Lower Risk Of Major Adverse Cardiovascular Events Research Articles

Symptom-to-balloon time and risk of ventricular arrhythmias in patients with STEMI undergoing percutaneous coronary intervention: The VERY-STEMI study

BackgroundVentricular arrhythmias (VAs) mainly occur in the early post-myocardial infarction (MI) period. However, studies examining the association between total myocardial ischemia time interval and the risk of new-onset VAs during a long-term follow-up are scarce. MethodsThis study (symptom-to-balloon time and VEntricular aRrhYthmias in patients with STEMI, VERY-STEMI study) was a multicenter, observational cohort and real-world study, which included patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI). The primary endpoint was cumulative new-onset VAs during follow-up. The secondary endpoints were the major adverse cardiovascular events (MACE) and changes in left ventricular ejection fraction (ΔLVEF, %). ResultsA total of 517 patients with STEMI were included and 236 primary endpoint events occurred. After multivariable adjustments, compared to patients with S2BT of 24 h-7d, those with S2BT ≤ 24 h and S2BT > 7d had a lower risk of primary endpoint. RCS showed an inverted U-shaped relationship between S2BT and the primary endpoint, with an S2BT of 68.4 h at the inflection point. Patients with S2BT ≤ 24 h were associated with a lower risk of MACE and a 4.44 increase in LVEF, while there was no significant difference in MACE and LVEF change between the S2BT > 7d group and S2BT of 24 h-7d group. ConclusionsS2BT of 24 h-7d in STEMI patients was associated with a higher risk of VAs during follow-up. There was an inverted U-shaped relationship between S2BT and VAs, with the highest risk at an S2BT of 68.4 h.

Cardioprotective Effect of SGLT2 Inhibitor in Diabetic Kidney Transplant Recipients: A Multicenter Propensity Score Matched Study

BackgroundKidney transplantation improves the cardiovascular outcomes of patients with end-stage kidney disease. However, cardiovascular disease remains the leading cause of premature death and graft loss in kidney transplant recipients (KTRs) with diabetes. We evaluated the cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in KTRs with diabetes. MethodsA total of 750 KTRs with diabetes were enrolled from six tertiary hospitals. Among them, 129 (17.2%) patients were prescribed SGLT2i. The primary outcome was the incidence of major adverse cardiovascular events (MACE), which comprised of myocardial infarction (MI), death from cardiovascular causes, hospitalization for heart failure, and stroke. Multivariable Cox regression analysis and propensity score matching were used to investigate the effect of SGLT2i on clinical outcomes. ResultsIn the matched cohort, MACE occurred in 5 (3.9%) patients in the SGLT2i group and 15 (11.8%) patients in the non-SGLT2i group, out of 127 patients in each group over 55.3 months. The incidence of MACE and MI was lower in the SGLT2i group than in the non-SGLT2i group (P=0.036 and 0.008, respectively). In multivariate analysis, the SGLT2i group had a lower risk of MACE and MI than the non-SGLT2i group (adjusted hazard ratio, 0.30 and 0.04; 95% confidence interval, 0.10–0.88 and 0.004–0.40; P=0.028 and 0.006, respectively). There was no difference in the incidence of urinary tract infection between the two groups. ConclusionsSGLT2i significantly decreased the risk of cardiovascular events in KTRs with diabetes, particularly lowering the incidence of MI and death from cardiovascular causes. Therefore, SGLT2i can be used to reduce the burden of cardiovascular disease in KTRs with diabetes.

Intravascular imaging-guided percutaneous coronary intervention in patients with acute myocardial infarction and cardiogenic shock

Introduction and objectivesThere are no clinical data on the efficacy of intravascular imaging-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI in patients with acute myocardial infarction (AMI) and cardiogenic shock. The current study sought to evaluate the impact of intravascular imaging-guided PCI in patients with AMI and cardiogenic shock. MethodsAmong a total of 28 732 patients from the nationwide pooled registry of KAMIR-NIH (November, 2011 to December, 2015) and KAMIR-V (January, 2016 to June, 2020), we selected a total of 1833 patients (6.4%) with AMI and cardiogenic shock who underwent PCI of the culprit vessel. The primary endpoint was major adverse cardiovascular events (MACE) at 1 year, a composite of cardiac death, myocardial infarction, repeat revascularization, and definite or probable stent thrombosis. ResultsAmong the study population, 375 patients (20.5%) underwent intravascular imaging-guided PCI and 1458 patients (79.5%) underwent angiography-guided PCI. Intravascular imaging-guided PCI was associated with a significantly lower risk of 1-year MACE than angiography-guided PCI (19.5% vs 28.2%; HR, 0.59; 95%CI, 0.45-0.77; P<.001), mainly driven by a lower risk of cardiac death (13.7% vs 24.0%; adjusted HR, 0.53; 95%CI, 0.39-0.72; P<.001). These results were consistent in propensity score matching (HR, 0.68; 95%CI, 0.46-0.99), inverse probability weighting (HR, 0.61; 95%CI, 0.45-0.83), and Bayesian analysis (Odds ratio, 0.66, 95% credible interval, 0.49-0.88). ConclusionsIn AMI patients with cardiogenic shock, intravascular imaging-guided PCI was associated with a lower risk of MACE at 1-year than angiography-guided PCI, mainly driven by the lower risk of cardiac death.

