Risk Of Primary Composite Outcome Research Articles

Impact of Everolimus Initiation and Corticosteroid Weaning During Acute Phase After Heart Transplantation on Clinical Outcome: Data from the Korean Organ Transplant Registry (KOTRY).

The effect of changes in immunosuppressive therapy during the acute phase post-heart transplantation (HTx) on clinical outcomes remains unclear. This study aimed to investigate the effects of changes in immunosuppressive therapy by corticosteroid (CS) weaning and everolimus (EVR) initiation during the first year post-HTx on clinical outcomes. We analyzed 622 recipients registered in the Korean Organ Transplant Registry (KOTRY) between January 2014 and December 2021. The median age at HTx was 56years (interquartile range [IQR], 45-62), and the median follow-up time was 3.9years (IQR 2.0-5.1). The early EVR initiation within the first year post-HTx and maintenance during the follow-up is associated with reduced the risk of primary composite outcome (all-cause mortality or re-transplantation) (HR, 0.24; 95% CI 0.09-0.68; p < 0.001) and cardiac allograft vasculopathy (CAV) (HR, 0.39; 95% CI 0.19-0.79; p = 0.009) compared with EVR-free or EVR intermittent treatment regimen, regardless of CS weaning. However, the early EVR initiation tends to increase the risk of acute allograft rejection compared with EVR-free or EVR intermittent treatment.

Associations of Angiopoietin 2 and Vascular Endothelial Growth Factor-A Concentrations with Clinical End Points.

Angiopoietin 2 regulates endothelial function partially mediated by vascular endothelial growth factor-A (VEGF-A) and may play a role in diabetic kidney disease (DKD). We assessed the association of angiopoietin 2 and VEGF-A with cardiorenal outcomes and investigated the effect of canagliflozin on angiopoietin 2 and VEGF-A concentrations. Two thousand five hundred sixty-five study participants with DKD and available plasma samples treated with canagliflozin or placebo in the Canagliflozin and Kidney Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial were included. Angiopoietin 2 and VEGF-A concentrations were measured at baseline, year 1, and year 3. The primary composite end point of the trial was a composite of kidney failure, doubling of the serum creatinine level, and kidney or cardiovascular death. Patients with the highest baseline quartile of angiopoietin 2, but not VEGF-A, concentration had the highest risk clinical profile. Treatment with canagliflozin significantly lowered concentrations of angiopoietin 2 (adjusted geometric mean ratio: 0.94; 95% confidence interval, 0.92 to 0.95; P < 0.001), but not VEGF-A. In multivariable-adjusted modeling, each 50% increment in log baseline angiopoietin 2 concentrations was associated with a higher risk of primary composite outcome (hazard ratio, 1.27; 95% confidence interval, 1.13 to 1.43). Angiopoietin 2 change at year 1 compared with baseline explained 10% of the effect of canagliflozin on the primary composite outcome. VEGF-A concentrations were not associated with outcomes, alone or in combination with angiopoietin 2. Higher angiopoietin 2 levels were associated with cardiorenal risk among individuals with DKD independent of VEGF-A. Canagliflozin lowered angiopoietin 2 concentrations. Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy, NCT02065791 .

The Impact of Renal Insufficiency upon Admission on the Clinical Outcome of Patients with Acute ST-elevation Myocardial Infarction undergoing Primary Percutaneous Coronary Intervention

Background: Coronary artery disease is common in patients with renal insufficiency. In acute coronary syndrome, impaired renal function is present in approximately 30-40% of patients and is associated with worse prognosis. Local data regarding the risks and benefits for those patients suffering from acute ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) is scarce. We evaluated the clinical outcomes of patients suffering from STEMI with and without renal insufficiency upon admission who underwent PPCI. Methods: From 1st January 2009 to 30th September 2017, all patients with STEMI treated with PPCI were identified. The primary composite endpoint was defined as a composite outcome of all-cause mortality and MACE (cardiovascular mortality, non-fatal MI, stroke and target vessel revascularization). The secondary endpoints were the individual components of the primary composite endpoint. Estimated GFR was calculated by the CKD-EPI equation. Renal insufficiency was defined as eGFR <60mL/min/1.73m2. Results: The cohort consisted of 450 patients of whom 191 patients (42.4%) had renal insufficiency. Compared with patients with normal renal function, they were older, more often female and more likely to have other co-morbidities. After taking potential confounders into account in the multivariate analysis, patients with renal insufficiency had a higher risk of primary composite outcome during long-term follow up with an adjusted hazard ratio of 1.48 (95% CI 1.02-2.15, p=0.038). They also had significantly higher risk of all-cause mortality, MACE and cardiovascular death with adjusted hazard ratios of 1.66, 1.90 and 2.01 respectively (p Conclusion: In an unselected cohort of STEMI patients treated with PPCI, renal insufficiency was associated with adverse clinical outcome when compared to STEMI patients without renal insufficiency.

