P2Y12 Inhibitor Monotherapy after Short Term Dual Antiplatelet Therapy in Acute Coronary Syndrome.

Recent studies have shown similar safety and efficacy of short-term dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor (P2Y12i) monotherapy when compared with standard DAPT. However, the optimal DAPT duration and regimen in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) is still unclear. Online databases were searched for randomized controlled trials (RCTs) evaluating P2Y12i monotherapy after short DAPT (≤3 months) vs standard DAPT (≥12 months) in ACS patients. The outcomes of interest were all cause death, cardiovascular (CV) death, myocardial infarction (MI), stent thrombosis (ST), target-vessel revascularization (TVR) and major bleeding. Random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Six RCTs with a total of 23,884 patients (n=11,904 P2Y12i monotherapy, n=11,980 standard DAPT) were included. Compared with standard DAPT, P2Y12i monotherapy after short DAPT was associated with similar odds of all cause death (OR 0.86, 0.65-1.12, p = 0.26) and CV death (OR 0.75, 0.43-1.29, p = 0.29) at 1 year. Similarly, there were no significant differences in rates of MI (OR 1.09, 0.83-1.43, p = 0.53), ST (OR 1.09, 0.71-1.67, p = 0.70) and TVR (OR 0.81, 0.65-1.01, p = 0.07) between the P2Y12i monotherapy and standard DAPT arms. The P2Y12i monotherapy group had significantly lower major bleeding (OR 0.49, 0.38-0.64, p<0.001) when compared to standard DAPT. In conclusion, among patients with ACS undergoing PCI, P2Y12i monotherapy after short DAPT significantly reduces bleeding without increasing ischemic risk when compared to standard DAPT therapy.

Systemic hypertension with VEGFR inhibitor (axitinib) therapy in cancer patients: A meta-analysis and systematic review of randomized controlled trials.

Vascular endothelial growth factor receptor inhibitors (VEGFRi), namely axitinib, are commonly used chemotherapeutic agents in patients with cancer; however, this medication has a significant cardiovascular side effect profile, such as high-grade hypertension. We performed this updated meta-analysis of RCTs to compile cardiovascular adverse events, such as all-grade and high-grade (>3) hypertension, the risk for thrombosis (DVT and PE), and peripheral edema. A systematic search was performed on PubMed, Cochrane, and Embase from inception until October 2023 for studies using axitinib to treat various cancers. Trials with patients randomly allocated for VEGFRi drug therapy with axitinib and reported all-grade hypertension as an outcome were included. Statistical analysis was performed using Cochrane Review Manager to calculate pooled proportions of odds ratios (OR) with a 95 % confidence interval (CI) using the random-effects model, Mantel-Haenszel method. A total of 8 RCTs and 2502 patients were included in the review. Compared with the placebo group, the VEGFRi (Axitinib) therapy group was associated with a higher risk of all-grade and high-grade hypertension, hand-foot syndrome, and fatigue. Furthermore, there was no increased risk of thromboembolism (DVT/PE) or hypothyroidism. However, a lower risk of peripheral edema was noted between the two groups. Screening for patients with preexisting hypertension, identifying risk factors for cardiovascular diseases before the initiation of VEGFRi therapy, and careful monitoring of high-risk patients during VEGFRi therapy, as well as prompt treatment with antihypertensive drugs, will help mitigate the adverse effects. Further evaluation using prospective designs is required to study the clinical significance and develop mitigation strategies.

Cardiovascular Outcomes With Empagliflozin and Dapagliflozin in Patients Without Diabetes.

