Risk Of Primary Outcome Events Research Articles

The relationship between HBV antigens deposition in kidneys and renal prognosis in IgA nephropathy patients infected with HBV

Background Hepatitis B virus (HBV) is a risk factor for the progression of immunoglobulin A (IgA) nephropathy. The effect of HBV antigens deposition in kidneys and treatment influencing HBV deposition requires further investigation. Methods We analyzed 198 patients with IgAN, including 99 patients with HBV infection and 99 propensity score-matched patients without HBV infection. The primary outcome was a composite of 30% decrease in eGFR from the baseline, kidney failure and all-cause mortality. A Cox proportional hazard model was used to assess the impact of both HBV positive in the serum and HBV antigens deposition in the kidneys on renal outcomes. Results Among 198 individuals, 27 primary composite outcome events were observed, of which 20 (20%) in the HBV positive group and seven (7%) were in the HBV-negative group. The former had a 2.72-fold increased risk of primary outcome events (adjusted hazard ratio: 2.22; 95% confidence interval: 0.89–5.53). HBV antigens deposition in kidneys increased the risk significantly after adjusting for confounders at the latest follow-up (adjusted hazard ratio: 7.49; 95% confidence interval: 1.00–56.04). Antiviral treatment did not influence the deposition of HBV antigens. Conclusions HBV antigen deposition in the kidneys, compared with no deposition in the kidneys, was associated with a 7.49-fold increased risk of renal prognosis in patients with IgA nephropathy.

Conventional versus minimally invasive extra-corporeal circulation in patients undergoing cardiac surgery: A randomized controlled trial (COMICS).

The trial hypothesized that minimally invasive extra-corporeal circulation (MiECC) reduces the risk of serious adverse events (SAEs) after cardiac surgery operations requiring extra-corporeal circulation without circulatory arrest. This is a multicentre, international randomized controlled trial across fourteen cardiac surgery centres including patients aged ≥18 and <85 years undergoing elective or urgent isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR) surgery, or CABG + AVR surgery. Participants were randomized to MiECC or conventional extra-corporeal circulation (CECC), stratified by centre and operation. The primary outcome was a composite of 12 post-operative SAEs up to 30 days after surgery, the risk of which MiECC was hypothesized to reduce. Secondary outcomes comprised: other SAEs; all-cause mortality; transfusion of blood products; time to discharge from intensive care and hospital; health-related quality-of-life. Analyses were performed on a modified intention-to-treat basis. The trial terminated early due to the COVID-19 pandemic; 1071 participants (896 isolated CABG, 97 isolated AVR, 69 CABG + AVR) with median age 66 years and median EuroSCORE II 1.24 were randomized (535 to MiECC, 536 to CECC). Twenty-six participants withdrew after randomization, 22 before and four after intervention. Fifty of 517 (9.7%) randomized to MiECC and 69/522 (13.2%) randomized to CECC group experienced the primary outcome (risk ratio = 0.732, 95% confidence interval (95% CI) = 0.556 to 0.962, p = 0.025). The risk of any SAE not contributing to the primary outcome was similarly reduced (risk ratio = 0.791, 95% CI 0.530 to 1.179, p = 0.250). MiECC reduces the relative risk of primary outcome events by about 25%. The risk of other SAEs was similarly reduced. Because the trial terminated early without achieving the target sample size, these potential benefits of MiECC are uncertain.

Long-term risk assessment in athletes with ventricular arrhythmias: the key roles of arrhythmia morphology, complexity, and substrate

Abstract Background Ventricular arrhythmias (VAs) are an important source of concern among athletes. Purpose To determine the prognostic role of non-invasive and invasive diagnostic assessments among athletes with complex VAs. Methods We included 215 athletes (83% male; 28 [19-43] years) with complex VAs in a prospective, multi-center cohort study. At baseline, each athlete underwent a prespecified comprehensive diagnostic workup, which included cardiac magnetic resonance (CMR) in 202 subjects, and electrophysiology study (EPS)/electroanatomical mapping (EAM) in 190. The primary study endpoint was the occurrence of sudden death or sustained VAs during long-term follow-up. Results During a median follow-up of 6.2 (4.4-8.1) years, 16 (7%) athletes had a primary outcome event, including one sudden cardiac death. In univariable Cox models, sustained VAs at presentation (p&amp;lt;0.001), uncommon VA morphology(p=0.004), syncope(p=0.005), abnormal ECG (p=0.003), VAs induction/persistence at exercise testing(p=0.021), late gadolinium enhancement (LGE;p=0.006), low-voltage areas (p=0.003) and late potentials (p&amp;lt;0.001) at EAM, and sustained VA induction by EPS (p&amp;lt;0.001) were all associated with increased risk of primary outcome events. The association of late potentials and EPS inducibility with primary outcome events was confirmed after controlling for all non-invasive predictors at univariable analysis, and the incorporation of findings of invasive tests allowed improved prediction of primary outcome events over clinical/non-invasive findings in isolation (log-likelihood ratio for nested models, p=0.043). Younger age (p=0.032), being a professional athlete (p=0.006), and absence of LGE (p=0.029) were independently associated with higher odds of uninterrupted competitive sports practice until last follow-up. Conclusions A comprehensive diagnostic assessment integrating clinical/ECG findings with CMR and EPS/EAM in selected cases may provide important prognostic information among athletes with complex VAs.

