Risk Factors In Clinical Trials Research Articles

Semaglutide 2.4 mg clinical outcomes in patients with obesity or overweight in a real‐world setting: A 6‐month retrospective study in the United States (SCOPE)

AbstractBackgroundManagement guidelines for obesity suggest maintaining a minimum of 5% body weight reduction to help prevent or lower the risk of developing conditions such as hypertension and type 2 diabetes. However, achieving long‐term weight control is difficult with lifestyle modification alone, making it essential to combine pharmacotherapy with diet and exercise in individual cases. Semaglutide 2.4 mg has demonstrated significant reductions in body weight and cardiometabolic risk factors in clinical trials, but information on outcomes in a real‐world setting is limited.ObjectiveTo assess changes in body weight and other clinical outcomes at 6‐month follow‐up among adults on semaglutide 2.4 mg in a real‐world setting in the United States (US).MethodsObservational and retrospective cohort study of patients initiating treatment between 15 June 2021, and 31 March 2022, using a large US claims‐linked electronic health record database.ResultsMean (±SD) body mass index (BMI) of the 343 patients included in the analysis was 37.9 ± 5.5 kg/m2. After 6 months, mean body weight change was −10.5 ± 6.8 kg (95% CI: −11.2; −9.8, p < 0.001) and mean percentage body weight change was −10.0% ± 6.6% (95% CI: −10.7; −9.3, p < 0.001). Most (79.0%) patients had ≥5% body weight reduction, 48.1% had ≥10% body weight reduction, and 19.0% had ≥15% body weight reduction. Among patients with available data, the mean change in HbA1c (n = 30) was −0.6% ± 1.2% (95% CI: −1.0; −0.1, p = 0.016) and nearly two‐thirds of patients with prediabetes or diabetes at baseline reverted to normoglycemia. Mean reductions of −4.4 ± 12.3 mmHg (95% CI: −5.7; −3.0, p < 0.001) and −1.7 ± 8.4 mmHg (95% CI: −2.6; −0.7, p < 0.001) were observed in systolic and diastolic blood pressure, respectively (n = 307). Statistically significant reductions in mean total cholesterol (−12.2 ± 38.8 mg/dl [95% CI: −24.3 to −0.06, p < 0.049]) and triglycerides (−18.3 ± 43.6 mg/dl [95% CI: −4.7; −31.9, p < 0.009]) were also observed (n = 42).ConclusionsThis study demonstrated the effectiveness of semaglutide 2.4 mg in reducing body weight and improving cardiometabolic parameters in adults with overweight or obesity in a real‐world clinical practice setting, showing a significant mean body weight reduction and improvements in biomarkers like blood pressure and HbA1c over a 6‐month period. These findings, aligning with previous clinical trials at comparable time points, highlight the clinical relevance of semaglutide as an effective therapeutic option for obesity.

Abstract 14297: The Portfolio Dietary Pattern and Risk of Cardiovascular Disease Mortality During 1988-2019 in US Adults: Findings From the Third National Health and Nutrition Examination Survey

Introduction: The Portfolio Diet, a dietary pattern that combines cholesterol-lowering plant foods, reduces several cardiovascular disease (CVD) risk factors in clinical trials and has been associated with reduced CVD risk predominately in White populations. As NHANES III (1988-1994) purposely over-sampled non-Hispanic Blacks and Mexican Americans, undertaking an analysis of the Portfolio Dietary Pattern in NHANES III will expand the generalizability of previous findings. Objective: To examine the relation of the Portfolio Dietary Pattern with CVD and all-cause mortality in NHANES III. Methods: We included 14,035 adults (76% non-Hispanic White, 11% non-Hispanic Blacks, 5% Mexican Americans, 8% other) without reported CVD. Diet was assessed by a 24-hour recall and supplemented with a food frequency questionnaire using the Portfolio Diet Score (PDS), with positive points given to nuts, plant protein, viscous fibre, phytosterols and plant monosaturated fat sources, and negative points given to foods high in saturated fat and cholesterol. To identify cause of death we used the NHANES III Linked Morality File (2019). SAS PROC SURVEYPHREG was used to run Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) by tertiles of PDS for CVD and all-cause mortality with adjustment for behavioral, sociodemographic, family history, and baseline clinical and dietary characteristics. Results: During a median follow-up of 23 years, a total of 1,809 CVD deaths were documented over 321,950 person-years. After multivariable adjustment, higher PDS was associated with a lower risk of CVD mortality (HR 0.85; 95% CI: 0.73-0.99) and all-cause mortality (HR 0.86; 95% CI: 0.77-0.95) when comparing the highest to lowest tertiles of intake. A 25-percentile increase in PDS (6 points) tended towards an association with a lower risk of CVD mortality (HR: 0.88; 95% CI: 0.76-1.01) and was associated with lower risk of all-cause mortality (HR: 0.90; 95% CI: 0.85-0.96). Conclusion: Among US adults greater adherence to the Portfolio Dietary Pattern was inversely associated with CVD and all-cause mortality. These findings improve the generalizability of the Portfolio Dietary Pattern for CVD prevention in diverse populations.