Although the cardiovascular (CV) benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with diabetes mellitus (DM) are well known, their effects in patients without DM continue to be explored. We provide a meta-analysis of the available evidence. Online databases were searched for randomized controlled trials (RCTs) comparing SGLT2i to placebo/control in patients without DM. The end points of interest were composite CV death/hospitalization for heart failure (HF) with individual components, all-cause death, major adverse CV events, and serious adverse events. Subgroup analysis was performed according to the type of SGLT2i. Pooled odds ratios (OR) and 95% confidence intervals (CI) were generated through a random-effects model. A total of 6 RCTs with 12,984 patients (6,501 in the SGLT2i group and 6,483 in the placebo group) were included, followed over a mean duration of 17.7 months. Four RCTs had patients with HF, 1 with chronic kidney disease, and 1 with myocardial infarction. The mean age was 64 years, 72% of patients were men and mean hemoglobin A1C was 5.7%. As compared with a placebo, SGLT2i treatment was associated with significant reduction in composite CV death or hospitalization for HF (OR 0.77, 95% CI 0.68 to 0.87, p <0.0001), primarily because of a decrease in hospitalization for HF (OR 0.70, 95% CI 0.60 to 0.81, p <0.00001). No significant differences were found pertaining to CV death (OR 0.86, 95% CI 0.74 to 1.01, p = 0.06), all-cause death (OR 0.89, 95% CI 0.71 to 1.11, p = 0.29) and major adverse CV events (OR 0.95, 95% CI 0.68 to 1.32, p = 0.75). Serious adverse events were lower with use of empagliflozin vs placebo. In conclusion, this study shows significant CV benefits in terms of reduction in CV death or hospitalization for HF in patients without DM treated with SGLT2i as compared with placebo. The underlying heterogeneity of patients in terms of co-morbidities (HF, chronic kidney disease, or myocardial infarction) needs to be considered while interpreting the results.

Development of a routine bedside CYP2C19 genotype assessment program for antiplatelet therapy guidance in a community hospital catheterization laboratory.

Genotype based personalized antiplatelet therapy in the setting of percutaneous coronary intervention (PCI) has been studied in clinical trials. Despite the demonstrated risk associated with CYP2C19 loss-of-function (LoF) carriage in clopidogrel-treated PCI patients, real-world implementation of genotyping for PCI has been low. The goal of the current study was to provide CYP2C19 genotype information to the interventionalist prior to the completion of the catheterization to facilitate immediate personalized antiplatelet therapy. Routine personalization of P2Y12 inhibitor therapy for PCI in a community hospital cardiac catheterization laboratory by POC genotyping with the SpartanRx system was first offered in February 2017. A best practice advisory (BPA) based on the Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 genotype and clopidogrel therapy was placed in the electronic health record prescription medication ordering system. By December 2019, 1,052 patients had CYP2C19 genotype testing, 429 patients underwent PCI with genotype guided antiplatelet therapy, and 250 patients underwent PCI without genotype testing and received antiplatelet therapy at the discretion of the treating physician. BPA compliance was 93. 87% of LoF allele carriers were prescribed ticagrelor or prasugrel whereas 96% of non-LoF allele carriers were prescribed clopidogrel. The genotyping results were available within 1 h and made immediately available for decision making by the interventional cardiologist. POC CYP2C19 genotyping is feasible in a community hospital catheterization laboratory and is associated with high rate of best practice compliance.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03040622.

Utility of VerifyNow to assess the immediate pharmacodynamic response of chewed and swallowed aspirin: comparison with aggregometry.

VerifyNow (VN) test is a less laborious method to assess pharmacodynamics (PD) compared to light transmittance aggregometry (LTA). VN assay has not been used to study the immediate PD effects of acetylsalicylic acid (ASA). Ten healthy volunteers were randomly assigned to a single 162 or 650 mg dose of chewed and swallowed ASA. Pharmacodynamic and pharmacokinetic measurements were performed at baseline and serially up to 60 min after ASA administration. Onset by VN was 20 ± 7 min with 162 mg and 13 ± 7 min with 650 mg ASA (p = .07). Onset by 1 mM AA-induced PA was 13 ± 12 min with 162 mg and 7 ± 3 min with 650 mg ASA (p=NS). VN correlated with AA-induced PA (r = 0.80, p < .001) and serum TxB2 levels (r = 0.76, p < .001). 95% inhibition of serum TxB2 was achieved at 38 ± 22 min and 22 ± 8 min with the 162 and 650 mg ASA, respectively (p = .08). The onset and extent of the antiplatelet effect of 650 mg ASA is numerically faster and greater than the 162 mg dose. VN identifies the onset, extent, and dose response to ASA therapy. The ease of using VN should facilitate multicenter PD investigations of ASA.

