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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].

Safety of clopidogrel being continued until the time of coronary artery bypass grafting in patients with acute coronary syndrome: a meta-analysis of 34 studies

SS Nijjer, G Watson, T Athanasiou, and IS Malik.

Review published: 2011.

Link to full article: [Journal publisher]

CRD summary

This review found that patients with acute coronary syndrome who required urgent coronary artery bypass graft surgery could proceed with surgery without a washout period delay to cease clopidogrel use. Methodological flaws mean the results should be interpreted with caution and the authors' conclusion is uncertain.

Authors' objectives

To determine the risk of mortality, reoperation, perioperative myocardial infarction, and stroke in patients with acute coronary syndrome undergoing coronary artery bypass grafting surgery.

Searching

MEDLINE and EMBASE were searched up to 2011; search terms were reported. Reference lists from retrieved articles were checked to identify additional references.

Study selection

Studies that compared patients who had used clopidogrel prior to coronary artery bypass graft surgery versus patients who were clopidogrel-naive or patients with a clopidogrel-free period prior to surgery were eligible for inclusion. Studies had to report at least one of the endpoints of reoperation, mortality, postoperative myocardial infarction or stroke

The included populations in the trials were patients with acute coronary syndrome. Included patients were undergoing surgery on both an urgent and an elective basis and had presented with unstable or stable angina, and previous myocardial infarction. The mean age of the patients ranged from 54 to 68.3 years. Some studies assessed patients in whom clopidogrel was stopped five to seven days prior to surgery. It was presumed that most patients received loading doses of 300mg to 600mg of aspirin or clopidogrel prior to surgery. There was variable reporting of aspirin use across the studies and the control groups varied in their use of aspirin. There was insufficient data reported to determine whether there was an impact according to the precise day that clopidogrel use ceased. For surgery, the mean cross-clamp times were similar in the intervention group (50.7 minutes) and the control group (50.8 minutes); the mean cardiopulmonary bypass times was 77.9 minutes for the intervention group and 77 minutes for the control group.

Two reviewers performed the study selection; any disagreements were resolved by a third reviewer.

Assessment of study quality

Methodological quality was assessed using a star-rating system for the use of patient selection, comparability of patient groups, and the methods of assessment. A risk of bias analysis was performed that evaluated allocation concealment, blinding, the assessment of incomplete data and freedom from selective reporting.

The authors did not state how many reviewers assessed methodological quality.

Data extraction

Data were extracted by two reviewers to calculate odds ratios (OR) and 95% confidence intervals (CI) for the outcomes. Any discrepancies between the reviewers were resolved by a third reviewer.

Methods of synthesis

Pooled odds ratios and 95% confidence intervals were calculated using a random-effects model. Aggregation of overall rates of events was performed using the Mantel-Haenszel Χ² test.

Interaction analyses were performed on the basis of year of study, the use of on-pump surgery, patient urgency status, the use of concomitant anti-platelet agents including aspirin and glycoprotein IIb/IIIa inhibitors.

Results of the review

Thirty-four studies (22,584 patients) were included in the review. There were five randomised controlled trials (RCTs), three of which were subgroup analyses from larger trials and two that assessed clopidogrel exposure prior to surgery. There were 29 observational studies, comprising 17 retrospective studies and 12 prospective studies. The median quality rating was 10 stars (range 0 to 16 stars). Nineteen studies stated that enrolments were consecutive. Follow-up was one month post-surgery (where stated).

There was a higher risk of mortality (OR 1.6, 95% CI 1.30 to 1.96) and increased rates of reoperation (OR 2.32, 95% CI 1.76 to 3.06) in patients undergoing coronary artery bypass grafting surgery with recent clopidogrel exposure. There was also an increased length of intensive-care unit stay (mean difference 0.31 days, 95% CI 0.06 to 0.56) in patients with recent clopidogrel exposure, although this finding was unlikely to be clinically significant. There were no differences between clopidogrel and control groups for combined major cardiovascular events (stroke, myocardial infarction, or death).

Subgroup analyses of patients with acute coronary syndrome found that there was no difference between groups in postoperative myocardial infarction (OR 0.57, 95% CI 0.31 to 1.07) and stroke rates (OR 1.23, 95% CI 0.66 to 2.29).

Authors' conclusions

Although the use of clopidogrel seemed to be well established in patients with acute coronary syndrome, guidelines on the cessation of clopidogrel prior to coronary artery bypass graft surgery were based on limited data. Patients with acute coronary syndrome who required urgent coronary artery bypass graft surgery could proceed with surgery without a washout period delay to cease clopidogrel use.

CRD commentary

The review was to address a clear question, although patient groups were included that were different from that in the stated aim of the research. Two appropriate databases were searched for relevant studies, but it was not clear if language restrictions were applied to the search. There were no attempts to identify unpublished studies, which meant there was some risk of publication bias. Steps were taken to minimise errors and biases for study selection and data extraction, but were not reported for the assessment of methodological quality.

The authors' decision to combine the results from different study designs in meta-analyses may not be justified because the results from observational studies were associated with a number of potential biases.

Some methodological flaws mean that the results of the review should be interpreted with substantial caution and the reliability of the authors' conclusion is uncertain.

Implications of the review for practice and research

Practice: The authors stated that modern surgical techniques should aim to reduce reoperation rates and minimise unnecessary transfusion. For elective patients without acute coronary syndrome, the bleeding risk was more important and clopidogrel should be stopped for five days. The authors suggested that patients with acute coronary syndrome with surgical anatomy should have coronary artery bypass graft surgery at the earliest clinical opportunity while on clopidogrel without a delay for washout.

Research: The authors stated that a large international well-designed randomised controlled trial was required to assess differing cessation times of clopidogrel prior to coronary artery bypass graft surgery.

Funding

Not stated.

Bibliographic details

Nijjer SS, Watson G, Athanasiou T, Malik IS. Safety of clopidogrel being continued until the time of coronary artery bypass grafting in patients with acute coronary syndrome: a meta-analysis of 34 studies. European Heart Journal 2011; 32(23): 2970-2988. [PubMed: 21609973]

Indexing Status

Subject indexing assigned by NLM

MeSH

Acute Coronary Syndrome /drug therapy /mortality /surgery; Blood Transfusion /mortality /statistics & numerical data; Coronary Artery Bypass /methods /mortality; Female; Hemorrhage /chemically induced /mortality; Humans; Intensive Care /statistics & numerical data; Length of Stay /statistics & numerical data; Male; Myocardial Infarction /chemically induced /mortality; Platelet Aggregation Inhibitors /adverse effects; Postoperative Complications /chemically induced /mortality; Preoperative Care; Reoperation /mortality /statistics & numerical data; Research Design; Risk Assessment; Risk Factors; Stroke /chemically induced /mortality; Ticlopidine /adverse effects /analogs & derivatives; Treatment Outcome

AccessionNumber

12012000068

Database entry date

13/09/2012

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: 21609973

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