Higher Risk Of Major Adverse Cardiovascular Events Research Articles

Day-to-day fasting plasma glucose variability on the short-term prognosis of ST-segment elevation myocardial infarction: A retrospective cohort study.

Glycemic variability in one fact that explain the differences in cardiovascular outcomes. The short-term fasting plasma glucose (FPG) variability may have an on major adverse cardiovascular events (MACE) in type 2 diabetes mellitus (T2DM) patients with ST-segment elevation myocardial infarction (STEMI). This study retrospectively analyzed T2DM patients who underwent emergent percutaneous coronary intervention (PCI) due to STEMI in Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, between January 2016 and March 2020. All patients underwent at least 5 FPG measurements during the perioperative period. FPG variability score (FPG-VS) was defined as the percentage of the number of FPG variations > 1 mmol/L between two adjacent FPG measurements. The Cox proportional-hazards model was used to estimate the relationship between FPG-VS and MACE. A validation set was utilized to further evaluate the prognostic value of FPG-VS in a standardized STEMI diabetic diet cohort following PCI intervention. A total of 612 patients were included in the retrospective cohort study. In comparison to the minimum quintile, FPG-VS > 60% was associated with an increased risk of 30-day MACE. Moreover, compared to FPG-VS ≤ 20%, the FPG-VS > 80% group had a higher risk of MACE (odd ratio [OR] = 4.87, 95% confidence interval [CI]: 2.55-5.28), recurrent angina pectoris (OR = 5.43, 95%CI: 2.27-8.27), nonfatal myocardial infarction (OR = 5.00, 95%CI: 2.47-7.69), heart failure (OR = 3.70, 95%CI: 1.92-5.54), malignant arrhythmia (OR = 4.63, 95%CI: 1.12-6.25) and cardiac death (OR = 1.41, 95%CI: 0.17-1.97). Consistent results were obtained after adjustment for HbA1c, demonstrating the robustness of FPGFPG-VS. Moreover, the standard diet intervention group had a lower FPG-VS index as well as a lower incidence of MACE. Higher FPG variability is associated with an increased risk of MACE within 30 days in diabetes patients receiving PCI for STEMI. A standardized diet may improve the prognosis of STEMI patients by reducing the FPG-VS.

Association between Serum Cystatin C levels and long-term cardiovascular outcomes and all-cause mortality in older patients with obstructive sleep apnea.

Background and Aims: To investigate the association between obstructive sleep apnea (OSA) severity and baseline serum cystatin C (Cys-C) concentration and to explore the association between baseline serum Cys-C and long-term cardiovascular outcomes and mortality in older patients with OSA. Methods: Between January 2015 and October 2017, a total of 1107 consecutive eligible older patients (≥60 years) with OSA were included in this multicenter, prospective cohort study, and baseline demographics, clinical characteristics, sleep parameters, and follow-up outcomes were collected. Participants were divided into different groups based on baseline serum Cys-C levels. The primary end point was major adverse cardiovascular events (MACE) and the secondary end point was all-cause mortality. The correlation between OSA severity and baseline serum Cys-C was evaluated by Spearman correlation analysis. Multivariate Cox regression was used to analyze the association between Cys-C and the incidence of MACE and mortality. Results: Participants included 672 men and 435 women, with a median age of 66 (range, 60–96) years. At baseline, apnea–hypopnea index (AHI) (r = 0.128, p < 0.05), oxygen desaturation index (ODI) (r = 0.116, p < 0.05), and the lowest pulse oxygen saturation (LSpO2) (r = −0.097, p < 0.05) were correlated with serum Cys-C concentration. During the median follow-up period of 42 months, 97 patients (8.8%) experienced MACE and 40 patients (3.6%) experienced death. The association between serum Cys-C levels and the risk of MACE and all-cause mortality was slow rising shaped. The multivariable Cox regression analysis showed patients with a serum Cys-C concentration of ≥1.14 mg/L had higher risks of MACE (HR = 5.30, 95% CI: 2.28–12.30, p < 0.05) and all-cause mortality (HR = 9.66, 95% CI: 2.09–44.72, p < 0.05) compared with patients with serum Cys-C of ≤0.81 mg/L in older patients with OSA. The receiver-operating characteristic curve showed baseline serum Cys-C levels exhibited moderately capable of identifying patients with a long-term risk of clinical adverse events (MACE and mortality). Conclusion: OSA severity was positively correlated with serum Cys-C concentration. High levels of Cys-C were independently associated with increased risks of MACE and all-cause mortality in older patients with OSA, suggesting that lowering Cys-C levels should be considered as a therapeutic target, and monitoring serum Cys-C may be beneficial to the favorable prognosis of older patients with OSA.

A nomogram risk prediction model for no-reflow after primary percutaneous coronary intervention based on rapidly accessible patient data among patients with ST-segment elevation myocardial infarction and its relationship with prognosis.

