Secondary Prevention In Patients Research Articles

Assessment of hypertriglyceridemia associated residual cardiovascular risk in secondary prevention patients

Assessment of hypertriglyceridemia associated residual cardiovascular risk in secondary prevention patients

Clinical outcomes of generic versus brand-name clopidogrel for secondary prevention in patients with acute myocardial infarction: A nationwide cohort study.

Skepticism exists among healthcare workers and patients regarding the efficacy and safety of generic medication, despite its potential to lower healthcare costs. This study aimed to compare the outcomes of a generic clopidogrel and its brand-name counterpart for secondary prevention in patients with acute myocardial infarction (AMI). Using the Taiwan National Health Insurance Research Database, we identified 49,325 patients who were hospitalized for AMI between January 1, 2008 and December 31, 2013 and prescribed either generic or brand-name clopidogrel. Among them, 2419 (4.9%) were prescribed the generic clopidogrel. After propensity score matching, both the generic and brand-name groups consisted of 2382 patients. The primary efficacy outcome was a composite of myocardial infarction, coronary revascularization, ischemic stroke, and all-cause death. The primary safety outcome was major bleeding requiring hospitalization. At a mean follow-up of 2.5 years, the generic and brand-name clopidogrel groups had comparable risks of primary efficacy outcome (41.9% vs. 42%; hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.88-1.04), and the risks of the individual components were also similar. There were no significant differences between the two groups in major bleeding (7.9% vs. 7.9%; HR 0.99; 95% CI 0.81-1.21). Subgroup analyses also revealed no statistically significant interactions between the treatment effect and various subgroups. In this retrospective database analysis, the generic clopidogrel was comparable to its brand-name counterpart regarding cardiovascular and bleeding outcomes for the treatment of patients with AMI.

Association between statin therapy and mortality in patients on dialysis after atherosclerotic cardiovascular diseases

Statin therapy is essential for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD). However, the effects of statin therapy in patients receiving chronic dialysis remain uncertain. We aimed to evaluate the effect of statin therapy on long-term mortality in patients on dialysis after a first-time ASCVD. Patients receiving maintenance dialysis aged ≥ 18 years with a first-time ASCVD event between 2013 and 2018 were included in the Korean National Health Insurance Service database. Associations of statin use with long-term mortality were examined using Cox proportional hazards regression models adjusted for demographics and comorbidities. Among 17,242 patients on dialysis, 9611 (55.7%) were prescribed statins after a first-time ASCVD event. Among statin users, 7376 (76.7%) used moderate-intensity statins. During a mean follow-up of 32.6 ± 20.9 months, statin use was associated with a lower risk of all-cause mortality than statin nonuse after adjusting for confounding factors (hazard ratio [HR]: 0.92; 95% confidence interval [CI] 0.88–0.97; p = 0.0009). Despite a lack of evidence, more than half of patients on dialysis were prescribed statins after an ASCVD event. In patients on dialysis after ASCVD, statin therapy significantly reduced the risk of long-term all-cause mortality.

RBP4-based Multimarker Score: A Prognostic Tool for Adverse Cardiovascular Events in Acute Coronary Syndrome Patients.

Retinol binding protein 4 (RBP4) has been implicated in the progression of cardiovascular diseases. However, its association with major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) remains obscure. Here, we examined the prognostic value of baseline RBP4 and its derived multimarker score for MACEs in ACS patients. A total of 826 patients with ACS were consecutively recruited from the department of cardiology and prospectively followed up for a median of 1.95 years (interquartile range, 1.02-3.25 years). Plasma RBP4 was measured using enzyme-linked immunosorbent assay. Adjusted associations between RBP4 and its derived multimarker score (1 point was assigned when RBP4 ≥ 38.18μg/mL, left ventricular ejection fraction [LVEF] ≤ 55%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥ 450 ng/L, estimated glomerular filtration rate [eGFR] ≤ 90 mL/min/1.73 m2, and age ≥60) with MACEs were analyzed. In total, 269 ACS patients (32.57%) experienced MACEs. When patients were grouped by multimarker score (0-1, n = 315; 2-3, n = 406; 4-5, n = 105), there was a significant graded association between RBP4-based multimarker score and risk of MACEs (intermediate score (2-3): HRadj: 1.80; 95% CI, 1.34-2.41; high score (4-5): HRadj: 3.26; 95% CI, 2.21-4.81) and its components (P < .05 for each). Moreover, the prognostic and discriminative value of the RBP4-derived multimarker score remained robust in ACS patients with various high-risk anatomical or clinical characteristics. The RBP4-derived 5-item score serves as a useful risk stratification and decision support for secondary prevention in patients with ACS.

