Эпизоды
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Contemporary Use of β-Blockers in Heart Failure Patients With and Without Atrial Fibrillation: A NationwideDatabase Analysis
Clin Pharmacol Ther. 2024 Nov 18. doi: 10.1002/cpt.3496.
Abstract
Evidence of the effectiveness of β-blockers in heart failure (HF) and atrial fibrillation (AF) in a contemporary cohort is controversial. This study investigated the association between the use of β-blockers and prognosis in hospitalized heart failure patients with and without atrial fibrillation in Japan. Patients hospitalized with the first episode of acute heart failure were identified from the National Database of Health Insurance Claims and Specific Health Checkupsof Japan between April 2014 and March 2021. Associations of β-blocker use and prognosis were compared by propensity score matching among the atrial fibrillation or non- atrial fibrillation group. A mixed-effects survival modelwas used, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Among 428,650 patients discharged with Heart Failure in 4,433 hospitals, 175,174 (40.9%) were ≥ 85 years old, 151,873 (35.4%) hadcomplicated atrial fibrillation, and 236 ,457 (55.2%) were β-blocker users. In a matched atrial fibrillation group, β-blocker use was associated with a lower composite outcome of all-cause mortality or HF rehospitalization (HR [95% CI], 0.95 [0.93-0.97]). A similar result was obtained in a matched non- atrial fibrillation group (0.95 [0.94-0.96]). Inaddition, the hazard ratios in patients aged ≥ 85 years and female patients were 1.00 [0.98-1.02] and 1.01 [0.98-1.03]in the atrial fibrillation group and 1.03 [1.01-1.05] and 0.98 [0.97-1.00] in the non- atrial fibrillation group, respectively. The favorable prognostic associations of β-blocker usewere observed regardless of atrial fibrillation in patients across a broad spectrum of heart failure in a superaged society.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Guideline-directed medical therapy improves cell viability in an iPSC-derived cardiomyocyte hypoxia injury model
https://doi.org/10.1161/circ.150.suppl_1.4147229
Abstract
Introduction: Beta blockers, renin-angiotensin-aldosterone antagonists, and mineralocorticoid antagonists are mainstays of current guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction. Theyhave been shown to reduce morbidity and mortality in heart failure patients, reverse remodeling, and improve left ventricular ejection fraction (LVEF) in landmark human clinical trials. Guideline-directed medical therapy has beenhypothesized to interact and have protective effects in bioenergetics in cardiac injury by reducing cardiac workload and energy demand. We have previously used a human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCM) injury model to provide an in vitro validation of bioenergetics through measurement of cell viability and proliferation, intracellular measurement of ATP, contractility, and respiratory function. The application of guideline-directed medical therapy in this in vitro model hasnot been previously assessed.
Methods: Highly pure cardiomyocytes were differentiated from a healthy, human monoclonal induced pluripotent stem cell line using CHIR99021 followed by C59 to modulate Wnt pathway activity. Upon spontaneous contractility, cardiomyocytes were replated for purification. Prior to hypoxia exposure, cardiomyocytes were treated with either 5uM metoprolol, 5uM losartan, 5uM spironolactone, or acontrol for 24 hours. To mimic in vivo ischemia, cardiomyocytes are placed in a glucose deprived media (GDM) in a hypoxia inductor chamber with <1% oxygen-containing mixed gas in a 37°C incubator for 18 hours. A second cardiomyocytes group is similarly treated in GDM for 18 hours in a normoxic setting. Cell viability and proliferation was then studied using MTT assay.
Results: The metoprolol, losartan, and spironolactone treatment groups significantly improved cell viability after hypoxic injury when compared to the control treatment groups. Metoprolol treatment had the highest cell viabilityafter hypoxic injury (46%), followed by spironolactone (23%) and losartan (22%), compared to control (13%). In the normoxic group, metoprolol, losartan, and spironolactone treatment showed no significant difference in viabilitycompared to the control group.
Conclusion:iPSC-derived iCMs treated with guideline-directed medical therapy improved cell viability after hypoxic injury. The iPSC hypoxia-injury model appears to be a promising in vitro platform for studying the effects of guideline-directedmedical therapy on cellular bioenergetics.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Пропущенные эпизоды?
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Exploring The Risks And Benefits ofUpstream Loading of P2Y12 inhibitors In Acute Coronary Syndrome Patients
https://doi.org/10.1161/circ.150.suppl_1.4139561
Abstract
Background: Acute coronary syndrome (ACS) is theleading cause of heart disease, resulting in over 300,000 deaths annually. The 2014 ACC/AHA guideline recommends a loading dose of a P2Y12 receptor inhibitorprior to PCI with stenting (Class IA).
Objective: This study aims to evaluate therisks and benefits of upstream loading of P2Y12 inhibitors in Acute coronary syndrome patients.
Methodology: We retrospectively analyzed thecharts of all Acute coronary syndrome patients over 18 years old admitted to our community hospital in Michigan from August 2022 to July 2023. Exclusion criteria included patients with type II NSTEMI, hypersensitivity to P2Y12 inhibitors, active bleeding, hemoglobin levels less than 7 g/dl, those already on P2Y12 inhibitors, and pregnant patients.
Results: Out of 518 patients reviewed, 399 were included in the study. Among 285 NSTEMI patients, 89.5% were not loaded with P2Y12 inhibitors in the ED, while 10.5% were. In the loaded group, 3% underwent CABG, 90% required PCI, and 6% received medical treatment. In the non-loadedgroup, 12.5% underwent CABG, one patient had an aortic dissection, and 53.8% and 33.7% required PCI and medical treatment, respectively. Among 114 STEMI patients, 74.5% were not loaded with P2Y12 inhibitors in the ED, while 25.5% were. In the loaded group, 100% required PCI. In the non-loaded group, 8.2% underwent CABG, and 92% requiredPCI.