BackgroundNo-reflow occurring after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) can increase the incidence of major adverse cardiovascular events (MACE). The present study aimed to construct a nomogram prediction model that can be quickly referred to before surgery to predict the risk for no-reflow after PCI in STEMI patients, and to further explore its prognostic utility in this patient population.MethodsResearch subjects included 443 STEMI patients who underwent primary PCI between February 2018 and February 2021. Rapidly available clinical data obtained from emergency admissions were collected. Independent risk factors for no-reflow were analyzed using a multivariate logistic regression model. Subsequently, a nomogram for no-reflow was constructed and verified using bootstrap resampling. A receiver operating characteristic (ROC) curve was plotted to evaluate the discrimination ability of the nomogram model and a calibration curve was used to assess the concentricity between the model probability curve and ideal curve. Finally, the clinical utility of the model was evaluated using decision curve analysis.ResultsThe incidence of no-reflow was 18% among patients with STEMI. Killip class ≥2 on admission, pre-operative D-dimer and fibrinogen levels, and systemic immune–inflammation index (SII) were independent risk factors for no-reflow. A simple and quickly accessible prediction nomogram for no-reflow after PCI was developed. This nomogram demonstrated good discrimination, with an area under the ROC curve of 0.716. This nomogram was further validated using bootstrapping with 1,000 repetitions; the C-index of the bootstrap model was 0.706. Decision curve analysis revealed that this model demonstrated good fit and calibration and positive net benefits. Kaplan–Meier survival curve analysis revealed that patients with higher model scores were at a higher risk of MACE. Multivariate Cox regression analysis revealed that higher model score(s) was an independent predictor of MACE (hazard ratio 2.062; P = 0.004).ConclusionsA nomogram prediction model that can be quickly referred to before surgery to predict the risk for no-reflow after PCI in STEMI patients was constructed. This novel nomogram may be useful in identifying STEMI patients at higher risk for no-reflow and may predict prognosis in this patient population.

Outcomes after coronary angiography for unstable angina compared to stable angina, myocardial infarction and an asymptomatic general population.

BackgroundThe outcomes of real-world unstable angina (UA) in the high-sensitivity troponin era are unclear. We aimed to investigate the outcomes of UA referred to coronary angiography compared to stable angina (SA), non-ST-segment elevation myocardial infarction (NSTEMI), STEMI and a general population.MethodsWe included the 9,694 patients with no prior coronary artery disease (CAD) referred to invasive or CT coronary angiography from 2013 to 2018 in Northern Norway (51% SA, 12% UA, 23% NSTEMI and 14% STEMI), and 11,959 asymptomatic individuals recruited from the Tromsø Study. We used Cox models to estimate the hazard ratios (HR) for all-cause mortality and major adverse cardiovascular events (MACE), defined as cardiovascular death, MI or obstructive CAD.ResultsThe median follow-up time was 2.8 years. The incidence rate of death was 8.5 per 1000 person-years (95 % confidence interval [CI] 8.0–9.0) in the general population, 9.7 (95 % CI 8.3–11.5) in SA, 14.9 (95 % CI 11.4–19.6) in UA, 29.7 (95 % CI 25.6–34.3) in NSTEMI and 36.5 (95 % CI 30.9–43.2) in STEMI. In multivariable adjusted analyses, compared with UA, SA had a 38 % lower risk of death and a non-significant lower risk of MACE (HR 0.62, 95 % CI 0.44–0.89; HR 0.86, 95 % CI 0.66–1.11). NSTEMI had a 2.4-fold higher risk of death (HR 2.39, 95 % CI 1.38–4.14) and a 1.6-fold higher risk of MACE (HR 1.62, 95 % CI 1.11–2.38) compared tox UA during the first year after coronary angiography, but a similar risk thereafter. There was no difference in the risk of death for UA with non-obstructive CAD and obstructive CAD (HR 0.78, 95 % CI 0.39–1.57).ConclusionUA had a higher risk of death but a similar risk of MACE compared to SA and a lower 1-year risk of death and MACE compared to NSTEMI.

The Prognostic Value of Cardiac Troponin I in Patients with or without Three-Vessel Disease Undergoing Complete Percutaneous Coronary Intervention.

Postprocedural cardiac troponin I (cTnI) elevation commonly occurs in patients undergoing percutaneous coronary intervention (PCI); however, its prognostic value remains controversial. This study aimed to investigate the prognostic value of peak postprocedural cTnI in cardiac patients with or without three-vessel disease (TVD) undergoing complete PCI. A total of 1237 consecutive patients (77% males, mean age 58 ± 10 years) with normal baseline cTnI levels were enrolled, 439 patients (77% males, 59 ± 10 years) with TVD, and 798 patients (77% males, 57 ± 10 years) with single- or double-vessel disease (non-TVD). The primary outcome was the occurrence of major adverse cardiovascular events (MACE), defined as a composite of non-fatal MI, non-fatal stroke, unplanned revascularization, re-hospitalization due to heart failure or severe arrhythmias, and all-cause death. During the median follow-up of 5.3 years, a total of 169 patients (13.7%) developed MACE, including 73 (16.6%) in the TVD group and 96 (12.0%) in the non-TVD group (p = 0.024). After adjustment, the multivariate Cox analysis showed that hypertension (HR 1.50; 95% CI: 1.01–2.20; p = 0.042), TVD (HR 1.44; 95% CI: 1.03–2.02; p = 0.033), and cTnI ≥ 70× URL (HR 2.47; 95% CI: 1.28–4.78, p = 0.007) were independently associated with increased MACE during long-term follow-up. Further subgroup analyses showed that cTnI ≥ 70× URL was an independent predictor of MACE in TVD patients (HR 3.32, 95% CI: 1.51–7.34, p = 0.003), but not in non-TVD patients (HR 1.01, 95%CI: 0.24–4.32, p = 0.991). In conclusion, elevation of post-PCI cTnI ≥ 70× URL is independently associated with a high risk of MACE during long-term follow-up in patients with TVD, but not in those with non-TVD.