P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events

BackgroundAspirin is the only antiplatelet agent with a Class I recommendation for long-term prevention of cardiovascular events in patients with coronary artery disease (CAD). There is inconsistent evidence on how it compares with alternative antiplatelet agents. ObjectivesThis study compared P2Y12 inhibitor monotherapy vs aspirin in patients with CAD. MethodsWe conducted a patient-level meta-analysis of randomized trials comparing P2Y12 inhibitor monotherapy vs aspirin monotherapy for the prevention of cardiovascular events in patients with established CAD. The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. Prespecified key secondary outcomes were major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data were pooled in a 1-step meta-analysis. ResultsPatient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y12 inhibitor monotherapy (clopidogrel in 7,545 [62.0%], ticagrelor in 4,633 [38.0%]) and 12,147 assigned to receive aspirin. Risk of the primary outcome was lower with P2Y12 inhibitor monotherapy compared with aspirin over 2 years (HR: 0.88; 95% CI: 0.79-0.97; P = 0.012), mainly owing to less myocardial infarction (HR: 0.77; 95% CI: 0.66-0.90; P < 0.001). Major bleeding was similar (HR: 0.87; 95% CI: 0.70-1.09; P = 0.23) and net adverse clinical events were lower (HR: 0.89; 95% CI: 0.81-0.98; P = 0.020) with P2Y12 inhibitors. The treatment effect was consistent across prespecified subgroups and types of P2Y12 inhibitors. ConclusionsGiven its superior efficacy and similar overall safety, P2Y12 inhibitor monotherapy might be preferred over aspirin monotherapy for long-term secondary prevention in patients with established CAD. (P2Y12 Inhibitor or Aspirin Monotherapy as Secondary Prevention in Patients With Coronary Artery Disease: An Individual Patient Data Meta-Analysis of Randomized Trials [PANTHER collaborative initiative]; CRD42021290774)

Coste-efectividad de la polipíldora CNIC frente a los monocomponentes separados en prevención secundaria cardiovascular en España

Introduction and objectivesDespite advances in treatment, cardiovascular disease is the second leading cause of death in Spain. The objective of this study was to determine the cost-effectiveness of the CNIC-Polypill strategy (acetylsalicylic acid 100mg, atorvastatin 20/40mg, ramipril 2.5/5/10mg) compared with the same separate monocomponents for the secondary prevention of recurrent cardiovascular events in adults in Spain. Materials and methodsA Markov cost-utility model was adapted considering four health states (stable, subsequent major adverse cardiovascular event, subsequent ischemic stroke and death) and the SMART risk equation over a lifetime horizon from the perspective of the Spanish National Healthcare System. The CNIC-Polypill strategy was compared with monocomponents in a hypothetical cohort of 1000 secondary prevention patients. Effectiveness, epidemiological, cost and utilities data were obtained from the NEPTUNO study, official databases and literature. Outcomes were costs (in 2021euros) per life-year (LY) and quality-adjusted LY (QALY) gained. A 3% discount rate was applied. Deterministic one-way and probabilistic sensitivity analyses evaluated the robustness of the model. ResultsThe CNIC-Polypill strategy in secondary prevention results in more LY (13.22) and QALY (11.64) gains at a lower cost than monocomponents. The CNIC-Polypill is dominant and saves €280.68 per patient compared with monocomponents. The probabilistic sensitivity analysis shows that 82.4% of the simulations are below the threshold of €25,000 per QALY gained. ConclusionsThe CNIC-Polypill strategy in secondary cardiovascular prevention is cost-effective compared with the same separate monocomponents, resulting in a cost-saving strategy to the Spanish National Healthcare System.