Abstract 11854: Intensive vs Standard Blood-Pressure Control ni Individuals With Polyvascular Disease

Introduction: In the SPRINT trial, intensive blood pressure control reduced all-cause mortality and major adverse cardiovascular events in individuals at high risk for cardiovascular events. However, it is unclear whether individuals with polyvascular disease, compared to individuals without established atherosclerosis, similarly benefit from intensive blood pressure control. Methods: We performed a post-hoc analysis of the SPRINT trial to determine the efficacy of intensive versus standard blood pressure control on the primary composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death); and secondary outcomes (cardiovascular death, myocardial infarction). Individuals were stratified by severity of atherosclerosis: no known atherosclerotic disease (Framingham Risk Score &gt; 15%), subclinical atherosclerosis, symptomatic single-bed atherosclerosis, and symptomatic polyvascular atherosclerosis. Uni- and multivariable Cox regression models were used to compute the crude and adjusted hazard ratios. Interaction between intensive vs standard blood pressure control and atherosclerotic burden was evaluated. Results: In the SPRINT trial, 6,837 individuals had elevated Framingham Risk Score, 128 had subclinical atherosclerosis, 1,207 had symptomatic single-bed atherosclerosis, and 254 had symptomatic polyvascular disease. There was graded increase in risk of primary composite outcome and secondary outcomes with more atherosclerotic burden, even when controlling for differences in baseline characteristics (Figure). There was no interaction among groups between treatment assignment and primary or secondary outcomes. Conclusions: This post-hoc analysis of SPRINT trial demonstrates a higher risk of adverse in patients with escalating atherosclerotic burden. Individuals derive benefit from intensive blood pressure control regardless of burden of atherosclerosis.

Sex Difference in Effectiveness of Early Rhythm- over Rate-Control in Patients with Atrial Fibrillation

Background: This study aimed to investigate the associations between sex and the relative effect of rhythm control over rate control in patients with atrial fibrillation. Methods: We used the National Health Insurance Service database to select patients treated for atrial fibrillation within one year after diagnosis. The primary composite outcome comprised cardiovascular death, ischemic stroke, heart failure hospitalization, or acute myocardial infarction. Results: During the mean follow-up (4.9 ± 3.2 years), the benefit of rhythm control over rate control on the primary composite outcome became statistically insignificant after 3 months from atrial fibrillation diagnosis in women while remained steadily until 12 months in men. The risk of primary composite outcome for rhythm control was lower than that for rate control in both sexes if it was initiated within 6 months (men: HR = 0.86, 95%CI = 0.79–0.94; women: HR = 0.85, 95%CI = 0.78–0.93; P for interaction = 0.844). However, there was significant interaction between sex and the relative effect of rhythm control if it was initiated after 6 months (men: HR = 0.72, 95%CI = 0.52–0.99; women: HR = 1.32, 95%CI = 0.92–1.88; P for interaction = 0.018). Conclusion: Rhythm control resulted in lower risk of primary composite outcome than rate control in both sexes; however, the treatment initiation at an earlier stage might be considered in women.