Aspirin (acetylsalicylic acid) is an important drug widely used to prevent adverse ischemic events in patients with cardiovascular disease. Platelet aggregation and thromboxane B₂ levels in blood samples by complex laboratory methods are used to assess platelet response to aspirin. VerifyNow assay is a simple laboratory test that has not been used to assess the immediate effect of aspirin. In this study, conducted in 10 healthy volunteers, we compared the immediate platelet response to aspirin by serially assessing platelet aggregation by aggregometry and VerifyNow assay, and thromboxane B₂ levels. We also measured plasma levels of acetylsalicylic acid and salicylic acid. Our study demonstrated that the VerifyNow Aspirin test identifies the onset, extent, and dose-response to aspirin therapy. The ease of using the VerifyNow test should facilitate multicenter pharmacodynamic investigations of aspirin.

Safety and efficacy of glucagon-like peptide-1 receptor agonists on cardiovascular events in overweight or obese non-diabetic patients.

BACKGROUND: Randomized controlled trials (RCTs) have shown variable cardiovascular (CV) outcomes in overweight or obese patients without diabetes mellitus (DM) who are treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) vs. placebo. We conducted a meta-analysis of the available studies. METHODS: Online databases were searched for RCTs comparing GLP-1 RA to placebo in overweight or obese non-diabetic patients. The clinical endpoints of interest were major adverse CV events (MACE), CV death, all cause death, myocardial infarction (MI), stroke, revascularization, total adverse events and their subtypes. Pooled odds ratios (OR) and 95 % confidence intervals (CI) were calculated using a random-effects model. RESULTS: A total of 10 RCTs with 29,325 patients (n = 16,900 GLP-1 RA, n = 12,425 placebo) were included. The mean age was 48 years and 34 % of patients were men. As compared with placebo, the GLP-1 RA group was associated with significant reduction of MACE (OR 0.79, 95 % CI 0.71-0.89, p < 0.0001), all cause death (OR 0.80, 95 % CI 0.70-0.92, p = 0.002), MI (OR 0.72, 95 % CI 0.61-0.85, p = 0.0001) and revascularization (OR 0.76, 95 % CI 0.67-0.86, p < 0.0001), without any differences in CV death or stroke. Total adverse events, gastrointestinal and gallbladder-related disorders were higher in the GLP-1 RA group, with a similar rate of renal adverse events, malignant neoplasms and acute pancreatitis to placebo. CONCLUSION: In overweight or obese patients without DM, patients treated with GLP-1 RAs had significantly reduced MACE, all cause death, MI and revascularization when compared with placebo.

Early assessment of the pharmacokinetic and pharmacodynamic effects following acetylsalicylic acid loading: toward a definition for acute therapeutic response.

Despite decades of investigations, the optimal assessment of the "therapeutic response" to early after loading dose of acetylsalicylic acid (ASA) remains unclear. Limited information is available on the relation between pharmacodynamic (PD) and pharmacokinetic (PK) measurements assessed immediately after ASA administration. Serial PD and PK analyses were performed immediately after a single 162 or 650 mg dose of chewed and swallowed ASA in ten healthy adults. ASA response was defined as > 95% inhibition of serum thromboxane (Tx)B2, < 550 aspirin reaction units (ARU) by VerifyNow Aspirin (VN) test, and ≤ 20% arachidonic acid (AA)-induced platelet aggregation (PA). Correlation analyses between PK and PD measurements and receiver operating characteristic (ROC) curve analyses were performed. ASA response measured by VN test and AA-induced PA was achieved within 30 min of ASA administration. A correlation was observed between ARU and AA-induced maximum PA (r = 0.69, p < 0.001), serum TxB2 (r = 0.74 and p < 0.001), and serum TxB2 inhibition (r = 0.79, p < 0.001). In ROC curve analyses, ≤ 558 ARU and ≤ 7% AA-induced PA were associated with > 95% inhibition of TxB2. 686 ng/ml plasma ASA cut-off point was associated with > 95% inhibition of serum TxB2, ≤ 7% 1 mM AA-induced PA, and ≤ 585 ARU. A modest ~ 50% inhibition of TxB2 inhibition was associated with marked inhibition of 1 mM AA-induced platelet aggregation by LTA. Our analyses demonstrated important relationships between pharmacodynamic, and pharmacokinetic parameters measured immediately following oral ASA and cutoff values for ARU and AA-induced PA that is associated with > 95% inhibition of serum TxB2.