Conclusion: Our real-world data from a communityhospital indicate that most Acute coronary syndrome patients benefit from P2Y12 loading, with only a minority experiencing adverse effects. To address this, weplan to collaborate with our information technology department to implement reminders for ED physicians to consult with cardiologists about P2Y12 inhibitorloading in Acute coronary syndrome patients.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Ticagrelor monotherapy the wayforward after Percutaneous Coronary Interventions: An updated meta-analysis
https://doi.org/10.1161/circ.150.suppl_1.4124335
Abstract
Background: With the advent of newer generation drug eluting stents, the chorus for shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary interventions (PCI) is getting louder and louder.Ticagrelor monotherapy after a short course of dual antiplatelet therapy has been studied in a few randomized controlled trials with promising results. Weconducted a systematic review and meta-analysis comparing the ticagrelor monotherapy with dual antiplatelet therapy after short duration dual antiplatelet therapy in patients undergoing percutaneous coronaryinterventions.
Methods: PubMed, Embase and Cochrane databases were searched for Randomized Control Trials comparing ticagrelor monotherapy to dual antiplatelet therapy after percutaneous coronary interventions and reported the outcomes of Major Adverse Cardiac Events including death, myocardial infarction or stroke (MACE); Major AdverseCardiac and Cerebrovascular Events including death, myocardial infarction, stroke, stent thrombosis or target vessel revascularization (MACCE); Major bleeding; Death from any cause; CV death; Stent thrombosis and Target vessel revascularization (TVR). Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Statistical analysis wasperformed using Review Manager Web (Cochrane Collaboration). Heterogeneity was examined with I2test.
Results: Out of 3208 database results, 5 Randomized Control Trials with 32,393 patients were included; 16,188 (50%) received Ticagrelor monotherapy. Studieshad mean follow-up ranging from 12 months to 24 months. Baseline characteristics are as per Table 1. Safety endpoints of major bleeding (HR 0.50; 95% CI 0.38-0.66; p < 0.0001; I2= 23 %; Figure 1A), was significantly less with ticagrelor monotherapy. Efficacy endpoints of MACE ,MACCE, Death from any cause, CV Death, target vessel revascularization (TVR) and stent thrombosis were not significantly different between ticagrelor and dual antiplatelettherapy (Figure 1 and 2).
Conclusion:Ticagrelor monotherapy reduces major bleeding as compared to continued dual antiplatelet therapy for 12 months after percutaneous coronary interventions.Major ischemic outcomes were similar in both groups. Ticagrelor monotherapy may be the way forward after short duration of dual antiplatelet therapy in patients undergoing percutaneous coronary interventions.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Position of Beta-blockers in the Treatment of Hypertension Today: An Indian Consensus
J Assoc Physicians India . 2024 Oct;72(10):83-90. doi:10.59556/japi.72.0715.
Abstract
Background: Management of essential hypertension(HTN) remains challenging, with contemporary control being achieved in <1/10 of the cases, especially when aligned with the recently updated guidelines ofAmerican College of Cardiology (ACC) or International Society of Hypertension (ISH). The place and positioning of beta-blockers have been evolving, withrecent focused updates, such as the European Society of Hypertension (ESH) 2023 guidelines, that may hold relevance for the Indian phenotypic traits of prematurecardiovascular disease (CVD), fragile coronary architecture, and/or high resting heart rate. To further develop consensus on the clinical role andrelevance of beta-blockers, including nebivolol, an Indian consensus was evolved with graded recommendations on their clinical role in hypertension,hypertension with additional cardiovascular (CV) risk, or type 2 diabetes mellitus (T2DM).
Methodology: An expert review panel was constituted,comprising interventional and clinical cardiologists as experts, to synthesize the literature for the development of a validated knowledge, attitude, and practice (KAP) survey questionnaire. Research databases, including Cochrane Systematic Reviews, PubMed, and Google Scholar, were accessed for contemporaryinformation and guidelines on beta-blockers updated until Dec 2023. Delphi rounds were conducted to develop graded recommendations based on the strength, quality of evidence, and the agreement among the panelists (n = 9). Consensus was achieved on the graded recommendations, with ≥70% of national panelists in agreement.
Results: Ninety-six percent of respondents opinedthat the new European Society of Hypertension guidelines (2023) help gain confidence in using beta-blockers, which are considered first-line drugs forthe treatment of Hypertension. Beta-blockers, including nebivolol, can be recommended in patients with Hypertension with high resting heart rates,including young hypertensive patients under 40 years of age. For people under 60 years old with Hypertension, regardless of whether they have comorbiddiseases, beta-blockers are the recommended drug choice. Ninety-five percent of respondents opined that nebivolol is the preferred beta-blocker in hypertensivepatients with T2DM, followed by bisoprolol and metoprolol. More than 90% of respondents opined that the three most commonly preferred beta-blockers byexperts in patients with angina were nebivolol, metoprolol, and bisoprolol.
Conclusion: Beta-blockers, including metoprolol and nebivolol, can be considered initial-line therapy for Hypertension management in real-lifesettings in India and nebivolol is preferred because of its two important properties: highest beta-1 selectivity and endothelial-dependent vasodilation.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Short-Term Dual Antiplatelet TherapyAfter Drug-Eluting Stenting in Patients With Acute Coronary Syndromes. A Systematic Review and Network Meta-Analysis
JAMA Cardiol. Published online October 9, 2024.doi:10.1001/jamacardio.2024.3216
Abstract
Importance : The optimal duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) remains under debate.