Comparison of risk profiles of participants in the Women's IschemiA TRial to Reduce events In non-ObstRuctive CAD (WARRIOR) trial, using Coronary Computed Tomography Angiography vs Invasive Coronary Angiography

ObjectiveTo compare baseline characteristics of participants in the Women's IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR) trial by qualification by Coronary Computed Tomography Angiography (CCTA) or Invasive Coronary Angiography (ICA). MethodsThe WARRIOR trial (NCT03417388) is an ongoing multicenter, prospective, randomized, blinded outcome evaluation of intensive medical therapy vs. usual care in women with suspected Ischemia and No Obstructive Coronary Artery Disease (INOCA) identified by either CCTA or ICA on the outcome of major adverse cardiovascular events (MACE). No obstructive coronary artery disease is defined as <50% luminal stenosis and normal coronary arteries is defined as no evidence of atherosclerosis including calcified and non-calcified plaque. Data presented was extracted on May 27, 2020. No clinical outcomes were assessed. ResultsAn initial sample cohort of 797 women was included. The majority were younger than 65 years, White participants (73.3%), 159 had diabetes (19.9%), and 676 had angina (84.8%) with the remainder having symptoms of suspected ischemic heart disease. Over 50% of randomized participants had normal coronaries without luminal irregularities by ICA or CCTA. Participants randomized to ICA were more likely to have worse baseline clinical risk profiles with older age, higher burden of cardiac risk factors and poor quality of life with disabling angina. ConclusionsAmong this initial sample of women with suspected INOCA randomized in the WARRIOR trial, there is a differential baseline cardiac risk of participants enrolled after CCTA or ICA. However, the majority had no evidence of atherosclerotic plaque or obstructive stenosis, after evaluation by ICA or CCTA. These results suggest that non-invasive evaluation with CCTA is likely to be associated with lower risk of MACE.

Outcomes of SGLT-2i and GLP-1RA Therapy Among Patients With Type 2 Diabetes and Varying NAFLD Status

Nonalcoholic fatty liver disease (NAFLD) is a cardiovascular risk factor, but whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with reduced cardiovascular risk in patients with type 2 diabetes (T2D) and concomitant NAFLD remains uncertain. To investigate the outcomes of SGLT-2i and GLP-1RA therapy among patients with T2D varied by the presence or absence of NAFLD. This retrospective, population-based, nationwide cohort study used an active-comparator new-user design. Two distinct new-user active-comparator cohorts of patients aged 40 years and older who initiated SGLT-2i or GLP-1RA were propensity score matched to patients who initiated dipeptidyl peptidase-4 inhibitors (DPP-4i). The study was conducted in South Korea from January 2013 to December 2020, and data analysis was conducted from October 2022 to March 2023. The main outcomes were (1) major adverse cardiovascular events (MACE), a composite end point of hospitalization for myocardial infarction, hospitalization for stroke, and cardiovascular death, and (2) hospitalization for heart failure (HHF). Cox proportional hazards models were used to estimate hazard ratios (HRs). The Wald test was applied to assess heterogeneity by NAFLD. After 1:1 propensity score matching, 140 438 patients were retrieved in the first cohort (SGLT-2i vs DPP-4i; mean [SD] age, 57.5 [10.3] years; 79 633 [56.7%] male) and 34 886 patients were identified in the second cohort (GLP-1RA vs DPP-4i; mean [SD] age, 59.5 [10.5] years; 17 894 [51.3%] male). Compared with DPP-4i, SGLT-2i therapy was associated with a lower risk of MACE (HR, 0.78 [95% CI, 0.71-0.85]) and HHF (HR, 0.62 [95% CI, 0.48-0.81]). GLP-1RA therapy was associated with a decreased risk of MACE (HR, 0.49 [95% CI, 0.39-0.62]) but had statistically nonsignificant findings regarding HHF (HR, 0.64 [95% CI, 0.39-1.07]). Stratified analysis by NAFLD status yielded consistent results for SGLT-2i (MACE with NAFLD: HR, 0.73 [95% CI, 0.62-0.86]; without NAFLD: HR, 0.81 [95% CI, 0.72-0.91]; HHF with NAFLD: HR, 0.76 [95% CI, 0.49-1.17]; without NAFLD: HR, 0.56 [95% CI, 0.40-0.78]) and for GLP-1RA (MACE with NAFLD: HR, 0.49 [95% CI, 0.32-0.77]; without NAFLD: HR, 0.49 [95% CI, 0.37-0.65]; HHF with NAFLD: HR, 0.82 [95% CI, 0.38-1.76]; without NAFLD: HR, 0.54 [95% CI, 0.27-1.06]). In this population-based cohort study, SGLT-2i therapy was associated with a decreased risk of MACE and HHF, while GLP-1RA therapy was associated with a decreased risk of MACE among patients with T2D, irrespective of baseline NAFLD status.

