A Systematic Review On The Hazards Of A Systematic Review On The Hazards Of

Aspirin Discontinuation Among 50279 Aspirin Discontinuation Among 50279

Patients With Or At Risk For Coronary Patients With Or At Risk For Coronary

Artery DiseaseArtery Disease

Giuseppe Biondi ZoccaiGiuseppe Biondi Zoccai

Hemodynamics and Cardiovascular Interventions ServiceHemodynamics and Cardiovascular Interventions Service

Abano Terme Hospital, Abano Terme (PD)Abano Terme Hospital, Abano Terme (PD)

and Institute of Cardiology, University of Turin, Turinand Institute of Cardiology, University of Turin, Turin

gbiondizoccai@gmail.comgbiondizoccai@gmail.com

Funding and conflict Funding and conflict

of interest disclosureof interest disclosure

• NoneNone

BackgroundBackground

• The role of aspirin in patients with The role of aspirin in patients with coronary artery disease (CAD) is well coronary artery disease (CAD) is well establishedestablished11

• Patients however happen to discontinue Patients however happen to discontinue aspirin according to physician advice or aspirin according to physician advice or unsupervisedunsupervised22

• To date, there is no conclusive evidence To date, there is no conclusive evidence on the risk of aspirin withdrawal in such on the risk of aspirin withdrawal in such patients, despite several reports on its patients, despite several reports on its potentially ominous consequencespotentially ominous consequences33

1 – ATC BMJ 2002 2 – Eagle Am J Med 2004 3 - McFadden Lancet 2004

ObjectivesObjectives

• We aimed to systematically search, We aimed to systematically search, appraise, and pool clinical studies appraise, and pool clinical studies reporting on the impact of aspirin reporting on the impact of aspirin discontinuation among patients with discontinuation among patients with or at risk for CADor at risk for CAD

Study search and selectionStudy search and selection• BioMedCentral, Google Scholar, and PubMed BioMedCentral, Google Scholar, and PubMed

were searched, without language restrictionswere searched, without language restrictions

• Inclusion criteria: a) human studies, b) Inclusion criteria: a) human studies, b) reporting on the quantitative appraisal of the reporting on the quantitative appraisal of the cardiovascular risk of aspirin withdrawal, and cardiovascular risk of aspirin withdrawal, and c) in patients at risk for or with established c) in patients at risk for or with established coronary artery diseasecoronary artery disease

• Exclusion criteria: a) non-human setting, b) Exclusion criteria: a) non-human setting, b) duplicate reporting (in which case the duplicate reporting (in which case the manuscript reporting the largest sample or manuscript reporting the largest sample or the longest follow-up was selected), c) the longest follow-up was selected), c) inability to compute risk estimates due to inability to compute risk estimates due to case report or series designcase report or series design

Data abstraction and appraisalData abstraction and appraisal

• We abstracted: We abstracted: authors, journal, years of authors, journal, years of conduct and publication, study design, conduct and publication, study design, sample size, patient characteristics, index sample size, patient characteristics, index diagnosis, prevention stage (primary vs diagnosis, prevention stage (primary vs secondary), lesion characteristics, raw secondary), lesion characteristics, raw numbers and risks for death, myocardial numbers and risks for death, myocardial infarction, stroke, major adverse infarction, stroke, major adverse cardiovascular events (as defined and cardiovascular events (as defined and reported by each investigator) and major reported by each investigator) and major bleedingbleeding

• Quality of included studies was appraised Quality of included studies was appraised according to the Cochrane Collaboration according to the Cochrane Collaboration methodsmethods

Data analysis and synthesisData analysis and synthesis

• A random effect model with generic inverse A random effect model with generic inverse variance weighting was used to compute risk variance weighting was used to compute risk estimates by means of RevMan 4.2estimates by means of RevMan 4.2

• Hypothesis testing was set at the 2-tailed Hypothesis testing was set at the 2-tailed 0.05 level0.05 level

• A 2-tailed 0.10 p value at chi-square test was A 2-tailed 0.10 p value at chi-square test was considered as cutoff for statistical considered as cutoff for statistical heterogeneityheterogeneity

