Journal of Cardiovascular Pharmacology and Therapeutics最新文献

{"title":"Antiplatelet Therapy and Bleeding Outcomes With CYP2C19 Genotyping.","authors":"James C Coons,&nbsp;James M Stevenson,&nbsp;Ami Patel,&nbsp;A J Conrad Smith,&nbsp;Linda Prebehalla,&nbsp;Philip E Empey","doi":"10.1177/10742484221143246","DOIUrl":"https://doi.org/10.1177/10742484221143246","url":null,"abstract":"<p><strong>Purpose: </strong>The impact of antiplatelet therapy with availability of CYP2C19 genotyping on bleeding in a real-world setting has not been extensively studied.</p><p><strong>Methods: </strong>Prospective, single-center, cohort study conducted between December 2015 and October 2019 with 1-year follow-up. Patients underwent percutaneous coronary intervention (PCI), CYP2C19 genotyping, and received P2Y12 inhibitor therapy. The primary outcome was time to first bleed of any severity using Bleeding Academic Research Consortium criteria. Secondary outcomes included time to first major bleed and rates of antiplatelet switching.</p><p><strong>Results: </strong>The primary outcome occurred in 697 of 2091 (33%) participants at a median of 15 days. Major bleeding occurred in 176 (8%) of patients. Compared to clopidogrel, treatment with ticagrelor or prasugrel was associated with increased risk of any bleeding (adjusted HR [aHR] 2.04, 95% CI 1.69-2.46). For patients without CYP2C19 no function alleles, treatment with prasugrel or ticagrelor was associated with increased risk of any bleeding (aHR 2.31, 95% CI 1.83-2.90). Similar associations were observed for major bleeding. No difference in ischemic events was observed. Among patients discharged on ticagrelor or prasugrel, 199 (36%) were de-escalated to clopidogrel within 1 year. De-escalation was more likely after a bleed if patients did not have a no function allele (35.9% vs 19.1%; <i>P</i> = .02).</p><p><strong>Conclusion: </strong>Bleeding is common in post-PCI patients on antiplatelet therapy. Patients on high potency agents had higher bleeding risk in the population at-large and in non-carriers of CYP2C19 no function alleles. Genotype-guided antiplatelet de-escalation should be further explored in prospective studies.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221143246"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10354586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 3 Randomized Controlled Trial to Evaluate Efficacy and Safety of New-Formulation Zenon (Rosuvastatin/Ezetimibe Fixed-Dose Combination) in Primary Hypercholesterolemia Inadequately Controlled by Statins.","authors":"Alberico L Catapano,&nbsp;Michal Vrablik,&nbsp;Yuri Karpov,&nbsp;Baptiste Berthou,&nbsp;Megan Loy,&nbsp;Marie Baccara-Dinet","doi":"10.1177/10742484221138284","DOIUrl":"https://doi.org/10.1177/10742484221138284","url":null,"abstract":"<p><strong>Objective: </strong>In primary hypercholesterolemia many people treated with statins do not reach their plasma LDL-C goals and are at increased risk of cardiovascular disease (CVD). This study aimed to evaluate efficacy and safety of a new fixed-dose combination (FDC) formulation of rosuvastatin/ezetimibe (R/E) in this population.</p><p><strong>Methods: </strong>This was a multicenter, multinational, randomized, double-blind, double-dummy, active-controlled, parallel-arm study of FDC R/E in people with primary hypercholesterolemia at very high risk (VHR) or high risk (HR) of CVD, inadequately controlled with 20 mg or 10 mg stable daily dose of rosuvastatin or equipotent dose of another statin. The primary objective was to demonstrate superiority of FDC R/E versus rosuvastatin monotherapy uptitrated to 40 mg (R40) or 20 mg (R20) in reduction of LDL-C after 6 weeks.</p><p><strong>Results: </strong>Randomized VHR participants (n = 244) were treated with R40, R40/E10, or R20/E10; randomized HR participants (n = 208) received R10/E10 or R20. In VHR participants, superiority of R40/E10 and R20/E10 versus R40 was demonstrated on LDL-C percent change from baseline to Week 6 with least squares mean differences (LSMD) of -19.66% (95% CI: -29.48% to -9.84%; <i>P</i> < .001) and -12.28% (95% CI: -22.12% to -2.44%; <i>P</i> = .015), respectively. In HR participants, superiority of R10/E10 over R20 was not demonstrated (LSMD -5.20%; 95% CI: -15.18% to 4.78%; <i>P</i> = .306), despite clinically relevant LDL-C reduction with R10/E10. No unexpected safety findings were reported.</p><p><strong>Conclusions: </strong>The results from this study suggest that R/E FDCs improve LDL-C reduction and goal achievement in people with primary hypercholesterolemia inadequately controlled with statins and at VHR/HR of CVD.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221138284"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10466359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis.","authors":"Jorge L Reyes,&nbsp;Charles A Herzog,&nbsp;Heng Yan,&nbsp;Nicholas S Roetker,&nbsp;James B Wetmore","doi":"10.1177/10742484221142220","DOIUrl":"https://doi.org/10.1177/10742484221142220","url":null,"abstract":"<p><strong>Background: </strong>The association of patient and prescriber characteristics with use of warfarin versus direct-acting oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is not well studied.