Cardiovascular Risks of Hydroxychloroquine vs Methotrexate in Patients With Rheumatoid Arthritis

BackgroundHydroxychloroquine is often used as a first-line treatment of rheumatoid arthritis despite limited evidence on its cardiovascular risk. ObjectivesWe conducted a cardiovascular safety evaluation comparing hydroxychloroquine to methotrexate among patients with rheumatoid arthritis. MethodsUsing Medicare data (2008-2016), we identified 54,462 propensity score–matched patients with rheumatoid arthritis, aged ≥65 years, who initiated hydroxychloroquine or methotrexate. Primary outcomes were sudden cardiac arrest or ventricular arrythmia (SCA/VA) and major adverse cardiovascular event (MACE). Secondary outcomes were cardiovascular mortality, all-cause mortality, myocardial infarction, stroke, and hospitalized heart failure (HF). We also examined treatment effect modification by history of HF. ResultsHydroxychloroquine was not associated with risk of SCA/VA (HR: 1.03; 95% CI: 0.79-1.35) or MACE (HR: 1.07; 95% CI: 0.97-1.18) compared with methotrexate. In patients with history of HF, hydroxychloroquine initiators had a higher risk of MACE (HR: 1.30; 95% CI: 1.08-1.56), cardiovascular mortality (HR: 1.34; 95% CI: 1.06-1.70), all-cause mortality (HR: 1.22; 95% CI: 1.04-1.43), myocardial infarction (HR: 1.74; 95% CI: 1.25-2.42), and hospitalized HF (HR: 1.29; 95% CI: 1.07-1.54) compared to methotrexate initiators. Cardiovascular risks were not different in patients without history of HF except for an increased hospitalized HF risk (HR: 1.57; 95% CI: 1.30-1.90) among hydroxychloroquine initiators. ConclusionsIn older patients with rheumatoid arthritis, hydroxychloroquine and methotrexate showed similar SCA/VA and MACE risks; however, hydroxychloroquine initiators with history of HF had higher risks of MACE, cardiovascular mortality, all-cause mortality, and myocardial infarction. An increased hospitalized HF risk was observed among hydroxychloroquine initiators regardless of an HF history.

Predictive Value of Free Triiodothyronine in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Homeostasis of thyroid hormones has significant effects on the cardiovascular system. The aim of this study was to investigate the association between free triiodothyronine (FT3) and adverse cardiovascular events in patients with acute coronary syndrome (ACS) who were undergoing percutaneous coronary intervention (PCI). A total of 1701 patients with ACS undergoing PCI were included in this study. All patients were divided into three groups according to the tertiles of FT3 level: the lowest tertile (FT3 4.51 pmol/L), the middle tertile (4.51 pmol/L FT3 4.89 pmol/L) and the highest tertile group (FT3 4.89 pmol/L). The primary study endpoint was a composite of major adverse cardiovascular events (MACE), which included all-cause death, ischemic stroke, myocardial infarction, or unplanned repeat revascularization. During a median follow-up period of 927 days, 349 patients had at least one event. Compared with patients with the highest tertile, those with the lowest tertile had a significantly higher incidence of MACE, all-cause death, MI, ischemic stroke and repeat revascularization (all p values 0.05). In the multivariate Cox regression analysis, the middle tertile had similar risk of MACE (HR = 0.986, 95% CI 0.728-1.336, p = 0.929) as the highest tertile, but the patients with the lowest tertile had a 92.9% higher risk of MACE (HR = 1.929, 95% CI 1.467-2.535, p 0.001). There was a non-linear relationship between FT3 and MACE and unplanned repeat revascularization (all p values for non-linear association 0.001). Adding the tertiles of FT3 level into the baseline model yielded a significant improvement in discrimination for predicting MACE ( AUC = 0.013, p = 0.025). A significantly reduced FT3 level was independently associated with a worse prognosis in patients with ACS undergoing PCI.

Major adverse cardiovascular events after diagnosis of myocardial injury and types 1 and 2 myocardial infarction.

Limited US outcome data exist among patients with myocardial injury and types 1 and 2 myocardial infarction (MI) evaluated with high-sensitivity cardiac troponin (hs-cTn). This is an observational US cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Post-discharge major adverse cardiovascular events (MACE) included death, MI, heart failure (HF) hospitalization, stroke or transient ischaemic attack, and new-onset atrial fibrillation or flutter during 2 years follow-up. Among 2002 patients, 857 (43%) had ≥1 hs-cTnT >99th percentile. Among these, 702 (81.9%) had myocardial injury, 64 (7.5%) had type 1 MI, and 91 (10.6%) had type 2 MI. Compared with patients without myocardial injury, type 2 MI [8.4 vs. 50%; adjusted hazard ratio (HR) 2.31, 95% confidence interval (CI) 1.49-3.58] and myocardial injury (8.4 vs. 47%; adjusted HR 3.13, 95% CI 2.39-4.09) had a higher risk of MACE, in large part because of death and HF hospitalizations. Compared with patients with type 1 MI, type 2 MI (23 vs. 50%; adjusted HR 2.24; 95% CI 1.23-4.10) and myocardial injury (23 vs. 47%; adjusted HR 2.02; 95% CI 1.20-3.40) also have a higher risk of MACE. Among unselected US ED patients undergoing hs-cTnT measurement, most increases are due to myocardial injury, and type 2 MI is more frequent than type 1 MI. Patients with myocardial injury and type 2 MI have morbid outcomes, in large part due to death and HF.

Major adverse cardiovascular events in older emergency department patients presenting with non-cardiac medical complaints.