Risk of Cardiovascular Events After COVID-19

We aimed to determine absolute and relative risks of either symptomatic or asymptomatic SARS-CoV-2 infection for late cardiovascular (CV) events and all-cause mortality. We conducted a retrospective double cohort study of patients with either symptomatic or asymptomatic SARS-CoV-2 infection (COVID-19+ cohort) and its documented absence (COVID-19− cohort). The study investigators drew a simple random sample of records from all patients under the Oregon Health & Science University Healthcare (n = 65,585), with available COVID-19 test results, performed March 1, 2020 to September 13, 2020. Exclusion criteria were age <18 years and no established Oregon Health & Science University care. The primary outcome was a composite of CV morbidity and mortality. All-cause mortality was the secondary outcome. The study population included 1,355 patients (mean age 48.7 ± 20.5 years; 770 women [57%], 977 White non-Hispanic [72%]; 1,072 ensured [79%]; 563 with CV disease history [42%]). During a median 6 months at risk, the primary composite outcome was observed in 38 of 319 patients who were COVID-19+ (12%) and 65 of 1,036 patients who were COVID-19− (6%). In the Cox regression, adjusted for demographics, health insurance, and reason for COVID-19 testing, SARS-CoV-2 infection was associated with the risk for primary composite outcome (hazard ratio 1.71, 95% confidence interval 1.06 to 2.78, p = 0.029). Inverse probability-weighted estimation, conditioned for 31 covariates, showed that for every patient who was COVID-19+, the average time to all-cause death was 65.5 days less than when all these patients were COVID-19−: average treatment effect on the treated −65.5 (95% confidence interval −125.4 to −5.61) days, p = 0.032. In conclusion, either symptomatic or asymptomatic SARS-CoV-2 infection is associated with an increased risk for late CV outcomes and has a causal effect on all-cause mortality in a late post-COVID-19 period.

The Efficacy and Safety of SGLT2 Inhibitor in Diabetic Kidney Transplant Recipients.

The efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) have not been investigated in kidney transplant recipients (KTRs) with diabetes. We evaluated the impact of SGLT2i in a multicenter cohort of diabetic KTRs. A total of 2083 KTRs with diabetes were enrolled from 6 transplant centers in Korea. Among them, 226 (10.8%) patients were prescribed SGLT2i for >90 d. The primary outcome was a composite outcome of all-cause mortality, death-censored graft failure (DCGF), and serum creatinine doubling. An acute dip in estimated glomerular filtration rate (eGFR) over 10% was surveyed after SGLT2i use. During the mean follow-up of 62.9 ± 42.2 mo, the SGLT2i group had a lower risk of primary composite outcome than the control group in the multivariate and propensity score-matched models (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.78; P = 0.006 and adjusted hazard ratio, 0.45; 95% confidence interval, 0.24-0.85; P = 0.013, respectively). Multivariate analyses consistently showed a decreased risk of DCGF and serum creatinine doubling in the SGLT2i group. The overall eGFR remained stable without the initial dip after SGLT2i use. A minority (15.6%) of the SGLT2i users showed acute eGFR dip during the first month, but the eGFR recovered thereafter. The risk factors for the eGFR dip were time from transplantation to SGLT2i usage and mean tacrolimus trough level. SGLT2i improved a composite of all-cause mortality, DCGF, or serum creatinine doubling in KTRs. SGLT2i can be used safely and have beneficial effects on preserving graft function in diabetic KTRs.

Prognostic Impact of Mildly Impaired Renal Function in Patients Undergoing Multivessel Coronary Revascularization

BackgroundThe long-term prognostic impact of mildly decreased renal function in patients undergoing coronary revascularization is still unknown. ObjectivesThe goal of this study was to investigate the long-term prognostic impact of mildly decreased renal function and comparative outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in such a risk group of patients. MethodsFrom the Asan Medical Center–Multivessel Revascularization registry, 10,354 eligible patients who underwent coronary revascularization were classified into 3 groups (stage I [n = 3,735]: normal renal function; stage II [n = 5,122]: mild dysfunction; and stage III [n = 1,497]: moderate dysfunction) according to estimated glomerular filtration rate. The primary outcome was the composite of death, spontaneous myocardial infarction, or stroke. Propensity score matching was used to assemble a cohort of patients with similar baseline characteristics. ResultsAfter propensity matching, the risk for primary composite outcome was not different between the stage I and the stage II group (HR: 1.12; 95% CI: 0.97-1.30). However, the risk of the primary outcome was significantly higher in the stage III group than in the stage I group (HR: 1.50; 95% CI: 1.22-1.84). The relative effect of PCI vs CABG for the primary outcome was similar in the matched cohort of each renal function group of stages I, II, and III. ConclusionsIn patients with multivessel disease after revascularization by PCI or CABG, the presence of mildly decreased renal function was not significantly associated with an increased risk of the primary composite outcome and mortality. Comparative outcomes after PCI and CABG were similar in the borderline-risk group. (Asan Medical Center–Multivessel Revascularization registry; NCT02039752)

