Star Update Podcast - Cardiology News Summaries

The goal of the trial was to assess the efficacy and safety of sacubitril/valsartan compared with ramipril in a contemporary acute myocardial infarction (AMI) IN THIS, 5,660 PATIENTS FROM 43 COUNTRIES WITH MEAN AGE OF 64 YEARS WITH PRIOR MI WITH Left ventricular ejection fraction ≤40% with or without pulmonary congestion WERE RANDOMIZED TO RECEIVE EITHER sacubitril/valsartan OR RAMIPRIL AND WERE FOLLOWED UP FOR 23 MONTHS. THE RESULT OF THE TRIAL SHOWED THAT, The primary outcomes of CV death or HF hospitalization were not statistically different between the groups. In the secondary outcomes, the composite endpoint of all Heart Failure events & mortality showed a significance of 0.02 No major adverse events were seen either in both arms. Interestingly, although the events were numerically lower, the trial did not reach its statistical target to show the clinical benefit of sacubitril/valsartan over standard Ramipril in post-MI patients. 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 this website.

In this trial, 15,000 patients from 40 centers across the U.S. were self-enrolled and self-randomized between 2016 & 2019. The Participants were of median age of 67 years With 35.3% had a history of myocardial infarction (MI) and 53% had coronary revascularization within the previous five years. The Results showed after median 26 months of follow-up were as follows No significant difference in the primary effective outcome of all-cause death, MI, or stroke OR Primary safety outcome of major bleeding requiring blood transfusion at 12 months. But there was a high rate of dose switching and discontinuation in patients on a higher dose of Aspirin. Thus this study is very illustrative of fact that low dose Aspirin is equally effective as high dose, and the switch over and discontinuation may be due to GI. 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 this website.

The goal of the trial was to assess the efficacy and safety of Apixaban 5 mg BID compared with standard of care (antiplatelet therapy [APT] or oral anticoagulant [OAC]) among patients undergoing transcatheter aortic valve replacement commonly known as (TAVR). In this study 1500 patients of mean age of 82 years, with 53% having a Self-expanding valve; 47% with balloon-expandable valve and 3% with valve-in-valve were included. The trial was divided into 2 layers, in one stratum Apixaban was compared to standard Vitamin K Antagonist requiring Oral Anti-Coagulant therapy and in other stratum Apixaban was compared to standard Antiplatelet therapy (Single or Dual) not requiring an Anti-Coagulant therapy. The results after a median follow up of 1 year showed that The composite primary endpoint of time to death, stroke, myocardial infarction (MI), systemic emboli, intracardiac or valve thrombosis, deep vein thrombosis/pulmonary embolism, or major bleeding between Apixaban and standard of care with Vitamin K Antagonist or DAPT/SAPT was not statistically significant. Similar results were also seen with Primary safety outcomes. In the secondary outcome of all-cause mortality, death, MI and stroke was higher in the Apixaban group The major bleeding events were more in Apixaban compared to standard of care Non-cardiovascular death was higher with Apixaban in patients that did not require anti-coagulation therapy. The venous thromboembolism was significantly lower in the Apixaban treatment arm compared to standard of care, this was also confirmed with subset 4D-CT imaging analysis The results of this trial indicate that apixaban is not superior to the standard of care among patients undergoing TAVR. Valve leaflet thrombosis was lower with apixaban compared with Anti-Platelet Therapy, but this did not translate into an improvement in clinical outcomes. In fact, among patients without an indication for OAC, apixaban use resulted in higher noncardiovascular mortality compared with APT use. Results are similar to the GALILEO trial with low-dose rivaroxaban. These data do, however, support the use of apixaban instead of VKA if needed among patients requiring long-term OAC. 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 this website.