Intensity of and adherence to lipid-lowering therapy as predictors of goal attainment and major adverse cardiovascular events in primary prevention

The effectiveness of lipid-lowering therapy (LLT) for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in routine care may depend on treatment intensity and adherence. Observational study of adults with newly initiated LLT for primary prevention of ASCVD in Stockholm, Sweden, during 2017-2021. Study exposures were LLT adherence [proportion of days covered (PDC)], LLT intensity (expected reduction of LDL cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity were calculated during the previous 12 months, and the patients estimated ASCVD risk was categorized. Study outcomes were major adverse cardiovascular events (MACE) and LDL-C goal attainment. Thirty-six thousand two hundred eighty-three individuals (mean age 63 years, 47% women, median follow-up 2 years), with a baseline low-moderate (40%), high (49%), and very-high (11%) ASCVD risk started LLT. Increases in LLT adherence, intensity, or adherence-adjusted intensity of 10% over 1 year were associated with lower risks of MACE (with hazard ratios of 0.95 [95% CI, 0.93-0.98]; 0.93 [0.86-1.00]; and 0.90 [0.85-0.95], respectively) and higher odds of attaining LDL goals. Patients with good adherence (≥80%) had similar risks of MACE and similar odds ratios for LDL-C goal attainment with low-moderate and high-intensity LLT. Treatment discontinuation was associated with increased MACE risk. The relative and absolute benefits of good adherence were greatest in patients with very high ASCVD risk. In routine-care primary prevention, better adherence to LLT was associated with a lower risk of MACE across all treatment intensities. Improving adherence is especially important among patients with very high ASCVD risk.

Coffee consumption and adverse outcome events in patients with atrial fibrillation

Abstract Background/Introduction Moderate coffee consumption has been associated with a lower risk of major adverse cardiovascular events (MACE) in the general population. However, there are some concerns that coffee consumption might be harmful for patients with atrial fibrillation (AF). Purpose The aim of this study was to investigate the association of coffee consumption with MACE and other adverse outcome events in AF patients. Methods Data of AF patients from two large prospective, multicenter cohort studies (yearly based follow-up data from Swiss-AF and Beat-AF) were used for this analysis. Coffee consumption was assessed and categorized into two main groups "not-daily" and "daily" consumers and subcategories (&amp;lt;1, 1, 2-3 and ≥4cups/day). The primary endpoint was defined as a composite of stroke or systemic embolism, myocardial infarction, hospitalization for acute heart failure and cardiovascular death (MACE). We performed time-updated multivariable adjusted Cox regression analyses to investigate the association of coffee consumption with MACE and other adverse outcome events. Results Among 3,835 patients (mean age 71.4 years, 28.0% females), 3,095 (80.7%) reported daily coffee consumption. The incidence rate for MACE was 5.09 in daily and 7.49 per 100py in not-daily consumers. Cumulative incidence curves are presented in Figure 1. After comprehensive multivariable adjustment, daily coffee consumption was associated with a 23% relative risk reduction for MACE compared to not-daily consumption (hazard ratio (HR) (95% confidence interval (CI)) 0.77 (0.67-0.89), p&amp;lt;0.001;). Compared to patients with not-daily coffee consumption, patients with moderate coffee consumption (2-3 cups/day) had the lowest hazard for MACE (HR (95%CI) 0.73 (0.62; 0.85), p&amp;lt;0.001). The associations between coffee consumption and all adverse outcome events are presented in Figure 2. Conclusion In a population of AF patients, daily coffee consumption was associated with a lower risk of MACE and other adverse outcomes. These findings seem to be similar to those in the general population.

Exercise performance and the risk of incident atrial fibrillation

Abstract Background Atrial fibrillation (AF) is a global health problem that correlates with the increased risks of cardiovascular diseases, quality of life, mortality and global health expenditures. While many of cardiovascular risk factors have been related to the development of AF, a satisfied lifestyle behavior, including regular exercise and a good cardiorespiratory fitness, could be the upstream intervention to modify the risk factors and reduce the AF incidence. Purpose We examined the relationship of the exercise performance with risk of incident atrial fibrillation and its subsequent comorbidities. Methods From 2003 to 2012, we retrospectively included 19,680 consecutive patients without previous diagnosis of AF, who were referred to exercise treadmill testing for clinical reasons. The baseline characteristics and the exercise parameters during exercise testing were accessed in all enrolled subjects. Multivariable Cox proportional hazard models identified the independent association between exercise performance and risk of new-onset atrial fibrillation, risk of ischemic stroke and major adverse cardiovascular events (MACE). Cubic spline regression model assessed the risk of new-onset AF across fitness level. Results Among a total of 15,450 subjects (mean age, 54.9 ± 11 years; 59% male) with a median follow-up duration of 137 months, 515 (3.33%) new-onset AF cases were found. There was an 8% lower risk of AF incidence (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97), a 12% lower risk of ischemic stroke incidence (hazard ratio, 0.88; 95% confidence interval, 0.83-0.94), and a 14% lower risk of MACE (hazard ratio, 0.86; 95% confidence interval, 0.84-0.88) for every 1 peak achieved metabolic equivalents (METs) increase in the exercise treadmill testing after adjusting confounding factors. In the subgroup analysis, the peak achieved METs during exercise treadmill testing was significantly associated with the risk of new-onset AF across various subgroups, including age, gender, body mass index (BMI) and underlying diseases. There were significant interactions in age subgroup (P for interaction 0.0047) and subgroup stratified by the presence of chronotropic incompetence (P for interaction 0.0212). Conclusions Exercise capacity is inversely correlated with AF incidence across fitness level. A better exercise performance indicates a lower AF incidence, ischemic stroke incidence and MACE. Regular physical activity may help to reduce inflammation and improve the function of the heart, which may help to prevent the development of AF. Further research is needed to fully understand the underlying mechanisms.Kaplan–Meier curveSubgroup analysis