Inter-racial differences in patients undergoing transcatheter aortic valve implantation

ObjectiveLittle information exists about inter-racial differences in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). We investigated whether differences in baseline characteristics between Asian and non-Asian population...

Effect of SGLT-2 inhibitors on cardiovascular outcomes in heart failure patients: A meta-analysis of randomized controlled trials

BackgroundTo investigate the overall effect of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on cardiovascular outcomes in a broad spectrum of heart failure (HF) patients, and further stratified by status of ejection fraction and diabetes mellitus. MethodsElectronic databases were searched to identify randomized controlled trials that compared SGLT-2i with placebo in patients with HF. Efficacy outcomes included the composite of cardiovascular death (CVD) or hospitalization for heart failure (HHF), individual CVD, individual HHF, and all-cause mortality (ACM). ResultsA total of 8 large trials comprising 16,460 HF patients were enrolled. Pooled data demonstrated that SGLT-2i significantly reduced the risk for primary composite outcome (CVD or HHF) by 23% (HR: 0.77, 95% CI: 0.72–0.82) in HF patients. Use of SGLT-2i was associated with a statistically significant 32% reduction in HHF (HR: 0.68, 95% CI: 0.62–0.75), a 15% reduction in CVD (HR: 0.85, 95% CI: 0.76–0.94) and a 16% reduction in ACM (HR: 0.84, 95% CI: 0.77–0.92). Sensitivity analyses using Mantel-Haenszel method displayed consistent results. Subgroup analyses demonstrated that SGLT-2i were robustly effective in HFrEF subgroup as well as in HF with absence/presence of T2DM, and displayed a strong trend to be effective in HFpEF. Safety analysis demonstrated SGLT-2i group had a lower proportion of serious adverse events than placebo group (RR 0.89, 95% CI: 0.86–0.93). ConclusionsCompared with placebo, SGLT-2 inhibitors have remarkable cardiovascular benefits in a broad range of HF patients. Beneficial effects were robust in HF patients regardless of T2DM status, and a strong trend to be effective in HFpEF.

Hospitalization and Mortality in Patients With Heart Failure Treated With Sacubitril/Valsartan vs. Enalapril: A Real-World, Population-Based Study.

Background: The effect of sacubitril/valsartan on survival and hospitalization risk in older patients with heart failure has not been explored. We aimed to investigate the risk of hospitalization and mortality with the use of sacubitril/valsartan vs. enalapril in patients with heart failure.Methods: This was a population-based cohort study using the Hong Kong-wide electronic healthcare database. Patients diagnosed with heart failure and newly prescribed sacubitril/valsartan or enalapril between July 2016 and June 2019 were included. The risk of primary composite outcome of cardiovascular mortality or heart failure-related hospitalization, all-cause hospitalization, heart failure-related hospitalization, cardiovascular mortality and all-cause mortality were compared using Cox regression with inverse probability treatment weighting. Additional analysis was conducted by age stratification.Results: Of the 44,503 patients who received sacubitril/valsartan or enalapril, 3,237 new users (sacubitril/valsartan, n = 1,056; enalapril, n = 2,181) with a diagnosis of heart failure were identified. Compared with enalapril, sacubitril/valsartan users were associated with a lower risk of primary composite outcome [hazard ratio (HR) 0.58; 95% confidence interval (CI), 0.45–0.75], heart failure-related hospitalization (HR 0.59; 95% CI, 0.45–0.77), all-cause mortality (HR 0.51; 95% CI, 0.36–0.74) and borderline non-significant reductions in all-cause hospitalization (HR 0.85; 95% CI, 0.70–1.04) and cardiovascular mortality (HR 0.63; 95% CI, 0.39–1.02). The treatment effect of sacubitril/valsartan remains unaltered in the patient subgroup age ≥ 65 years (73%).Conclusions: In real-world settings, sacubitril/valsartan was associated with improved survival and reduced heart failure-related hospitalization compared to enalapril in Asian patients with heart failure. The effectiveness remains consistent in the older population.