Kidney transplantation waiting times and risk of cardiovascular events and mortality: a retrospective observational cohort study in Taiwan

ObjectivesPatients with end-stage renal disease (ESRD) are at a high risk of cardiovascular events (CVEs), and kidney transplantation (KT) has been reported to improve risk of CVEs and survival. As...

Prevalence and prognostic significance of ischemic late gadolinium enhancement pattern in non-ischemic dilated cardiomyopathy

Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronary artery disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischemic LGE pattern in DCM. A total of 611 DCM patients with available cardiac magnetic resonance were retrospectively analyzed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation. Ischemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischemic LGE, those with ischemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischemic LGE was associated with worse long-term outcomes compared to non-ischemic LGE (36% vs 23% risk of primary outcome events at 5 years respectively, P=.006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables (adjusted hazard ratio 2.059 [1.055-4.015], P=.034 with respect to non-ischemic LGE). The ischemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes.

73 Prevalence and prognostic significance of ischaemic late gadolinium enhancement pattern in non-ischaemic dilated cardiomyopathy

Abstract Aims Typical late gadolinium enhancement (LGE) patterns in dilated cardiomyopathy (DCM) include intramyocardial and subepicardial distribution. However, the ischaemic pattern of LGE (subendocardial and transmural) has also been reported in DCM without coronary artery disease (CAD), but its correlates and prognostic significance are still not known. On these bases, this study sought to describe the prevalence and prognostic significance of the ischaemic LGE pattern in DCM. Methods and results 611 DCM patients with available cardiac magnetic resonance were retrospectively analysed. A composite of all-cause-death, major ventricular arrhythmias (MVAs), heart transplantation (HTx) or ventricular assist device (VAD) implantation was the primary outcome of the study. Secondary outcomes were a composite of sudden cardiac death or MVAs and a composite of death for refractory heart failure, HTx or VAD implantation. Ischaemic LGE was found in 7% of DCM patients without significant CAD or history of myocardial infarction, most commonly inferior/inferolateral/anterolateral. Compared to patients with non-ischaemic LGE, those with ischaemic LGE had higher prevalence of hypertension and atrial fibrillation or flutter. Ischaemic LGE was associated with worse long-term outcomes compared to non-ischaemic LGE (36% vs. 23% risk of primary outcome events at 5 years, respectively, P = 0.006), and remained an independent predictor of primary outcome after adjustment for clinically and statistically significant variables [adjusted hazard ratio 2.059 (1.055–4.015), P = 0.034 with respect to non-ischaemic LGE]. Conclusions The ischaemic pattern of LGE is not uncommon among DCM patients without CAD and is independently associated with worse long-term outcomes.

CHA2DS2-VASc score in acute ischemic stroke with atrial fibrillation: results from the Clinical Research Collaboration for Stroke in Korea

We investigated a multicenter registry to identify estimated event rates according to CHA2DS2-VASc scores in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). The additional effectiveness of antiplatelets (APs) plus oral anticoagulants (OACs) compared with OACs alone considering the CHA2DS2-VASc scores was also explored. This study retrospectively analyzed a multicenter stroke registry between Jan 2011 and Nov 2017, identifying patients with acute ischemic stroke with AF. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 1 year. A total of 7395 patients (age, 73 ± 10 years; men, 54.2%) were analyzed. The primary outcome events at one year ranged from 5.99% (95% CI 3.21–8.77) for a CHA2DS2-VASc score of 0 points to 30.45% (95% CI 24.93–35.97) for 7 or more points. After adjustments for covariates, 1-point increases in the CHA2DS2-VASc score consistently increased the risk of primary outcome events (aHR 1.10 [1.06–1.15]) at 1-year. Among OAC-treated patients at discharge (n = 5500), those treated with OAC + AP (vs. OAC alone) were more likely to experience vascular events, though among patients with a CHA2DS2-VASc score of 5 or higher, the risk of primary outcome in the OAC + AP group was comparable to that in the OAC alone group (Pint = 0.01). Our study found that there were significant associations of increasing CHA2DS2-VASc scores with the increasing risk of vascular events at 1-year in AIS with AF. Further study would be warranted.