Association of medical therapy with cardiovascular outcomes in patients with myocardial infarction with nonobstructive coronary arteries

Abstract Background Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a disease that has been poorly characterized with unclear clinical and therapeutic outcomes. The association of medical therapy with cardiovascular outcomes in patients with MINOCA has been inadequately assessed. The purpose of this meta-analysis is to evaluate the association of medical therapy with cardiovascular outcomes in patients with MINOCA. Methods A literature search was conducted for studies reporting on the association of medical therapy with clinical endpoints in patients with MINOCA. Clinical endpoints include all-cause mortality, recurrence of acute coronary syndrome (ACS), and major adverse cardiovascular events (MACE). Databases searched included Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. Results A total of 9 studies with 27731 MINOCA patients (17816 on medical therapy, 9915 not on medical therapy) met inclusion criteria. Mean follow-up duration was 56 months, mean age was 63 years old, 52% were men. Medical therapy did not significantly reduce risk of MACE compared to no medical therapy (OR 0.99, 95% CI 0.91-1.07; p=0.73). Subgroup analysis demonstrated no significant reduction in risk of MACE regardless of ACE inhibitors/ARBs, antiplatelet therapy, or beta blocker therapy (OR 1.03, 95% CI 0.91-1.17; p=0.62; OR 1.00, 95% CI 0.87-1.14; p=0.98; OR 0.92, 95% CI 0.79-1.06; p=0.22). However, there is a trend toward lower risk of MACE in MINOCA patients on beta blocker therapy. Analysis of MINOCA patients by presence of vasospasm did not demonstrate any significant reduction in risk of MACE with antiplatelet use in either subgroups (OR 1.03, 95% CI 0.71-1.49; p=0.89 without vasospasm; OR 0.92, 95% CI 0.74-1.14; p=0.44 with vasospasm). Use of antiplatelet therapy in patients with vasospasm did not significantly reduce risk of mortality or recurrent ACS (OR 0.80, 95% CI 0.37-1.75; p=0.58; OR 1.21, 95% CI 0.89-1.64; p=0.22). Conclusions Standard medical therapy using antiplatelet agents, beta blockers, or ACE inhibitors/ARBs are not associated with lower risk of cardiovascular outcomes in patients with MINOCA regardless of presence of vasospasm. However, there is a paucity in literature evaluating agents other than antiplatelet therapies. Additional high-quality studies are required to evaluate the utility of specific medication classes for treatment of specific etiologies of MINOCA.

Adherence to guideline-directed medical therapy and 3-year clinical outcome following acute myocardial infarction

Abstract Aims Despite the well-established clinical benefits and strong recommendations in clinical guidelines, adherence to guideline-directed medical therapy (GDMT) is known to be insufficient. We investigated the adherence to GDMT and its impact on the 3-year clinical outcomes in patients with acute myocardial infarction (AMI). Methods and results Source data were obtained from KAMIR-NIH, a Korean multicenter observational registry. GDMT was defined according to the ACC/AHA class I recommendations. Adherence to GDMT was assessed at discharge and every year thereafter. The differences in clinical characteristics between patients receiving and those not receiving GDMT were adjusted using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary endpoint was major adverse cardiovascular events (MACE), which was a composite of all-cause death and non-fatal MACE, including MI, revascularization, or stroke. Of 12,815 patients, GDMT adherence was 70.2% at discharge, and decreased gradually into 54.6% at 3-year. GDMT at discharge was associated with lower MACE risk in the unadjusted analysis (HR=0.51, 95%CI=0.47–0.55, p&amp;lt;0.001) and also in the PSM- or IPTW-adjusted analyses (HR=0.77, 95%CI=0.69–0.86; HR=0.79, 95%CI=0.72–0.86; p&amp;lt;0.001, all). These findings were replicated in the 1-year or 2-year landmark analyses (HR=0.58 to 0.82, p&amp;lt;0.01, all). Conclusion Adherence to GDMT was suboptimal among patients with AMI in Korea. As the adherence to GDMT was associated with a lower incidence of MACE during 3-year follow-up, the maintenance of long-term GDMT might be crucial for patients with AMI.Structured Graphical Abstract

An Updated Meta-Analysis of Clinical Trials and Observational Studies of Intravascular Ultrasound- versus Angiography-guided Left Main Stenting