The goal of the trial was to evaluate surgical left atrial appendage occlusion compared with no occlusion among patients with atrial fibrillation undergoing open-heart surgery. In this trial, 4770 patients on anticoagulation therapy for over 3 years with atrial fibrillation with CHA2DS2-VASc ≥2, were randomized to undergo open-heart surgery with or without left atrial appendage occlusion In results: The primary outcome of ischemic stroke or systemic embolism after 3.8 years occurred in 4.8% of the occlusion group compared with 7.0% of the no occlusion group with a significance of 0.001 In the Secondary outcomes, the event of Ischemic stroke was also significantly lesser to the non-occlusion arm. Among patients with atrial fibrillation undergoing cardiac surgery, left atrial appendage occlusion was found to be superior to no occlusion. More benefit was observed when the results were landmarked at 30 days versus <30 days. Major bleeding was similar between the treatment groups. Thus to conclude the benefit of surgical left atrial appendage occlusion appeared to be additive to anticoagulation therapy; therefore, this trial does not support surgical left atrial appendage occlusion as a replacement to anticoagulation therapy. 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 this website.

In patients with myocardial infarction (MI) and anemia, a "liberal" red blood cell (RBC)transfusion strategy significantly reduce the risk of recurrent MI or death within 30 days compared with a "restrictive" transfusion strategy, in the 3500-patient MINT trial. A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI We cannot claim that a liberal transfusion strategy is definitively superior based on our primary outcome," he said, but "the 95% confidence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant benefit with the liberal strategy." The number needed to treat was 40 to see a benefit in the combined outcome of death or recurrent MI at 30 days, The P-value for this was 0.07, "right on the edge" of statistical significance. "In contrast to other trials in other settings," such as anemia and cardiac surgery, "the results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm." "While not statistically significant, the results consistently favored a liberal transfusion strategy," Notably, cardiovascular death, which was not a specified outcome, was significantly lower in the group who received a liberal transfusion strategy. 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 this website.

Sex-stratified differences in early antithrombotic treatment response in patients presenting with ST-segment elevation myocardial infarction Am Heart J 2023 Apr; 258:17-26 doi: 10.1016 Background: The mechanisms underlying the increased risk of bleeding that female patients with ST-segment Elevation Myocardial Infarction (STEMI) exhibit, remains unclear. The present report assessed sex-related differences in response to pre-hospital dual antiplatelet therapy (DAPT) initiation in patients with STEMI. Methods: The COMPARE CRUSH trial randomized patients presenting with STEMI to receive a pre-hospital loading dose of crushed or integral prasugrel tablets in the ambulance. In this substudy, we compared platelet reactivity levels and the occurrence of high platelet reactivity (HPR; defined as platelet reactivity ≥208) between sexes at 4 prespecified time points after DAPT initiation, and evaluated post-PCI bleeding between groups. Results: Out of 633 STEMI patients, 147 (23%) were female. Females compared with males presented with significantly higher levels of platelet reactivity and higher HPR rates at baseline (232 [IQR, 209-256] vs 195 [IQR, 171-220], P < .01, and 76% vs 41%, OR 4.58 [95%CI, 2.52-8.32], P < .01, respectively). Moreover, female sex was identified as the sole independent predictor of HPR at baseline (OR 5.67 [95%CI, 2.56-12.53], P < .01). Following DAPT initiation, levels of platelet reactivity and the incidence of HPR were similar between sexes. Post-PCI bleeding occurred more frequently in females compared with males (10% vs 2%, OR 6.02 [95%CI, 2.61-11.87], P < .01). Female sex was an independent predictor of post-PCI bleeding (OR 3.25 [95%CI, 1.09-9.72], P = .04). Conclusions: In this contemporary STEMI cohort, female STEMI patients remain at risk of bleeding complications after primary PCI. However, this is not explained by sex-specific differences in the pharmacodynamic response to pre-hospital DAPT initiation. Abstract