189-LB: LDL Cholesterol Reduction and Cardiovascular Outcomes in High-Risk Primary Prevention Patients

Background: Current guidelines recommend reducing LDL cholesterol in patients at high risk for a first major adverse cardiovascular event (primary prevention). However, these recommendations are predominately based on clinical trials conducted many years ago. Most contemporary trials of LDL-cholesterol lowering therapies have enrolled only secondary prevention patients. Some authorities have questioned whether the benefits of cholesterol lowering exceed the harms in primary prevention patients. Currently, lipid-lowering therapies are underutilized in high-risk patients without a prior event, particularly in women and patients with diabetes. More than half of eligible patients are not currently receiving LDL-cholesterol lowering therapies. Methods: The CLEAR Outcomes trial reported cardiovascular outcomes for bempedoic acid treatment compared with placebo in a mixed population of primary and secondary prevention patients unable or unwilling to take guideline-recommended doses of statins (N=13,970). The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization. The results of the CLEAR OUTCOMES trial were presented and simultaneously published in the NEJM on March 4. The hazard ratio for the primary end point for the full population was 0.87 (95% CI 0.79-0.96), P=0.004. Results: In the CLEAR Outcomes trial, 4206 patients (30%) met high risk primary prevention entry criteria, two thirds with diabetes. The HR in these primary prevention patients was lower than the HR for secondary prevention patients, 0.68 (95% CI 0.53-0.87), with a significant interaction P value (0.03). The current Late Breaking Trial will report detailed results for the primary and all key secondary endpoints for the 4206 patients enrolled based on high risk primary prevention criteria. Full results will be available in mid-April for simultaneous presentation and publication during the ADA meeting. Disclosure S. Nissen: Research Support; Eli Lilly and Company, AbbVie Inc., AstraZeneca, Bristol-Myers Squibb Company, ESPERION Therapeutics, Inc., New Amsterdam Pharma, Novartis, Patient-Centered Outcomes Research Institute, Silence Therapeutics. For the clear outcomes trial investigators: n/a. Funding National Heart, Lung, and Blood Institute (K23HL153774 to J.E.T.); University of Toronto (to B.R.S.)

Cost-effectiveness of the CNIC-Polypill versus separate monocomponents in cardiovascular secondary prevention in Spain

Introduction and objectivesDespite advances in treatment, cardiovascular disease is the second leading cause of death in Spain. The objective of this study was to determine the cost-effectiveness of the CNIC-Polypill strategy (acetylsalicylic acid 100 mg, atorvastatin 20/40 mg, ramipril 2.5/5/10 mg) compared with the same separate monocomponents for the secondary prevention of recurrent cardiovascular events in adults in Spain. Materials and methodsA Markov cost-utility model was adapted considering 4 health states (stable, subsequent major adverse cardiovascular event, subsequent ischemic stroke and death) and the SMART risk equation over a lifetime horizon from the perspective of the Spanish National Healthcare System. The CNIC-Polypill strategy was compared with monocomponents in a hypothetical cohort of 1000 secondary prevention patients. Effectiveness, epidemiological, cost and utilities data were obtained from the NEPTUNO study, official databases and literature. Outcomes were costs (in 2021 euros) per life-year (LY) and quality-adjusted LY (QALY) gained. A 3% discount rate was applied. Deterministic one-way and probabilistic sensitivity analyses evaluated the robustness of the model. ResultsThe CNIC-Polypill strategy in secondary prevention results in more LY (13.22) and QALY (11.64) gains at a lower cost than monocomponents. The CNIC-Polypill is dominant and saves є280.68 per patient compared with monocomponents. The probabilistic sensitivity analysis shows that 82.4% of the simulations are below the threshold of є25,000 per QALY gained. ConclusionsThe CNIC-Polypill strategy in secondary cardiovascular prevention is cost-effective compared with the same separate monocomponents, resulting in a cost-saving strategy to the Spanish National Healthcare System.

Comparison and predictors of implantable cardioverter-defibrillator therapy for primary and secondary prevention.