The risk of major adverse cardiovascular events (MACE) for older emergency department (ED) patients presenting with non-cardiac medical complaints is unknown. To apply preventive measures timely, early identification of high-risk patients is incredibly important. We aimed at investigating the incidence of MACE within one year after their ED visit and the predictive value of high-sensitivity cardiac troponinT (hs-cTnT) and N‑terminal pro-B-type natriuretic peptide (NT-proBNP) for subsequent MACE. This is asubstudy of aDutch prospective cohort study (RISE UP study) in older (≥ 65years) medical ED patients who presented with non-cardiac complaints. Biomarkers were measured upon ED arrival. Cox-regression analysis was used to determine the predictive value of the biomarkers, when corrected for other possible predictors of MACE, and area under the curves (AUCs) were calculated. Of 431patients with amedian age of 79years, 86(20.0%) developed MACE within 1year. Both hs-cTnT and NT-proBNP were predictive of MACE with an AUC of 0.74 (95% CI 0.68-0.80) for both, and ahazard ratio (HR) of 2.00 (95% CI 1.68-2.39) and 1.82 (95% CI 1.57-2.11) respectively. Multivariate analysis correcting for other possible predictors of MACE revealed NT-proBNP as an independent predictor of MACE. Older medical ED patients are at high risk of subsequent MACE within 1year after their ED visit. While both hs-cTnT and NT-proBNP are predictive, only NT-proBNP is an independent predictor of MACE. It is likely that early identification of those at risk offers awindow of opportunity for prevention.

18-OR: Discontinuation of Renin Angiotensin System Inhibitor and Cardiovascular-Renal Events in Advanced Diabetic Kidney Disease

Introduction: Whether angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) should be discontinued in advanced diabetic kidney disease (DKD) remains controversial. We examined the association of discontinuation of ACEi/ARBs when estimated glomerular filtration rate (eGFR) reached &amp;lt;30 ml/min/1.73m2 with risk of death, major adverse cardiovascular events (MACE) , and end-stage-kidney-disease (ESKD) defined as dialysis and/or eGFR &amp;lt;15/ml/min/1.73m2 in Chinese patients with type 2 diabetes (T2D) . Methods: We performed a prospective analysis of a register including 11,323 patients stratified by continuation of ACEi/ARBs within 6 months of reaching eGFR &amp;lt;30 ml/min/1.73m2 in 2002-2018 followed up until 2019. We used Cox model with time-dependent exposure and covariates to estimate the hazard ratio (HR) of outcomes in the overlap propensity score weighted cohort. Results: Of 11,323 ACEi/ARBs users with new-onset eGFR&amp;lt;30 ml/min/1.73m2, 2,055 (18.5%) discontinued ACEi/ARBs within 6 months whereas 9,268 (81.5%) had continuation of ACEi/ARBs. During a mean follow-up of 4.3 years, 13.5% and 28.4% had incident MACE and ESKD respectively, and 36.2% died. Compared to ACEi/ARBs continuation, discontinuation of ACEi/ARBs was associated with higher risk of MACE (HR=1.26, 95% CI: 1.15-1.39) and ESKD (HR=1.26, 95% CI: 1.14-1.40) , and neutral risk of death (HR=0.96, 95% CI: 0.89-1.04) . Results were consistent when modeling ACEi/ARBs as a time-dependent exposure using a marginal structural model. Conclusions: Discontinuation of ACEi/ARBs was associated with increased risk of cardiovascular-renal events in support of their continued use in patients with advanced DKD. Disclosure M.Shi: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp &amp; Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. A.Yang: None. E.S.H.Lau: None. H.Wu: None. X.Zhang: None. B.Fan: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. A.Luk: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc.

Increased risk of cardiovascular events and death in the initial phase after discontinuation of febuxostat or allopurinol: another story of the CARES trial

ObjectivesThe Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout (CARES) trial suggested a higher risk of cardiovascular (CV) death from febuxostat than from allopurinol. However, a significant number...

Prognostic value of a novel dNLR-PNI score in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

There is currently limited information on the prognostic value of the dNLR-PNI (the combination of the derived neutrophil-to-lymphocyte ratio [dNLR] and prognostic nutritional index [PNI]) score for patients with acute coronary syndrome (ACS). We aimed to explore the predictive value of a dNLR-PNI score on the long-term prognosis of patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 1773 patients with ACS who underwent PCI were consecutively enrolled from January 2016 to December 2018. The cutoff values of dNLR and PNI to predict major adverse cardiovascular events (MACE) were calculated using receiver operating characteristic curves. The patients were divided into three groups based on the dNLR-PNI score, and Kaplan-Meier curves and Cox regression models were used for survival analysis. The endpoints were MACE, including all-cause mortality and rehospitalisation for severe heart failure during follow-up. A total of 1542 patients with ACS who underwent PCI were included. Kaplan-Meier curves showed that a higher level of dNLR, PNI, or dNLR-PNI score was associated with a higher risk of MACE (all p < .001). In multivariate Cox regression models, the dNLR-PNI two score (hazard ratio 3.049, 95% confidence interval 1.503-6.184, p = .002) was found to be an independent predictor of all-cause mortality and rehospitalization for severe heart failure. A high dNLR-PNI score was independently associated with a higher risk of developing MACE in patients with ACS undergoing PCI. The dNLR-PNI score may be a useful prognostic parameter for identifying high-risk ACS patients after PCI.