Ticagrelor Treatment is Associated With Increased Coronary Flow Reserve in Survivors of Myocardial Infarction https://doi.org/10.1016/j.hlc.2023.03.010 Abstract Background: The pleiotropic action of ticagrelor, with effects in addition to platelet inhibition, has been shown to improve endothelial function in patients with coronary artery disease. These positive effects are possibly adenosine mediated. This study investigated the association of ticagrelor therapy and coronary artery flow reserve in survivors of myocardial infarction (MI).   Methods: This was an exploratory, cross-sectional, open substudy of PROFLOW. High-risk individuals with a history of MI were identified. Coronary flow reserve (CFR) was measured non-invasively in the left anterior descending artery using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperaemia by intravenous infusion of adenosine at 140 μg/kg/min. Patients receiving ticagrelor (n=75) were compared with those not receiving ticagrelor (n=506), using simple and multiple linear regression models. Most patients in both groups were treated with aspirin (97% in the ticagrelor and 94% in the non-ticagrelor group). Adjustment for traditional risk factors was conducted.   Results: The mean age at study inclusion was 68.5±6.8 years, and most patients were male (81.8%). The simple linear regression analysis showed ticagrelor treatment to be significantly associated with increased CFR: ticagrelor 2.95±0.76 (mean±SD), non-ticagrelor 2.70±0.77, (coefficient 0.25; 95% CI 0.063–0.438; p=0.009). This association was significant in two of the three multiple linear regression models with increasing numbers of variables: Model 1 (0.28; 0.06–0.50; p=0.014), Model 2 (0.26; 0.03–0.48; p=0.025), and borderline significant in Model 3 (0.21; –0.01 to 0.43; p=0.058).   Conclusions: Ticagrelor treatment was associated with increased CFR in this high-risk population. Increased CFR may be a clinically important therapeutic effect of ticagrelor in addition to platelet inhibition.

Sex-related bleeding risk in acute coronary syndrome patients receiving dual antiplatelet therapy with aspirin and a P2Y12 inhibitor Med Princ Pract. 2023 Mar 22. Abstract Aims To study sex differences in major bleeding in relation to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Methods and results The Collective Cardiology Research registry was designed to evaluate the application and outcomes of DAPT after ACS/PCI in the Rijnmond region in the Netherlands. Overall, 1172 women (median age 67.5 years) and 3087 men (62.2 years) with ACS/PCI were enrolled between August 2011 and June 2013. Based on a tailored regional DAPT guideline aiming at bleeding risk minimization, 52.6% women and 66.9% men received prasugrel as first-choice P2Y12 inhibitor, additional to aspirin. Women more frequently had contraindications for the use of prasugrel (and therefore received clopidogrel) than men (47.9 vs. 26.9%, p<0.001). Femoral access was more common in women than in men (47.6 vs. 38.1%, p<0.001). Women had higher incidence of TIMI major bleeding at 1 year than men (2.6 vs. 1.6%, p=0.018). After adjustment for established bleeding risk factors, female sex was associated with over two-fold higher risk of TIMI major bleeding (adjusted hazard ratio 2.33; 95% confidence interval 1.26 to 4.32). This difference was already apparent at discharge, and appeared to be caused by access site bleedings (0.9 vs. 0.1%, p<0.001). No sex differences were found in non-access site related TIMI major bleeding up to 1 year. Conclusion Women with ACS/PCI receiving DAPT had higher TIMI major bleeding risk caused by an excess in access-site bleeds, mainly in relation to the femoral approach. 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 this website.

Effect of early metoprolol before PCI in ST-segment elevation myocardial infarction on infarct size and left ventricular ejection fraction. A systematic review and meta-analysis of clinical trials Clin Cardiol. 2022 Oct;45(10):1011-1028. Abstract Aim: This meta-analysis aims to look at the impact of early intravenous Metoprolol in ST-segment elevation myocardial infarction (STEMI) before percutaneous coronary intervention (PCI) on infarct size, as measured by cardio magnetic resonance (CMR) and left ventricular ejection fraction. Methods: We searched the following databases: PubMed, Scopus, Cochrane library, and Web of Science. We included only randomized control trials that reported the use of early intravenous Metoprolol in STEMI before PCI on infarct size, as measured by CMR and left ventricular ejection fraction. RevMan software 5.4 was used for performing the analysis. Results: Following a literature search, 340 publications were found. Finally, 18 studies were included for the systematic review, and 8 clinical trials were included in the meta-analysis after the full-text screening. At 6 months, the pooled effect revealed a statistically significant association between Metoprolol and increased left ventricular ejection fraction (LVEF) (%) compared to controls (mean difference [MD] = 3.57, [95% confidence interval [CI] = 2.22-4.92], p < .00001), as well as decreased infarcted myocardium(g) compared to controls (MD = -3.84, [95% [CI] = -5.75 to -1.93], p < .0001). At 1 week, the pooled effect revealed a statistically significant association between Metoprolol and increased LVEF (%) compared to controls (MD = 2.98, [95% CI = 1.26-4.69], p = .0007), as well as decreased infarcted myocardium(%) compared to controls (MD = -3.21, [95% CI = -5.24 to -1.18], p = .002). Conclusion: A significant decrease in myocardial infarction and increase in LVEF (%) was linked to receiving Metoprolol at 1 week and 6-month follow-up. 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 this website.