Meta-analysis of immediate complete vs staged complete revascularization in patients with acute coronary syndrome and multivessel disease.

BACKGROUND: Randomized controlled trials (RCTs) have shown varying results between immediate and staged complete percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and multivessel disease (MVD). We conducted a meta-analysis to reconcile the findings. METHODS: Online databases were searched for RCTs comparing immediate vs staged complete PCI in patients presenting with ACS. The outcomes of interest were major adverse cardiovascular events (MACE), all cause death, myocardial infarction (MI), cardiovascular death, stent thrombosis, target vessel revascularization (TVR), cerebrovascular events, bleeding and acute kidney injury (AKI)/contrast induced nephropathy (CIN). Risk ratios (RR) with 95 % confidence intervals (CI) were calculated using the random-effects model. RESULTS: Nine RCTs with a total of 3637 patients - 1821 in the immediate PCI group and 1816 in the staged PCI group, were included. The mean age was 64 years, 78 % of patients were men and the mean duration of follow up was 1 year. As compared with staged complete PCI, the immediate PCI group was associated with significant reduction of MI (RR 0.53, 95 % CI 0.36-0.77) and TVR (RR 0.69, 95 % CI 0.53-0.90). The risks of all-cause death, cardiovascular death, MACE, cerebrovascular events, stent thrombosis, bleeding and AKI/CIN were similar in the two groups. CONCLUSIONS: In ACS patients selected for complete revascularization strategy, multivessel PCI during the index procedure may be associated with significant reduction in the risk of MI and TVR without harm when compared with a staged PCI strategy.

An overview of the utility of prasugrel hydrochloride as a treatment option for ischemic stroke.

INTRODUCTION: Prasugrel, a potent P2Y12 receptor inhibitor, is not currently recommended in patients with stroke due to a higher rate of recurrent stroke. Prasugrel was associated with comparable efficacy to clopidogrel in reducing the risk of ischemic stroke in a recent phase III study. AREAS COVERED: The authors provide an overview of the potential role of prasugrel in the management of ischemic stroke. The authors searched PUBMED, MEDLINE, and clinicaltrials.org and recently presented trials at the conferences for clinical trials of prasugrel therapy in patients with stroke and TIA, and important original investigations are reviewed. EXPERT OPINION: The recent PRASTRO-trials demonstrated comparable outcomes of lower maintenance dose (3.5 mg daily dose) with clopidogrel in East Asian stroke patients, thus can be a credible option as a P2Y12 receptor inhibitor. It can also be considered as a credible option in other races and ethnicities and in other clinical situations that may require DAPT, such as intracranial or carotid stenting. Since prasugrel is associated with a superior antiplatelet effect and is not influenced by genetic polymorphisms, there is no need for platelet function or genetic testing. More work is needed to establish the safety and efficacy of low-dose prasugrel plus aspirin in comparison with currently used clopidogrel plus aspirin in non-East Asian populations.

Meta-Analysis of the Performance of AI-Driven ECG Interpretation in the Diagnosis of Valvular Heart Diseases.

