Mitral Annular Tissue Velocity Predicts Survival in Patients With Primary Mitral Regurgitation.

BACKGROUND AND OBJECTIVES: Early diastolic mitral annular tissue (e') velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e' velocity in patients with mitral regurgitation (MR). METHODS: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. According to the current guidelines, the cut-off value of e' velocity was defined as 7 cm/s. RESULTS: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e' velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634-0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477-0.998; p=0.049). Abnormal e' velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170-5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189-21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e' velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308-0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680-1.356; p<0.001). CONCLUSIONS: In patients aged <65 years with primary MR, e' velocity served as an independent predictor of all-cause and cardiovascular deaths.

Machine Learning-Based Discrimination of Cardiovascular Outcomes in Patients With Hypertrophic Cardiomyopathy.

Background: Current risk stratification strategies for patients with hypertrophic cardiomyopathy (HCM) are limited to traditional methodologies. Objectives: The authors aimed to establish machine learning (ML)-based models to discriminate major cardiovascular events in patients with HCM. Methods: We enrolled consecutive HCM patients from 2 tertiary referral centers and used 25 clinical and echocardiographic features to discriminate major adverse cardiovascular events (MACE), including all-cause death, admission for heart failure (HF-adm), and stroke. The best model was selected for each outcome using the area under the receiver operating characteristic curve (AUROC) with 20-fold cross-validation. After testing in the external validation cohort, the relative importance of features in discriminating each outcome was determined using the SHapley Additive exPlanations (SHAP) method. Results: In total, 2,111 patients with HCM (age 61.4 ± 13.6 years; 67.6% men) were analyzed. During the median 4.0 years of follow-up, MACE occurred in 341 patients (16.2%). Among the 4 ML models, the logistic regression model achieved the best AUROC of 0.800 (95% CI: 0.760-0.841) for MACE, 0.789 (95% CI: 0.736-0.841) for all-cause death, 0.798 (95% CI: 0.736-0.860) for HF-adm, and 0.807 (95% CI: 0.754-0.859) for stroke. The discriminant ability of the logistic regression model remained excellent when applied to the external validation cohort for MACE (AUROC = 0.768), all-cause death (AUROC = 0.750), and HF-adm (AUROC = 0.806). The SHAP analysis identified left atrial diameter and hypertension as important variables for all outcomes of interest. Conclusions: The proposed ML models incorporating various phenotypes from patients with HCM accurately discriminated adverse cardiovascular events and provided variables with high importance for each outcome.

Mildly Reduced Renal Function Is Associated With Increased Heart Failure Admissions in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The association between renal dysfunction and cardiovascular outcomes has yet to be determined in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate whether mildly reduced renal function is associated with the prognosis in patients with HCM. METHODS: Patients with HCM were enrolled at two tertiary HCM centers. Patients who were on dialysis, or had a previous history of heart failure (HF) or stroke were excluded. Patients were categorized into 3 groups by estimated glomerular filtration rate (eGFR): stage I (eGFR ≥ 90 mL/min/1.73 m², n = 538), stage II (eGFR 60-89 mL/min/1.73 m², n = 953), and stage III-V (eGFR < 60 mL/min/1.73 m², n = 265). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, hospitalization for HF (HHF), or stroke during median 4.0-year follow-up. Multivariable Cox regression model was used to adjust for covariates. RESULTS: Among 1,756 HCM patients (mean 61.0 ± 13.4 years; 68.1% men), patients with stage III-V renal function had a significantly higher risk of MACEs (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.39-5.27; P = 0.003), which was largely driven by increased incidence of cardiovascular death and HHF compared to those with stage I renal function. Even in patients with stage II renal function, the risk of MACE (vs. stage I: aHR, 2.21' 95% CI, 1.23-3.96; P = 0.008) and HHF (vs. stage I: aHR, 2.62; 95% CI, 1.23-5.58; P = 0.012) was significantly increased. CONCLUSION: This real-world observation showed that even mildly reduced renal function (i.e., eGFR 60-89 mL/min/1.73 m²) in patients with HCM was associated with an increased risk of MACEs, especially for HHF.

Accelerometer-derived physical activity and the risk of death, heart failure, and stroke in patients with atrial fibrillation: a prospective study from UK Biobank.