Spironolactone Use and Improved Outcomes in Patients With Heart Failure With Preserved Ejection Fraction With Resistant Hypertension.

BackgroundResistant hypertension is a salt‐retaining condition possibly attributable to inappropriate aldosterone secretion.Methods and ResultsThis study was a secondary analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial. Patients with heart failure with preserved ejection fraction (HFpEF) with (n=1004) and without (n=2437) resistant hypertension were included. Resistant hypertension was defined as systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥80 mm Hg in a patient with hypertension, despite the concurrent use of a renin‐angiotensin system blocker (angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker), a calcium channel blocker, and a diuretic; or as those patients using ≥4 classes of antihypertensive medication. The primary outcome was a composite of cardiovascular death, aborted cardiac arrest, or heart failure hospitalization. We analyzed hazard ratios (HRs) for outcomes with 95% CIs in the spironolactone group and compared them with the placebo group using Cox proportional hazard models. The risk of primary outcome events in patients with HFpEF with resistant hypertension was significantly lower in the spironolactone group than in the placebo group (HR, 0.70; 95% CI, 0.53–0.91; P=0.009), whereas the risk of primary outcome events in patients with HFpEF without resistant hypertension was not significantly different between the 2 groups (HR, 1.00; 95% CI, 0.83–1.20; P=0.97). There was a significant interaction between spironolactone use and resistant hypertension (P=0.03). Similar associations were also observed in patients with HFpEF from the Americas (United States, Canada, Brazil, and Argentina) only.ConclusionsSpironolactone may be an effective add‐on medication for patients with HFpEF with resistant hypertension taking angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, calcium channel blockers, and diuretics.

Thiazide Use and Decreased Risk of Heart Failure in Nondiabetic Patients Receiving Intensive Blood Pressure Treatment

The SPRINT (Systolic Blood Pressure Intervention Trial) study reported that intensive blood pressure (BP) treatment with a systolic BP target of <120 mm Hg decreased the risks of cardiovascular events. However, it remains unknown whether specific medications can further improve cardiovascular outcome in patients receiving intensive BP treatment. This study examined whether thiazide use improves cardiovascular outcome in patients receiving intensive BP treatment. We used data of nondiabetic patients receiving intensive BP treatment in the SPRINT study. The primary outcome was a composite end point of myocardial infarction, acute coronary syndrome, stroke, heart failure, or cardiovascular death. We analyzed hazard ratios for outcomes with 95% CIs in patients taking thiazides compared with those not taking thiazides using Cox proportional hazard models. This study included 2847 patients and the mean follow-up period was 3.3 years. The risk of primary outcome events was significantly lower in patients taking thiazides than in those not taking thiazides in both entire and propensity score-matched cohorts. Particularly, heart failure risk was significantly lower in those taking thiazides. These associations were also observed in various subgroups. In addition, thiazide use was associated with decreased risk of all-cause mortality. Hypokalemia occurred more frequently in patients taking thiazides than in those not taking thiazides. Thiazide use decreased risk of cardiovascular events, particularly heart failure, in nondiabetic high-risk patients receiving intensive BP treatment.

Use of Nitrates and Risk of Cardiovascular Events in Patients With Heart Failure With Preserved Ejection Fraction

ObjectiveTo assess the association of nitrate use with cardiovascular events in patients with heart failure with preserved ejection fraction (HFpEF). Patients and MethodsPatient data were collected from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist trial, which had been conducted at 233 sites in 6 countries from August 10, 2006, through January 31, 2012. The primary outcome was the occurrence of a major adverse cardiovascular event (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) or heart failure hospitalization. The association between nitrate use and cardiovascular risk was evaluated using Cox proportional hazards analysis. In addition, we verified the results using propensity score–matched patients. ResultsA total of 3417 patients with HFpEF were evaluated over a mean follow-up of 3.1 years, and 778 experienced a primary outcome event. The risk of primary outcome events was significantly higher in patients taking nitrates than in those not taking nitrates (hazard ratio [HR], 1.21; 95% CI, 1.01-1.46, P=.04). The risk of major adverse cardiovascular events was significantly higher in patients taking nitrates than in those not taking nitrates (HR, 1.32; 95% CI, 1.05-1.66, P=.01). Furthermore, the risk of hospitalization for heart failure was higher in patients taking nitrates (HR, 1.25; 95% CI, 0.99-1.60, P=.06), with propensity score–matched analyses revealing similar findings. In addition, a similar association was observed in various subgroups. ConclusionThis study reported that nitrate use in patients with HFpEF was associated with a significantly increased risk of cardiovascular events.

