Search

This article discusses the results of a post-hoc analysis of the VERTIS CV trial, which examined the effects of the medication ertugliflozin on the risk of hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease. The study found that ertugliflozin significantly reduced the risk of first HHF in the overall cohort of participants. However, the treatment effect was more pronounced in individuals with a pre-trial ejection fraction (EF) of less than 45% and attenuated in those with an EF greater than 60%. These findings contribute to the understanding of the efficacy of SGLT2 inhibitors in reducing the risk of HHF across different EF ranges. [Extracted from the article]

Aims Levels of growth differentiation factor 15 (GDF-15), a cytokine secreted in response to cellular stress and inflammation, have been associated with multiple types of cardiovascular (CV) events. However, its comparative prognostic performance across different presentations of atherosclerotic cardiovascular disease (ASCVD) remains unknown. Methods and results An individual patient meta-analysis was performed using data pooled from eight trials including 53 486 patients. Baseline GDF-15 concentration was analyzed as a continuous variable and using established cutpoints (<1200 ng/L, 1200–1800 ng/L, > 1800 ng/L) to evaluate its prognostic performance for CV death/hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE), and their components using Cox models adjusted for clinical variables and established CV biomarkers. Analyses were further stratified on ASCVD status: acute coronary syndrome (ACS), stabilized after recent ACS, and stable ASCVD. Overall, higher GDF-15 concentration was significantly and independently associated with an increased rate of CV death/HHF and MACE (P < 0.001 for each). However, while GDF-15 showed a robust and consistent independent association with CV death and HHF across all presentations of ASCVD, its prognostic association with future myocardial infarction (MI) and stroke only remained significant in patients stabilized after recent ACS or with stable ASCVD [hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.17–1.31 and HR: 1.16, 95% CI: 1.05–1.28 for MI and stroke, respectively] and not in ACS (HR: 0.98, 95% CI: 0.90–1.06 and HR: 0.87, 95% CI: 0.39–1.92, respectively). Conclusion Growth differentiation factor 15 consistently adds prognostic information for CV death and HHF across the spectrum of ASCVD. GDF-15 also adds prognostic information for MI and stroke beyond clinical risk factors and cardiac biomarkers but not in the setting of ACS. [ABSTRACT FROM AUTHOR]

Aims Interest in targeted screening programmes for atrial fibrillation (AF) has increased, yet the role of genetics in identifying patients at highest risk of developing AF is unclear. Methods and results A total of 36,662 subjects without prior AF were analyzed from four TIMI trials. Subjects were divided into quintiles using a validated polygenic risk score (PRS) for AF. Clinical risk for AF was calculated using the CHARGE-AF model. Kaplan–Meier event rates, adjusted hazard ratios (HRs), C -indices, and net reclassification improvement were used to determine if the addition of the PRS improved prediction compared with clinical risk and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Over 2.3 years, 1018 new AF cases developed. AF PRS predicted a significant risk gradient for AF with a 40% increased risk per 1-SD increase in PRS [HR: 1.40 (1.32–1.49); P < 0.001]. Those with high AF PRS (top 20%) were more than two-fold more likely to develop AF [HR 2.45 (1.99–3.03), P < 0.001] compared with low PRS (bottom 20%). Furthermore, PRS provided an additional gradient of risk stratification on top of the CHARGE-AF clinical risk score, ranging from a 3-year incidence of 1.3% in patients with low clinical and genetic risk to 8.7% in patients with high clinical and genetic risk. The subgroup of patients with high clinical risk, high PRS, and elevated NT-proBNP had an AF risk of 16.7% over 3 years. The C -index with the CHARGE-AF clinical risk score alone was 0.65, which improved to 0.67 (P < 0.001) with the addition of NT-proBNP, and increased further to 0.70 (P < 0.001) with the addition of the PRS. Conclusion In patients with cardiovascular conditions, AF PRS is a strong independent predictor of incident AF that provides complementary predictive value when added to a validated clinical risk score and NT-proBNP. [ABSTRACT FROM AUTHOR]

*Based on the available data the risk of statin-associated muscle symptoms with pitavastatin is similar to placebo [3]; #with low-to moderate intensity statin therapy; $ moderate intensity statin therapy for partial statin intolerance patients; **preferably with ezetimibe. We can consider four different scenarios when a patient presents with adverse effects that they perceive to be due to statin therapy, each requiring a different approach: (i) The adverse effect may be entirely unrelated to statin therapy. This enables the treatment regimen to be matched to the patients' needs at the outset, potentially commencing therapy with more than one drug, rather than starting the patient on a single drug, which could not conceivably enable them to reach treatment targets. [Extracted from the article]