Valvular heart diseases (VHDs) significantly impact morbidity and mortality rates worldwide. Early diagnosis improves patient outcomes. Artificial intelligence (AI) applied to electrocardiogram (ECG) interpretation presents a promising approach for early VHD detection. We conducted a meta-analysis on the efficacy of AI models in this context. We reviewed databases including PubMed, MEDLINE, Embase, Scopus, and Cochrane until August 20, 2023, focusing on AI for ECG-based VHD detection. The outcomes included pooled accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value. The pooled proportions were derived using a random-effects model with 95% confidence intervals (CIs). Study heterogeneity was evaluated with the I-squared statistic. Our analysis included 10 studies, involving ECG data from 713,537 patients. The AI algorithms mainly screened for aortic stenosis (n = 6), mitral regurgitation (n = 4), aortic regurgitation (n = 3), mitral stenosis (n = 1), mitral valve prolapse (n = 2), and tricuspid regurgitation (n = 1). A total of 9 studies used convolution neural network models, whereas 1 study combined the strengths of support vector machine logistic regression and multilayer perceptron for ECG interpretation. The collective AI models demonstrated a pooled accuracy of 81% (95% CI 73 to 89, I² = 92%), sensitivity was 83% (95% CI 77 to 88, I² = 86%), specificity was 72% (95% CI 68 to 75, I² = 52%), PPV was 13% (95% CI 7 to 19, I² = 90%), and negative predictive value was 99% (95% CI 97 to 99, I² = 50%). The subgroup analyses for aortic stenosis and mitral regurgitation detection yielded analogous outcomes. In conclusion, AI-driven ECG offers high accuracy in VHD screening. However, its low PPV indicates the need for a combined approach with clinical judgment, especially in primary care settings.

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events Comparing East Asians With Westerners: A Meta-Analysis.

Background: East Asians have shown different risk profiles for both thrombophilia and bleeding than Western counterparts. Objectives: The authors sought to evaluate the effect of low-dose aspirin for primary prevention between these populations. Methods: We searched randomized clinical trials (RCTs) for intervention with low-dose aspirin (≤100 mg once daily) in participants without symptomatic cardiovascular disease until December 31, 2021. The number of events between the arms was extracted for analysis. Pooled risk ratios (RRs) and risk differences (RDs) were analyzed in each population. Outcomes included a major adverse cardiovascular event (MACE), cardiovascular death, myocardial infarction, stroke, and major bleeding (intracranial hemorrhage and major gastrointestinal bleeding). Results: Two RCTs included 17,003 East Asians, and 9 RCTs had 117,467 Western participants. Aspirin treatment showed a similar effect in reducing the MACE rate (RR of East Asians: 0.87; 95% CI: 0.71-1.05; RR of Westerners: 0.90; 95% CI: 0.85-0.95) (Pinteraction = 0.721). In contrast, the risk of major bleeding during aspirin vs control was greater in the East Asian population (RR: 2.48; 95% CI: 1.86-3.30) compared with the Western population (RR: 1.45; 95% CI: 1.26-1.66) (Pinteraction = 0.001), which was driven by more frequent gastrointestinal bleeding (RR of East Asians: 3.29; 95% CI: 2.26-4.80 vs RR of Westerners: 1.56; 95% CI: 1.29-1.88) (Pinteraction < 0.001). The net RDs (RD of MACE plus RD of major bleeding) were 8.04 and 0.72 per 1,000 persons in East Asian and Western participants, indicating 124 and 1,389 of the net number needed to harm, respectively. Conclusions: Low-dose aspirin for primary prevention in East Asians must be cautiously prescribed because of the increased risk of major bleeding relative to Western counterparts.

Oxygen Targets After Cardiac Arrest: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Optimal oxygen saturation target in patients resuscitated after cardiac arrest is unknown. Previous randomized controlled trials (RCTs) comparing restrictive oxygen therapy with liberal therapy have shown conflicting results. STUDY QUESTION: We performed a meta-analysis of available RCTs to consolidate the contrasting findings regarding the oxygen targets after cardiac arrest. DATA SOURCES: We searched electronic databases for RCTs comparing restrictive versus liberal oxygen targets in patients resuscitated after cardiac arrest. STUDY DESIGN: End points of interest were mortality, unfavorable neurological outcomes, and rearrests. Random-effects meta-analysis was performed to estimate the risk ratio (RR) with a 95% confidence interval (CI). RESULTS: Eight RCTs with 1641 patients (restrictive n = 833, liberal n = 808) were included in the analysis. The oxygen targets were defined by either saturation, partial pressure (PaO2), or supplementation rates. The mean age and male percentage were 63 years and 80%, respectively. There was no significant difference observed in the 2 groups for overall mortality (RR = 0.91, 95% CI = 0.75-1.10, P = 0.33), unfavorable neurological outcomes (RR = 0.93, 95% CI = 0.74-1.18, P = 0.56), and rearrests (RR = 0.67, 95% CI = 0.22-1.98, P = 0.47). CONCLUSIONS: Overall, this meta-analysis shows no significant difference in mortality, unfavorable neurological outcomes, and rearrests when using restrictive or liberal oxygen targets in patients after cardiac arrest. The limitations in the newer trials should be kept in mind while interpreting the overall results.