Objectives: To analyze the efficacy and safety of dual antiplatelet therapy strategies in patients with acute coronary syndromes using a bayesian network meta-analysis.
Data Sources : MEDLINE, Embase, Cochrane, and LILACS databases were searched from inception to April 8, 2024.
Study Selection : Randomized clinical trials (RCTs) comparing dual antiplatelet therapy duration strategiesin patients with acute coronary syndromes undergoing percutaneous coronary intervention were selected. Short-term strategies (1 month of DAPT followed byP2Y12 inhibitors, 3 months of dual antiplatelet therapy followed by P2Y12 inhibitors, 3 months of DAPT followed by aspirin, and 6 months of dual antiplatelet therapy followed by aspirin) were compared with conventional 12 months of dual antiplatelet therapy.
Data Extraction and Synthesis: This systematic reviewand network meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The risk ratio (RR) with a 95% credible interval (CrI) was calculated within a bayesian random-effects network meta-analysis. Treatments were ranked using surface under the cumulative ranking (SUCRA).
Main Outcomes and Measures : The primary efficacy end point was major adverse cardiac and cerebrovascular events (MACCE); the primary safety end point was major bleeding.
Results: A total of 15 RCTs randomizing 35 ,326 patients (mean [SD] age, 63.1 [11.1] years; 26 ,954 male [76.3%]; 11 ,339 STEMI [32.1%]) withacute coronary syndromes were included. A total of 24, 797 patients (70.2%)received potent P2Y12 inhibitors (ticagrelor or prasugrel). Compared with 12 months of dual antiplatelet therapy, 1 month of dual antiplatelet therapyfollowed by P2Y12 inhibitors reduced major bleeding (RR, 0.47; 95% CrI, 0.26-0.74) with no difference in major adverse cardiac and cerebrovascular events (RR, 1.00; 95% CrI, 0.70-1.41). No significant differences were observed in major adverse cardiac andcerebrovascular events incidence between strategies, although CrIs were wide. SUCRA ranked 1 month of dual antiplatelet therapy followed by P2Y12 inhibitors as the best for reducing major bleeding and 3 months of dual antiplatelet therapy followed by P2Y12 inhibitors as optimal for reducing major adverse cardiac andcerebrovascular events (RR, 0.85; 95% CrI, 0.56-1.21).
Conclusion and Relevance: Results of this systematic review and network meta-analysis reveal that, in patients with acute coronary syndromes undergoing percutaneous coronary intervention with DES, 1 month of dual antiplatelet therapy followed by potent P2Y12 inhibitor monotherapy was associated with a reduction in major bleeding without increasing major adverse cardiac and cerebrovascular events when compared with 12 months of dual antiplatelet therapy. However, anincreased risk of major adverse cardiac and cerebrovascular events cannot be excluded, and 3 months of dual antiplatelet therapy followed by potent P2Y12 inhibitor monotherapy was ranked as the best option to reduce major adverse cardiac and cerebrovascular events. Because most patients receiving P2Y12 inhibitor monotherapy were taking ticagrelor, the safety of stopping aspirin in those taking clopidogrel remains unclear.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Antihypertensive therapy in patients with arterial hypertension and concomitant diseases in real clinical practice (according to the National Registry of Arterial Hypertension, 2019–2022)
https://doi.org/10.26442/00403660.2024.09.202848
Abstract
Background. Arterial hypertension remains theleading risk factor associated with cardiovascular diseases (CVDs), cerebrovascular disease and chronic kidney disease. About 70% of patients with Arterialhypertension who are on monotherapy cannot achieve blood pressure (BP) targets, and therefore all guidelines for the management of Arterial hypertension haverecently recommended prescribing combination therapy (PCT). In real clinical practice (RCP), there remains significant uncertainty in the effectiveness andrationality of therapy, despite the wide availability of antihypertensive drugs (AHD) and the presence of recommendations for a stepwise approach toprescribing combinations of specific groups of antihypertensive drugs in different clinical situations.
Aim. Analyze the real ongoing antihypertensivetherapy, including the prescribing combination therapy; international nonproprietary names of drugs and their dosages in real clinical practice; compliance of therapy with clinical recommendations; changing trends in the prescribing combination therapy.
Materials and methods. An analysis was carried out ofthe data from the register of Arterial hypertension, the compliance of treatment in different clinical groups of patients and the achievement of BP and low-density lipoprotein cholesterol targets in the sample of 2019–2022 (n=5012). The prescription of antihypertensive drugs and achievement of targets values wereassessed in accordance with current clinical guidelines for the management of Arterial hypertension and hypercholesterolemia. Data from 2010 (n=7782) and 2020 (n=3061) were analyzed to assess the dynamics of prescription of monotherapy and prescribing combination therapy.
Results. The greatest increase in the number of antihypertensive drugs was observed in patients withhypertension in combination with coronary heart disease, heart failure, and atrial fibrillation. In a small group of patients with hypertension withoutother cardiovascular diseases, the recommended combinations of antihypertensive drugs were not prescribed; preference was given to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-Adreno blocker (β-AB). Prescribing combination therapy mainly differed from therecommended combinations by the wider use of drugs from the β-AB group. The prescribing combination therapy of recommended drugs was highest in patients with hypertension and coronary artery disease – more than 90%, hypertension and heart failure in 56.2%, hypertension and atrial fibrillation – 33.3%,hypertension and chronic kidney disease – 19.6%. Achievement of BP and low-density lipoprotein cholesterol targets was insufficient in all analyzed groups. Among the international nonproprietary names of drugs, the mostfrequently prescribed are the following:, metoprolol, bisoprolol, lisinopril, perindopril, losartan, spironolactone, amlodipine, torasemide, indapamide,hypochlorothiazide, moxonidine. The prescribed daily dosages were closer to the initial recommended ones. By 2020, the prescription of PCT with β-AB and a moreuniform prescription of various combinations will come to the fore, while PCT in 2010 is characterized by the presence of one or two leaders combinations.