</p><p><strong>Methods: </strong>The 20% Centers for Medicare & Medicaid Services Parts A, B, and D claims data from 2010 to 2017 were used to identify patients with stage 3, 4, or 5 CKD and AF who received a DOAC (apixaban, dabigatran, rivaroxaban) or warfarin. Prescribers were categorized as cardiologists, primary care providers (PCPs), and others. Using logistic regression, we estimated odds ratios (ORs) for the association of baseline characteristics and prescriber specialty with first use of a DOAC, relative to warfarin.</p><p><strong>Results: </strong>We identified 22,739 individuals with CKD who were newly initiated on oral anticoagulation for AF. New DOAC prescriptions increased from 490 in 2011 to 3261 in 2017, and displaced warfarin over time (1849, 2011; 945, 2017). By Q4 of 2014, cardiologists prescribed DOACs as initial treatment more frequently than warfarin, but non-cardiologists did not do so until 2015. As of 2017, apixaban was the most widely prescribed anticoagulant, comprising 56% and 50% of prescriptions by cardiologists and non-cardiologists, respectively. PCPs (OR 0.54, 0.51-0.58) and other providers (OR 0.55, 0.51-0.59) were less likely than cardiologists to prescribe DOACs.</p><p><strong>Conclusions: </strong>DOAC prescriptions, particularly apixaban, increased over time and gradually displaced warfarin. The total number of patients with AF and CKD receiving anticoagulation increased over time. Cardiologists increased DOAC prescriptions more rapidly than non-cardiologists.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"27 ","pages":"10742484221142220"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10479707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QT Prolongation in Critically Ill Patients With SARS-CoV-2 Infection.","authors":"Wasim S El Nekidy,&nbsp;Khalid Almuti,&nbsp;Hazem ElRefaei,&nbsp;Bassam Atallah,&nbsp;Lana M Mohammad,&nbsp;Wael AlMahmeed,&nbsp;Mohamed Badr,&nbsp;Khaled Abdallah,&nbsp;Fadi Hamed,&nbsp;Jihad Mallat","doi":"10.1177/10742484211069479","DOIUrl":"https://doi.org/10.1177/10742484211069479","url":null,"abstract":"<p><strong>Background: </strong>Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms).</p><p><strong>Results: </strong>Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], <i>P</i> < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], <i>P</i> = .04), and male gender (95% vs. 82.8%, <i>P</i> = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation (<i>P</i> = .004 for the likelihood-ratio test).</p><p><strong>Conclusion: </strong>The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":" ","pages":"10742484211069479"},"PeriodicalIF":2.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39803409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective and Vasoprotective Effects of Corticotropin-Releasing Hormone and Urocortins: Receptors and Signaling.","authors":"Sergey V Popov,&nbsp;Ekaterina S Prokudina,&nbsp;Alexander V Mukhomedzyanov,&nbsp;Natalia V Naryzhnaya,&nbsp;Huijie Ma,&nbsp;Jitka M Zurmanova,&nbsp;Peter F M van der Ven,&nbsp;Leonid N Maslov","doi":"10.1177/1074248420985301","DOIUrl":"https://doi.org/10.1177/1074248420985301","url":null,"abstract":"<p><p>Despite the recent progress in research and therapy, cardiovascular diseases are still the most common cause of death worldwide, thus new approaches are still needed. The aim of this review is to highlight the cardioprotective potential of urocortins and corticotropin-releasing hormone (CRH) and their signaling. It has been documented that urocortins and CRH reduce ischemic and reperfusion (I/R) injury, prevent reperfusion ventricular tachycardia and fibrillation, and improve cardiac contractility during reperfusion. Urocortin-induced increase in cardiac tolerance to I/R depends mainly on the activation of corticotropin-releasing hormone receptor-2 (CRHR2) and its downstream pathways including tyrosine kinase Src, protein kinase A and C (PKA, PKCε) and extracellular signal-regulated kinase (ERK1/2). It was discussed the possibility of the involvement of interleukin-6, Janus kinase-2 and signal transducer and activator of transcription 3 (STAT3) and microRNAs in the cardioprotective effect of urocortins. Additionally, phospholipase-A2 inhibition, mitochondrial permeability transition pore (MPT-pore) blockade and suppression of apoptosis are involved in urocortin-elicited cardioprotection. Chronic administration of urocortin-2 prevents the development of postinfarction cardiac remodeling. Urocortin possesses vasoprotective and vasodilator effect; the former is mediated by PKC activation and prevents an impairment of endothelium-dependent coronary vasodilation after I/R in the isolated heart, while the latter includes both cAMP and cGMP signaling and its downstream targets. As CRHR2 is expressed by both cardiomyocytes and vascular endothelial cells. Urocortins mediate both endothelium-dependent and -independent relaxation of coronary arteries.