Related Experiment Video
Updated: Jul 19, 2025
Interventional Diagnostic Procedure: A Practical Guide for the Assessment of Coronary Vascular Function
Published on: March 15, 2022
Guided Anti-P2Y12 Therapy in Patients Undergoing PCI: Three Systematic Reviews with Meta-analyses of Randomized
Simone Birocchi1, Matteo Rocchetti2, Alessandro Minardi2
1Divisione di Medicina Generale II, Dipartimento di Scienze della Salute, ASST Santi Paolo e Carlo, Università degli Studi di Milano, Milan, Italy.
Background:
The value of guided therapy (GT) with anti-P2Y12 drugs in percutaneous coronary intervention (PCI) is unclear. Meta-analyses lumped together randomized controlled trials (RCTs) with heterogeneous designs, comparing either genotype-GT or platelet function test (PFT)-GT with unguided therapy. Some meta-analysis also included RCTs that did not explore GT, but included the effects of switching patients with high on-treatment platelet reactivity (HTPR) to alternative therapies (HTPR-Therapy). We performed three distinct systematic reviews/meta-analyses, each exploring only RCTs with homogeneous design.
Methods:
MEDLINE, Embase, and Central databases were searched for RCTs testing genotype-GT, PFT-GT, or HTPR-Therapy in PCI-treated patients, through October 1, 2022. Two reviewers extracted the data. Risk ratios (RRs) (95% confidence intervals) were calculated. Primary outcomes were major bleedings (MBs) and major adverse cardiovascular events (MACE).
Results:
In seven genotype-GT RCTs, RRs were: MB, 1.06 (0.73-1.54; p = 0.76); MACE, 0.65 (0.47-0.91; p = 0.01), but significant risk reduction was observed in RCTs performed in China (0.30, 0.16-0.54; p < 0.0001) and not elsewhere (0.75, 0.48-1.18; p = 0.21). In six PFT-GT RCTs, RRs were: MB, 0.91 (0.64-1.28, p = 0.58); MACE, 0.82 (0.56-1.19; p = 0.30): 0.62 (0.42-0.93; p = 0.02) in China, 1.08 (0.82-1.41; p = 0.53) elsewhere. In eight HTPR-Therapy RCTs, RRs were: MB, 0.71 (0.41-1.23; p = 0.22); MACE, 0.57 (0.44-0.75; p < 0.0001): 0.56 (0.43-0.74, p < 0.0001) in China, 0.58 (0.27-1.23, p = 0.16) elsewhere.
Conclusion:
No GT strategy affected MB. Overall, genotype-GT but not PFT-GT reduced MACE. However, genotype-GT and PFT-GT reduced MACE in China, but not elsewhere. PFT-GT performed poorly compared to HTPR-Therapy, likely due to inaccurate identification of HTPR patients by PFT.
Insights
Guided therapy (GT) using genetic testing or platelet function tests (PFTs) did not increase major bleeding in percutaneous coronary intervention (PCI) patients. While genotype-GT reduced major adverse cardiovascular events (MACE) overall, both genotype-GT and PFT-GT showed benefits in China, unlike elsewhere.
Area of Science:
- Cardiology
- Pharmacogenomics
- Interventional Cardiology
Background:
- The clinical utility of guided therapy (GT) with anti-P2Y12 drugs post-percutaneous coronary intervention (PCI) remains uncertain.
- Previous meta-analyses combined heterogeneous randomized controlled trials (RCTs), including those not directly assessing GT.
- This study provides distinct systematic reviews of homogeneous RCTs for genotype-GT, PFT-GT, and high on-treatment platelet reactivity (HTPR)-Therapy.
Purpose of the Study:
- To evaluate the efficacy and safety of different guided therapy (GT) strategies in patients undergoing PCI.
- To compare genotype-guided GT, platelet function test-guided GT (PFT-GT), and high on-treatment platelet reactivity (HTPR) therapy.
- To analyze outcomes based on geographical location, specifically China versus elsewhere.
Main Methods:
- Systematic reviews and meta-analyses of RCTs published up to October 1, 2022, sourced from MEDLINE, Embase, and Central databases.
- Data extraction by two independent reviewers.
- Calculation of risk ratios (RRs) with 95% confidence intervals for major bleeding (MB) and major adverse cardiovascular events (MACE).
Main Results:
- No GT strategy significantly impacted major bleeding (MB).
- Genotype-guided GT demonstrated a significant reduction in MACE (RR 0.65, P=0.01), particularly in Chinese RCTs (RR 0.30, P<0.0001).
- PFT-guided GT showed significant MACE reduction in China (RR 0.62, P=0.02) but not globally, and HTPR-Therapy significantly reduced MACE (RR 0.57, P<0.0001).
Conclusions:
- Guided therapy strategies did not increase major bleeding events.
- Genotype-guided GT, and PFT-guided GT in China, reduced MACE, suggesting regional variations in efficacy.
- PFT-guided GT's poorer performance compared to HTPR-Therapy may stem from inaccurate HTPR identification.
Related Concept Videos
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:27Peripheral Artery Disease III: Interprofessional Care
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:27Coronary Artery Disease V: Interprofessional Care
01:29Pulmonary Embolism II: Diagnostic Studies and Interprofessional Care
01:26Angina IV: Management