Conclusion. The described features of prescribing antihypertensive drugs partially reproduce clinical recommendations for the management of Arterialhypertension. Differences in therapy provided in real clinical practice may be associated with an attempt to intensify the treatment of hypertension inpatients with other concomitant CVDs. At the same time, analysis of combinations and dosages of prescribed drugs suggests the presence of wideopportunities for further escalation of therapy. The presented data can provide insight into current patterns of antihypertensive therapy prescription in patients in real clinical practice and lay the foundation for optimizing therapy in different categories hypertensive patients.
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Role of ticagrelor in the peri-thrombolytic phase for patients with ST-segment elevation myocardialinfarction: a comprehensive review
Thromb J . 2024 Oct 11;22(1):90. doi: 10.1186/s12959-024-00658-9
Abstract
Recent years have seen ticagrelor, a potent P2Y12 inhibitor, emerge as a significant advancement in the peri-thrombolytic management of patients with ST-segment elevation myocardial infarction (STEMI), offering a promising alternative to traditional antiplatelet drugs like clopidogrel. This review critically examines the efficacy and safety of ticagrelor during theperi-thrombolytic phase in ST-segment elevation myocardial infarction patients, drawing on evidence from key clinical trials such as TREAT and MIRTOS, as well as other relevant studies. These investigations underscore ticagrelor's superior platelet inhibitioncapabilities, which are crucial for minimizing thrombotic complications post-thrombolysis without increasing bleeding risks. Despite its potential, clopidogrel remains the guideline-recommended choice for such patients, leaving the appropriateness of ticagrelor in this context open to debate. By summarizing the current evidence and identifying gaps in our understanding, this study advocates for targeted research to clarify the long-term benefits and optimal deployment of ticagrelor, highlighting its evolving significance in cardiovascular care.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Pulmonary Vein Isolation vs Sham Intervention in Symptomatic Atrial Fibrillation: The SHAM-PVI Randomized Clinical Trial
JAMA 2024 Sep 2:e2417921. doi: 10.1001/jama.2024.17921
Abstract
Importance: There are concerns that pulmonary vein isolation for atrial fibrillation may have a profound placebo effect, but no double-blind randomized clinical trials have been conducted.
Objective: To determine whether pulmonary vein isolation is more effective than a sham procedure for improving outcomes in atrial fibrillation.
Design, setting, and participants:Double-blind randomized clinical trial conducted at 2 tertiary centers in the UK between January 2020 and March 2024 among patients with symptomaticparoxysmal or persistent atrial fibrillation. Major exclusion criteria included long-standing persistent atrial fibrillation, prior left atrium ablation, otherarrhythmias requiring ablative therapy, a left atrium of 5.5 cm or larger, and ejection fraction of less than 35%.
Intervention: Participants were randomly assigned to receive pulmonary vein isolation with cryoablation (n = 64) or a sham procedure with phrenic nerve pacing (n = 62).
Main outcomes and measures: The primary end point was atrial fibrillation burden at 6 months, excluding a3-month blanking period. Secondary outcomes included quality-of-life measures, time to events, and safety. Atrial fibrillation burden was measured by an implantable loop recorder.
Results: A total of 126 participants were randomized (mean age, 66.8 years; 89 men [70.63%]; 20.63% with paroxysmal atrial fibrillation). The absolute mean atrial fibrillation burden change from baseline to 6 monthswas 60.31% in the ablation group and 35.0% in the sham group (geometric mean difference, 0.25; 95% CI, 0.15-0.42; P < .001). The estimated difference in theoverall Atrial Fibrillation Effect on Quality of Life score at 6 months, favoring catheter ablation, was 18.39 points (95% CI, 11.48-25.30 points). The Short Form 36general health score also improved substantially more with ablation, with an estimated difference of 9.27 points at 6 months (95% CI, 3.78-14.76 points).
Conclusions and relevance: Pulmonary vein isolation resulted in a statistically significant and clinically important decrease in atrial fibrillation burden at 6 months, with substantial improvements in symptoms and quality of life, compared with a sham procedure.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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2024 European Society of Cardiology Guidelines for Management of Chronic Coronary Syndromes: Key Points
European Heart Journal, ehae177, https://doi.org/10.1093/eurheartj/ehae177
The key points to remember from the 2024European Society of Cardiology (ESC) guidelines for the management of chronic coronary syndromes (CCS) are:
· The term chronic coronary syndromes describesthe clinical presentations of coronary artery disease (CAD) during stable periods, particularly those preceding or following an acute coronary syndrome (ACS). Of note, symptoms of myocardial ischemia due to obstructiveatherosclerotic CAD overlap with those of coronary microvascular disease or vasospasm. Characterization of endotypes is important to guide appropriate medical therapy for angina with nonobstructive coronary arteries(ANOCA)/ischemia with nonobstructive coronary arteries (INOCA) patients.