Role of Intravascular Imaging in Complex Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials.

Intravascular imaging (IVI) during percutaneous coronary intervention (PCI) has been shown to improve clinical outcomes. However, data is limited in complex PCI and the adoption remains low. We aimed to conduct a meta-analysis of all available randomized controlled trials comparing IVI with conventional angiography in patients who underwent complex PCI. The primary outcomes of interest were major adverse cardiovascular events, all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, target lesion revascularization and target vessel revascularization. Random-effects model was used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). A total of 10 randomized controlled trials comprising 6,368 patients with 3,452 in the IVI group and 2,916 in the angiography group were included. The mean duration of follow up was 2 years, mean age was 65 years and 73% of patients were men. As compared with PCI with routine angiography, the IVI-guided PCI group had significantly lower risks of major adverse cardiovascular events (RR 0.65, 95% CI 0.56 to 0.75, p <0.00001), stent thrombosis (RR 0.57, 95% CI 0.36 to 0.92, p = 0.02), cardiovascular deaths (RR 0.46, 95% CI 0.31 to 0.68, p = 0.0001), target lesion revascularization (RR 0.61, 95% CI 0.48 to 0.78, p <0.0001) and target vessel revascularization (RR 0.62, 95% CI 0.48 to 0.80, p = 0.0003). All-cause deaths and MI were similar in the 2 groups. In conclusion, among patients who underwent complex PCI, IVI reduces adverse events, importantly stent thrombosis and repeat revascularizations, compared with angiography alone guided PCI.

Effect of Furosemide Versus Torsemide on Hospitalizations and Mortality in Patients With Heart Failure: A Meta-Analysis of Randomized Controlled Trials.

Loop diuretics are essential in the treatment of patients with heart failure (HF) who develop congestion. Furosemide is the most commonly used diuretic; however, some randomized controlled trials (RCTs) have shown varying results associated with torsemide and furosemide in terms of hospitalizations and mortality. We performed an updated meta-analysis of currently available RCTs comparing furosemide and torsemide to see if there is any difference in clinical outcomes in patients treated with these loop diuretics. PubMed, MEDLINE, Cochrane, and Embase databases were searched for RCTs comparing the outcomes in patients with HF treated with furosemide versus torsemide. The primary end points included all-cause mortality, all-cause hospitalizations, cardiovascular-related hospitalizations, and HF-related hospitalizations. A random-effects meta-analysis was performed to estimate the risk ratio (RR) with a 95% confidence interval (CI). A total of 10 RCTs with 4,127 patients (2,088 in the furosemide group and 2,039 in the torsemide group) were included in this analysis. A total of 56% of the patients were men and the mean age was 68 years. No significant difference was noted in all-cause mortality between the furosemide and torsemide groups (RR 1.02, 95% CI 0.91 to 1.15, p = 0.70); however, patients treated with furosemide compared with torsemide had higher risks of cardiovascular hospitalizations (RR 1.36, 95% CI 1.13 to 1.65, p = 0.001), HF-related hospitalizations (RR 1.65, 95% CI 1.21 to 2.24, p = 0.001), and all-cause hospitalizations (RR 1.06, 95% CI 1.01 to 1.11, p = 0.02). In conclusion, patients with HF treated with torsemide have a reduced risk of hospitalizations compared with those treated with furosemide, without any difference in mortality. These data indicate that torsemide may be a better choice to treat patients with HF.