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"26 6","pages":"575-584"},"PeriodicalIF":2.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1074248420985301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39286851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Cholesterol Paradigm in the Risk Reduction for Atherosclerotic Cardiovascular Disease: Does the Mechanism of Action of Pharmacotherapy Matter for Clinical Outcomes?","authors":"Ruihai Zhou,&nbsp;George A Stouffer,&nbsp;Sidney C Smith","doi":"10.1177/10742484211023632","DOIUrl":"https://doi.org/10.1177/10742484211023632","url":null,"abstract":"<p><p>Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as \"bad\" cholesterol and high-density lipoprotein cholesterol (HDL-C) as \"good\" cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"26 6","pages":"533-549"},"PeriodicalIF":2.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/10742484211023632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39246501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Pyroptosis in Ischemic and Reperfusion Injury of the Heart.","authors":"Sergey V Popov,&nbsp;Leonid N Maslov,&nbsp;Natalia V Naryzhnaya,&nbsp;Alexandr V Mukhomezyanov,&nbsp;Andrey V Krylatov,&nbsp;Sergey Y Tsibulnikov,&nbsp;Vyacheslav V Ryabov,&nbsp;Michael V Cohen,&nbsp;James M Downey","doi":"10.1177/10742484211027405","DOIUrl":"https://doi.org/10.1177/10742484211027405","url":null,"abstract":"<p><p>While ischemia itself can kill heart muscle, much of the infarction after a transient period of coronary artery occlusion has been found to result from injury during reperfusion. Here we review the role of inflammation and possible pyroptosis in myocardial reperfusion injury. Current evidence suggests pyroptosis's contribution to infarction may be considerable. Pyroptosis occurs when inflammasomes activate caspases that in turn cleave off an N-terminal fragment of gasdermin D. This active fragment makes large pores in the cell membrane thus killing the cell. Inhibition of inflammation enhances cardiac tolerance to ischemia and reperfusion injury. Stimulation of the purinergic P2X7 receptor and the β-adrenergic receptor and activation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) by toll-like receptor (TLR) agonists are all known to contribute to ischemia/reperfusion (I/R) cardiac injury through inflammation, potentially by pyroptosis. In contrast, stimulation of the cannabinoid CB2 receptor reduces I/R cardiac injury and inhibits this pathway. MicroRNAs, Akt, the phosphate and tension homology deleted on chromosome 10 protein (PTEN), pyruvate dehydrogenase and sirtuin-1 reportedly modulate inflammation in cardiomyocytes during I/R. Cryopyrin and caspase-1/4 inhibitors are reported to increase cardiac tolerance to ischemic and reperfusion cardiac injury, presumably by suppressing inflammasome-dependent inflammation. The ambiguity surrounding the role of pyroptosis in reperfusion injury arises because caspase-1 also activates cytotoxic interleukins and proteolytically degrades a surprisingly large number of cytosolic enzymes in addition to activating gasdermin D.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"26 6","pages":"562-574"},"PeriodicalIF":2.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/10742484211027405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39186480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Oral Anticoagulants: A Delicate and Dynamic Balance.","authors":"Massimo Giordan","doi":"10.1177/10742484211037764","DOIUrl":"https://doi.org/10.1177/10742484211037764","url":null,"abstract":"I read with interest the article by Raccah et al, focusing on the impact of prescribing errors with direct oral anticoagulants (DOACs) on the risk of bleeding in patients with atrial fibrillation (AF). The prevalence of errors, consisting in either unjustified low dosage or inappropriate drugs combinations, with a consequent higher major bleeding risk, appears significantly high (33%), but not surprising, since adhering to clinical reality, as we similarly observe in our routine practice. We totally agree with the authors, who remark the importance of being aware of the potential negative impact of prescribing errors and regular follow-up. Moreover, a recent retrospective analysis conducted by Chaudhry et al, focusing on outcome of patients 80 years receiving low dose DOACs, evidenced in the low dose group a higher all-cause mortality rate, as long as higher rate of major bleeding, while the thromboembolic events were not significantly lower than the warfarin group. These results represent a mirror of clinical practice also in our daily experience. About these observations, I would like to stress some trends we commonly encounter with patients affected by AF taking DOACs, which we believe many of our colleagues will share:","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"26 6","pages":"739-740"},"PeriodicalIF":2.