· Managing individuals with suspected CCS involvesfour steps:
The first step is a general clinical evaluation that focuses on assessing symptoms and signs of chroniccoronary syndromes, differentiating noncardiac causes of chest pain and ruling out acute coronary syndrome. This initial clinical evaluation requires recording a 12-lead resting electrocardiogram, basic blood tests, and inselected individuals, chest X-ray imaging and pulmonary function testing. This evaluation can be done by the general practitioner. The second step is a furthercardiac examination, including echocardiography at rest to rule out left ventricular (LV) dysfunction and valvular heart disease. After that, it is recommended to estimate the clinical likelihood of obstructive CAD to guidedeferral or referral to further noninvasive and invasive testing. The third step involves diagnostictesting to establish the diagnosis of CCS and determine the patient’s risk of future events. The final step includes lifestyle and risk factor modification combined with disease-modifying medications. A combination of antianginal medications is frequently needed, and coronary revascularization is considered if symptoms are refractory to medical treatment or if high-risk CAD is present. If symptoms persist after obstructive CAD is ruled out, coronary microvascular disease and vasospasm should be considered.
· The inclusion of risk factors to classic pretestlikelihood models of obstructive atherosclerotic CAD improves the identification of patients with very low (≤5 %) pretest likelihood of obstructive CAD in whom deferral of diagnostic testing should be considered.
· First-line diagnostic testing of suspected CCSshould be done by noninvasive anatomic or functional imaging. Selection of the initial noninvasive diagnostic test should be based on the pretest likelihoodof obstructive CAD, other patient characteristics that influence the performance of noninvasive tests, and local expertise and availability.
· Coronary computed tomography angiography (CCTA)is preferred to rule out obstructive CAD and detect nonobstructive CAD. Functional imaging is preferred to correlate symptoms to myocardial ischemia, estimate myocardial viability, and guide decisions on coronary revascularization. Positron emission tomography is preferred for absolute myocardial blood flow measurements, but cardiac magnetic resonance perfusion studies may offer an alternative. Selective second-line cardiac imaging with functional testing in patients with abnormal CCTA and CCTA after abnormalfunctional testing may improve patient selection for invasive coronary angiography (ICA).
· Invasive coronary angiography is recommended todiagnose obstructive CAD in individuals with a very high pre- or post-test likelihood of disease, severe symptoms refractory to guideline-directed medical therapy (GDMT), angina at a low level of exercise, and/or high event risk. When ICA is indicated, it is recommended to evaluate the functional severity of ‘intermediate’ stenoses by invasive functional testing (fractional flow reserve, instantaneous wave-free ratioi) before revascularization.
· A single antiplatelet agent, aspirin or clopidogrel, is generally recommended long term in CCS patients withobstructive atherosclerotic CAD. For high-thrombotic-risk CCS patients, long-term therapy with two antithrombotic agents is reasonable, as long asbleeding risk is not high.
· Among CCS patients with normal LV function andno significant left main or proximal left anterior descending lesions, current evidence indicates that myocardial revascularization over GDMT alone does notprolong overall survival.
· Among patients with complex multivessel CADwithout left main CAD, particularly in the presence of diabetes, who are clinically and anatomically suitable for both revascularization modalities, current evidence indicates longer overall survival after coronary artery bypass grafting than percutaneous coronary intervention.
· Lifestyle and risk factor modification combinedwith disease-modifying and antianginal medications are cornerstones in the management of CCS. Furthermore, shared decision making between patients and health care professionals, based on patient-centered care, is paramount in defining the appropriate therapeutic pathway for CCS patients. Patient education is key to improve risk factor control in the long term.
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2024 European Society of Cardiology Guidelines for Management of Elevated BP and Hypertension: Key Points
European Heart Journal, ehae178, https://doi.org/10.1093/eurheartj/ehae178
The key points to remember from the 2024European Society of Cardiology (ESC) guidelines for the management of elevated blood pressure (BP) and hypertension are:
· The most important point is that the targetsystolic BP (SBP) for adults receiving BP medications should be 120-129 mm Hg. One can “opt-out” of this goal for patients who cannot tolerate that level ofBP, patients who have orthostatic symptoms, patients who are over 85 years old or have frailty, or patients with limited life expectancy. For those patients, the goal is as low a pressure toward that goal as can be achieved.
· Blood Pressure is defined as having a continued risk rooted in time of exposure to higher Blood Pressure. For this reason, hypertension is defined as an systolic BP (SBP) >140 mm Hg or diastolic BP (DBP) >90 mm Hg, but a new category of “elevated BP” has been introduced that is an office systolic BP of 120-139 mm Hg or diastolic BP 70-89 mm Hg. This guideline recognizes that risk increases across this scale, rather than starts at a certain level that is defined as “hypertension.” This category of “elevated BP” reminds us of the term “prehypertension” used in JNC-7 (Seventh Report ofthe Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure).
· The guideline focuses on true risk reductionrelated to fatal and nonfatal cardiovascular outcomes. The longstanding tendency of using the surrogate marker of Blood Pressure alone does not supporta Class I indication in this guideline, except for lifestyle and low-risk nondrug interventions.
· Out-of-office BP is recommended for diagnosticpurposes as it can detect white-coat and masked hypertension. Office measurements can be used when out-of-office readings are not obtainable.
· Lifestyle interventions are recommended for 3months. If not fully successful, then drug therapy should be started.
· In pregnant women without contraindications andin consultation with an obstetrician, low- to moderate-intensity exercise can reduce the risk of gestational hypertension and pre-eclampsia and should beconsidered.
· A risk-based approach to hypertension treatmentis recommended, noting that those with diabetes, kidney disease, cardiovascular disease, target organ damage, and diabetes of familial hypercholesterolemia areat increased risk for cardiovascular disease. More time and resources should be devoted to patients at higher overall risk from elevated BP.
· Screening for secondary hypertension is recommended for adults diagnosed with hypertension before the age of 40 years, except for obese young adults for whom screening for sleep apnea should be a first step.
· Self-measurement of BP is recognized to improvepatient empowerment and adherence to treatment.
· It is recognized that the major weakness ofclinical hypertension guidelines is poor implementation. The document includes sections on how to overcome barriers to implementation.