OBJECTIVE: Data on cardiovascular outcomes according to objectively measured physical activity (PA) in patients with atrial fibrillation (AF) are scarce. This study explored the associations between PA derived from wrist-worn accelerometers and the risk of death, incident heart failure (HF), and incident stroke in patients with AF. METHODS: From 37 990 patients with AF in UK Biobank, 2324 patients with accelerometer data were included. Weekly moderate-to-vigorous PA (MVPA) duration was computed from accelerometer data. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, incident HF, and incident stroke. Restricted cubic splines estimated the dose-response associations between MVPA duration and the outcomes. The adjusted HRs (aHRs) of the outcomes according to adherence to PA standard guidelines (performing MVPA≥150 min/week) were also evaluated. RESULTS: The mean age was 66.9±6.2 years and 64.9% were male. During a median follow-up of 6.7 years, there were 181 all-cause deaths, 62 cardiovascular deaths, 225 cases of incident HF, and 91 cases of incident stroke; the overall incidence rate per 1000 patient-years was 11.76, 4.03, 15.16 and 5.99, respectively. There was a linear inverse dose-response relationship between MVPA (≥108 min/week) and all-cause mortality. Performing MVPA for 105-590 min/week was associated with a lower risk of HF than those with no measurable MVPA. The risk of stroke and cardiovascular mortality was not associated with MVPA. Performing guideline-adherent MVPA was related to a 30% lower risk of all-cause mortality (aHR: 0.70 (0.50-0.98), p=0.04) and 33% lower risk of HF (aHR 0.67 (0.49-0.93), p=0.02). CONCLUSION: In patients with AF, accelerometer-derived PA data supports lower risks of all-cause mortality and HF according to a greater level of MVPA and adherence to PA guidelines. Regular MVPA should be encouraged in patients with AF as a part of integrated management.

Neuroticism and the Risk of Atrial Fibrillation: An Observational Epidemiologic and Mendelian Randomization Study.

Background: The association between neuroticism and atrial fibrillation (AF) remains unknown. Objectives: This study aimed to assess the epidemiological and causal relationships between neuroticism and AF. Methods: Individuals without AF history were selected From the UK Biobank nationwide prospective cohort study. Participants were divided into 2 groups (high and low) based on the median summary score from a self-questionnaire of 12 neurotic behavior domains. The 10-year AF risk was compared between the neuroticism score groups using inverse probability of treatment weighting. The causal relationship between neuroticism and AF was evaluated using a 2-sample summary-level Mendelian randomization with the inverse variance-weighted method. Results: Of 394,834 participants (mean age 56.3 ± 8.1 years, 45.9% male), AF occurred in 23,509 (6.0%) during a 10-year follow-up. The risk of incident AF significantly increased in the high neuroticism score group (score ≥4) (inverse probability of treatment weighting-adjusted HR: 1.05; 95% CI: 1.02-1.09; P = 0.005) compared with the low neuroticism group. In the subgroup analysis, younger age, lower body mass index, or nonsmoker/ex-smoker participants were particularly susceptible to increased AF risk due to high neuroticism scores. A Mendelian randomization analysis showed a significant causal relationship between an increase in neuroticism score and increased risk of AF (OR by inverse variance-weighted method 1.06; 95% CI: 1.02-1.11; P = 0.007) without evidence of reverse causality. Conclusions: There was a significant longitudinal and causal relationship between neuroticism and AF. An integrated care including active mental health screening and management may benefit in high-risk populations.

Association between Cumulative Metabolic Risk Exposure and Cardiovascular Disease: A Nationwide Cohort of Over 3.6 Million Young Adults.

