Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis

Galli, Mattía; Benenati, Stefano; Capodanno, Davide; Franchi, Francesco; Rollini, Fabiana; D’Amario, Domenico; Porto, Italo; Angiolillo, Dominick J.

doi:10.1016/s0140-6736(21)00533-x

Cited by 172 publications

(137 citation statements)

References 35 publications

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“…Additionally, due to a lower-than-expected event rate, they recalculated their power calculation as to not increase the number of patients needed in the trial [10]. Contrary to the trial by Pereira et al, our results are in line with a recently published meta-analysis by Galli et al, comparing guidedtherapy, either by genotyping or by using platelet function testing to standard treatment [29,30]. It included 20,743 patients and concluded that guided-therapy resulted in a significant reduction in MACE (relative risk 0.78, 95% CI 0.63-0.95, P = 0.015).…”

Section: Discussionsupporting

confidence: 78%

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

Al-Rubaish

Al-Muhanna

Alshehri

et al. 2021

International Journal of Cardiology

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Background: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y 12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y 12 inhibitor. Methods: This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. Results: STEMI patients (755) were randomized into a genotype-guided-(383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20-0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11-0.53), cardiovascular death (OR 0.16, 95%CI0.06-0.42) and major bleeding (OR 0.49, 95%CI 0.32-0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43-1.71). Conclusion:A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy.

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Section: Discussionsupporting

confidence: 78%

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

Al-Rubaish

Al-Muhanna

Alshehri

et al. 2021

International Journal of Cardiology

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“…However, pooled data from meta-analysis ( 7 ) have shown a possible increase of ischemic events in the dual therapy with clopidogrel, for example Galli et al confirmed that dual therapy with clopidogrel with a significant increase of stent thrombosis risk in the overall population and a significant 43% increase of MI in the ACS/PCI subgroup ( 8 ) sparkling the interest for the use of alternative antithrombotic agents. In addition to this, clopidogrel, but not ticagrelor, is characterized by an interindividual variability in the pharmacodynamic profile, leading to insufficient platelet inhibition and increased ischemic events in up to 40% of treated patients and thus Most recent investigations support the clinical benefit of a genetic guided selection of antiplatelet therapy in patients undergo PCI (i.e., switching to prasugrel or ticagrelor) ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

Antithrombotic Therapy With Ticagrelor in Atrial Fibrillation Subjects After Percutaneous Coronary Intervention

Wang

Chen

et al. 2021

Front. Cardiovasc. Med.

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Background: Warfarin, along with aspirin and clopidogrel, has long been recommended for patients with atrial fibrillation (AF) who are undergoing percutaneous coronary intervention with a drug-eluting stent (PCI-DES). However, this triple therapy has been known to increase the risk of bleeding complications. Meanwhile, there is no evidence from prospective trials on the use of ticagrelor in a dual therapy. We here aimed to compare the antiplatelet drug ticagrelor as a dual antithrombotic agent to aspirin and clopidogrel in bleeding events.Methods: In this multicenter, active-controlled, open-label, randomized trial, patients with AF taking warfarin who had undergone PCI-DES were randomly assigned to the ticagrelor therapy group (Dual group) or the clopidogrel plus aspirin therapy group (Triple group). The primary and secondary endpoints were overall bleeding events and major bleeding events, respectively, according to the Thrombolysis in Myocardial Infarction (TIMI) criteria at 6 months. Cardiovascular events [re-PCI, surgical bypass, myocardial infarction (MI), heart failure, rehospitalization due to angina pectoris, stent thrombosis and death due to cardiovascular causes] at 6 months were also recorded.Results: A total of 296 patients from 12 medical centers in China were randomized after PCI-DES to either the Dual therapy group (n = 148) or the Triple group (n = 146) for 6 months. The overall incidence of bleeding events at 6 months was 36.49% in the Dual therapy group and 35.62% in the Triple group [hazard ratio, 0.930; 95% confidence interval (CI), 0.635 to 1.361; P = 0.7088]. The incidence of the secondary endpoint over 6 months was 4.73% in the Dual therapy group and 1.37% in the Triple group (hazard ratio, 0.273; 95% CI, 0.057 to 1.315; P = 0.1056). Cardiovascular event occurrence was also comparable in both groups at 6 months (18.24 vs. 16.44%; hazard ratio, 0.845; 95% CI, 0.488 to 1.465; P = 0.5484).Conclusions: The incidence of total bleeding events in AF patients treated with ticagrelor was comparable to that in patients treated with clopidogrel plus aspirin at 6 month; Meanwhile, the incidence of cardiovascular events were also comparable between the groups.Clinical Trial Registration: MANJUSRI, ClinicalTrials.gov# NCT02206815, 2014, August 1st

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“…In the escalation subgroup, MACE was significantly lower in the guided arm (RR 0.74, 95% CI 0.57–0.95), while the risk of any bleeding was similar between the two arms (RR 1.00, 95% CI 0.80–1.25). In the de-escalation subgroup, guided therapy results in a 10% risk reduction in MACE without statistical significance (RR 0.90, 95% CI 0.72–1.14), and resulted in a statistically lower risk of any bleeding (RR 0.81, 95% CI 0.68–0.96) when compared to standard therapy ( 92 ).…”

Section: Meta-analysismentioning

confidence: 98%

“…Another meta-analysis included a total of 14 studies (11 RCTs, and 3 non-RCTs), and 20,743 patients aimed to assess the efficacy of guided antiplatelet therapy vs. conventional therapy in patients undergoing PCI ( 92 ). In this analysis, guided therapy was defined by genotype testing or PFT.…”

Section: Meta-analysismentioning

confidence: 99%

Genotype-Guided Use of P2Y12 Inhibitors: A Review of Current State of the Art

Al-abcha

Radwan

Blais

et al. 2022

Front. Cardiovasc. Med.

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The pharmacodynamics of the purinergic receptor type Y, subtype 12 (P2Y12) inhibitors has evolved. Our understanding of the metabolism of P2Y12 inhibitors has revealed polymorphisms that impact drug metabolism and antiplatelet efficacy, leading to genetic testing guided therapy. In addition, assays of platelet function and biochemistry have provided insight into our understanding of the efficacy of “antiplatelet” therapy, identifying patients with high or low platelet reactivity on P2Y12 therapy. Despite the data, the implementation of these testing modalities has not gained mainstream adoption across hospital systems. Given differences in potency between the three clinically available P2Y12 inhibitors, the balance between thrombotic and bleeding complications must be carefully considered, especially for the large proportion of patients at higher risk for bleeding. Here we review the current data for genetic and functional testing, risk assessment strategies, and guidelines for P2Y12 inhibitors guided therapy.

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Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis

Cited by 172 publications

References 35 publications

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients

Antithrombotic Therapy With Ticagrelor in Atrial Fibrillation Subjects After Percutaneous Coronary Intervention

Genotype-Guided Use of P2Y12 Inhibitors: A Review of Current State of the Art

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