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/10742484211037764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39286850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Triple Therapy With Ticagrelor or Prasugrel Versus Clopidogrel After Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.","authors":"Kristina Gill,&nbsp;Nicholas Servati,&nbsp;Julie Flahive,&nbsp;Kyle Fraielli","doi":"10.1177/10742484211031436","DOIUrl":"https://doi.org/10.1177/10742484211031436","url":null,"abstract":"<p><strong>Background: </strong>Patients on dual antiplatelet therapy following percutaneous coronary intervention often have indications for concomitant oral anticoagulation, known as triple antithrombotic therapy. Majority of literature evaluating triple antithrombotic therapy fails to adequately represent patients with ST-elevation myocardial infarction and those prescribed potent P2Y12 inhibitors, ticagrelor or prasugrel. The purpose of this study was to evaluate the safety and efficacy of triple antithrombotic regimens containing ticagrelor or prasugrel versus clopidogrel after percutaneous coronary intervention in the setting of ST-elevation myocardial infarction.</p><p><strong>Methods: </strong>This was a single-center, retrospective cohort trial. The primary endpoint was net adverse clinical event, defined as the primary efficacy endpoint of death, myocardial infarction, or cerebrovascular accident and the primary safety endpoint of any bleeding event.</p><p><strong>Results: </strong>Between October 2017 and October 2019, a total of 65 patients with ST-elevation myocardial infarction were initiated on triple therapy. Forty-six patients were included in the primary analysis, of which 26 were discharged on triple antithrombotic therapy with clopidogrel and 20 discharged on potent P2Y12 inhibitors (ticagrelor or prasugrel). The primary endpoint occurred in 27% of the clopidogrel group and 40% of the potent P2Y12 inhibitor group (<i>P</i> = 0.35). Bleeding occurred in 23% of the clopidogrel group and 35% of the potent P2Y12 inhibitor group (<i>P</i> = 0.37).</p><p><strong>Conclusions: </strong>This small cohort study suggests, in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention, the net adverse clinical event rate does not differ between clopidogrel and potent P2Y12 inhibitors in the setting of triple antithrombotic therapy. The results of this exploratory analysis warrant confirmation in a larger, randomized study.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"26 6","pages":"625-629"},"PeriodicalIF":2.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/10742484211031436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39164179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitric Oxide-cGMP Pathway Modulation in an Experimental Model of Hypoxic Pulmonary Hypertension.","authors":"Melanie Reinero,&nbsp;Maurice Beghetti,&nbsp;Piergiorgio Tozzi,&nbsp;Ludwig K von Segesser,&nbsp;Michele Samaja,&nbsp;Giuseppina Milano","doi":"10.1177/10742484211014162","DOIUrl":"https://doi.org/10.1177/10742484211014162","url":null,"abstract":"<p><p>Manipulation of nitric oxide (NO) may enable control of progression and treatment of pulmonary hypertension (PH). Several approaches may modulate the NO-cGMP pathway in vivo. Here, we investigate the effectiveness of 3 modulatory sites: (i) the amount of l-arginine; (ii) the size of plasma NO stores that stimulate soluble guanylate cyclase; (iii) the conversion of cGMP into inactive 5'-GMP, with respect to hypoxia, to test the effectiveness of the treatments with respect to hypoxia-induced PH. Male rats (n = 80; 10/group) maintained in normoxic (21% O₂) or hypoxic chambers (10% O₂) for 14 days were subdivided in 4 sub-groups: placebo, l-arginine (20 mg/ml), the NO donor molsidomine (15 mg/kg in drinking water), and phoshodiesterase-5 inhibitor sildenafil (1.4 mg/kg in 0.3 ml saline, i.p.). Hypoxia depressed homeostasis and increased erythropoiesis, heart and right ventricle hypertrophy, myocardial fibrosis and apoptosis inducing pulmonary remodeling. Stimulating anyone of the 3 mechanisms that enhance the NO-cGMP pathway helped rescuing the functional and morphological changes in the cardiopulmonary system leading to improvement, sometimes normalization, of the pressures. None of the treatments affected the observed parameters in normoxia. Thus, the 3 modulatory sites are essentially similar in enhancing the NO-cGMP pathway, thereby attenuating the hypoxia-related effects that lead to pulmonary hypertension.</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"26 6","pages":"665-676"},"PeriodicalIF":2.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/10742484211014162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38966702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}