Role of platelet function testing in acute coronary syndromes: a meta-analysis

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Acute coronary syndromes (ACS) (n=7691). Intervention: Platelet function testing (PFT)-guided antiplatelet therapy vs. Standard dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist (clopidogrel, prasugrel, or ticagrelor). Primary outcome: Major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction (MI), target vessel revascularisation (TVR), definite/probable stent thrombosis (and stroke/TIA in a few studies) (RR 0.95, p=0.42).

Q: What does this research mean for the field?

Using platelet function testing to personalize antiplatelet therapy does not significantly reduce major adverse cardiovascular events or bleeding risks compared with standard dual antiplatelet therapy in patients with acute coronary syndromes. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

Anastasia Aluvilu; Albert Ferro

doi:10.1136/openhrt-2022-002129

December 1, 2022Open HeartOpen Access

Role of platelet function testing in acute coronary syndromes: a meta-analysis

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Key result

Platelet function testing-guided antiplatelet therapy shows no benefit over standard DAPT for MACE in ACS.

RR 0.95
P=0.42
n=7,691

Figures

Why the study?

It was unclear whether using platelet function testing in acute coronary syndromes to personalise antiplatelet therapy offers clinical benefits warranting incorporation into routine practice.

Does platelet function testing-guided adjustment of dual antiplatelet therapy including a P2Y12 antagonist reduce major adverse cardiovascular events or bleeding compared to standard dual antiplatelet therapy in patients with acute coronary syndromes?

Key Points

To determine whether tailoring P2Y12 antagonist therapy using platelet function testing improves clinical outcomes in patients presenting with acute coronary syndromes.
Systematic review and meta-analysis of five randomized controlled trials including 7691 patients with acute coronary syndromes published between 2014 and 2020.
Evaluated studies using ADP-specific platelet function assays (including VerifyNow, Multiplate, and VASP) to guide dual antiplatelet therapy escalation or de-escalation versus standard care.
Guided therapy showed no significant reduction in major adverse cardiovascular events (RR=0.95, p=0.42) or overall clinical outcomes (RR=0.90, p=0.22).
No significant risk reductions were observed for cardiovascular death (RR=0.76, p=0.26), myocardial infarction (RR=0.96, p=0.74), stent thrombosis (RR=0.92, p=0.83), stroke (RR=0.91, p=0.72), or target vessel revascularisation (RR=1.06, p=0.47).
Bleeding rates showed no significant difference between guided and standard therapies for major bleeding (RR=0.97, p=0.78), minor bleeding (RR=0.89, p=0.19), or any bleeding (RR=1.04, p=0.33).

Study Design

Type

Meta-Analysis (n=7,691)

Structured PICO

Does platelet function testing-guided adjustment of dual antiplatelet therapy including a P2Y12 antagonist reduce major adverse cardiovascular events or bleeding compared to standard dual antiplatelet therapy in patients with acute coronary syndromes?

P

Population

7,691 patients with acute coronary syndromes across 5 RCTs undergoing dual antiplatelet therapy including a P2Y12 antagonist.

I

Intervention

Platelet function testing (PFT)-guided dual antiplatelet therapy (DAPT) adjustment (escalation, de-escalation, or both) using ADP-specific assays (VerifyNow P2Y12, Multiplate analyser with ADP assay, VASP phosphorylation index assay, or light transmission aggregometry) and P2Y12 antagonists (clopidogrel, prasugrel, or ticagrelor).

C

Comparator

Standard unguided dual antiplatelet therapy (DAPT) comprising aspirin with a P2Y12 receptor antagonist (clopidogrel, prasugrel, or ticagrelor).

O

Outcome

Major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction (both NSTEMI and STEMI), target vessel revascularisation (TVR), and definite/probable stent thrombosis (with a few studies also including stroke or transient ischaemic attack).composite

Main Result

Relative Risk: 0.95

p-value: p=0.42

Using platelet function testing to guide P2Y12 inhibitor therapy in acute coronary syndromes does not reduce major adverse cardiovascular events or bleeding compared with standard dual antiplatelet therapy, supporting current guidelines against routine testing.