AIMS: Since lifetime accumulation of cardiovascular risk factors is getting important, early identification and management of risk factors are emphasised. The global prevalence of metabolic syndrome (MetS), a constellation of these risk factors, is increasing, particularly among young adults. We aimed to investigate the association between cumulative exposure to metabolic risk and cardiovascular disease (CVD) in young adults. METHODS: In this nationwide population-based cohort, we analysed 3,688,787 young adults (<40 years) with two biennial National Health Screening examinations from 2009 to 2012. Participants were categorised into MetS-free, MetS-developed, MetS-recovered, or MetS-persistent group, based on MetS presence at each examination. The endpoint was new CVD development, including myocardial infarction (MI), and ischaemic stroke. RESULTS: During follow-up (median, 7.7 years), CVD occurred in 19,219 individuals (0.5%). CVD incidence rates were 0.58, 1.17, 1.20, and 1.83 (1,000 person-year) in the MetS-free, MetS-developed, MetS-recovered, and MetS-persistent groups, respectively. CVD risk was proportionally associated with cumulative metabolic risk exposure, with a maximum 2-fold increase in the MetS-persistent group (aHR 1.94, 95% CI 1.84-2.04), and followed by the MetS-recovered and MetS-developed groups with similar risks. Among the MetS components, persistent exposure to elevated blood pressure (BP) had the greatest association with CVD risk (aHR 1.69, 95% CI 1.63-1.76). This tendency was consistent in the analyses of the risk of MI and ischaemic stroke. CONCLUSIONS: CVD risk increased in an exposure-dependent manner among young adults. Efforts to optimise cardiometabolic profile, particularly BP, even after the establishment of MetS, might help promote long-term cardiovascular prognosis.

In this large-scale nationwide cohort comprising 3,688,787 asymptomatic young adults under 40 years, we showed that the long-term risk of cardiovascular disease (CVD) increased in proportion with cumulative exposure to metabolic risk, as assessed by the temporal changes in metabolic syndrome (MetS) status, with blood pressure (BP) demonstrating the greatest impact. The risk of CVD exhibited a gradual increase in accordance with cumulative metabolic risk exposure, with a 2-fold increment in the MetS-persistent group. Among the MetS components, persistent exposure to elevated BP had the most profound impact to increase the risk of CVD, and the optimisation of BP levels might be helpful to promote long-term cardiovascular health in young adults.

Differing Efficacy of Dapagliflozin Versus Empagliflozin on the Risk of Incident Atrial Fibrillation in Patients With Type 2 Diabetes: A Real-World Observation Using a Nationwide, Population-Based Cohort.

BACKGROUND: Meta-analyses of large clinical trials investigating SGLT2 (sodium-glucose cotransporter-2) inhibitors have suggested their protective effects against atrial fibrillation in patients with type 2 diabetes. However, the results were predominantly driven from trials involving dapagliflozin. METHODS AND RESULTS: We used a nationwide, population-based cohort of patients with type 2 diabetes who initiated either dapagliflozin or empagliflozin between May 2016 and December 2018. An active-comparator, new-user design was used, and the 2 groups of patients were matched using propensity scores. The primary outcome was incident nonvalvular atrial fibrillation, which was analyzed using both the main intention-to-treat and sensitivity analysis that censored patients who skipped their medications for ≥30 days. Men ≥55 years of age and women ≥60 years of age with ≥1 traditional risk factor or those with established cardiovascular disease were categorized as high cardiovascular risk group. Patients not included in the high-risk group were categorized as low risk. After 1:1 propensity-score matching, a total of 137 928 patients (mean age, 55 years; 58% men) were included and followed up for 2.2±0.6 years. The risk of incident atrial fibrillation was significantly lower in the dapagliflozin group in both the main (hazard ratio [HR], 0.885 [95% CI, 0.789-0.992]) and sensitivity analyses (HR, 0.835 [95% CI, 0.719-0.970]). Notably, this was consistent in both the low and high cardiovascular risk groups. There was no effect modification by age, sex, body mass index, duration of diabetes, or renal function. CONCLUSIONS: This real-world, population-based study demonstrates that patients with type 2 diabetes using dapagliflozin may have a lower risk of developing nonvalvular atrial fibrillation than those using empagliflozin.

Sacubitril/valsartan and the risk of incident dementia in heart failure: a nationwide propensity-matched cohort study.