Aims To study the relation between visit-to-visit variability of blood pressure (BP) and cardiovascular risk in patients with stable coronary heart disease. Methods and results In 15 828 patients from the STABILITY trial (darapladib vs. placebo in patients with established coronary heart disease), BP variability was assessed by the standard deviation (SD) of systolic BP, the SD of diastolic BP, maximum BP and minimum BP, from 5 measurements (baseline and months 1, 3, 6, and 12) during the first year after randomisation. Mean (SD) average BP during the first year of study was 131.0 (13.7) mmHg over 78.3 (8.3) mmHg. Mean (SD) of the visit-to-visit SD was 9.8 (4.8) mmHg for systolic and 6.3 (3.0)mmHg for diastolic BP. During the subsequent median follow-up of 2.6 years, 1010 patients met the primary endpoint, a composite of time to cardiovascular death, myocardial infarction, or stroke. In Cox regression models adjusted for average BP during first year of study, baseline vascular disease, treatment, renal function and cardiovascular risk factors, the primary endpoint was associated with SD of systolic BP (hazard ratio for highest vs. lowest tertile, 1.30, 95% CI 1.10-1.53, P = 0.007), and with SD of diastolic BP (hazard ratio for highest vs. lowest tertile, 1.38, 95% CI 1.18-1.62, P < 0.001). Peaks and troughs in BP were also independently associated with adverse events. Conclusion In patients with stable coronary heart disease, higher visit-to-visit variabilities of both systolic and diastolic BP are strong predictors of increased risk of cardiovascular events, independently of mean BP. [ABSTRACT FROM AUTHOR]

Aims To examine the efficacy and safety of ezetimibe added to statin in patients with prior coronary artery bypass graft surgery (CABG) following hospitalization for an acute coronary syndrome (ACS). Methods and results In the IMPROVE-IT trial, post-ACS patients with mean low density lipoprotein cholesterol (LDL-C) of 93.8mg/dL at presentation were randomized to simvastatin/ezetimibe or simvastatin/placebo. The primary endpoint was cardiovascular death, major coronary event or stroke, and the median follow-up was 6 years. Efficacy and safety endpoints were examined by prior CABG status. Among 18 134 patients, 1684 (9.3%) had a prior CABG (median age 69 years, 82% male). During the trial, the median time-weighted LDL-C level was 55.0mg/dL with simvastatin/ezetimibe vs. 69.9 mg/dL with simvastatin/placebo in patients with prior CABG (P<0.001), and it was 53.6mg/dL vs. 69.5mg/dL, respectively, in patients without prior CABG (P<0.001). The rate of the primary endpoint was higher in patients with vs. without prior CABG [56% vs. 32%, adj. hazard ratio 1.45, 95% confidence interval (CI) 1.33-1.58]. Patients with prior CABG receiving simvastatin/ezetimibe had an 8.8% (95% CI 3.1-14.6%) lower absolute risk over simvastatin/placebo in the primary endpoint, whereas patients without prior CABG had a 1.3% (95% CI 0-2.6%) lower absolute risk (P-interaction=0.02). There were no between-group significant differences in safety endpoints. Conclusion The clinical benefit of adding ezetimibe to statin appears to be enhanced in patients with prior CABG, supporting the use of intensive lipid lowering therapy in these high-risk patients following ACS. [ABSTRACT FROM AUTHOR]

Aims: To investigate the association between neutrophil count, outcomes, and benefit of clopidogrel therapy in ST-elevation myocardial infarction (STEMI). [ABSTRACT FROM PUBLISHER]

Aims There have been no large observational studies attempting to identify predictors of major bleeding in patients with acute coronary syndromes (ACS), particularly from a multinational perspective. The objective of our study was thus to develop a prediction rule for the identification of patients with ACS at higher risk of major bleeding.Methods and results Data from 24 045 patients from the Global Registry of Acute Coronary Events (GRACE) were analysed. Factors associated with major bleeding were identified using logistic regression analysis. Predictive models were developed for the overall patient population and for subgroups of patients with ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina. The overall incidence of major bleeding was 3.9% (4.8% in patients with STEMI, 4.7% in patients with NSTEMI and 2.3% in patients with unstable angina). Advanced age, female sex, history of bleeding, and renal insufficiency were independently associated with a higher risk of bleeding (P<0.01). The association remained after adjustment for hospital therapies and performance of invasive procedures. After adjustment for a variety of potential confounders, major bleeding was significantly associated with an increased risk of hospital death (adjusted odds ratio 1.64, 95% confidence interval 1.18, 2.28).Conclusions In routine clinical practice, major bleeding is a relatively frequent non-cardiac complication of contemporary therapy for ACS and it is associated with a poor hospital prognosis. Simple baseline demographic and clinical characteristics identify patients at increased risk of major bleeding. [ABSTRACT FROM PUBLISHER]