Objectives: This updated meta-analysis aimed to consolidate clinical evidence comparing the clinical outcomes of intravascular ultrasound (IVUS)-guided LMCA stenting versus conventional angiography-guided LMCA stenting. Methodology: We included “randomized controlled trials” and “observational studies” published in peer-reviewed English language journals that compared the clinical outcomes of LMCA revascularization using “drug-eluting stents (DES)” via “IVUS-guided” versus “angiography-guided” stenting. The primary outcome of interest was “major adverse cardiovascular events (MACE)”, while secondary outcome variables included “all-cause mortality”, “myocardial infarction (MI)”, “target vessel/lesion revascularization (TVR/TLR)”, and “stent thrombosis (ST)”. Risk ratios (RRs) for each outcome variable were calculated using the “Mantel-Haenszel method”. Results: The analysis included nine studies involving a total of 5,344 patients, with 2,282 undergoing “IVUS-guided” LMCA stenting and 3,062 undergoing “angiography-guided” LMCA stenting. “IVUS-guided” LMCA stenting showed a significant reduction in the risk of MACE compared to “angiography-guided” LMCA stenting, with a RR of 0.46 [95% CI: 0.27 - 0.79]. However, a high level of heterogeneity (I2=94%; p&lt;0.01) was observed among the included studies. Additionally, “IVUS-guided” LMCA stenting was associated with significant reductions in all-cause mortality, MI, and ST, with RRs of 0.38 [0.21 - 0.66], 0.45 [0.26 - 0.77], and 0.24 [0.10 - 0.57], respectively. There was no statistically significant difference in TVR/TLR between “IVUS-guided” and “angiography-guided” LMCA stenting, with an RR of 0.64 [0.27 - 1.51]. Conclusion: “IVUS-guided” LMCA revascularization using DES was associated with a lower risk of MACE, death, MI, and ST compared to conventional “angiography-guided” LMCA stenting.

Brief bouts of device-measured intermittent lifestyle physical activity and its association with major adverse cardiovascular events and mortality in people who do not exercise: a prospective cohort study

Guidelines emphasise the health benefits of bouts of physical activity of any duration. However, the associations of intermittent lifestyle physical activity accumulated through non-exercise with mortality and major adverse cardiovascular events (MACE) remain unclear. We aimed to examine the associations of bouts of moderate-to-vigorous intermittent lifestyle physical activity (MV-ILPA) and the proportion of vigorous activity contributing within these bouts with mortality and MACE. In this prospective cohort study, we used data from the UK Biobank on adults who do not exercise (ie, those who did not report leisure-time exercise) who had wrist-worn accelerometry data available. Participants were followed up until Nov 30, 2022, with the outcome of interest of all-cause mortality obtained through linkage with NHS Digital of England and Wales, and the NHS Central Register and National Records of Scotland, and MACE obtained from inpatient hospitalisation data provided by the Hospital Episode Statistics for England, the Patient Episode Database for Wales, and the Scottish Morbidity Record for Scotland. MV-ILPA bouts were derived using a two-level Random Forest classifier and grouped as short (<1 min), medium (1 to <3 min; 3 to <5 min), and long (5 to <10 min). We further examined the dose-response relationship of the proportion of vigorous physical activity contributing to the MV-ILPA bout. Between June 1, 2013, and Dec 23, 2015, 103 684 Biobank participants wore an accelerometer on their wrist. 25 241 adults (mean age 61·8 years [SD 7·6]), of whom 14 178 (56·2%) were women, were included in our analysis of all-cause mortality. During a mean follow-up duration of 7·9 years (SD 0·9), 824 MACE and 1111 deaths occurred. Compared with bouts of less than 1 min, mortality risk was lower for bouts of 1 min to less than 3 min (hazard ratio [HR] 0·66 [0·53-0·81]), 3 min to less than 5 min (HR 0·56 [0·46-0·69]), and 5 to less than 10 min (HR 0·48 [0·39-0·59]). Similarly, compared with bouts of less than 1 min, risk of MACE was lower for bouts of 1 min to less than 3 min (HR 0·71 [0·54-0·93]), 3 min to less than 5 min (0·62 [0·48-0·81]), and 5 min to less than 10 min (0·59 [0·46-0·76]). Short bouts (<1 min) were associated with lower MACE risk only when bouts were comprised of at least 15% vigorous activity. Intermittent non-exercise physical activity was associated with lower mortality and MACE. Our results support the promotion of short intermittent bouts of non-exercise physical activity of moderate-to-vigorous intensity to improve longevity and cardiovascular health among adults who do not habitually exercise in their leisure time. Australian National Health, Medical Research Council, and Wellcome Trust.

Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular events.