BACKGROUND: Sacubitril acts to inhibit neprilysin and as neprilysin is involved in amyloid-beta degradation in the central nervous system, and there is concern that sacubitril/valsartan may increase the risk of dementia. We aimed to compare the risk of incident dementia associated with sacubitril/valsartan and angiotensin II receptor blockers (ARBs). METHODS: Patients with heart failure with reduced ejection fraction treated with either sacubitril/valsartan or ARB, identified from the Korean National Health Insurance Service database, were matched in a 1:2 ratio using propensity scores (6789 on sacubitril/valsartan and 13,578 on ARBs) and followed up for incident dementia. RESULTS: During a mean follow-up of 2.5 years, 526 (2.6%) patients were newly diagnosed with dementia: Alzheimer dementia in 282, vascular dementia in 8, and other dementia in 236. There was no significant difference in the risk of overall dementia (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.70-1.01), Alzheimer dementia (HR 0.85, 95% CI 0.67-1.10), vascular dementia (HR 0.98, 95% CI 0.23-4.11), and all other dementias (HR 0.81, 95% CI 0.62-1.07) between sacubitril/valsartan users and ARB users. These results were consistent regardless of initial sacubitril/valsartan dose and subgroups including old age, previous mild cognitive impairment, previous stroke, and concomitant antiplatelet or anticoagulation. Sensitivity analysis with a 1-year lag period for dementia assessment confirmed the main analysis. Meanwhile, risk of incident stroke was lower in sacubitril/valsartan users compared to ARBs users. CONCLUSIONS: In a nationwide propensity-matched cohort of patients with heart failure, sacubitril/valsartan was not associated with an increased risk of incident dementia compared to ARBs. Sacubitril/valsartan and the risk of incident dementia in heart failure. ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor.

Prognostic and Safety Implications of Renin-Angiotensin-Aldosterone System Inhibitors in Hypertrophic Cardiomyopathy: A Real-World Observation Over 2,000 Patients.

BACKGROUND AND OBJECTIVES: The prognostic or safety implication of renin-angiotensin-aldosterone system inhibitors (RASi) in hypertrophic cardiomyopathy (HCM) are not well established, mainly due to concerns regarding left ventricular outflow tract (LVOT) obstruction aggravation. We investigated the implications of RASi in a sizable number of HCM patients. METHODS: We enrolled 2,104 consecutive patients diagnosed with HCM in 2 tertiary university hospitals and followed up for five years. RASi use was defined as the administration of RASi after diagnostic confirmation of HCM. The primary and secondary outcomes were all-cause mortality and hospitalization for heart failure (HHF). RESULTS: RASi were prescribed to 762 patients (36.2%). During a median follow-up of 48.1 months, 112 patients (5.3%) died, and 94 patients (4.5%) experienced HHF. Patients using RASi had less favorable baseline characteristics than those not using RASi, such as older age, more frequent history of comorbidities, and lower ejection fraction. Nonetheless, there was no difference in clinical outcomes between patients with and without RASi use (log-rank p=0.368 for all-cause mortality and log-rank p=0.443 for HHF). In multivariable analysis, patients taking RASi showed a comparable risk of all-cause mortality (hazard ratio [HR], 0.70, 95% confidence interval [CI], 0.43-1.14, p=0.150) and HHF (HR, 1.03, 95% CI, 0.63-1.70, p=0.900). In the subgroup analysis, there was no significant interaction of RASi use between subgroups stratified by LVOT obstruction, left ventricular (LV) ejection fraction, or maximal LV wall thickness. CONCLUSIONS: RASi use was not associated with worse clinical outcomes. It might be safely administered in patients with HCM if clinically indicated.

Neuroticism and sudden cardiac death: a prospective cohort study from UK biobank.

OBJECTIVE: There is a paucity of evidence on the risk of sudden cardiac death (SCD) according to the degree of neuroticism. We sought to evaluate the association between neuroticism and the long-term risk of SCD. METHODS: From the UK Biobank nationwide prospective cohort, participants free from previous SCD, ventricular arrhythmias, implantable cardioverter-defibrillator (ICD) insertion, depression, schizophrenia, and bipolar disorder were selected. The 12-item scale of neuroticism measurement (neuroticism score) was categorized into high (≥ 3) and low (< 3) groups. The primary outcome was SCD including ventricular fibrillation (VF) at median 12.6 years of follow-up. The outcomes were compared between the groups using multivariable Cox regression and inverse probability of treatment weighting (IPTW). RESULTS: A total of 377,563 participants (aged 56.5 ± 8.1, 53.1% women) were analyzed. The high neuroticism score group had a significantly lower risk of SCD (adjusted hazard ratio [aHR] = 0.87, 95% confidence interval [CI] 0.79-0.96, P = 0.007; IPTW-adjusted HR [IPTW-HR] 0.87 [0.77-0.97], P = 0.016) than the low neuroticism score group. The effect of a high neuroticism score on the decreased risk of SCD was more prominent in women (IPTW-HR 0.71 [0.56-0.89], P = 0.003) than in men (IPTW-HR 0.93 [0.82-1.07], P = 0.305, P-for-interaction = 0.043). Sex differences were observed among independent predictors for incident SCD, emphasizing the protective role of a high neuroticism score and moderate-to-vigorous physical activity only in women. CONCLUSIONS: A high neuroticism score was significantly associated with a lower risk of SCD, particularly in women. Efforts to unveil the causal and mechanistic relationship between personality phenotypes and the risk of SCD should be continued.