POS0110 INCIDENCE OF MAJOR ADVERSE CARDIOVASCULAR EVENTS STRATIFIED BY GEOGRAPHIC REGION AND BASELINE CARDIOVASCULAR RISK: A POST HOC ANALYSIS OF ORAL SURVEILLANCE

BackgroundORAL Surveillance was a post-authorisation safety study of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in patients (pts) with rheumatoid arthritis (RA) aged ≥50 yrs with ≥1 additional cardiovascular (CV) risk factor and an inadequate response to methotrexate (MTX).ObjectivesTo examine associations between major adverse CV events (MACE) and the geographic region and baseline (BL) CV risk profile of pts in ORAL Surveillance.MethodsPts on stable MTX were randomised 1:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID) or a TNFi (adalimumab 40 mg every 2 weeks in North America [NA] or etanercept 50 mg once weekly in the rest of the world [RoW]). Incidence rates (IRs; pts with first events/100 pt-yrs) were evaluated for adjudicated MACE, as well as myocardial infarction (MI) and stroke. MACE was defined as CV death (excluding CV death due to pulmonary embolism), non-fatal MI and non-fatal stroke. IRs were stratified by geographic region (NA vs RoW) and BL CV risk profile: pts were first categorised by history of coronary artery disease (HxCAD); pts without a HxCAD were then categorised by 10-yr risk of MACE (high [≥20%], intermediate [≥7.5–&lt;20%], borderline [≥5–&lt;7.5%] and low [&lt;5%] risk), per the ASCVD-pooled cohort equations calculator1 with a 1.5 multiplier applied.2ResultsOverall, 4362 pts were included in the study (tofacitinib 5 mg BID, n=1455; tofacitinib 10 mg BID, n=1456; TNFi, n=1451). Across treatments, a higher proportion of pts in NA vs RoW had a HxCAD (Table 1). In pts without a HxCAD, across treatments, higher percentages of pts had a high 10-yr risk of MACE in NA vs RoW (Table 1). Across treatments, overall MACE IRs were higher in pts in NA vs RoW (Figure 1). Incidence and risk of MACE were higher with tofacitinib vs TNFi in both NA and RoW (Figure 1). In NA, MACE IRs were higher for tofacitinib 5 mg BID vs TNFi in pts with a HxCAD, and tofacitinib 10 mg BID vs TNFi for pts with a high 10-yr risk of MACE; pts with low or borderline 10-yr MACE risk had no MACE across tofacitinib groups (Figure 1). Compared with NA, similar trends for MACE were generally observed across treatments in RoW, particularly for intermediate, borderline and low CV risk categories (Figure 1).Table 1.Percentages of pts in NA and RoW with a HxCAD and pts without a HxCAD categorised by 10-yr risk of MACE, per ASCVD-pooled cohorts equation risk calculator1 with a 1.5 multiplier applied2NAaRoWTofacitinib 5 mg BID (N=402)Tofacitinib 10 mg BID (N=409)TNFib (N=432)Tofacitinib 5 mg BID (N=1053)Tofacitinib 10 mg BID (N=1047)TNFib (N=1019)HxCAD, n (%)58 (14.4)64 (15.6)81 (18.8)103 (9.8)108 (10.3)83 (8.1)No HxCAD: 10-yr risk of MACE, n (%)High (≥20%)97 (24.1)108 (26.4)113 (26.2)177 (16.8)195 (18.6)183 (18.0)Intermediate (≥7.5–&lt;20%)131 (32.6)144 (35.2)137 (31.7)359 (34.1)372 (35.5)368 (36.1)Borderline (≥5–&lt;7.5%)49 (12.2)31 (7.6)31 (7.2)151 (14.3)143 (13.7)124 (12.2)Low (&lt;5%)60 (14.9)54 (13.2)65 (15.0)253 (24.0)218 (20.8)250 (24.5)Missing data7 (1.7)8 (2.0)5 (1.2)10 (0.9)11 (1.1)11 (1.1)HxCAD was defined as any history of MI, coronary heart disease, stable angina pectoris or coronary artery procedures. aUnited States, Puerto Rico and Canada. bFor pts randomised to the TNFi group, adalimumab and etanercept were administered in NA and RoW, respectivelyn, number of pts with specified characteristics; N, number of evaluable ptsConclusionThis post hoc analysis of data from ORAL Surveillance suggests that differences in MACE IRs across geographic regions are largely driven by HxCAD and high BL CV risk scores in NA vs RoW. Results should be interpreted with caution due to low pt and event numbers, particularly restricting the evaluation of tofacitinib vs TNFi in NA and RoW. Noting this limitation, these findings emphasise the importance of assessing and addressing BL CV risk when treating pts with RA.

OP0264 IMPACT OF BASELINE CARDIOVASCULAR RISK ON THE INCIDENCE OF MAJOR ADVERSE CARDIOVASCULAR EVENTS IN THE TOFACITINIB RHEUMATOID ARTHRITIS CLINICAL PROGRAMME