Long-chain omega-3 polyunsaturated fatty acids (OM3 PUFA) are commonly used for cardiovascular disease prevention. High-dose eicosapentaenoic acid (EPA) is reported to reduce major adverse cardiovascular events (MACE); however, a combined EPA and docosahexaenoic acid (DHA) supplementation has not been proven to do so. This study aimed to evaluate the potential interaction between EPA and DHA levels on long-term MACE. We studied a cohort of 987 randomly selected subjects enrolled in the INSPIRE biobank registry who underwent coronary angiography. We used rapid throughput liquid chromatography-mass spectrometry to quantify the EPA and DHA plasma levels and examined their impact unadjusted, adjusted for one another, and fully adjusted for comorbidities, EPA + DHA, and the EPA/DHA ratio on long-term (10-year) MACE (all-cause death, myocardial infarction, stroke, heart failure hospitalization). The average subject age was 61.5 ± 12.2 years, 57% were male, 41% were obese, 42% had severe coronary artery disease (CAD), and 311 (31.5%) had a MACE. The 10-year MACE unadjusted hazard ratio (HR) for the highest (fourth) vs. lowest (first) quartile (Q) of EPA was HR = 0.48 (95% CI: 0.35, 0.67). The adjustment for DHA changed the HR to 0.30 (CI: 0.19, 0.49), and an additional adjustment for baseline differences changed the HR to 0.36 (CI: 0.22, 0.58). Conversely, unadjusted DHA did not significantly predict MACE, but adjustment for EPA resulted in a 1.81-fold higher risk of MACE (CI: 1.14, 2.90) for Q4 vs. Q1. However, after the adjustment for baseline differences, the risk of MACE was not significant for DHA (HR = 1.37; CI: 0.85, 2.20). An EPA/DHA ratio ≥1 resulted in a lower rate of 10-year MACE outcomes (27% vs. 37%, adjusted p-value = 0.013). Higher levels of EPA, but not DHA, are associated with a lower risk of MACE. When combined with EPA, higher DHA blunts the benefit of EPA and is associated with a higher risk of MACE in the presence of low EPA. These findings can help explain the discrepant results of EPA-only and EPA/DHA mixed clinical supplementation trials.

Comparative effectiveness of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, and sulfonylureas on risk of major adverse cardiovascular events: emulation of a randomised target trial using electronic health records

Randomised clinical trials showed that compared with placebo, SGLT2 inhibitors and GLP-1 receptor agonists reduced risk of adverse cardiovascular events. The evidence base for the older antihyperglycaemic drug classes (DPP-4 inhibitors and sulfonylureas) is generally less well developed. Because most randomised trials evaluated one antihyperglycaemic medication versus placebo, a head-to-head comparative effectiveness analysis of the newer drug classes (SGLT2 inhibitors vs GLP-1 receptor agonists) or newer (SGLT2 inhibitors or GLP-1 receptor agonists) versus older (DPP-4 inhibitors or sulfonylureas) drug classes on risk of major adverse cardiovascular events (MACE) is not available. In this study, we aimed to evaluate the comparative effectiveness of incident use of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or sulfonylureas on risk of MACE. We first specified the protocol of a four-arm randomised pragmatic clinical trial and then emulated it using the health-care databases of the US Department of Veterans Affairs. We built a cohort of metformin users with incident use of SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, or sulfonylureas between Oct 1, 2016 and Sept 30, 2021, and followed up until Dec 31, 2022. We used the overlap weighting approach to balance the treatment groups using a battery of predefined variables and a set of algorithmically selected variables from high-dimensional data domains. Both intention-to-treat and per-protocol analyses (the latter estimated the effect of maintained use of the antihyperglycaemic throughout follow-up) were conducted to estimate risk of MACE-defined as a composite endpoint of stroke, myocardial infarction, and all-cause mortality. The final cohort consisted of 283 998 new users of SGLT2 inhibitors (n=46 516), GLP-1 receptor agonists (n=26 038), DPP-4 inhibitors (n=55 310), or sulfonylureas (n=156 134). In intention-to-treat analyses, compared with sulfonylureas, SGLT2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors were associated with lower risk of MACE (hazard ratio [HR] 0·77 [95% CI 0·74-0.80], 0·78 [0·74-0·81), and 0·90 [0·86-0.93], respectively). Both SGLT2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of MACE when compared with DPP-4 inhibitors (HR 0·86 [0·82-0·89] and 0·86 [0·82-0·90], respectively). The risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists yielded an HR of 0·99 (0·94-1·04). In per-protocol analyses, compared with sulfonylureas, SGLT2 inhibitors, GLP1 receptor agonists, and DPP-4 inhibitors were associated with reduced risk of MACE (HR 0·77 [95% CI 0·73-0·82], 0·77 [0·72-0·82], and 0·88 [0·83-0·93], respectively). Both SGLT2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of MACE when compared with DPP-4 inhibitors (HR 0·88 [0·83-0·93] and 0·88 [0·82-0·93], respectively). The risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists yielded an HR of 1·01 (0·94-1·07). Both SGLT2 inhibitors and GLP-1 receptor agonists were associated with reduced risk of MACE compared with DPP-4 inhibitors or sulfonylureas. DPP-4 inhibitors were associated with reduced risk of MACE compared with sulfonylureas. There was no statistically significant difference in risk of MACE between SGLT2 inhibitors and GLP-1 receptor agonists. The results provide evidence of the real-world comparative effectiveness of the four most commonly used second-line antihyperglycaemics and could guide choice of antihyperglycaemic therapy. US Department of Veterans Affairs and the American Society of Nephrology.

Relationship Between Paraoxonase-1 Genotype and Activity, and Major Adverse Cardiovascular Events and Malignancies in Patients with Rheumatoid Arthritis Receiving Tofacitinib.