Left ventricular global longitudinal strain as a prognosticator in hypertrophic cardiomyopathy with a low-normal left ventricular ejection fraction.

AIMS: The aim of this study was to investigate the prognostic utility of left ventricular (LV) global longitudinal strain (LV-GLS) in patients with hypertrophic cardiomyopathy (HCM) and an LV ejection fraction (LVEF) of 50-60%. METHODS AND RESULTS: This retrospective cohort study included 349 patients with HCM and an LVEF of 50-60%. The primary outcome was a composite of cardiovascular death, including sudden cardiac death (SCD) and SCD-equivalent events. The secondary outcomes were SCD/SCD-equivalent events, cardiovascular death (including SCD), and all-cause death. The final analysis included 349 patients (mean age 59.2 ± 14.2 years, men 75.6%). During a median follow-up of 4.1 years, the primary outcome occurred in 26 (7.4%), while the secondary outcomes of SCD/SCD-equivalent events, cardiovascular death, and all-cause death occurred in 15 (4.2%), 20 (5.7%), and 34 (9.7%), respectively. After adjusting for age, atrial fibrillation, ischaemic stroke, LVEF, and left atrial volume index, absolute LV-GLS (%) was independently associated with the primary outcome [adjusted hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.788-0.988, P = 0.029]. According to receiver operating characteristic analysis, 10.5% is an optimal cut-off value for absolute LV-GLS in predicting the primary outcome. Patients with an absolute LV-GLS ≤ 10.5% had a higher risk of the primary outcome than those with an absolute LV-GLS > 10.5% (adjusted HR 2.54, 95% CI 1.117-5.787, P = 0.026). Absolute LV-GLS ≤ 10.5% was an independent predictor for each secondary outcome (P < 0.05). CONCLUSIONS: LV-GLS was an independent predictor of a composite of cardiovascular death, including SCD/SCD-equivalent events, in patients with HCM and an LVEF of 50-60%. Therefore, LV-GLS can help in risk stratification in these patients.

Comparative cardiovascular outcomes in type 2 diabetes patients taking dapagliflozin versus empagliflozin: a nationwide population-based cohort study.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea. METHODS: Korean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome. RESULTS: A total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855-1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714-0.989) and cardiovascular death (HR 0.76, 95% CI 0.618-0.921), which were significantly lower in the dapagliflozin users. CONCLUSIONS: This large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus.

Predictive Value of Electromechanical Window for Risk of Fatal Ventricular Arrhythmia.

BACKGROUND: As an indicator of electro-mechanical coupling, electromechanical window (EMW) can be used to predict fatal ventricular arrhythmias. We investigated the additive effect of EMW on the prediction of fatal ventricular arrhythmias in high-risk patients. METHODS: We included patients who had implantable cardioverter-defibrillator (ICD) implanted for primary or secondary prevention. The event group was defined as those who received an appropriate ICD therapy. We acquired echocardiograms at ICD implantation and follow-up. The EMW was calculated as the difference between the interval from QRS onset to aortic valve closure and QT interval from the electrocardiogram embedded in the continuous wave doppler image. We evaluated the predictive value of EMW for predicting fatal ventricular arrhythmia. RESULTS: Of 245 patients (67.2 ± 12.8 years, 63.7% men), the event group was 20.0%. EMW at baseline (EMW-Baseline) and follow-up (EMW-FU) was significantly different between event and control groups. After adjustment, both EMW-Baseline (odds ratio [OR]adjust 1.02 [1.01-1.03], P = 0.004) and EMW-FU (ORadjust 1.06 [1.04-1.07], P < 0.001) remained as significant predictors for fatal arrhythmic events. Adding EMW-Baseline significantly improved the discriminating ability of the multivariable model including clinical variables (area under the curve [AUC] 0.77 [0.70-0.84] vs. AUC 0.72 [0.64-0.80], P = 0.004), while a univariable model using EMW-FU alone showed the best performance among models (AUC 0.87 [0.81-0.94], P = 0.060 against model with clinical variables; P = 0.030 against model with clinical variables and EMW-Baseline). CONCLUSION: The EMW could effectively predict severe ventricular arrhythmia in ICD implanted patients. This finding supports the importance of incorporating the electro-mechanical coupling index into the clinical practice for predicting future fatal arrhythmia events.