High Platelet Reactivity Combined with CYP2C19 Genotype in Predicting Outcomes in East Asian Patients Undergoing Percutaneous Coronary Intervention.

Loss-of-function (LoF) alleles of cytochrome P450 2C19 (CYP2C19), which are prevalent in East Asians, are linked to high platelet reactivity (HPR) phenotype and poor prognosis. We aimed to investigate the incremental predictive value of HPR combined with CYP2C19 genotype in predicting outcomes after drug-eluting stent (DES) implantation. The patients treated with platelet function and genotype-related long-term prognosis in drug-eluting stent (PTRG-DES) consortium enrolled a total of 13,160 Korean patients treated with DES who had platelet function test (PFT) or CYP2C19 genotype, of which, 6,717 patients with PFT and genotype together were categorized. HPR was defined as VerifyNow ≥ 252 P2Y12 reaction unit. The primary outcome was the incidence of major adverse cardiac and cerebrovascular event (MACCE) 5 years after treatment. The patients with both HPR and CYP2C19 LoF/LoF had the highest MACCE rates (6.2%) and increased MACCE risk (adjusted hazard ratio: 1.89, 95% confidence interval: 1.20-2.91, P = 0.006) compared with those without both HPR and CYP2C19 LoF/LoF. There was no effect of interaction between HPR and CYP2C19 genotype on the primary outcome (P = 0.424). Adding combined HPR and CYP2C19 genotype to the conventional model had an incremental influence in predicting MACCE and stent thrombosis. Compared to the model including HPR or CYP2C19 genotype alone, a combination model significantly improved the risk stratification for stent thrombosis but not MACCE. In DES-treated East Asian patients, the combined evaluation of PFT results and CYP2C19 genotyping might improve risk prediction of ischemic events during clopidogrel treatment.

Safety and Effectiveness of Adjunctive Posterior Wall Isolation in Atrial Fibrillation Patients: An Updated Meta-Analysis.

As the atrial fibrillation (AF) recurrence rate remains high after pulmonary vein isolation (PVI), additional left atrial posterior wall isolation (PWI) has been studied in randomized controlled trials, however, the results are conflicting. We performed an updated meta-analysis by searching online databases for the randomized controlled trials comparing the PWI + PVI group to the PVI alone group in patients with AF. The outcomes of interest were AF recurrence, all atrial arrhythmia recurrence, and atrial flutter/atrial tachycardia (AT) recurrence. Risk ratio (RR) with a 95% confidence interval (CI) was estimated using a random effects model. A total of 1,612 patients, with 807 in the PWI + PVI group and 805 in the PVI alone group were included. The mean age was 60 (9) years, 75% were men and 71% had persistent AF. The PWI + PVI group had lower AF recurrence as compared with the PVI alone group (25% vs 32%, RR 0.73, 95% CI 0.56 to 0.96, p = 0.02). There were no significant differences in all atrial arrhythmia recurrence (RR 0.90, 95% CI 0.78 to 1.04, p = 0.16), atrial flutter/AT recurrence (RR 1.19, 95% CI 0.92 to 1.55, p = 0.19) or adverse event rates in the 2 groups (36 vs 31; RR 1.09, 95% CI 0.67 to 1.77, p = 0.73). In conclusion, adjunctive PWI in addition to PVI can be achieved with lower AF recurrence but with a nonsignificant increase in atrial flutter/AT recurrence, resulting in an overall similar rate of all atrial arrhythmia recurrence without increasing the risk of adverse events, when compared with PVI alone strategy.

An evaluation of the AggreGuide A-100 ADP Assay for measuring the effect of antiplatelet agents targeting the P2Y12 receptor.

INTRODUCTION: Currently available platelet function assays largely ignore the important characteristics of in vivo thrombus generation, such as flow conditions and shear. The AggreGuide A-100 ADP Assay detects platelet aggregation in whole blood using light scattering under flow conditions. AREAS COVERED: In this review article, we discuss the limitations of currently available platelet function assays and the technology underlying the AggreGuide A-100 ADP assay. We also discuss the results of the validation assay study. EXPERT OPINION: By incorporating arterial flow conditions and shear, the AggreGuide assay may be more indicative of in vivo thrombus generation as compared to currently available platelet function assays. As per the United States, Food and Drug administration, the AggreGuide A-100 ADP test has been cleared to assess antiplatelet effects of prasugrel and ticagrelor. The assay results are comparable to widely used VerifyNow PRU assay. The utility of AggreGuide A100-ADP Assay in guiding P2Y12 receptor inhibitor therapy in patients with cardiovascular disease needs to be explored in clinical studies.

