Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events

Tamargo, Juan; Kaski, Juan Carlos; Kimura, Takeshi; Barton, Jack; Yamamoto, Ko; Komiyama, Maki; Drexel, Heinz; Lewis, Basil S.; Agewall, Stefan; Hasegawa, Koji

doi:10.1093/ehjcvp/pvac040

Cited by 32 publications

(25 citation statements)

References 48 publications

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“…East Asians have a higher frequency of the CYP2C19 loss-of-function alleles, and tend to have a lower incidence of ischemic outcomes and a higher incidence of bleeding outcomes compared to Caucasians. Black individuals have a higher prevalence of CV risk factors, and higher thrombogenic, proinflammatory, and dysfunctional endothelial profiles than Caucasians [ 50 ]. Future studies are needed to explore the efficacy and safety of P2Y12 inhibitor monotherapy in ACS in different races.…”

Section: Discussionmentioning

confidence: 99%

P2Y12 Inhibitor Monotherapy versus Conventional Dual Antiplatelet Therapy in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Meta-Analysis

et al. 2023

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P2Y12 inhibitor monotherapy is a feasible alternative treatment for patients after percutaneous coronary intervention (PCI) in the modern era. Clinical trials have shown that it could lower the risk of bleeding complications without increased ischemic events as compared to standard dual antiplatelet therapy (DAPT). However, the efficacy and safety of this novel approach among patients with acute coronary syndrome (ACS) are controversial because they have a much higher risk for recurrent ischemic events. The purpose of this study is to evaluate the efficacy and safety of this novel approach among patients with ACS. We conducted a meta-analysis of randomized controlled trials that compared P2Y12 inhibitor monotherapy with 12-month DAPT in ACS patients who underwent PCI with stent implantation. PubMed, Embase, the Cochrane library database, ClinicalTrials.gov, and other three websites were searched for data from the earliest report to July 2022. The primary efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause mortality, myocardial infarction, stent thrombosis, or stroke. The primary safety outcome was major or minor bleeding events. The secondary endpoint was net adverse clinical events (NACE), defined as a composite of major bleeding and adverse cardiac and cerebrovascular events. Five randomized controlled trials with a total of 21,034 patients were included in our meta-analysis. The quantitative analysis showed a significant reduction in major or minor bleeding events in patients treated with P2Y12 inhibitor monotherapy as compared with standard DAPT(OR: 0.59, 95% CI: 0.46–0.75, p < 0.0001) without increasing the risk of MACCE (OR: 0.98, 95% CI: 0.86–1.13, p = 0.82). The NACE was favorable in the patients treated with P2Y12 inhibitor monotherapy (OR: 0.82, 95% CI: 0.73–0.93, p = 0.002). Of note, the overall clinical benefit of P2Y12 inhibitor monotherapy was quite different between ticagrelor and clopidogrel. The incidence of NACE was significantly lower in ticagrelor monotherapy as compared with DAPT (OR: 0.79, 95% CI: 0.68–0.91), but not in clopidogrel monotherapy (OR: 1.14, 95% CI: 0.79–1.63). Both clopidogrel and ticagrelor monotherapy showed a similar reduction in bleeding complications (OR: 0.46, 95% CI: 0.22–0.94; OR: 0.60, 95% CI: 0.44–0.83, respectively). Although statistically insignificant, the incidence of MACCE was numerically higher in clopidogrel monotherapy as compared with standard DAPT (OR: 1.50, 95% CI: 0.99–2.28, p = 0.06). Based on these findings, P2Y12 inhibitor monotherapy with ticagrelor would be a better choice of medical treatment for ACS patients after PCI with stent implantation in the current era.

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Section: Discussionmentioning

confidence: 99%

P2Y12 Inhibitor Monotherapy versus Conventional Dual Antiplatelet Therapy in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Meta-Analysis

et al. 2023

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“…We exclusively enrolled Korean patients. The response to lipid-lowering therapy could differ across ethnicities, 25 and thereby the generalizability of our findings might be limited. In addition, most of the included patients had a mild stroke, which could limit the applicability of our findings to patients with more severe strokes.…”

Section: Discussionmentioning

confidence: 92%

Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial

et al. 2023

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Background and Purpose Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. Methods This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events. Results Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1. 944 [1.352-2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups.

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“…The trials investigating clopidogrel monotherapy were conducted in Japan or Korea. East Asian patients have a higher frequency of CYP2C19 loss-of-function alleles and may therefore be more prone to no or poor response to clopidogrel. On the other hand, East Asian populations have a lower incidence of ischemic heart disease and a decreased risk of post-PCI atherothrombotic complications compared with White populations .…”

Section: Discussionmentioning

confidence: 99%

“…East Asian patients have a higher frequency of CYP2C19 loss-of-function alleles and may therefore be more prone to no or poor response to clopidogrel. On the other hand, East Asian populations have a lower incidence of ischemic heart disease and a decreased risk of post-PCI atherothrombotic complications compared with White populations . In a global trial of patients at high bleeding risk, abbreviated DAPT was noninferior to standard DAPT for ischemic events and superior for bleeding .…”

Section: Discussionmentioning

confidence: 99%

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

Valgimigli,

Gragnano,

Branca

et al. 2024

JAMA Cardiol

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ImportanceAmong patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor.ObjectiveTo assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI.Data SourcesMEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction.Study SelectionIncluded studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI.Data Extraction and SynthesisPatient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data.Main Outcomes and MeasuresThe primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding.ResultsAnalyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority &gt; .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P &lt; .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P &lt; .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04).Conclusions and RelevanceThis systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

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Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events

Cited by 32 publications

References 48 publications

P2Y12 Inhibitor Monotherapy versus Conventional Dual Antiplatelet Therapy in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Meta-Analysis

P2Y12 Inhibitor Monotherapy versus Conventional Dual Antiplatelet Therapy in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Meta-Analysis

Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial

Ticagrelor or Clopidogrel Monotherapy vs Dual Antiplatelet Therapy After Percutaneous Coronary Intervention

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