Cost-Effectiveness of Clopidogrel vs Aspirin Monotherapy After Percutaneous Coronary Intervention: Results From the HOST-EXAM Study.

Background: The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Disease-Extended Antiplatelet Monotherapy) trial showed superior efficacy and safety of clopidogrel monotherapy compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention (PCI). Objectives: The goal of this study was to investigate the cost-effectiveness of clopidogrel monotherapy compared with that of aspirin monotherapy. Methods: A Markov model was developed for patients in the stable phase after PCI. From the perspectives of the South Korean, UK, and U.S. health care systems, the lifetime health care costs and quality-adjusted life-years (QALYs) of each strategy were estimated. Transition probabilities were obtained from the HOST-EXAM trial, and health care costs and health-related utilities were obtained from data and literature for each country. Results: From the perspective of the South Korean health care system, the base-case analysis showed that clopidogrel monotherapy was $3,192 higher in lifetime health care costs and 0.139 lower in QALYs compared with aspirin. This result was greatly influenced by the numerically but insignificantly higher cardiovascular mortality of clopidogrel compared with aspirin. In the analogous UK and U.S. models, clopidogrel monotherapy was projected to decrease health care costs by £1,122 and $8,920 per patient compared with aspirin monotherapy while reducing QALYs by 0.103 and 0.175, respectively. Conclusions: Based on empirical data from the HOST-EXAM trial, clopidogrel monotherapy was projected to lead to reduced QALYs compared with aspirin during the chronic maintenance period after PCI. These results were affected by a numerically higher rate of cardiovascular mortality in clopidogrel monotherapy reported from the HOST-EXAM trial. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250).

Association of Clinical Outcomes With Sex in Patients Receiving Chronic Maintenance Antiplatelet Monotherapy After Percutaneous Coronary Intervention: A Post Hoc Gender Analysis of the HOST-EXAM Study.

Background Clopidogrel monotherapy was more effective in reducing the risk of adverse clinical events than aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES), according to the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it remains unknown whether these effects differ based on sex. Methods and Results This was a prespecified secondary analysis of HOST-EXAM in South Korea. Patients who maintained dual antiplatelet therapy without adverse clinical events for 6 to 18 months after PCI with DES were included. The primary end point was a composite of all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndrome, or Bleeding Academic Research Consortium (BARC) bleeding type ≥3 at 24 months after randomization. The bleeding end point was BARC types 2 to 5. The primary end point was comparable between the sexes (adjusted hazard ratio [HR], 0.79 [95% CI, 0.62-1.02]; P=0.067), and the bleeding end point (adjusted HR, 0.79 [95% CI, 0.54-1.17]; P=0.240) was also similar. Compared with aspirin, clopidogrel was associated with lower risk of primary composite end point (adjusted HR, 0.70 [95% CI, 0.55-0.89]; P=0.004) and bleeding end point (adjusted HR, 0.65 [95% CI, 0.44-0.96]; P=0.031) in men but not in women. Conclusions The primary composite end point and bleeding events were comparable between the sexes during chronic maintenance antiplatelet monotherapy after PCI with DES. Clopidogrel monotherapy, compared with aspirin, significantly reduced the risk of the primary composite end point and bleeding events in men. However, the beneficial effect of clopidogrel on the primary end point and bleeding events was mitigated in women. Registration Information clinicaltrials.gov. Identifier: NCT02044250.

Aspirin vs Clopidogrel for Long-term Maintenance After Coronary Stenting in Patients With Diabetes: A Post Hoc Analysis of the HOST-EXAM Trial.