Beta-Blockers for Primary Prevention of Anthracycline-Induced Cardiac Toxicity: An Updated Meta-Analysis of Randomized Clinical Trials Cardiovasc Ther. 2022 Dec 29;2022:8367444. Abstract Aim: Cardiotoxicity is a well-recognized complication of chemotherapy with Anthracyclines. However, results from trials evaluating beta-blockers for prevention are controversial. Therefore, we performed a meta-analysis to find whether prophylactic administration of beta-blockers can help prevent Anthracyclines-induced cardiotoxicity. Methods: We assessed randomized trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal left ventricular ejection fraction (LVEF) receiving Anthracyclines. The primary outcome was EF reduction. The secondary outcome was the development of Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD), defined as a decrease in the LVEF of >10% to a value of <53%. Results: We included 17 trials comprising 1291 patients (671 patients in the intervention arm and 620 in the control arm). Carvedilol was administered in eight studies, and others used bisoprolol, metoprolol, or nebivolol. Compared with baseline, LVEF reduced in both intervention and control groups after chemotherapy (MD = -1.93%, 95% CI: -2.94, -0.92, p = 0.001, I2 = 72.1% vs. MD = -4.78%, 95% CI: -6.51, -3.04, p = 0.001, I 2 = 91.6%, respectively). LVEF was less reduced among the beta-blocker receivers (MD = 3.44%, 95% CI: 1.41-5.46, p = 0.001, I2 = 94.0%). Among the eight studies reporting the incidence of CTRCD, 45 out of 370 participants in the intervention arm and 54 out of 341 in the control arm were reported to experience this complication (RR = 0.76; 95% CI: 0.53,1.09; I 2 = 24.4%; p = 0.235). Conclusion: Treatment with beta-blockers prevents dilatation of the left ventricle, development of diastolic dysfunction, and reduction of LVEF. However, these hemodynamic effects do not translate into a significant reduction in CTRCD incidence and prevention of hospitalization for heart failure or cardiac death. 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 this website.

Can platelet count be controlled with ticagrelor in patients with essential thrombocythaemia? A case series Eur Heart J Case Rep. 2023 Feb 14;7(2):ytad051 Abstract Background: Essential thrombocythaemia (ET) is defined as a myeloproliferative neoplasm with a tendency to haemorrhage and thrombosis. Acute coronary thrombosis can be observed in 1 out of 10 patients. The management of ET patients with acute coronary syndrome (ACS) is a complex clinical condition that requires close follow-up. Case summary: Case-1: a 52-year-old female patient with a diagnosis of ET with Janus kinase (JAK)--2 mutation, despite using cytoreductive agents, platelet counts could not be controlled. Platelet counts started to follow a normal course with the ticagrelor treatment given after ACS. Case-2: a 49-year-old female patient who was given ticagrelor treatment after ACS was found to have JAK-2+ ET. The patient whose platelet count returned to normal after ticagrelor treatment was using a cytoreductive agent before the index event. Case-3: a 54-year-old female patient with ET without any genetic mutation. In the patient whose platelet count did not decrease despite ticagrelor treatment and cytoreductive agents given after ACS, platelet counts returned to normal with interferon therapy. Discussion: Platelet counts returned to the normal range with ticagrelor treatment given after ACS in patients with JAK+ ET. Monitoring platelet reduction in JAK+ patients with P2Y12 inhibition is thought to be important for new treatment options. 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 this website.

