to ascertain the risk of selection bias.

At the longest follow-up, there were fewer deaths and recurrent myocardial infarctions when angiography was performed within 48 hours of initial symptom presentation than when angiography was performed more than 48 hours after the initial event (data not shown).

Patients receiving angiography more than 48 hours after initial symptoms were significantly more likely to die or experience recurrent myocardial infarction than patients who received angiography between 24 and 48 hours after symptom onset (OR 0.64, 95% CI 0.52 to 0.79; Ι²=0%; two observational studies; one RCT) for both one-month follow-up and longest follow-up.

Patients who received angiography within 12 to 24 hours of symptom onset were significantly less likely to die or experience recurrent myocardial infarction than patients who began angiography between 24 to 48 hours after symptom onset (OR 0.85, 95% CI 0.75 to 0.97; Ι²=50%; two RCTs, three observational studies) combined at both one month follow-up and longest follow-up.

There were no differences at one month follow-up, longest follow-up or overall for angiography commencing less than 12 hours after initial symptom presentation and angiography performed 12 to 24 hours after initial symptom presentation.

Rates of death or recurrent myocardial infarction were lower in patients treated with angiography from three to 48 hours after initial symptom presentation than for patients in which angiography commenced within three hours of symptom presentation at one-month follow-up (OR 0.42, 95% CI 0.25 to 0.69, Ι²=0%, two randomised trials).

Analyses of the RCTs comparing deaths or recurrent myocardial infarction found no statistically significant differences between different periods (12 to 24 hours compared with 48 hours and less than 12 hours and 12 to 24 hours after symptom presentation) of initiation of angiography.

There was no evidence of publication bias identified for the results in the review.

Authors' conclusions

Performing angiography within 24 hours may provide some benefit to patients in reduced rates of death or recurrent myocardial infarction, although immediate angiography (less than three hours) after symptom presentation did not provide any benefit and may be harmful.

CRD commentary

The review addressed a clear question. Criteria for the inclusion of studies were stipulated. Appropriate databases were used to search for relevant studies. No language restrictions were applied. Although the restriction to published studies meant that there may have been a risk of publication bias, the authors evaluated the potential for publication bias using validated measures and found no evidence of its presence. Steps were reported to minimise reviewer error and bias for the selection of studies, but not for data extraction or the assessment of methodological quality.

The methodological quality of the included studies was evaluated using criteria appropriate to the study designs; study quality was found to be moderate to good across the studies. The combination of results from studies of heterogeneous design and with wide variations in follow-up may be problematical, with results from observational studies being vulnerable to various biases; this could lead to an over-estimation of effect. However, there was little evidence of heterogeneity in the analyses and the studies were grouped based on clinical and treatment characteristics. In particular, analyses of the RCTs showed few differences between different timing of the interventions. Similar results were observed in the analyses of non-RCTs. The longest follow-up durations and doses of medical treatment were also not specified.

In general, the results of the review were consistent across the study designs and are likely to be moderately reliable.

Implications of the review for practice and research

Practice: The authors stated that performing angiography within 24 hours may be beneficial to patients with moderate to high risk acute coronary syndrome but that there was no requirement to initiate very early angiography as was recommended in patients with ST-elevated myocardial infarction.

Research: The authors stated that prospective trials were required that focused on angiography stratified by time to randomisation as there was some potentially some heterogeneity in the definitions of the timing to angiography. RCTs were also required to provide evidence on optimal timing for angiography, but these could be difficult to design and conduct.


Natural Science Foundation of China; Program of Shanghai Subject Chief Scientist; Shanghai Rising Star Program; Med-X Program.

Bibliographic details

Jiang M, He B, Zhang Q. Timing of early invasive intervention in patients with moderate to high risk acute coronary syndromes. Journal of Interventional Cardiology 2012; 25(1): 10-18. [PubMed: 22003815]

Other publications of related interest

Corrigendum in: Journal of Interventional Cardiology 2012; 25(3): 321 (corrected table for Figure 2D).

Indexing Status

Subject indexing assigned by NLM


Acute Coronary Syndrome /mortality /therapy; Angiography /methods; Cardiac Catheterization; Clinical Trials as Topic; Humans; Myocardial Infarction /epidemiology /prevention & control; Recurrence; Risk Factors; Time Factors; Treatment Outcome



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 22003815