This post hoc analysis investigated the relationship between paraoxonase-1 (PON1) genotype and activity, and risk of major adverse cardiovascular events (MACE) and malignancies in tofacitinib rheumatoid arthritis (RA) clinical studies. Data were pooled from 9 phase II/III studies and the associated long-term extension studies (all completed by October 2017). PON1 activities in plasma were measured using paraoxon (paraoxonase activity), dihydrocoumarin (lactonase activity), and phenylacetate (arylesterase activity) as substrates. PON1 Q192R genotype effect on baseline PON1 activity was assessed using linear regression for each study, with fixed-effects meta-analysis across studies. MACE and malignancy risk by time-varying enzyme activity was determined using Cox proportional hazards regression. The analysis included 1,969 patients with RA. Compared with the QQ genotype, RR had a significant positive association with baseline paraoxonase activity and a significant negative association with baseline lactonase and arylesterase activity (all p < 0.001). Time-varying models demonstrated a significant association of increased paraoxonase activity over time with lower risk of MACE (p < 0.001) and malignancies (excluding non-melanoma skin cancer [NMSC]; p ≤ 0.05), even after controlling for risk factors identified in univariate analysis and RA disease activity. A similar trend was observed for lactonase and arylesterase for MACE. Higher paraoxonase activity over time was associated with significantly reduced risk of future MACE and malignancies (excluding NMSC), but not NMSC, in patients with RA receiving tofacitinib. Further investigation of PON1 as a novel functional lipid biomarker of MACE/malignancy risk in patients with RA is warranted.

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndrome and on Dialysis: A Meta-Analysis.

This study aims to compare the safety and efficacy of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS) and undergoing dialysis.This study was conducted per the guidelines of the Preferred Reporting of Systematic Reviews and Meta-Analyses (PRISMA). A comprehensive search was performed using electronic databases, including PubMed, EMBASE, and Web of Science, to identify relevant studies comparing clopidogrel and ticagrelor in patients undergoing dialysis. To ensure the inclusion of all relevant articles, a combination of the following keywords, along with medical subject heading(MeSH) terms, was used: "clopidogrel," "ticagrelor," "acute coronary syndrome," and "dialysis."The primary endpoint of this meta-analysis was the incidence of major adverse cardiovascular events (MACE), which consisted of cardiovascular death, myocardial infarction, stroke, and revascularization. The secondary endpoint was all-cause mortality. The occurrence of any bleeding events (including major and nonmajor bleeding events) and major bleeding events was chosen as the safety endpoints. A total of four studies were included in the pooled analysis.The pooled sample size was 5,417 patients, including 892 in the ticagrelor group and4525 in the clopidogrel group.The findings indicate that ticagrelor, compared to clopidogrel, is associated with a significantly higher risk of MACEs, all-cause death, and major bleeding events.The findings suggest that clopidogrel may be a better choice for individuals with ACS undergoing dialysis due to its lower risk of MACE, all-cause death, and major bleeding events compared to ticagrelor.

Association between Coronary Artery Disease Reporting and Data System–recommended Post–Coronary CT Angiography Management and Clinical Outcomes in Patients with Stable Chest Pain from a Chinese Registry

Background Coronary Artery Disease Reporting and Data System (CAD-RADS) was developed to standardize and optimize disease management in patients after coronary CT angiography (CCTA), but the impact of CAD-RADS management recommendations on clinical outcomes remains unclear. Purpose To retrospectively assess the association between the appropriateness of post-CCTA management according to CAD-RADS version 2.0 and clinical outcomes. Materials and Methods From January 2016 to January 2018, consecutive participants with stable chest pain referred for CCTA were prospectively included in a Chinese registry and followed for 4 years. Retrospectively, CAD-RADS 2.0 classification and the appropriateness of post-CCTA management were determined. Propensity score matching (PSM) was used to adjust for confounding variables. Hazard ratios (HRs) for a major adverse cardiovascular event (MACE), relative risks for invasive coronary angiography (ICA), and the corresponding number needed to treat were estimated. Results Of the 14 232 included participants (mean age, 61 years ± 13 [SD]; 8852 male), 2330, 2756, and 2614 were retrospectively categorized in CAD-RADS 1, 2, and 3, respectively. Only 26% of participants with CAD-RADS 1-2 disease and 20% with CAD-RADS 3 received appropriate post-CCTA management. After PSM, appropriate post-CCTA management was associated with lower risk of MACEs (HR, 0.34; 95% CI: 0.22, 0.51; P < .001), corresponding to a number needed to treat of 21 in CAD-RADS 1-2 but not CAD-RADS 3 (HR, 0.86; 95% CI: 0.49, 1.85; P = .42). Appropriate post-CCTA management was associated with decreased use of ICA in CAD-RADS 1-2 (relative risk, 0.40; 95% CI: 0.29, 0.55; P < .001) and 3 (relative risk, 0.33; 95% CI: 0.28, 0.39; P < .001), resulting in a number needed to treat of 14 and 2, respectively. Conclusion In this retrospective secondary analysis, appropriate disease management after CCTA according to CAD-RADS 2.0 was associated with lower risk of MACEs and more prudent use of ICA. ClinicalTrials.gov registration no. NCT04691037 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Leipsic and Tzimas in this issue.