Implantable cardioverter-defibrillators (ICDs) are effective in detecting and treating ventricular arrhythmias. Studies on ICD therapy for different indications (primary and secondary prevention) and possible predictors of ICD therapy are limited. In this study, the incidence and type of ICD therapy were related to the indication and the underlying cardiac pathology. Asingle-centre, retrospective and observational study was performed of 482patients who underwent ICD implantation for primary (53.3%) or secondary prevention (46.7%) between 2015 and 2020 at the Radboud University Medical Centre. During amedian follow-up of 2.4years (interquartile range 0.2-3.9), the occurrence of appropriate ICD therapy for primary versus secondary prevention was 9.7% and 27.6%, respectively (p < 0.001). Time to appropriate ICD therapy was significantly shorter in the secondary prevention group (p < 0.001). No difference in ICD therapy was seen for different underlying aetiologies. In the majority of cases (70%) ICD therapy was given for ventricular tachycardia (VT). The occurrence of adverse events (16.3% vs 17.3%, p = 0.772), hospitalisation for cardiovascular reasons (29.2% vs 35.1%, p = 0.559) and all-cause mortality (12.5% vs 11.6%, p = 0.763) were similar in both groups. Male gender (3.53, 95% confidence interval (CI) (1.003, 12.403), p = 0.049) and secondary prevention indication (4.90, 95% CI (1.495, 16.066), p = 0.009) were predictors of appropriate ICD therapy. The risk associated with appropriate ICD therapy is higher in secondary prevention patients, who have their first therapy within ashorter time frame after device implantation. Rates of complications, hospitalisation and all-cause mortality are comparable. Future treatment options should target the prevention of ICD therapy, mainly by preventing the recurrence of VT.

Impact of Statin Therapy in Heart Failure Patients: Results of a Large Real-World Experience

BackgroundThe use of statins in patients with heart failure (HF) is controversial. In patients without HF, statins reduce atherosclerotic cardiovascular disease (ASCVD) risk, including HF-related events. However, in some large studies, no benefit was seen in statin-treated HF patients. ObjectivesThe purpose of this study was to determine the impact of statin therapy in HF with reduced ejection fraction (HFrEF). MethodsIntermountain Healthcare medical records identified patients with a HF diagnosis and an ejection fraction of ≤40%. Patients prescribed and not prescribed a statin were compared for major adverse cardiovascular events (MACE) (death, myocardial infarction, stroke) (median of 4.5 years follow-up). Statin use was defined as use at or after a HF diagnosis but at least 60 days before MACE or end of follow-up. Cox proportional hazards regression was used to determine the relationship between statin use and outcomes. ResultsA total of 15,010 patients (n = 9,641 [64%] on statins) were studied. Statin use was associated with more frequent ASCVD risk factors yet a lower risk of MACE risk (adjusted HR: 0.53; 95% CI: 0.51-0.56; P < 0.0001). Benefit was similar for primary and secondary prevention patients and for prior and new statin prescriptions. Using time-varying hazard ratio analysis, the longer the patient was on a statin, the greater the reduction in risk of MACE (P < 0.0001). ConclusionsThese results suggest a potential benefit of selective statin use in the real-world management of HFrEF patients with ASCVD or at high ASCVD risk.

Is bempedoic acid effective for secondary prevention of cardiovascular disease?