An update on novel therapies for treating patients with arterial thrombosis.

INTRODUCTION: Antithrombotic therapy field is undergoing rapid and significant changes during the past decade. In addition to new therapeutic strategies with existing targets, investigators are exploring the potential use of new targets to address unmet needs to treat patients with arterial diseases. AREAS COVERED: We aim to provide an update on and a comprehensive review of the antithrombic agents that are being explored in patients with arterial diseases. We discuss latest developments with respect to upstream antiplatelet agents, and collagen and thrombin pathway inhibitors. We searched PubMed databases for English language articles using keywords: antiplatelet agents, thrombin pathway inhibitors, collagen receptors, arterial disease. EXPERT OPINION: Despite implementation of potent P2Y12 inhibitors, there are numerous unmet needs in the treatment of arterial diseases including ceiling effect of currently available antiplatelet agents along with and an elevated risk of bleeding. The latter observations encouraged investigators to explore new targets that can attenuate the generation of platelet-fibrin clot formation and subsequent ischemic event occurrences with minimal effect on bleeding. These targets include collagen receptors on platelets and thrombin generation including FXa, FXIa, and FXIIa. In addition, investigators are studying novel antiplatelet agents/strategies to facilitate upstream therapy in high-risk patients.

Prognostic impact of hypercoagulability and impaired fibrinolysis in acute myocardial infarction.

AIMS: Atherothrombotic events are influenced by systemic hypercoagulability and fibrinolytic activity. The present study evaluated thrombogenicity indices and their prognostic implications according to disease acuity. METHODS AND RESULTS: From the consecutive patients undergoing percutaneous coronary intervention (PCI), those with thrombogenicity indices (n = 2705) were grouped according to disease acuity [acute myocardial infarction (AMI) vs. non-AMI]. Thrombogenicity indices were measured by thromboelastography (TEG). Blood samples for TEG were obtained immediately after insertion of the PCI sheath, and TEG tracing was performed within 4 h post-sampling. Major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) were evaluated for up to 4 years. Compared with non-AMI patients, AMI patients had higher platelet-fibrin clot strength [maximal amplitude (MA): 66.5 ± 7.8 vs. 65.3 ± 7.2 mm, P < 0.001] and lower fibrinolytic activity [clot lysis at 30 min (LY30): 0.9 ± 1.8% vs. 1.1 ± 1.9%, P < 0.001]. Index AMI presentation was associated with MA [per one-mm increase: odds ratio (OR): 1.024; 95% confidence interval (CI): 1.013-1.036; P < 0.001] and LY30 (per one% increase: OR: 0.934; 95% CI: 0.893-0.978; P = 0.004). The presence of high platelet-fibrin clot strength (MA ≥68 mm) and low fibrinolytic activity (LY30 < 0.2%) was synergistically associated with MACE occurrence. In the multivariable analysis, the combined phenotype of 'MA ≥ 68 mm' and 'LY30 < 0.2%' was a major predictor of post-PCI MACE in the AMI group [adjusted hazard ratio (HR): 1.744; 95% CI: 1.135-2.679; P = 0.011], but not in the non-AMI group (adjusted HR: 1.031; 95% CI: 0.499-2.129; P = 0.935). CONCLUSION: AMI occurrence is significantly associated with hypercoagulability and impaired fibrinolysis. Their combined phenotype increases the risk of post-PCI atherothrombotic event only in AMI patients. These observations may support individualized therapy that targets thrombogenicity for better outcomes in patients with AMI. CLINICAL TRIAL REGISTRATION: Gyeongsang National University Hospital (G-NUH) Registry, NCT04650529.