• Small study bias was appraised with funnel Small study bias was appraised with funnel plots and Egger testplots and Egger test

Review processReview process

612 citations retrieved from database searches

31 complete articles assessed according to the selection criteria

6 studies finally included in the systematic review

581 titles/abstracts excludedbecause non-relevant

25 articles excluded according to explicit inclusion/exclusion criteria

Included studiesIncluded studies

Major excluded studiesMajor excluded studies

Clinical impact of aspirin Clinical impact of aspirin withdrawal in included studieswithdrawal in included studies

Quality appraisal of included studiesQuality appraisal of included studies

Study or Risk estimate (random model) Risk estimate

sub-category 95% CI 95% CI Year

Coronary artery diseaseCollet

Ferrari

Newby

Subtotal (95% CI)

Heterogeneity: P = 0.60, I² = 0%Overall effect: P < 0.00001

Coronary artery stentingIakovou

Subtotal (95% CI)

Heterogeneity: not applicableOverall effect: P < 0.00001

Coronary artery bypass graftingDacey

Mangano

Subtotal (95% CI)

Heterogeneity: P = 0.76, I² = 0%Overall effect: P = 0.002

Total (95% CI)

89.78 [29.90, 269.60] 89.78 [29.90, 269.60]89.78 [29.90, 269.60]

2.05 [1.08, 3.89] 2004 2.13 [1.42, 3.22] 2005 1.72 [1.54, 2.38] 2006 1.82 [1.52, 2.18]1.82 [1.52, 2.18]

2005

1.82 [1.02, 3.23] 2000 2.44 [1.61, 3.70] 2002 2.20 [1.58, 3.08]2.20 [1.58, 3.08]

3.14 [1.75, 5.61]3.14 [1.75, 5.61]Heterogeneity: P < 0.00001, I² = 89.8%Overall effect: P = 0.0001

0.1 0.2 0.5 1 2 5 10

Favors withdrawal Favors control

30 100 300

Meta-analysisMeta-analysis

Additional analysesAdditional analyses

• On average 10.66 (95% confidence On average 10.66 (95% confidence interval 10.25-11.07) days elapsed interval 10.25-11.07) days elapsed between drug withdrawal and thrombotic between drug withdrawal and thrombotic eventsevents

• Testing for publication bias yielded non-Testing for publication bias yielded non-significant results (P=0.107 at Egger test) significant results (P=0.107 at Egger test)

• Selecting one of the subgroups only, or Selecting one of the subgroups only, or excluding one study at a time, did not excluding one study at a time, did not determine major changes in direction or determine major changes in direction or magnitude of statistical findingsmagnitude of statistical findings

Proposal for management of aspirin Proposal for management of aspirin

discontinuation in patients undergoing surgerydiscontinuation in patients undergoing surgeryHISTORY AND PHYSICAL EXAM and EVALUATION OF SURGICAL RISK

MINOR SURGERY CORONARY ARTERYBYPASS GRAFT

CONTINUE ASPIRIN

MAJOR SURGERY(excluding CABG)

LOW RISK OF MAJOR BLEED

HIGH RISK OF MAJOR BLEED

RECENT CORONARY STENT IMPLANTATION?

CONTINUE ASPIRIN + TNP OR RESCHEDULE AFTER >1 MONTHS

yes

STOP ASPIRIN FOR 3 DAYSHEPARIN BRIDGE RX

no

CONTINUE ASPIRIN

ConclusionsConclusions

• Aspirin withdrawal has ominous Aspirin withdrawal has ominous prognostic implication in subjects with or prognostic implication in subjects with or at moderate-to-high risk for CADat moderate-to-high risk for CAD

• While awaiting for randomized trials, While awaiting for randomized trials, aspirin discontinuation in such patients aspirin discontinuation in such patients should be advocated only when bleeding should be advocated only when bleeding risk clearly overwhelms that of risk clearly overwhelms that of atherothrombotic eventsatherothrombotic events

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