Bempedoic acid is a cholesterol-lowering drug approved for reduction of the risk of myocardial infarction (MI) and coronary revascularization in adults who are unable to take recommended statin therapy with established cardiovascular disease (CVD), or at high risk for a CVD event but without established CVD. However, reduction of CV events by bempedoic acid in patients with documented CVD is modest and not statistically significant. The CLEAR Outcomes trial is the largest randomized trial of bempedoic acid including 13,970 patients; 70% of whom had documented CVD (secondary prevention cohort), and 30% were considered high CV risk but without established CV disease (primary prevention cohort). The primary outcome of the CLEAR OUTCOMES trial was a composite of death from CV causes, nonfatal MI, nonfatal stroke, or coronary revascularization (MACE-4). After a median follow-up of 40.6 months, the incidence of CV event was significantly decreased in the bempedoic group versus the placebo group in the whole study population; hazard ratio (HR) 0.87; 95% CI, 0.79 to 0.96; P=0.004). However, this decrease in CV events was mainly driven by the reduction of MACE-4 in the primary prevention cohort; HR 0.68 (95% CI, 0.53 to 0.87), whereas the corresponding reduction in the secondary prevention cohort was more modest; HR 0.91 (95% CI 0.82 to 1.01), Pinteraction=0.03. Results of a post-hoc analysis of the CLEAR Outcomes trial suggested possible increase in all-cause mortality; risk ratio (RR) 1.15 and CV mortality RR 1.21 in the secondary prevention patients. Conversely, in the primary prevention group, there was decrease in all-cause mortality RR 0.70 and CV mortality RR 0.58. While the investigators of the CLEAR Outcomes trial published results of the primary prevention group separately, they did not report those results in the larger secondary group despite greater number of CV events. A randomized trial evaluating bempedoic acid in patients with documented CVD is required to clarify its efficacy and safety in this group of patients. Until such trial is available, the use of bempedoic acid is not recommended for secondary prevention of CV disease.

Telemedicine for Optimizing Secondary Prevention in Coronary Artery Bypass Grafting Patients during COVID-19 Pandemic.

(1) Background: The COVID-19 pandemic has introduced a major disruption to the delivery of secondary prevention measures in patients with established atherosclerotic cardiovascular disease (CVD). It required a rapid and widespread adoption of new medical services, including the use of telemedicine. This study aimed to examine the impact of COVID-19 on secondary prevention in patients with coronary artery bypass grafting (CABG) and to evaluate the effectiveness of the telemedicine application for the implementation of lifestyle change measures, remote monitoring, and treatment regimen adjustment; (2) Methods: This prospective study on 194 CABG patients evaluated three consecutive years between 2019 and 2022 in the pre-pandemic period by face-to-face visits and during the pandemic by teleconsultations or hybrid follow-up. Variables of interest were compared between four periods: pre-pandemic-pre-P (1 March 2019-29 February 2020), lockdown-Lock (1 March-31 August 2020), restrictive-pandemic-Restr-P (1 September 2020-28 February 2021), and relaxed-pandemic-Rel-P (1 March 2021-1 March 2022). (3) Results: The average values of the lipidogram, blood sugar, and uric acid increased during Lock and Restr-P, but, through the use of teleprevention, they returned to the pre-pandemic level or even below this level. The exception was blood sugar, which remained high in Rel-P. The number of newly diagnosed patients with diabetes also increased, with most of them having moderate forms of COVID. During Lock and Res-P, the percentage of obese, smoking, or hypertensive patients increased, but, through the use of teleprevention, we managed to reduce it, although it remained slightly higher than the pre-pandemic level. Physical activity decreased in the first year of the pandemic, but, in Rel-P, CABG patients became more active than before the pandemic (4) Conclusions: The use of telemedicine for cardiovascular secondary prevention allowed us to not only continue seeing CABG patients but, also, to adjust their medication and to expand cardiovascular preventive counseling and testing with favorable results, especially during the second year of the pandemic.

Effect of hybrid cardiac rehabilitation using a smart device: a randomized controlled trial

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Korea National Institute of Health. Background Although cardiac rehabilitation (CR) has been proven to be effective in secondary prevention for patients with cardiovascular diseases, the actual participation in CR is still unsatisfactory. Because home-based CR provides better access to patients and is as effective as center-based CR, it is considered a promising alternative that can overcome various barriers impeding CR implementation. However, home-based CR has not garnered enough attention due to a lack of proper communication, concerns about unexpected adverse events caused by non-monitored exercises, and the absence of supporting insurance services. Purpose We utilized a smart ring with a photoplethysmography to monitor heart rate. Recorded data were stored on a website where the researchers could remotely access and check the uploaded measurements. This study aims to identify the clinical effects of hybrid CR by weekly telephone counseling based on the patients' actual physical activities obtained from the device. Methods Cardiovascular disease patients were educated on concrete methods of home-based CR, including the type, intensity, and time of exercise as well as precautions. They were also instructed to wear the device during exercise. The patients were randomly enrolled into two groups: intervention and observation groups. The patients of the intervention group were given weekly telephone counseling and encouraged to maintain optimal physical activities. In the observational group, only exercise data were recorded without additional interventions. Before and after three months of training, the results of the symptom-limited cardiopulmonary exercise test between the two groups were compared. Results A total of sixty-four patients were enrolled (thirty-two in each group). The subjects were 59.8 ± 9.0 years old and fifty-three (82.8%) were male. There were no significant differences in diagnosis and results of baseline symptom-limited cardiopulmonary exercise test between the two groups (Table 1). After three months of training, peak oxygen consumption was significantly improved in both groups. However, the improvement was greater in the intervention group compared to the observation group (Table 2). Conclusion Home-based CR using a smart device was effective in improving oxygen consumption. For greater effectiveness, proper monitoring and timely counseling by medical experts are likely to be necessary.