· In patients with atrial fibrillation, manual BPsshould be used, as most automated devices have not been validated for BP measurement in patients with atrial fibrillation.
· The guidelines include sex and gender throughoutthe document. It defines sex as a biological condition of being male or female from conception, based on genes. Gender is a sociocultural dimension of being aman or a woman in a society based on gender roles and norms.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation
DOI: 10.1056/NEJMoa2314328
Background
Whether transcatheter mitral-valve repairimproves outcomes in patients with heart failure and functional mitral regurgitation is uncertain.
Methods
We conducted a randomized, controlled trialinvolving patients with heart failure and moderate to severe functional mitral regurgitation from 30 sites in nine countries. The patients were assigned in a1:1 ratio to either transcatheter mitral-valve repair and guideline-recommended medical therapy (device group) or medical therapy alone (control group). Thethree primary end points were the rate of the composite of first or recurrent hospitalization for heart failure or cardiovascular death during 24 months; therate of first or recurrent hospitalization for heart failure during 24 months; and the change from baseline to 12 months in the score on the Kansas CityCardiomyopathy Questionnaire–Overall Summary (KCCQ-OS; scores range from 0 to 100, with higher scores indicating better health status).
Results
A total of 505 patients underwent randomization: 250 were assigned to the device group and 255 to the control group. At 24 months, the rate of first or recurrent hospitalization for heart failure or cardiovascular death was 37.0 events per 100 patient-years in the device group and 58.9 events per 100 patient-years in the control group (rate ratio, 0.64; 95% confidence interval [CI], 0.48 to 0.85; P=0.002). The rate of first or recurrent hospitalization for heart failure was 26.9 events per 100 patient-years in the device group and 46.6 events per 100 patient-years in the control group (rate ratio, 0.59; 95% CI, 0.42to 0.82; P=0.002). The KCCQ-OS score increased by a mean (±SD) of 21.6±26.9 points in the device group and 8.0±24.5 points in the control group (mean difference, 10.9 points; 95% CI, 6.8 to 15.0; P<0.001). Device-specific safety events occurred in 4 patients (1.6%).
Conclusions
Among patients with heart failure with moderate to severe functional mitral regurgitation who received medical therapy, the addition of transcatheter mitral-valve repair led to a lower rate of first or recurrent hospitalization for heart failure or cardiovascular deathand a lower rate of first or recurrent hospitalization for heart failure at 24 months and better health status at 12 months than medical therapy alone.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Ticagrelor monotherapy in ST-elevation myocardial infarction: An individual patient-level meta-analysis from TICO and T-PASS trials
Med. 2024 Aug 10:S2666-6340(24)00301-5.doi: 10.1016/j.medj.2024.07.019.
Abstract
Background: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT).
Methods: Individual patient data were pooled from randomized clinical trials that included ST-elevation myocardial infarction STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) short-termdual antiplatelet therapy versus ticagrelor-based 12-month short-term dual antiplatelet therapy DAPT in terms of centrally adjudicated clinical outcomes. Theco-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding AcademicResearch Consortium type 3 or 5 bleeding) at 1 year.
Findings: The pooled cohort contained 2,253 patients with ST-elevation myocardial infarction. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based dual antiplatelet therapy group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%;HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups.
Conclusions: In patients with ST-elevationmyocardial infarction treated with drug-eluting stent implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients.
Disclaimer:
Lupin makes norepresentation or warranty of any kind, expressed or implied, regarding theaccuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. Youshould not allow the contents of this to substitute for your own medicaljudgment, which you should exercise in evaluating the information on thiswebsite.
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Efficacy and Safety of P2Y12 monotherapy vs DAPT in patients undergoing percutaneous coronary intervention: meta-analysis of randomized trials
Curr Probl Cardiol. 2024 Aug;49(8):102635. doi: 10.1016/j.cpcardiol.2024.102635
Abstract
Background: Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) afterpercutaneous coronary intervention (PCI) in coronary artery disease (CAD). Recent trials have introduced a novel approach involving P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel, after a short dual antiplatelet therapy (DAPT). However, the effectiveness and safety of this strategy remains to be established. We aimed to perform a meta-analysis comparing monotherapy with P2Y12 inhibitors versus standard dual antiplatelet therapy DAPT in patients undergoing percutaneous coronary intervention PCI at 12 months.
Methods: Multiple databases were searched. Six RCTs with a total of 24877 patients were included. The primary endpoint was all-cause mortality at 12 months of follow-up. The secondary endpoints were cardiovascular mortality, myocardial infarction, probable or definitestent thrombosis, stroke events, and major bleeding. The study is registered with PROSPERO (CRD42024499529).
Results: Monotherapy with P2Y12 inhibitor ticagrelor significantly reduced both all cause mortality (HR 0.71, 95 CI [0.55-0.91], P = 0.007) and cardiovascular mortality (HR 0.66, 95% CI [0.49-0.89], P = 0.006) compared to standard dual antiplatelet therapy DAPT. In contrast, clopidogrel monotherapy did not demonstrate a similar reduction. The decrease in mortality associated with ticagrelor was primarily due to a lower risk ofmajor bleeding (HR 0.56, 95% CI [0.43-0.72], P < 0.001), while the risk of myocardial infarction (MI) remained unchanged (HR 0.90, 95% CI [0.73-1.11], P = 0.32). The risk of stroke was found to be similar across treatments.