Interventional therapy of acute coronary syndromes in very old patient population and results of 2 years follow-up Egypt Heart J. 2023 Feb 22;75(1):14. doi: 10.1186/s43044-023-00340-x. Abstract Background:Research on cardiovascular treatment options and prognosis in very old age groups of patients is warranted. In our study, we evaluated and followed up on clinical conditions on admission and comorbidities of patients older than 80 years who were admitted to our hospital with acute myocardial infarction and shared our findings. Results:A total of 144 patients were included in the study, with a mean age of 84.56 ± 5.01 years. No complications resulting in death or requiring surgery were observed in the patients. All-cause mortality was found to be related to heart failure, chronic pulmonary disease shock, and C-reactive protein levels. Cardiovascular mortality was correlated to heart failure, shock on admission, and C-reactive protein levels. No significant difference in mortality was observed between Non-ST elevated myocardial infarction and ST-elevation myocardial infarction. Conclusions:Percutaneous coronary intervention is a safe treatment option with low complication and mortality rates in very old patients with acute coronary syndromes. 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 this website.

Blood pressure lowering effects of β-blockers as add-on or combination therapy: A meta-analysis of randomized controlled trials J Clin Hypertens (Greenwich). 2023 Feb 8. doi: 10.1111/jch.14616. Online ahead of print. Abstract: The authors performed a meta-analysis to assess the efficacy of non-atenolol β-blockers as add-on to monotherapy or as a component of combination antihypertensive therapy in patients with hypertension. The authors searched and identified relevant randomized controlled trials from PubMed until November 2021. Studies comparing blood pressure lowering effects of β-blockers with diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) were included. The analysis included 20 studies with 5544 participants. β-blockers add-on to monotherapy significantly reduced systolic and diastolic blood pressure as compared with non-β-blocker monotherapy (weighted mean difference in mm Hg [95% confidence interval]: -4.1 [-6.0, -2.2] and -3.7 [-4.6, -2.8], respectively). These results were consistent across the comparisons with diuretics (systolic pressure, -10.2 [-14.2, -6.2]; diastolic pressure, -5.4 [-8.2, -2.6]), CCBs (systolic pressure, -4.1 [-7.1, -1.0]; diastolic pressure, -2.8 [-4.1, -1.5]), and ACEIs/ARBs (systolic pressure, -2.9 [-4.3, -1.5]; diastolic pressure, -4.2 [-5.0, -3.4]). There was no significant difference in blood pressure lowering effects between combinations with and without a β-blocker (systolic pressure, -1.3 mm Hg [-5.8, 3.2]; diastolic pressure, -.3 mm Hg [-2.7, 2.1]). Metoprolol add-on or combination therapy had a significantly greater blood pressure reduction than non-β-blocker therapy (systolic pressure, -3.6 mm Hg [-5.9, -1.3]; diastolic pressure, -2.1 mm Hg [-3.5, -.7]). In conclusion, non-atenolol β-blockers are effective in lowering blood pressure as add-on to monotherapy or as a component of combination antihypertensive therapy. In line with the current hypertension guideline recommendations, β-blockers can and should be used in combination with other antihypertensive drugs. 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 this website.