Strategies for glycemic control in nonobese and obese type 2 diabetic patients with coronary artery disease

BackgroundThis study aimed to assess strategies of insulin-providing (IP) or insulin-sensitizing (IS) therapy for glycemic control in nonobese diabetic patients with coronary artery disease (CAD) with possibly higher cardiovascular risk and lower insulin secretion than obese diabetic patients with CAD. MethodsWe used data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial to calculate hazard ratio (HR) with 95% confidence interval (95%CI) for outcome events in patients with type 2 diabetes and CAD using Cox proportional hazard models. The comparison between the IP and IS groups was performed using the randomized design of the BARI 2D trial separately for nonobese (n = 1021) and obese (n = 1319) patients. The primary outcome was a composite endpoint including all-cause death, myocardial infarction, and stroke. ResultsDuring the follow-up, 231 nonobese and 295 obese patients had one confirmed primary outcome event. In nonobese patients, the risk of primary outcome events was significantly higher in the IP group than the IS group (HR: 1.30, 95%CI: 1.00–1.68, P = 0.04), whereas that in obese patients did not differ significantly between the two groups. Moreover, in nonobese patients, the risk of primary outcome events in those without abdominal obesity was significantly higher in the IP group than that in the IS group (HR: 1.51, 95%CI: 1.05–2.19, P = 0.02). There were no significant interactions between the strategy for glycemic control and various subgroups of nonobese patients. ConclusionsIn nonobese patients with type 2 diabetes and CAD, the IS treatment strategy may be more beneficial than the IP treatment strategy.

Geographic differences in outcomes in outpatients with established atherothrombotic disease: results from the REACH Registry

There are major differences in the prevalence and management of patients with atherothrombotic disease including coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD) across different geographical regions. There is, however, little data allowing comparisons of management and outcomes across broad geographic regions. We aimed to describe geographical differences in baseline characteristics, management and outcomes in stable outpatients with established atherothrombotic disease. From the REACH Registry of atherothrombosis, patients with documented CAD, PAD or CVD and with 4-year follow-up were included. Baseline characteristics, treatments and 4-year outcomes were recorded. Event rates were compared between geographical regions and were adjusted for risk scores predicting ischemic and bleeding events. The analyses of baseline characteristics and medications according to geographical region showed marked differences. For the composite primary outcome (cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke), rates ranged from 12.1% in Japan to 18.2% in Eastern Europe. After adjustment, substantial variations remained: taking North America as a reference, patients from Western Europe and Japan had a lower risk of primary outcome event (hazard ratio (HR) 0.93; p = 0.045, and HR = 0.67; p < 0.001 respectively) whereas patients from Eastern Europe had a higher risk (HR = 1.24; p < 0.001). There were no obvious differences between patients from North America and those from Latin America, the Middle East and Asia. There are important variations in the outcomes of patients with atherothrombotic across geographic regions. These observations have important implications for public health and clinical research.

Swedish Aspirin Low-dose Trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events

The efficacy of aspirin in daily doses of 300 mg and more as secondary prophylaxis after cerebrovascular events is well established. Since much lower doses of aspirin can inhibit platelet function, and carry a lower risk of adverse effects, the Swedish Aspirin Low-dose Trial (SALT) was set up to study the efficacy of 75 mg aspirin daily in prevention of stroke and death after transient ischaemic attack (TIA) or minor stroke. 1360 patients entered the study 1-4 months after the qualifying event: 676 were randomly assigned to aspirin treatment and 684 to placebo treatment. The median duration of follow-up was 32 months. Compared with the placebo group, the aspirin group showed a reduction of 18% in the risk of primary outcome events (stroke or death; relative risk 0·82, 95% confidence interval 0·67-0·99; log-rank analysis p=0·02), and reductions of 16-20% in the risks of secondary outcome events (stroke; stroke or two or more TIAs within a week of each other necessitating a change of treatment; or myocardial infarction). Adverse drug effects were reported by 147 aspirin-treated and 123 placebo-treated patients Gastrointestinal side-effects were only slightly more common in the aspirin-treated patients, but that group had a significant excess of bleeding episodes (p=0·04). Thus, we have found that a low dose (75 mg/day) of aspirin significantly reduces the risk of stroke or death in patients with cerebrovascular ischaemic events.