Importance: Selecting the optimal antiplatelet agent in patients who have received percutaneous coronary intervention is especially important in those with diabetes due to the heightened risk of ischemic events in this population. Studies on the efficacy and safety of clopidogrel vs aspirin for long-term maintenance after percutaneous coronary intervention in patients with diabetes are lacking. Objective: To investigate cardiovascular outcomes with clopidogrel vs aspirin in patients with and without diabetes. Design, Setting, and Participants: This was a post hoc analysis of the HOST-EXAM randomized clinical trial, an investigator-initiated, prospective, randomized, open-label, multicenter trial performed at 37 centers in Korea. Patients who received dual antiplatelet therapy without clinical events for 6 to 18 months after percutaneous coronary intervention with drug-eluting stents were enrolled from March 2014 to May 2018 with follow-up at 6, 12, 18, and 24 months. All 5438 patients in the original trial were included in this analysis, which was conducted from June to October 2021. Interventions and Exposures: Enrolled patients were randomized 1:1 to clopidogrel or aspirin monotherapy. Subgroup analyses were performed by the presence of diabetes. Main Outcomes and Measures: The main outcome was primary composite end point of all-cause death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type 3 or 5) at 24-month follow-up. Results: Of 5438 patients (mean [SD] age, 63.5 [10.7] years; 1384 [25.5%] female), 1860 (34.2%) had diabetes (925 in the clopidogrel arm and 935 in the aspirin arm), and 5338 (98.2%) completed follow-up. The rate of the primary composite end point was significantly lower in the clopidogrel group compared to the aspirin group in patients with diabetes (6.3% vs 9.2%; hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03; absolute risk difference [ARD], 2.7%; number needed to treat [NNT], 37) and without diabetes (5.3% vs 7.0%; HR, 0.76; 95% CI, 0.58-1.00; P = .046; ARD, 1.6%, NNT, 63; P for interaction = .65). The presence of diabetes was not associated with a difference in benefit observed with clopidogrel monotherapy over aspirin for the thrombotic composite end point (HR, 0.68; 95% CI, 0.45-1.04 for patients with diabetes vs HR, 0.68; 95% CI, 0.49-0.93 for those without; P for interaction = .99) and any bleeding with Bleeding Academic Research Consortium 2, 3, or 5 (HR, 0.65; 95% CI, 0.39-1.09 for patients with diabetes vs HR, 0.74; 95% CI, 0.48-1.13 for those without; P for interaction = .71). Conclusion and Relevance: In this study, clopidogrel monotherapy was associated with a lower rate of the primary composite end point compared to aspirin monotherapy as long-term maintenance therapy after dual antiplatelet therapy for coronary stenting in both patients with and without diabetes. Clopidogrel might thus be considered rather than aspirin in patients who have undergone coronary stenting and successfully completed dual antiplatelet therapy, regardless of diabetes status. Trial Registration: ClinicalTrials.gov Identifier: NCT02044250.

Impact of coronary artery revascularization on long-term outcome in hypertrophic cardiomyopathy patients: a nationwide population-based cohort study.

Limited data are available on the long-term outcomes in patients with hypertrophic cardiomyopathy (HCM) patients with significant coronary artery disease (CAD) requiring revascularization. We investigated the risk of cardiovascular outcomes in HCM patients who underwent coronary revascularization compared to the control group without HCM. HCM patients aged ≥ 20 years were enrolled from the Korean National Health Insurance Database. Information on the diagnosis and previous medical history was obtained from the claims data. Cardiovascular outcomes were identified during 8-year after coronary revascularization in HCM patients (HCM group) and matched controls without HCM (non-HCM control group). A total of 431 patients in the HCM group and 1968 in the non-HCM control group were analyzed. The risk of all-cause death, cardiovascular death, sudden cardiac death (SCD), ischemic stroke, and hospitalization due to heart failure was significantly higher in the HCM group than in the non-HCM group, with prominent risk increase of cardiovascular death (adjusted hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.63-3.15, P < 0.001) and ischemic stroke (adjusted HR 2.38, 95% CI 1.55-3.64, P < 0.001). Beyond 1-year after revascularization, the HCM group still had a significantly higher risk of cardiovascular death, SCD, and ventricular fibrillation/tachycardia compared to the non-HCM group. Mortality and major cardiovascular outcomes occurred more frequently in HCM patients with significant CAD requiring revascularization, compared to the matched non-HCM control group. Active and regular surveillance for concomitant risk factors and relevant intervention are warranted in HCM patients at increased risk for CAD.