A predictive model of response to metoprolol in children and adolescents with postural tachycardia syndrome World J Pediatr. 2023 Feb 13. doi: 10.1007/s12519-022-00677-4. Online ahead of print. Abstract Background:The present work was designed to explore whether electrocardiogram (ECG) index-based models could predict the effectiveness of metoprolol therapy in pediatric patients with postural tachycardia syndrome (POTS). Methods:This study consisted of a training set and an external validation set. Children and adolescents with POTS who were given metoprolol treatment were enrolled, and after follow-up, they were grouped into non-responders and responders depending on the efficacy of metoprolol. The difference in pre-treatment baseline ECG indicators was analyzed between the two groups in the training set. Binary logistic regression analysis was further conducted on the association between significantly different baseline variables and therapeutic efficacy. Nomogram models were established to predict therapeutic response to metoprolol. The receiver-operating characteristic curve (ROC), calibration, and internal validation were used to evaluate the prediction model. The predictive ability of the model was validated in the external validation set. Results:Of the 95 enrolled patients, 65 responded to metoprolol treatment, and 30 failed to respond. In the responders, the maximum value of the P wave after correction (Pcmax), P wave dispersion (Pd), Pd after correction (Pcd), QT interval dispersion (QTd), QTd after correction (QTcd), maximum T-peak-to-T-end interval (Tpemax), and T-peak-to-T-end interval dispersion (Tped) were prolonged (all P < 0.01), and the P wave amplitude was increased (P < 0.05) compared with those of the non-responders. In contrast, the minimum value of the P wave duration after correction (Pcmin), the minimum value of the QT interval after correction (QTcmin), and the minimum T-peak-to-T-end interval (Tpemin) in the responders were shorter (P < 0.01, < 0.01 and < 0.01, respectively) than those in the non-responders. The above indicators were screened based on the clinical significance and multicollinearity analysis to construct a binary logistic regression. As a result, pre-treatment Pcmax, QTcmin, and Tped were identified as significantly associated factors that could be combined to provide an accurate prediction of the therapeutic response to metoprolol among the study subjects, yielding good discrimination [area under curve (AUC) = 0.970, 95% confidence interval (CI) 0.942-0.998] with a predictive sensitivity of 93.8%, specificity of 90.0%, good calibration, and corrected C-index of 0.961. In addition, the calibration curve and standard curve had a good fit. The accuracy of internal validation with bootstrap repeated sampling was 0.902. In contrast, the kappa value was 0.769, indicating satisfactory agreement between the predictive model and the results from the actual observations. In the external validation set, the AUC for the prediction model was 0.895, and the sensitivity and specificity were 90.9% and 95.0%, respectively. Conclusions: A high-precision predictive model was successfully developed and externally validated. It had an excellent predictive value of the therapeutic effect of metoprolol on POTS among children and adolescents. 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 this website.

Ticagrelor With or Without Aspirin in High-Risk Patients With Anemia Undergoing Percutaneous Coronary Intervention: a subgroup analysis of the TWILIGHT trial Eur Heart J Cardiovasc Pharmacother. 2023 Jan 17;pvad006. Abstract Aim: The aim of this study was to assess the effect of ticagrelor monotherapy among high-risk patients with anemia undergoing percutaneous coronary intervention (PCI). Methods and results:In the TWILIGHT trial (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention), after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. Anemia was defined as hemoglobin <13 g/dL for men and <12 g/dL for women. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction, or stroke.Out of 6 828 patients, 1 329 (19.5%) had anemia and were more likely to have comorbidities, multivessel disease, and to experience bleeding or ischemic complications than non-anemic patients. Among anemic patients, BARC 2, 3, or 5 bleeding occurred less frequently with ticagrelor monotherapy than with ticagrelor plus aspirin (6.4% vs. 10.7%; HR 0.60; 95% CI 0.41 to 0.88; p = 0.009); the rate of the key secondary endpoint was similar in the two arms (5.2% vs. 4.8%; HR 1.07; 95% CI 0.66 to 1.74; p = 0.779). These effects were consistent in patients without anemia (interaction p-value 0.671 and 0.835, respectively). Conclusions:In high-risk patients undergoing PCI, ticagrelor monotherapy after 3 months of ticagrelor-based DAPT was associated with a reduced risk of clinically relevant bleeding without any increase in ischemic events irrespective of anemia status. 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 this website.