Limitations

Lack of patient-level data for baseline characteristics (including age, medical and medication history such as CYP2C19-affecting medicines) to examine relationships with treatment outcomes
All five included RCTs were assessed as high risk of bias in at least one domain
Potential underestimation of overall clinical benefit as only two out of five studies assessed and reported this outcome
Inability to perform meta-regression due to insufficient number of included studies (only 5 RCTs vs at least 10 required)
Substantial heterogeneity in RCT study designs, sample sizes, endpoint definitions, bleeding classifications, PFT timing, assays, and HPR cut-off targets
No assessments were possible on baseline characteristics on patient-level data, including age, medical and medication history (including CYP2C19-affecting medicines)
All five RCTs included in the pooled analysis were high-risk studies with at least a score of 'high risk' in one bias domain
Potential underestimation of overall clinical benefit of PFT since only two out of five studies assessed and reported this outcome
Meta-regression was not performed to study the impact of covariates as only five studies were included (at least 10 required)
Heterogeneity in RCT study designs, sample sizes, endpoint and bleeding definitions, strategies used to overcome HPR, assays, and cut-off targets

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Implication

Guided therapy confers no benefit in ACS; reinforces guidelines against routine platelet function testing.

Abstract

Objective This meta-analysis aimed to evaluate whether using platelet function testing (PFT) in acute coronary syndromes (ACS) to personalise antiplatelet therapy including a P2Y 12 antagonist offers any clinical benefits to indicate incorporation into routine practice. Methods A search was conducted on five databases for randomised controlled trials (RCTs) conducted between 1 January 2000 and 17 July 2022, which included an ADP-specific platelet function assays and P2Y 12 antagonists as part of dual antiplatelet therapy (DAPT) and have reported the efficacy and/or safety outcomes. The reported event frequencies were used to calculate the risk ratios (RRs) with a 95% CI. The χ 2 heterogeneity statistical test and sensitivity analysis were used for heterogeneity assessment. Results Five RCTs with 7691 patients were included in the analysis. No significant risk reduction was seen in major adverse cardiovascular events (RR=0.95, p=0.42), individual cardiac events (cardiovascular death: RR=0.76, p=0.26; myocardial infarction: RR=0.96, p=0.74; stent thrombosis: RR=0.92, p=0.83; stroke: RR=0.91, p=0.72; target vessel revascularisation: RR=1.06, p=0.47) and overall clinical outcome (RR=0.90, p=0.22). There was also no difference in the rate of bleeding between PFT-guided and standard therapies (major bleeding: RR=0.97, p=0.78, minor bleeding: RR=0.89, p=0.19 and any bleeding: RR=1.04, p=0.33). Conclusion Compared with standard DAPT with P2Y 12 antagonists, using PFT to adjust antiplatelet therapy does not improve clinical outcomes. Therefore, the positions of key guidelines on routine testing in ACS should remain unchanged. In addition, the study highlights the need for well-designed and powered RCTs and standardised testing methodologies to provide reliable findings and definitive conclusions.

Discussion

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Cite This Study

Aluvilu et al. (2022) conducted a meta-analysis in Acute coronary syndromes (ACS) (n=7,691). Platelet function testing (PFT)-guided antiplatelet therapy vs. Standard dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist (clopidogrel, prasugrel, or ticagrelor) was evaluated on Major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction (MI), target vessel revascularisation (TVR), definite/probable stent thrombosis (and stroke/TIA in a few studies) (RR 0.95, p=0.42). Platelet function testing-guided antiplatelet therapy did not significantly reduce major adverse cardiovascular events compared with standard dual antiplatelet therapy in ACS (RR 0.95, p=0.42).

synapsesocial.com/papers/6a79979914b028facf0dde6a https://doi.org/10.1136/openhrt-2022-002129

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Role of platelet function testing in acute coronary syndromes: a meta-analysis

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Role of platelet function testing in acute coronary syndromes: a meta-analysis

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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