Prognosis after discontinuing renin angiotensin aldosterone system inhibitor for heart failure with restored ejection fraction after acute myocardial infarction.

Prognostic effect of discontinuing renin-angiotensin-aldosterone-system-inhibitor (RAASi) for patients with heart failure (HF) after acute myocardial infarction (AMI) whose left ventricular (LV) systolic function was restored during follow-up is unknown. To investigate the outcome after discontinuing RAASi in post-AMI HF patients with restored LV ejection fraction (EF). Of 13,104 consecutive patients from the nationwide, multicenter, and prospective Korea Acute Myocardial Infarction-National Institutes of Health (KAMIR-NIH) registry, HF patients with baseline LVEF < 50% that was restored to ≥ 50% at 12-month follow-up were selected. Primary outcome was a composite of all-cause death, spontaneous MI, or rehospitalization for HF at 36-month after index procedure. Of 726 post-AMI HF patients with restored LVEF, 544 maintained RAASi (Maintain-RAASi) beyond 12-month, 108 stopped RAASi (Stop-RAASi), and 74 did not use RAASi (RAASi-Not-Used) at baseline and follow-up. Systemic hemodynamics and cardiac workloads were similar among groups at baseline and during follow-up. Stop-RAASi group showed elevated NT-proBNP than Maintain-RAASi group at 36-month. Stop-RAASi group showed significantly higher risk of primary outcome than Maintain-RAASi group (11.4% vs. 5.4%; adjusted hazard ratio [HRadjust] 2.20, 95% confidence interval [CI] 1.09-4.46, P = 0.028), mainly driven by increased risk of all-cause death. The rate of primary outcome was similar between Stop-RAASi and RAASi-Not-Used group (11.4% vs. 12.1%; HRadjust 1.18 [0.47-2.99], P = 0.725). In post-AMI HF patients with restored LV systolic function, RAASi discontinuation was associated with significantly increased risk of all-cause death, MI, or rehospitalization for HF. Maintaining RAASi will be necessary for post-AMI HF patients, even after LVEF is restored.

Association between renin-angiotensin-aldosterone system blockade and clinical outcomes in patients with hypertension: real-world observation from a nationwide hypertension cohort.

OBJECTIVE: We investigated the association between the use of ACEi, ARB, or non-renin-angiotensin-aldosterone system inhibitors (non-RASi) and incident cardiovascular events in an unselected nationwide hypertension cohort. METHODS: The information regarding 2,025,849 patients who underwent general health checkup between 2010 and 2011 and were on antihypertensive medication was collected. Patients were allocated into ACEi, ARB, and non-RASi groups and followed until 2019. The outcomes of interest were myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), heart failure (HF), and all-cause deaths. RESULTS: Patients on ACEi and ARB showed unfavorable baseline characteristics compared to those on non-RASi. After adjusting for covariates, the ACEi group showed lower risks of MI, AF, and all-cause deaths (HR (95% CI): 0.94 (0.89-0.99), 0.96 (0.92-1.00), and 0.93 (0.90-0.96), respectively), but similar risks of IS and HF (0.97 (0.92-1.01) and 1.03 (1.00-1.06), respectively), compared to the non-RASi group. Likewise, the ARB group showed decreased risks of MI, IS, AF, HF, and all-cause deaths (HR (95% CI): 0.93 (0.91-0.95), 0.88 (0.86-0.90), 0.86 (0.85-0.88), 0.94 (0.93-0.96), and 0.84 (0.83-0.85)), compared to the non-RASi group. Sensitivity analysis of patients taking a single antihypertensive medication showed similar results. In the propensity score matching (PSM) cohort, the ARB group showed similar risks of MI and decreased risks of IS, AF, HF, and all-cause deaths compared to the ACEi group. CONCLUSIONS: ACEi and ARB users were associated with decreased risks of MI, IS, AF, HF, and all-cause deaths, compared to non-RASi users.