Stroke Recurrence and Antiplatelets in Posterior Versus Anterior Circulation Minor Stroke or Transient Ischemic Attack Stroke. 2023 Feb 15. doi: 10.1161/STROKEAHA.122.041738. Abstract Background:It is unclear whether infarct location affects stroke recurrence after index ischemic stroke. We aimed to compare the risk of stroke recurrence and the responses to dual antiplatelets with ticagrelor-aspirin versus clopidogrel-aspirin between patients with posterior circulation infarct (PCI) and those with anterior circulation infarct (ACI) after minor stroke or transient ischemic attack. Methods:Data were obtained from the double-blind CHANCE-2 trial (Ticagrelor or Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II), which was conducted across 202 centers in China from September 2019 to March 2021. Patients with positive diffusion-weighted imaging were included and classified into PCI and ACI groups according to the hyperintense lesions on diffusion-weighted imaging. The primary efficacy and safety outcomes were a new stroke and severe or moderate bleeding within 90 days, respectively. Results: A total of 4168 patients were included in this substudy, with 1427 PCI and 2741 ACI. During the 90-day follow-up, the risk of stroke recurrence in patients with PCI was similar to that with ACI (7.4% versus 8.3%; adjusted hazard ratio, 1.01 [95% CI, 0.79-1.29]; P=0.94). In comparison with clopidogrel-aspirin, ticagrelor-aspirin significantly reduced the risk of stroke recurrence in both the PCI (hazard ratio, 0.59 [95% CI, 0.40-0.89]; P=0.01) and ACI groups (hazard ratio, 0.65 [95% CI, 0.50-0.85]; P=0.002). There was no treatment-by-infarct location interaction (P value for interaction, 0.92). The risk of severe or moderate bleeding was similar between PCI and ACI patients (P=0.19). However, the risk of any bleeding increased on ticagrelor-aspirin than clopidogrel-aspirin treatment in PCI and ACI patients (P=0.02 and 0.002, respectively). Conclusions:Our study demonstrated that stroke recurrence was similar between PCI and ACI in patients with minor stroke or transient ischemic attack. Additionally, ticagrelor-aspirin was superior to clopidogrel-aspirin in reducing the risk of stroke within 90 days in both PCI and ACI patients. 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 this website.

Abstract Background: Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria have been used to identify high-risk patients undergoing percutaneous coronary intervention (PCI) in current clinical practice. This study aimed to evaluate the association between the number of ARC-HBR criteria and clinical outcomes in patients with acute coronary syndrome (ACS) after an emergent PCI. Methods: We assessed 338 consecutive patients with ACS who underwent successful emergent PCI between January 2017 and December 2020. The ARC-HBR score was calculated by assigning 1 point to each major criterion and 0.5 points to each minor criterion. The patients were classified into low (ARC-HBR score < 1), intermediate (1 ≤ ARC-HBR score < 2), and high (ARC-HBR score ≥ 2) bleeding risk groups. We investigated the association between the ARC-HBR score and major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke. We also compared the diagnostic ability of the ARC-HBR score and Controlled Abciximab and Device Investigation and Lower Late Angiography Complications (CADILLAC) risk score. Results: The mean age of the patients was 67.6 ± 12.4 years, and 78.4 % were men. During the median follow-up of 864 (557-1309) days, 70 patients developed MACEs. Kaplan-Meier curves showed that the cumulative incidence of MACE was significantly higher as the ARC-HBR score increased in a stepwise manner (log-rank p < 0.001). There were no significant differences in the area under the receiver operating characteristic curve (AUC) for predicting MACE within two years after an emergent PCI between the ARC-HBR and CADILLAC risk scores (AUC: 0.763 vs. 0.777). Conclusions: ARC-HBR score was independently associated with an increased risk of MACE in patients with ACS after an emergent PCI. Moreover, it had a similar diagnostic ability for predicting MACE within two years compared to the CADILLAC risk score. 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 this website.

Abstract β-blockers have been widely utilized as a part of acute myocardial infarction (AMI) treatment for the past 40 years. Patients receiving β-adrenergic blockers for an extended period following myocardial infarction have a higher chance of surviving. Although many patients benefited from β-blockers, many do not, including those with myocardial infarction, left ventricle dysfunction, chronic pulmonary disease, and elderly people. In individuals with post-acute coronary syndrome and normal left ventricular ejection fraction (LVEF), the appropriate duration of beta-blocker therapy is still unknown. There is also no time limit for those without cardiac angina and who do not need β-blockers for dysrhythmia or hypertension. Interestingly, β-blockers have been prescribed for more than four decades. The novel mechanism of action on cellular compartments has been found continually, which opens a new way for their potential application in cardiac failure and other cardiac events like post-myocardial infarction. Here, in this review, we studied β-blocker usage in these circumstances and the current recommendations for β-blocker use from clinical practice guidelines. 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 this website.