Conclusions: In comparison to standard dual antiplatelet therapy DAPT, P2Y12 inhibitor monotherapy with ticagrelor may lead to a reduced mortality. The clinical benefits are driven by a reduction of bleeding risk without ischemic risk trade-off.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Early postoperative beta-blockers are associated with improved cardiac output after late complete repair of tetralogy of Fallot: a retrospective cohort study
Eur J Pediatr. 2024 Aug;183(8):3309-3317. doi: 10.1007/s00431-024-05597-1.
Abstract
Tetralogy of Fallot is the most common cyanotic congenital heart disease. For decades, our institution has cared for humanitarian patients with late presentation of tetralogy of Fallot. They are characterized by severe right ventricular hypertrophy with consecutive diastolic dysfunction, increasing the risk of postoperative low cardiac output syndrome (LCOS). By right ventricular restrictive physiology, we hypothesized that patients receiving early postoperative beta-blockers (within 48 h after cardiopulmonary bypass) may have better diastolic function and cardiac output. This is a retrospective cohort study in a single-center tertiary pediatricintensive care unit. We included > 1-year-old humanitarian patients with a confirmed diagnosis of tetralogy of Fallot undergoing a complete surgicalrepair between 2005 and 2019. We measured demographic data, preoperative echocardiographic and cardiac catheterization measures, postoperative mean heart rate, vasoactive-inotropic scores, low cardiac output syndrome scores, length of stay, and mechanical ventilation duration. One hundred sixty-five patientsmet the inclusion criteria. Fifty-nine patients (36%) received early postoperative beta-blockers, associated with a lower mean heart rate, higher vasoactive-inotropic scores, and lower low cardiac output syndrome scoresduring the first 48 h following cardiopulmonary bypass. There was no significant difference in lengths of stay and ventilation.
Conclusion: Early postoperative beta-blockers lower the prevalence of postoperative low cardiac output syndrome at the expense of a higher need for vasoactive drugs without any consequence on length of stay and ventilation duration. This approach may benefit the specific population of children undergoing a late complete repair of tetralogy of Fallot.
What is Known: • Prevalence of low cardiacoutput syndrome is high following a late complete surgical repair of tetralogyof Fallot.
What is New: • Early postoperative beta-blockade is associated with lower heart rate, prolonged relaxation time, and lower prevalence of low cardiac output syndrome. • Negative chronotropic agents like beta-blockers may benefit selected patients undergoing a latecomplete repair of tetralogy of Fallot, who are numerous in low-income countries.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Eligibility and Projected Benefits ofRapid Initiation of Quadruple Therapy for Newly Diagnosed Heart Failure
JACC Heart Fail. 2024 Aug;12(8):1365-1377. doi: 10.1016/j.jchf.2024.03.001.
Abstract
Background: U.S. nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized.
Objectives: This study sought to characterize the degree to which patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) are eligible for quadruple medical therapy, and the projected benefits of in-hospital initiation.
Methods: Among patients hospitalizedfor newly diagnosed heart failure with reduced ejection fraction (HFrEF) in the Get With The Guidelines-Heart Failure registry from 2016 to 2023, eligibilitycriteria based on regulatory labeling, guidelines, and expert consensus documents were applied for angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor therapies. Of those eligible, the projected effect of quadruple therapy on 12-month mortality was modeled using treatment effectsfrom pivotal clinical trials utilized by the American HeartAssociation/American College of Cardiology /HFSA Guideline for the Management of Heart Failure, and compared with observed outcomes among patients treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker andbeta-blockers.
Results: Of 33,036 patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF), 27,158(82%) were eligible for quadruple therapy, and 30,613 (93%) were eligible for ≥3 components. From 2021 to 2023, of patients eligible for quadruple therapy,15.3% were prescribed quadruple therapy and 41.5% were prescribed triple therapy. Among Medicare beneficiaries eligible for quadruple therapy, 12-monthincidence of mortality was 24.7% and Heart Failure hospitalization was 22.2%. Applying the relative risk reductions in clinical trials, complete implementation of quadruple therapy by time of discharge was projected to yield absolute risk reductions in 12-month mortality of 10.4% (number needed to treat = 10) compared with angiotensin-converting enzyme inhibitor/angiotensinreceptor blocker and beta-blocker, and 24.8% (number needed to treat = 4) compared with no guideline-directed medical therapy.
Conclusions: In this nationwide U.S. cohort of patients hospitalized for newly diagnosed heart failure with reduced ejection fraction (HFrEF), >4 of 5 patients were projected as eligible for quadruple therapy at discharge; yet, <1 in 6 were prescribed it. If clinical trial benefits can be fully realized, in-hospital initiation of quadruplemedical therapy for newly diagnosed heart failure with reduced ejection fraction (HFrEF) would yield large absolute reductions in mortality.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Non-ST-elevation acute coronary syndromeswith previous coronary artery bypass grafting: a meta-analysis of invasive vs. conservative management
Eur Heart J . 2024 Jul 12;45(27):2380-2391.doi: 10.1093/eurheartj/ehae245
Abstract
Background and aims: A routine invasive strategy is recommended in the management of higher risk patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs). However, patients with previous coronary artery bypass graft (CABG) surgery were excluded from key trials that informed these guidelines. Thus, the benefit of a routine invasive strategy is less certain in this specific subgroup.
Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. A comprehensive search was performed of PubMed, EMBASE , Cochrane, and ClinicalTrials.gov. Eligible studies were randomized controlled trials of routine invasive vs. a conservative or selective invasive strategy in patients presenting with non-ST-elevation acute coronary syndromes that included patients with previous coronary artery bypass graft. Summary data werecollected from the authors of each trial if not previously published. Outcomes assessed were all-cause mortality, cardiac mortality, myocardial infarction, and cardiac-related hospitalization. Using a random-effects model, risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.