BackgroundResults from ORAL Surveillance, a post-authorisation safety study, indicated that patients (pts) with rheumatoid arthritis (RA) aged ≥50 yrs with ≥1 additional cardiovascular (CV) risk factor have an increased risk of major adverse CV events (MACE) with tofacitinib vs tumour necrosis factor inhibitors.1ObjectivesTo evaluate the impact of baseline (BL) CV risk on MACE in the wider tofacitinib RA clinical programme.MethodsData for pts who received ≥1 tofacitinib dose in 21 Phase 1–3b/4 (excluding ORAL Surveillance) and 2 long-term extension tofacitinib RA studies were pooled and analysed post hoc as two cohorts: (1) overall cohort and (2) CV risk-enriched cohort (pts aged ≥50 yrs with ≥1 additional CV risk factor [current smoker, hypertension, HDL-cholesterol &lt;40 mg/dL, diabetes mellitus, history of myocardial infarction (MI) or coronary heart disease (CHD)]). Data were summarised by average tofacitinib 5 or 10 mg twice daily (BID; average total daily dose of &lt;15 or ≥15 mg, respectively). Incidence rates (IRs; pts with first events/100 pt-yrs) for adjudicated MACE were calculated. MACE IRs were stratified by pts’ BL CV risk profile: pts were first categorised by history of coronary artery disease (HxCAD), then pts without a HxCAD were categorised by 10-yr risk of MACE, per the ASCVD-PCE risk calculator2 with a 1.5 multiplier applied.3ResultsThe overall cohort included 7964 pts (average tofacitinib 5 mg BID, n=3969; average tofacitinib 10 mg BID, n=3995); of these, 3125 (39.2%) pts were included in the CV risk-enriched cohort (average tofacitinib 5 mg BID, n=1614; average tofacitinib 10 mg BID, n=1511). In both treatment arms, as expected, higher proportions of pts in the CV risk-enriched cohort had a HxCAD or a high or intermediate 10-yr predicted risk of MACE at BL vs the overall cohort (Table 1). MACE IRs (95% CIs) were lower in the overall cohort (0.38 [0.26, 0.54] and 0.37 [0.27, 0.48] for average tofacitinib 5 and 10 mg BID, respectively) vs the CV risk-enriched cohort (0.72 [0.46, 1.09] and 0.67 [0.46, 0.93], respectively), and were similar between treatment arms. MACE IRs were lower than reported in ORAL Surveillance.1 In the overall cohort, adjudicated MACE most commonly occurred in pts with a HxCAD (IR [95% CI] 0.98 [0.02, 5.47] and 1.05 [0.13, 3.78] for average tofacitinib 5 and 10 mg BID, respectively), or in pts with a high 10-yr risk of MACE at BL (Figure 1). A lower predicted 10-yr MACE risk was associated with lower MACE IRs (Figure 1); trends were similar for the CV risk-enriched cohort (data not shown).Table 1.Proportions of pts with a HxCAD and pts without a HxCAD categorised by 10-yr risk of MACE, per ASCVD-PCE risk calculator2 with a 1.5 multiplier applied3Average tofacitinib 5 mg BIDAverage tofacitinib 10 mg BIDOverall cohort(N=3969)CV risk-enriched cohort(N=1614)Overall cohort(N=3995)CV risk-enriched cohort(N=1511)HxCAD, n (%)61 (1.5)61 (3.8)65 (1.6)60 (4.0)No HxCAD: 10-yr risk of MACE, n (%)High (≥20%)440 (11.1)365 (22.6)337 (8.4)276 (18.3)Intermediate (≥7.5–&lt;20%)853 (21.5)593 (36.7)788 (19.7)530 (35.1)Borderline (≥5–&lt;7.5%)435 (11.0)234 (14.5)404 (10.1)195 (12.9)Low (&lt;5%)2133 (53.7)342 (21.2)2058 (51.5)307 (20.3)Missing data47 (1.2)19 (1.2)343 (8.6)143 (9.5)CAD is defined as any of MI or CHD.n, number of pts with specified characteristic; N, number of evaluable ptsConclusionIn the tofacitinib RA clinical programme, MACE were largely associated with BL CV risk in the overall cohort, consistent with results of ORAL Surveillance, although results should be interpreted with caution due to low pt-yrs of exposure in some pt groups. Noting this limitation, these findings emphasise the importance of assessing and addressing BL CV risk when treating pts with RA.

The prognostic value of global myocardium strain by CMR-feature tracking in immune checkpoint inhibitor-associated myocarditis.

Immune checkpoint inhibitor (ICI)-associated myocarditis is a potentially fatal complication. Sparse published researches evaluated the prognostic value of cardiovascular magnetic resonance feature tracking (CMR-FT) for ICI-associated myocarditis. In the single-center retrospective study, 52 patients with ICI-associated myocarditis and CMR were included from August 2018 to July 2021. The ICI-associated myocarditis was diagnosed by using the clinical criteria of the European Society of Cardiology guidelines. Major adverse cardiovascular events (MACE) were comprised of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. During a median follow-up of 171 days, 14 (27%) patients developed MACE. For patients with MACE, the global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF) were significantly worse and native T1 values and late gadolinium enhancement (LGE) extent were significantly increased, compared with patients without MACE (p < 0.05). The GLS remained the independent factor associated with a higher risk of MACE (hazard ratio (HR): 2.115; 95% confidence interval (CI): 1.379-3.246; p = 0.001) when adjusting for LVEF, LGE extent, age, sex, body mass index, steroid treatment, and prior cardiotoxic chemotherapy or radiation. After adjustment for LVEF, the GLS remained the independent risk factor associated with a higher rate of MACE among patients with a preserved LVEF (HR: 1.358; 95% CI: 1.007-1.830; p = 0.045). GLS could provide independent prognostic value over GCS, GRS, traditional CMR features, and clinical features in patients with ICI-associated myocarditis. • The global circumferential strain (GCS), global radial strain (GRS), and global longitudinal strain (GLS) by cardiovascular magnetic resonance feature tracking were significantly impaired in patients with an immune checkpoint inhibitor (ICI)-associated myocarditis. • GLS was still significantly impaired in patients with preserved left ventricular ejection fraction. • The worse GLS was an independent risk factor over GCS, GRS, traditional CMR features, and clinical features for predicting major adverse cardiovascular events in patients with ICI-associated myocarditis.