Abstract Objective: To determine if the baseline baroreflex sensitivity (BRS) could be a useful predictor for the metoprolol therapeutic efficacy on postural orthostatic tachycardia syndrome (POTS) in children. Methods: In this retrospective case-control study, 54 children suffering from POTS treated with metoprolol were recruited from the pediatric department of Peking University First Hospital. After 2-3 months of metoprolol treatment, all subjects were divided into responders and non-responders based on whether the symptom score (SS) was decreased by over 50% after metoprolol treatment at the follow-up. The baseline demographic parameters and the supine BRS during the head-up tilt test (HUTT) obtained by Finapres Medical System (FMS) were compared between the two groups. The value of BRS to predict the effectiveness of POTS was analyzed by a receiver-operating characteristic (ROC) curve. Results: The age, sex, height, weight, body mass index (BMI), course of the disease, baseline SS, medication time, metoprolol dose, and follow-up time of the subjects were not statistically different between the responders and non-responders (P > 0.05). The decline in symptom scores (ΔSS) of the responders was more obvious than that of the non-responders (P < 0.01). The supine BRS, BRS at maximum HR, supine heart rate (HR), and maximum HR were different between responders and non-responders (P < 0.01, P = 0.022, P < 0.01, P = 0.047). The binary multivariable analysis showed that baseline supine BRS was significantly associated with the response to metoprolol therapy [OR: 2.079, 95% CI: (1.077, 4.015), P = 0.029]. According to the ROC curve, the area under the curve (AUC) of baseline BRS was 0.912 (95% CI, 0.840-0.984), with a cut-off value of 8.045 ms/mmHg, yielding a sensitivity and specificity of 75.8% and 95.2%, respectively, in predicting the effectiveness of POTS. Conclusion: The baseline supine BRS level > 8.045 ms/mmHg can predict a good therapeutic response to metoprolol and the results would assist in guiding the individualized β-adrenoceptor blocker use in pediatric patients suffering from POTS. 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 this website.

Abstract Background: No study has compared pharmacologic properties of ticagrelor and clopidogrel in non-dialysis patients with stage 4-5 chronic kidney disease (CKD). Methods: We conducted a double-blind RCT to compare effects of ticagrelor and clopidogrel in 48 CKD, with the primary outcome of ADP-induced platelet aggregation (WBPA) after 2 weeks of DAPT. In a parallel arm, we compared effects of 2 weeks of ticagrelor plus aspirin on mean changes in WBPA and markers of thromboinflammation among non-CKD controls (n = 26) with that of CKD in the ticagrelor-arm. Results: Average age of CKD was 53.7 years, with 62% women, 54% African American, and 42% with stage 5 CKD. Ticagrelor generated statistically lower WBPA values post treatment [median 0 Ω (IQR 0, 2)] vs. clopidogrel [median 0 Ω (IQR 0, 5)] (P = 0.002); percent inhibition of WBPA was greater (87 ± 22% vs. 63 ± 50%; P = 0.04; and plasma IL-6 levels were much lower (8.42 ± 1.73 pg/ml vs. 18.48 ± 26.56 pg/ml; P = 0.04). No differences in mean changes in WBPA between CKD-ticagrelor and control groups were observed. Ticagrelor- DAPT reduced levels of IL-1α and IL-1β in CKD-ticagrelor and control groups, attenuated lowering of TNFα and TRAIL levels in CKD-ticagrelor (vs controls), and had global changes in correlation between various cytokines in a subgroup of CKD-ticagrelor subjects not on statins (n = 10). Peak/trough levels of ticagrelor/metabolite were not different between CKD-ticagrelor and control groups. Conclusions: We report significant differences in platelet aggregation and anti-inflammatory properties between ticagrelor- and clopidogrel-based DAPT in non-dialysis people with stage 4-5 CKD. These notable inflammatory responses suggest ticagrelor-based DAPT might lower inflammatory burden of asymptomatic patients with stage 4 or 5 CKD. 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 this website.