Eligibility to Intensified Antithrombotic Regimens for Secondary Prevention in Patients Who Underwent Percutaneous Coronary Intervention

Single antiplatelet therapy (SAPT) and intensified antithrombotic regimens (prolonged dual antiplatelet therapy [DAPT] or dual pathway inhibition [DPI]) are recommended for secondary prevention in patients who underwent percutaneous coronary intervention (PCI) after initial DAPT. We aimed to characterize eligibility to such strategies and to explore to what extent guidelines are applied in clinical practice. Patients who underwent PCI for acute or chronic coronary syndrome who completed initial DAPT were analyzed from a prospective registry. Patients were categorized into SAPT, prolonged DAPT/DPI, or DPI groups as per guideline indication by using a risk stratification algorithm. Predictors of receiving intensified regimens and the divergency of practice from guidelines were investigated. Between October 2019 and September 2021, a total of 819 patients were included. Based on the guidelines, 83.7% of patients qualified for SAPT, 9.6% for any intensified regimen (i.e., prolonged DAPT or DPI), and 6.7% for DPI only. At multivariable analysis, patients were more likely to receive an intensified regimen if they had diabetes, dyslipidemia, peripheral artery disease, multivessel disease, or previous myocardial infarction. Conversely, they were less likely to receive an intensified regimen if they had atrial fibrillation, chronic kidney disease, or previous stroke. Guidelines were not followed in 18.3% of cases. In particular, only 14.3% of candidates to intensified regimens were treated accordingly. In conclusion, although the majority of patients who underwent PCI after the initial period of DAPT were eligible for SAPT, 1 out of 6 had an indication to intensified regimens. However, such intensified regimens were underused among eligible patients.

Illness perception, health literacy, self-efficacy, adherence and quality of life in patients with intermittent claudication – a longitudinal cohort study

BackgroundPatients with intermittent claudication need lifelong treatment with secondary prevention to prevent cardiovascular events and progression of atherosclerotic disease. Illness perception, health literacy, self-efficacy, adherence to medication treatment, and quality of life are factors influencing patients’ self-management. Knowledge of these factors could be important when planning for secondary prevention in patients with intermittent claudication.Aimto compare illness perception, health literacy, self-efficacy, adherence to treatment, and quality of life in in patients with intermittent claudication.MethodsA longitudinal cohort study was conducted with 128 participants recruited from vascular units in southern Sweden. Data were collected through medical records and questionnaires regarding illness perception, health literacy, self-efficacy, adherence to treatment, and quality of life.ResultsIn the subscales in illness perception, patients with sufficient health literacy reported less consequences and lower emotional representations of the intermittent claudication. They also reported higher self-efficacy and higher quality of life than patients with insufficient health literacy. In comparison between men and women in illness perception, women reported higher illness coherence and emotional representations associated with intermittent claudication compared to men. A multiple regression showed that both consequences and adherence were negative predictors of quality of life. When examining changes over time, a significant increase in quality of life was seen between baseline and 12 months, but there were no significant differences in self-efficacy..ConclusionIllness perception differs in relation to level of health literacy and between men and women. Further, the level of health literacy seems to be of importance for patients’ self-efficacy and quality of life. This illuminates the need for new strategies for improving health literacy, illness perception, and self-efficacy over time. For example, more tailored information regarding secondary prevention could be provided to strengthen self-management to further improve quality of life in patients with intermittent claudication.