MO536: Cardiovascular Events in Patients With Anemia Associated With Non–Dialysis-Dependent Chronic Kidney Disease: Regional Analysis of Patients not Previously Treated With Erythropoiesis-Stimulating Agents in The PRO2TECT Trial

Abstract BACKGROUND AND AIMS Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being investigated for treatment of anemia due to chronic kidney disease (CKD). In global phase 3 trials, vadadustat has demonstrated non-inferiority to darbepoetin alfa for time to major adverse cardiovascular event (MACE) in patients with dialysis-dependent CKD (INNO2VATE trials), but not with non–dialysis-dependent CKD (NDD-CKD; PRO2TECT trials) [1,2]. In a prespecified subgroup analysis of the PRO2TECT trials, no difference in cardiovascular safety was observed in the USA, but a higher risk of MACE was found for patients treated with vadadustat outside the USA.1 We investigated regional differences in MACE in patients previously untreated with erythropoietin-stimulating agents (ESAs) in the PRO2TECT trial. METHOD Two phase 3, open-label, randomized, active-controlled clinical trials comparing vadadustat with darbepoetin alfa were conducted in North America, Latin America, Europe, Africa, and the Asia-Pacific region. This post hoc analysis evaluated MACE in patients in the PRO2TECT trial not treated with ESAs within 8 weeks of enrollment (correction trial; NCT02648347) and who received ≥1 dose of trial drug, stratified by region (USA versus Europe versus non-USA/non-Europe). MACE was defined as a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke. Expanded MACE was defined as MACE plus hospitalization for heart failure or thromboembolic event, excluding vascular access failure. RESULTS A total of 1748 ESA-untreated patients receiving ≥1 dose of study drug were enrolled in the PRO2TECT trial, including 1058 patients in the USA, 139 in Europe and 551 outside the USA and Europe. Patients in the non-USA/non-European countries were younger and had a lower mean eGFR than patients in the USA or Europe. Furthermore, 34.7% of patients randomized to vadadustat had a baseline eGFR &amp;lt;10 mL/min/1.73 m2 versus 24.0% of patients randomized to darbepoetin alfa in the non-USA/non-European countries. The hazard ratio for MACE in the overall population for vadadustat versus darbepoetin alfa was 1.16 [95% confidence interval (CI) 0.96–1.41]. When analyzed by region, higher event rate for MACE was observed in the vadadustat arm in the non-USA/non-European countries compared with the USA and Europe (Table 1). The higher event rates for MACE in the non-USA/non-European countries were driven by 21 excess MACEs reported in the vadadustat group. Many deaths in the non-USA/non-European countries were related to kidney failure (n = 25/43 in the vadadustat group; n = 20/30 in the darbepoetin alfa group; Table 2), and were concentrated in Brazil and South Africa, countries that enrolled a higher proportion of patients with end-stage kidney failure who may not have had access to dialysis. The adverse event profiles for vadadustat and darbepoetin alfa were similar across regions. CONCLUSION Regional differences in time to first MACE were observed in patients with NDD-CKD who were not previously treated with ESAs and randomized to receive vadadustat or darbepoetin alfa as part of the PRO2TECT trial. The higher event rate in the vadadustat group in non-USA/non-European countries may have been related to randomization imbalances and/or design and methodological issues. These findings should help inform care providers as they assess the overall safety of vadadustat for the treatment of anemia associated with NDD-CKD.

Prognosis impact of ticagrelor vs clopidogrel based DAPT discontinuation after acute coronary syndrome. Insights from the multicenter CREA ARIAM Andalucia registry

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The study project was financially supported by a non-conditional grant by Astrazeneca. Background/Introduction Premature cessation of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) has been associated with increased risk of major adverse cardiovascular events (MACE) Purpose To assess the relationship between premature DAPT discontinuation versus therapy continuation and outcomes in ACS patients discharged on ticagrelor or clopidogrel. Methods Prospective, observational, multicentre all-comers registry of ACS patients who were intended to receive 12-month DAPT with ticagrelor or clopidogrel. Adherence was defined by the medication possession ratio metric (MPA, proportion of days of medication supply within a time interval). Categories for DAPT cessation included: physician-recommended discontinuation, brief interruption (invasive procedures), or disruption due to non-compliance or because of bleeding. Fully-adjusted Cox models with time-varying covariates to account for informative censoring, were used to examine the effect of DAPT cessation on MACE (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, definite stent thrombosis, or target-lesion revascularization). Moderation analysis was also performed to assess for potential exposure-adherence interaction. Results Among 2070 patients included (mean age 63 years, 73% men), 150 (7.3%) prematurely discontinued DAPT, median (IQR) 214 (101-236) days. Significantly more clopidogrel than ticagrelor users discontinued medication (9.5% vs 5%, respectively; P = .001), though timing of cessation was similar in both groups. At 1 year, MPR was slightly higher, but not significantly different, in the clopidogrel group than in the ticagrelor group (70±30 vs 64±29; P = .06). Overall, physician-guided discontinuation and bleeding were the main reasons for DAPT cessation. These were observed with a similar rate in both groups, while non-compliant disruption was more common among ticagrelor- than clopidogrel-treated patients (8% vs 2%, respectively; P for trend .04). After adjustments, DAPT cessation was associated with significantly increased risk of MACE (adjusted HR 2.94; 95% CI 1.82 – 4.74; P &amp;lt; .0001), regardless of the P2Y12 inhibitor (P interaction = 0.665). Non-compliance related cessation resulted in higher risk of MACE (HR 6.04, 95%CI 2.15 – 16.95; P = .001). Conclusion(s) Overall, approximately 7% of patients discontinued DAPT. Early cessation of either ticagrelor- or clopidogrel-based DAPT portended to a near 3-fold increased risk of MACE. Disruption due to non-compliance resulted in higher risk for ischemic events. These data warrant efforts to focus on patient education in subgroups at high risk of non-compliance.