Urine albumin dipstick independently predicts cardiovascular and renal outcomes among rural Thai population: a 14-year retrospective cohort study

BackgroundAlbuminuria is an established risk marker for both cardiovascular and renal outcomes. In this study, we expected to use portable and inexpensive test strips to detect urine albumin level for risk stratification in cardiovascular and renal outcomes among rural Thai community.ObjectiveTo evaluate the relationship between urine albumin dipstick and cardiovascular and renal complications in rural Thai population.MethodsWe conducted a retrospective study in 635 rural Thai adults who tested urine albuminuria by using commercial urine albumin dipstick and the Micral-albumin test II strips at baseline. The subjects were divided into normoalbuminuria (albumin < 20 mg/L), microalbuminuria (albumin 20–200 mg/L), or macroalbuminuria (Urine dipstick at least 1+ or albumin > 200 mg/L). We collected data on the incidences of primary composite outcomes including cardiovascular or renal morbidity and mortality. Incident density and cox regression were analyzed to evaluate the association between albuminuria status and primary composite outcome.ResultsDuring an average 14-year follow-up, 102 primary composite events occurred including 59 (13.1%), 32 (20.6%) and 11 (39.3%) among 452, 155, and 28 subjects with normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively. Incident densities of primary composite outcome were elevated continually according to the degree of albuminuria (9.36, 17.11 and 38.12 per 1000 person-years). Compared with the subjects without albuminuria, subjects with microalbuminuria and macroalbuminuria at baseline had higher risk for primary composite outcome in univariate model. After multivariate analysis was performed, the effect of macroalbuminuria was only persisted with 3.13-fold risk (adjusted HR 3.13; 95% CI 1.40–6.96, P= 0.005).ConclusionAlbuminuria from semi-quantitative methods is an important factor predicting cardiovascular and renal risk among subjects in Thai rural population. Our findings support to also incorporating urine albumin dipstick into assessments of cardiovascular risk in the general population.

Long-Term Clinical Outcomes of Sirolimus- Versus Paclitaxel-Eluting Stents for Patients With Unprotected Left Main Coronary Artery Disease: Analysis of the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) Registry

The aim of this study was to evaluate long-term clinical outcomes after implantation of sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES) among patients with unprotected left main coronary artery (LMCA) disease. There have been few comparisons of long-term outcomes among currently available drug-eluting stents (DES) for the treatment of LMCA disease. A total of 858 consecutive patients with unprotected LMCA stenosis were treated with SES (n = 669) or PES (n = 189) between May 2003 and June 2006. Primary outcome was the composite of death, myocardial infarction (MI), or target vessel revascularization (TVR). Baseline clinical and angiographic characteristics were similar in the 2 groups. During 3 years of follow-up, the adjusted risk of primary composite outcome was similar among the groups (SES vs. PES: 25.8% vs. 25.7%, hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.64 to 1.41, p = 0.79). The 2 groups also showed a comparable adjusted rate of each component of outcome: death (9.1% vs. 11.0%, HR: 0.92, 95% CI: 0.47 to 1.80, p = 0.82), MI (8.1% vs. 8.0%, HR: 0.80, 95% CI: 0.43 to 1.48, p = 0.47), and TVR (12.1% vs. 10.6%, HR: 1.10, 95% CI: 0.53 to 2.29, p = 0.81). The 3-year rates of definite or probable stent thrombosis were 0.6% in the SES group and 1.6% in the PES group (adjusted p = 0.18). In consecutive patients with unprotected LMCA disease undergoing DES implantation, SES and PES showed similar long-term clinical outcomes in terms of death, MI, repeat revascularization, and stent thrombosis.