Efficacy and safety of inclisiran in patients with cerebrovascular disease: ORION-9, ORION-10, and ORION-11

Patients with cerebrovascular disease (CeVD) have been shown to benefit from lipid-lowering therapies, but guideline-recommended levels of low-density lipoprotein cholesterol (LDL-C) are often not attained with statin treatment alone. The ORION-9, ORION-10, and ORION-11 trials evaluated the efficacy and safety of inclisiran in 3660 primary and secondary prevention patients with hyperlipidemia despite maximum tolerated statin treatment. This pooled post hoc analysis comprised 202 randomized patients from those trials with established CeVD who had received either 284 mg inclisiran (equivalent to 300 mg inclisiran sodium, n = 110) or placebo (n = 92) on Days 1, 90, and 6-monthly thereafter up to Day 540. At baseline, mean (SD) LDL-C was 108.4 (34.3) mg/dL and 110.5 (35.3) mg/dL in inclisiran and placebo arms, respectively. Inclisiran produced a mean (95% CI) placebo-corrected percentage change in LDL-C from baseline to Day 510 of –55.2 (–64.5 to –45.9; p < 0.0001); the corresponding time-adjusted percentage change from baseline after Day 90 and up to Day 540 was –55.2 (–62.4 to –47.9; p < 0.0001). Treatment-emergent adverse events (TEAEs) and TEAEs at the injection site, mostly mild, were more frequent with inclisiran versus placebo (82.7% vs 70.7% and 3.6% vs 0%, respectively). In patients with CeVD, twice-yearly dosing with inclisiran (after the initial and 3-month doses) in combination with maximally tolerated statins provided effective and consistent LDL-C reductions and was well tolerated.

Bleeding risk and mortality according to antithrombotic agents’ exposure in cancer-related stroke patients: nationwide population-based cohort study in South Korea

BackgroundIschemic stroke with active cancer is thought to have a unique mechanism compared to conventional stroke etiologies. There is no gold standard guideline for secondary prevention in patients with cancer-related stroke, hence, adequate type of antithrombotic agent for treatment is controversial.MethodsSubjects who were enrolled in National Health Insurance System Customized Research data during the period between 2010 and 2015 were observed until 2019. Subject diagnosed with ischemic stroke within six months before and 12 months after a cancer diagnosis was defined as cancer-related stroke patient. To solve immeasurable time bias, the drug exposure evaluation was divided into daily units, and each person-day was classified as four groups: antiplatelet, anticoagulant, both types, and unexposed to antithrombotic drugs. To investigate bleeding risk and mortality, Cox proportional hazards regression model with time-dependent covariates were used.ResultsTwo thousand two hundred eighty-five subjects with cancer-related stroke were followed and analyzed. A group with anticoagulation showed high estimated hazard ratios (HRs) of all bleeding events compared to a group with antiplatelet (major bleeding HR, 1.35; 95% confidence interval [CI], 1.20–1.52; p < 0.001). And the result was also similar in the combination group (major bleeding HR, 1.54; 95% CI, 1.13–2.09; p = 0.006). The combination group also showed increased mortality HR compared to antiplatelet group (HR, 1.72; 95% CI, 1.47–2.00; p < 0.001).ConclusionsBleeding risk increased in the anticoagulant-exposed group compared to antiplatelet-exposed group in cancer-related stroke patients. Thus, this result should be considered when selecting a secondary prevention drug.

Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study

IntroductionIschemic stroke patients with diabetes are at high risk for recurrent stroke and cardiovascular complications. Pioglitazone, a type of thiazolidinedione, has been shown to reduce cardiovascular complications in patients with ischemic stroke and type 2 diabetes (T2D) or insulin resistance. Lobeglitazone is a novel thiazolidinedione agent that improves insulin resistance and has similar glycemic efficacy to pioglitazone. Using population-based health claims data, we evaluated whether lobeglitazone has secondary cardiovascular preventive effects in patients with ischemic stroke and T2D.MethodsThis study has a nested case-control design. From nationwide health claims data in Korea, we identified patients with T2D admitted for acute ischemic stroke in 2014–2018. Cases were defined who suffered the primary outcome (a composite of recurrent stroke, myocardial infarction, and all-cause death) before December 2020. Three controls were selected by incidence density sampling for each case from those who were at risk at the time of their case occurrence with exact matching on sex, age, the presence of comorbidities, and medications. As a safety outcome, we also evaluated the risk of heart failure (HF) according to the use of lobeglitazone.ResultsFrom the cohort of 70,897 T2D patients with acute ischemic stroke, 20,869 cases and 62,607 controls were selected. In the multivariable conditional logistic regression, treatment with lobeglitazone (adjusted OR 0.74; 95% CI 0.61–0.90; p = 0.002) and pioglitazone (adjusted OR 0.71; 95% CI 0.64–0.78; p < 0.001) were significantly associated with a lower risk for the primary outcome. In a safety outcome analysis for HF, treatment with lobeglitazone did not increase the risk of HF (adjusted OR 0.90; 95% CI 0.66–1.22; p = 0.492).ConclusionsIn T2D patients with ischemic stroke, lobeglitazone reduced the risk of cardiovascular complications similar to that of pioglitazone without an increased risk of HF. There is a need for further studies on the cardioprotective role of lobeglitazone, a novel thiazolidinedione.

PO-02-010 CRT COULD NOT MODIFY THE ARRHYTHMIC SUBSTRATE IN PATIENTS WITH PREVIOUS VENTRICULAR TACHYCARDIA/FIBRILLATION

Patients with low cardiac function are at high risk for ventricular arrhythmia (VA). Previous studies showed that cardiac resynchronization therapy (CRT) improved left ventricular remodeling and CRT responder had lower risk of VA than non-responder. However, little is known about the risk of VA among the CRT responder with or without history of VA. The purpose of this study is to investigate the association between VA risk and CRT response among the patients with or without history of VA. Among our cohort of 497 consecutive CRT patients, we retrospectively investigated 351 patients, which included primary and secondary prevention of VA. Exclusion criteria was hemodialysis, date deficit of left ventricular ejection fraction or ventricular volume. VA was defined as lasted ≥ 30s or treated by anti-tachycardia pacing or shock. CRT responders defined as ≥ 15% decrease of in left ventricular end-systolic volume and increase left ventricular ejection fraction ≥ 10% after CRT implantation. Two hundred and forty patients were CRT responder (68.4%), and 70 patients were indication for secondary prevention (19.9%). During a follow-up of 901 days (inter quartile range: 365-1737) 93 patients had VA events (CRT responder: 55pts, CRT non-responder: 38pts). Kaplan-Meier analysis showed the responder had lower risk of VA than the non-responder among all patients (log rank p=0.003) and patients for primary prevention (log rank p=0.004), though there was no significant difference among the patient for secondary prevention (log rank p=0.695). In addition, multivariate analysis showed that responder was independent predictor of VA among the patient for primary prevention (hazard ratio 0.50; 95% confidence interval 0.29-0.84, p=0.009), though responder was not predictor of VA among the patient for secondary prevention (p=0.83) The patients for secondary prevention remain at high risk of VA even among CRT responders. CRT response could not reduce VA substrate.

Aspirin Strategy for Secondary Prevention of Atherosclerotic Cardiovascular Diseases: A Narrative Review

Aspirin is the most used antiplatelet agent for secondary prophylaxis of atherosclerotic cardiovascular diseases. Individual variability in aspirin responsiveness has been widely reported. The current recommendations do not take these variations into consideration. Current guidelines recommend 75–100 mg of once-daily aspirin in all patients for secondary prevention. However, “one-dose-fits-all” may not be the appropriate aspirin dosing strategy. Based on our review, we suggest that patients with inadequate aspirin responsiveness are at increased risk of recurrent cardiovascular events. Noncompliance is the most common cause of poor aspirin response. Ensuring adequate compliance and avoiding concomitant ingestion of nonaspirin nonsteroidal anti-inflammatory drugs and bedtime ingestion of aspirin can help achieve adequate aspirin-mediated antiplatelet activity. A low-dose, twice-daily regimen is the preferred strategy in “high-risk” groups.