PD49-08 INCREASED RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS IN MEN RECEIVING TESTOSTERONE REPLACEMENT THERAPY

You have accessJournal of UrologyCME1 May 2022PD49-08 INCREASED RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS IN MEN RECEIVING TESTOSTERONE REPLACEMENT THERAPY Uday Mann, Ranveer Brar, and Premal Patel Uday MannUday Mann More articles by this author , Ranveer BrarRanveer Brar More articles by this author , and Premal PatelPremal Patel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002620.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Literature surrounding testosterone replacement therapy (TRT) and major adverse cardiovascular events (MACE) is conflicting. Currently, the Food and Drug Administration requires warnings regarding a possible increased cardiovascular risk for TRTs. This study sought to investigate the association between TRT and MACE using a large population based database. METHODS: A propensity-weighted, retrospective cohort study was conducted by accessing provincial health administrative databases. Eligibility criteria included men 18 years and older, with no prior TRT or MACE, who had at least 1 year of provincial health coverage from their index date between April 1st, 1995 to December 31st, 2018. TRT was defined as having at least two testosterone prescriptions filled within one year (including capsules, gels, patches, and/or injections). MACE was defined as myocardial infarction, coronary revascularization procedures, ischemic stroke, or hospitalizations for heart failure. Controls were assigned a pseudo-index date at random based on the frequency distribution of index dates in the study group. Logistic regression model that included age, socioeconomic status, index year, diabetes, hypertension, dyslipidemia and renal disease was used to determine the propensity score. Stabilized inverse propensity treatment weighting was then applied to the propensity score. A cox proportional hazard model was used to examine our primary outcome of time to a MACE. RESULTS: Among 7095 men receiving TRT and 392,204 controls, men receiving TRT were associated with a 76% higher risk of a MACE (Hazard Ratio 1.76, 1.63 – 1.89) in unweighted and 27% higher risk (Hazard Ratio 1.27, 1.16 – 1.39) in weighted analyses. The median time to a MACE was 2828 and 2707 days in the study and control cohort, respectfully. The proportion of individuals with a MACE was 9.9% and 5.6% in men receiving TRT and controls, respectfully. CONCLUSIONS: Our study demonstrates that men receiving TRT had a higher risk of MACE as compared to controls. Our study is limited by its retrospective nature and inability to capture for all confounders. Whether TRT itself increases the odds of MACE requires further elucidation. Nonetheless, men receiving TRT should be counselled about their increased rate of MACE and health care providers prescribing TRT should identify comorbid conditions to mitigate risk and discuss lifestyle modifications. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e833 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Uday Mann More articles by this author Ranveer Brar More articles by this author Premal Patel More articles by this author Expand All Advertisement PDF DownloadLoading ...

Association of Controlling Nutritional Status Score With Adverse Outcomes in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis sought to examine the association between the controlling nutritional status (CONUT) score and adverse outcomes in patients with coronary artery disease (CAD). PubMed and Embase databases were searched for eligible studies from their inceptions to December 12, 2021 to identify studies investigating the association of the CONUT score with major adverse cardiovascular events (MACEs) and all-cause mortality in CAD patients. Twelve studies (36,198 CAD) patients satisfied the criteria. Comparison of the high with low CONUT score, the pooled multivariate adjusted risk ratios (RR) was 1.78 (95% confidence intervals [CI] 1.36-2.32) for MACEs and 1.45 (95% CI 1.27-1.66) for all-cause mortality, respectively. When compared with patients with normal nutrition, malnourished (defined by the CONUT score ≥2) patients conferred a 52% increased risk of MACEs. Additionally, per point CONUT score increment was associated with 15% and 11% higher risk of MACEs and all-cause mortality, respectively. Higher CONUT score independently predicts the MACEs all-cause mortality in CAD patients. Estimation of nutritional status using the CONUT score could be helpful for improving risk classification of CAD.

Assessment of Visit-to-Visit Blood Pressure Variability in Adults With Optimal Blood Pressure: A New Player in the Evaluation of Residual Cardiovascular Risk?

BackgroundThere is a paucity of evidence regarding the association between visit‐to‐visit blood pressure variability and residual cardiovascular risk. We aimed to provide relevant evidence by determining whether high systolic blood pressure (SBP) variability in the optimal SBP levels still influences the risk of cardiovascular disease.Methods and ResultsWe studied 7065 participants (aged 59.3±5.6 years; 44.3% men; and 82.9% White) in the ARIC (Atherosclerosis Risk in Communities) study with optimal SBP levels from visit 1 to visit 3. Visit‐to‐visit SBP variability was measured by variability independent of the mean in the primary analysis. The primary outcome was the major adverse cardiovascular event (MACE), defined as the first occurrence of all‐cause mortality, coronary heart disease, stroke, and heart failure. During a median follow‐up of 19.6 years, 2691 participants developed MACEs. After multivariable adjustment, the MACE risk was higher by 21% in participants with the highest SBP variability (variability independent of the mean quartile 4) compared with the lowest SBP variability participants (variability independent of the mean quartile 1) (hazard ratio, 1.21; 95% CI, 1.09–1.35). The restricted cubic spline showed that the hazard ratio for MACE was relatively linear, with a higher variability independent of the mean being associated with higher risk. These association were also found in the stratified analyses of participants with or without hypertension.ConclusionsIn adults with optimal SBP levels, higher visit‐to‐visit SBP variability was significantly associated with a higher risk of MACE regardless of whether they had hypertension. Therefore, it may be necessary to further focus on the visit‐to‐visit SBP variability even at the guideline‐recommended optimal blood pressure levels.