Implementation of CYP2C19 genotyping and clinical outcomes following percutaneous coronary intervention in East Asian patients treated with oral P2Y12 inhibitors

BackgroundThe CYP2C19 loss-of-function variants have significant impact on response to clopidogrel. The efficacy and safety of tailored antiplatelet therapy under the guidance of CYP2C19 genetic polymorphisms remains elusive for patients undergoing percutaneous coronary intervention (PCI). ObjectivesThe aims of the present study were to investigate the impact of clinical implementation of CYP2C19 genotyping on the selection of oral P2Y12 inhibitor therapy following PCI, and to estimate the risk of adverse outcomes for patients with different genotype status treated with alternative or traditional P2Y12 inhibitor. MethodsData from a single-center registry enrolling 41,090 consecutive PCI patients treated with dual antiplatelet therapy after PCI were analyzed. Risk of major adverse cardiovascular events (MACEs) and bleeding events within 12 months after PCI were compared across CYP2C19 genotype and antiplatelet therapy groups using Cox proportional hazards models. ResultsCYP2C19 genotyping was successfully achieved for 9081 patients, of whom baseline characteristics significantly differed from non-genotyped patients. A higher proportion of genotyped patients were prescribed ticagrelor compared with non-genotyped patients (27.0 % vs. 15.5 %, P < 0.001). CYP2C19 metabolic status was an independent predictor for use of ticagrelor (P < 0.001). Ticagrelor was significantly associated with a lower risk of MACEs in poor metabolizers (adjusted hazard ratio 0.62, 95 % confidence interval 0.42 to 0.92, P = 0.017), but not in intermediate metabolizers or normal metabolizers. The interaction was not statistically significant (P for interaction = 0.252). ConclusionsGenotype information on CYP2C19 metabolic status was associated with an increase in the use of potent antiplatelet therapy in PCI patients. Patients prescribed with clopidogrel has a higher risk of MACEs among poor metabolizers, which suggested the potential application of genotype-guided P2Y12 inhibitor selection for improving clinical outcomes.

Association between regular exercise and the risk of major adverse cardiovascular events in patients with pacemaker

Abstract Funding Acknowledgements Type of funding sources: None. Background The optimal amount of exercise for preventing cardiovascular events in patients with pacemakers has not been revealed. Methods Using the Korean National Health Insurance Service database, patients who had newly implanted pacemakers between 2009 and 2018 were included. The amount of physical activity was measured by a self-reported questionnaire included in the national health examination. Performing regular exercise was defined as ≥5 days of moderate-intensity exercise or ≥3 days of vigorous-intensity exercise per week. The occurrence of major adverse cardiovascular events (MACE) defined as the composite of stroke, heart failure, myocardial infarction, and all-cause death was evaluated during follow-up. Results A total of 13,542 patients were included (mean age 68±11 years, 45% of men); 51% of patients were atrioventricular block and 39% of patients were sick sinus syndrome, and 85% of patients were implanted with dual-chamber pacemaker. During a median 2.5-year of follow-up, the incidence rates of MACE was 5.4 and 3.7 per 100 person-years in non-exerciser and exerciser, respectively (Figure A). Compared to non-exerciser, patients performing regular exercise were associated with a lower risk of MACE (hazard ratio, 95% confidence interval: 0.745, 0.661-0.839, p&amp;lt;0.001, Figure B). Patients with ≥450 metabolic equivalents (METs) which was the highest quartile cut-off of exercise amount were significantly associated with a lower risk of MACE (0.765, 0.686-0.853, p&amp;lt;0.001) than patients with &amp;lt;450 METs. Compared to persistent non-exerciser before and after pacemaker implantation, persistent exercisers and exercise-starters showed a significantly lower risk of MACE (0.788, 0.662-0.938, p=0.007 and 0.584, 0.462-0.738, p&amp;lt;0.001, respectively, Figure C). Conclusion Regular physical activity was related to the risk of MACE in patients with pacemaker. A proactive cardiac rehabilitation program would be considered for this population.

Pioglitazone, SGLT2 inhibitors and their combination for primary prevention of cardiovascular disease and heart failure in type 2 diabetes: Real-world evidence from a nationwide cohort database

ObjectiveTo evaluate the effect of SGLT2is, pioglitazone, and their combination on the risk of major adverse cardiovascular events (MACE) and heart failure in type 2 diabetes mellitus (T2DM) patients without a history of cardiovascular disease. Research design and methodsUsing Taiwan National Health Insurance Research Database, we identified four groups based on medication use, including 1) both SGLT2is and pioglitazone, 2) SGLT2i, 3) pioglitazone and 4) non-study drugs (reference group). The four groups were matched by propensity score. The primary outcome was 3-point MACE, which included myocardial infarction, stroke, cardiovascular death, and the secondary outcome was incidence of heart failure. ResultsAfter propensity-matching, each group included 15,601 patients. Compared with the reference group, the pioglitazone/SGLT2i combination group had a significantly lower risk for MACE (aHR 0.76, 95 % CI 0.66–0.88) and heart failure (aHR 0.67, 95 % CI 0.55–0.82). Pioglitazone was associated with a lower risk of MACE (aHR 0.82, 95 % CI 0.71–0.94) and there was no difference in risk of heart failure compared with the reference group. The incidence of heart failure was significantly decreased in the SGLT2i group (aHR 0.7, 95 % CI 0.58–0.86). ConclusionCombination therapy with pioglitazone and SGLT2is is an effective treatment in the primary prevention of MACE and heart failure in patients with type 2 diabetes.