Results: Summary data were obtained from 11 randomized controlled trials, including previously unpublished subgroup outcomes of nine trials, comprising 897 patients with previous CABG (477routine invasive, 420 conservative/selective invasive) followed up for a weighted mean of 2.0 (range 0.5-10) years. A routine invasive strategy did not reduce all-cause mortality (RR 1.12, 95% CI 0.97-1.29), cardiac mortality (RR 1.05, 95% CI 0.70-1.58), myocardial infarction (RR 0.90, 95% CI 0.65-1.23), or cardiac-related hospitalization (RR 1.05, 95% CI 0.78-1.40).
Conclusions: This is the first meta-analysis assessing the effect of a routine invasive strategy in patientswith prior coronary artery bypass graft who present with non-ST-elevation acute coronary syndromes. The results confirm the under-representation of this patient group in randomized controlled trials of invasive management in non-ST-elevation acute coronary syndromes and suggest that there is no benefit to a routine invasive strategy compared to a conservative approach with regard to major adverse cardiac events. These findings should be validated in an adequately powered randomized controlled trial.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Verification of haemoglobin level to prevent worsening of prognosis in heart failure with preserved ejection fraction patients from the PURSUIT-HFpEF registry
https://doi.org/10.1002/ehf2.14927
Abstract
Aim
Anaemia has been reported as poor predictorin heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the impact of changes in haemoglobin (Hb) from dischargeto 1 year after discharge on the prognosis using a lower cut-off value of Hb than the World Health Organization (WHO) criteria.
Methods and results
First, 547 heart failure with preserved ejection fraction cases were divided into two groups, Hb < 11.0 g/dL (n= 218) and Hb ≥ 11.0 g/dL (n = 329), according to Hbat discharge, and further were divided according to Hb 1 year after discharge into Hb < 11.0 g/dL (G1, n = 113), Hb ≥ 11.0 g/dL (G2, n = 105), Hb < 11.0 g/dL (G3, n = 66), and Hb ≥ 11.0 g/dL (G4, n = 263), respectively. Major adverse cardiovascular events (MACE) was defined as composite of all-cause death and heart failure readmission after a visit 1 year after discharge. The cut-off value of Hb was analysed by the receiver operating characteristics curvethat predicts Major adverse cardiovascular events. We examined the incidence rate of Major adverse cardiovascular events between G4 and other subgroups and verified predictors of improving or worsening anaemia and covarying factors with change in Hb.In multivariate Cox proportional hazard model, MACE was significantly higher in G3 with worsening anaemia from Hb ≥ 11.0 g/dL to <11.0 g/dL than G4 with persistently Hb ≥ 11 g/dL (adjusted hazard ratio (HR):3.14 [95% confidence interval (CI), 1.76–5.60], P < 0.001). Major adverse cardiovascular events was not significantly different between G2 with improving anaemia from Hb< 11.0 g/dL to ≥ 11.0 g/dL andG4 (adjusted HR: 1.37 [95%CI, 0.68–2.75], P = 0.38). In multivariate logistic regression analysis, independent predictors of improving anaemia were male [odds ratio (OR): 0.45], chronicobstructive pulmonary disease (OR: 10.3), prior heart failure hospitalization (OR: 0.38), and estimated glomerular filtration rate (OR: 1.04). Independent predictors of worsening anaemia were age (OR:1.07), body mass index (BMI) (OR: 0.86), clinical frailty scale score (OR: 1.29), Hb at discharge (OR: 0.63), and use of angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker (OR: 2.76). Inmultivariate linear regression analysis, covarying factors with change in Hb were BMI (β = −0.098), serum albumin (β = 0.411), and total cholesterol (β = 0.179).
Conclusions
Change in haemoglobin after discharge using alower cut-off value than World Health Organization criteria has prognostic impact in patients with heart failure with preserved ejection fraction.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Ticagrelor downregulates the expressionof proatherogenic and proinflammatory micro RNA 125-b compared to clopidogrel: A randomized, controlledtrial
Int J Cardiol . 2024 Jul 1:406:132073
Abstract
Background: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardialinfarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatorymicroRNAs, including microRNA -125a, microRNA -125b and microRNA-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel.
Objectives: We compared miR -125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel.
Methods: After percutaneous coronaryintervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel.Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 monthsof treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determineplatelet reactivity in response to P2Y12 inhibitors.
Results: Expression of miR-125b was higher inpatients with AMI 72 h and 6 months, compared to healthy volunteers (p =0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor.
Conclusions: Ticagrelor treatment leads to lower plasma expression of miR-125b after acute myocardial infarction, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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Clinical Pharmacogenetics ImplementationConsortium Guideline (CPIC) for CYP2D6, ADRB1,ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy
Clin Pharmacol Ther. 2024 Jul 1. doi: 10.1002/cpt.3351
Abstract
Beta-blockers are widely used medications fora variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic(e.g., CYP2D6) and pharmacodynamic (e.g., ADRB1, ADRB2, ADRA2C, GRK4, GRK5) genes have been studied in relation to beta-blocker exposure and response. Wesearched and summarized the strength of the evidence linking beta-blocker exposure and response with the six genes listed above. The level of evidence was high for associations between CYP2D6 genetic variation and both metoprolol exposure and heart rate response. Evidence indicates that CYP2D6 poor metabolizers experience clinically significant greater exposure and lower heart rate in response to metoprolol compared with those who are not poor metabolizers. Therefore, we provide therapeutic recommendations regardinggenetically predicted CYP2D6 metabolizer status and metoprolol therapy. However, there was insufficient evidence to make therapeutic recommendationsfor CYP2D6 and other beta-blockers or for any beta-blocker and the other five genes evaluated.
Disclaimer:
Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.
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