Abstract P214: The Portfolio Dietary Pattern and Risk of Cardiovascular Disease in US Adults

Introduction: The plant-based portfolio dietary pattern includes recognized cholesterol-lowering foods shown to improve several cardiovascular disease (CVD) risk factors in clinical trials. Epidemiological evidence on the association between longer-term adherence to the portfolio dietary pattern and CVD risk remains more limited. Objective: To examine whether the portfolio dietary pattern is associated with the risk of total CVD, coronary heart disease (CHD, including myocardial infarction and fatal coronary deaths), and stroke. Methods: Participants included 73,925 women in the Nurses’ Health Study (NHS) (1984-2014), 92,354 women in the NHS2 (1991-2017) and 43,970 men from the Health Professionals Follow-up Study (HPFS) (1986-2016) without CVD and cancer at baseline. Diet was assessed using validated food frequency questionnaires at baseline and every four years using a portfolio diet score (PDS) which positively ranks plant protein (soy & pulses), nuts, viscous fiber sources, phytosterols (mg/day) and plant monounsaturated fat sources, and negatively ranks foods high in saturated fat and dietary cholesterol. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for covariates. Results: During up to 30 years of follow-up, 16,917 incident CVD cases, including 10,666 CHD cases and 6,473 stroke cases, were documented. After multivariable adjustment of lifestyle and other dietary factors, comparing the highest to the lowest quintile, participants with a higher PDS had a lower risk of total CVD (pooled HR: 0.84; 95% CI: 0.80-0.89, P trend<0.001), CHD (pooled HR: 0.82; 95% CI: 0.76-0.87, P trend<0.001) and stroke (pooled HR: 0.88; 95% CI: 0.81-0.97, P trend=0.001). In addition, a 25-percentile higher PDS was associated with a lower risk of total CVD (pooled HR: 0.91; 95% CI: 0.88-0.93), CHD (pooled HR: 0.89; 95% CI: 0.86-0.92) and stroke (pooled HR: 0.93; 95% CI: 0.89-0.97). Results remained largely consistent across sensitivity and subgroup analyses. Conclusions: Greater adherence to the portfolio dietary pattern was consistently associated with lower risk of CVD, including CHD and stroke, in three large prospective cohorts of U.S. men and women.

Effects of Gut Microbiota and Metabolites on Heart Failure and Its Risk Factors: A Two-Sample Mendelian Randomization Study.

IntroductionPrevious observational studies have indicated that gut microbiota and metabolites may contribute to heart failure and its risk factors. However, with the limitation of reverse causality and confounder in observational studies, such relationship remains unclear. This study aims to reveal the causal effect of gut microbiota and metabolites on heart failure and its risk factors.MethodsThis study collected summary statistics regarding gut microbiota and metabolites, heart failure, diabetes, hypertension, chronic kidney disease, myocardial infarction, atrial fibrillation, hypertrophic cardiomyopathy, dilated cardiomyopathy, coronary heart disease, valvular heart disease, and myocarditis. Two-sample Mendelian randomization analysis was performed using MR-Egger, inverse variance weighted (IVW), MR-PRESSO, maximum likelihood, and weighted median.ResultsResults from gene prediction showed that among all gut microbiota, candida, shigella, and campylobacter were not associated with higher incidence of heart failure. However, genetic prediction suggested that for every 1 unit increase in shigella concentration, the relative risk increased by 38.1% for myocarditis and 13.3% for hypertrophic cardiomyopathy. Besides, for every 1 unit increased in candida concentration, the relative risk of chronic kidney disease increased by 7.1%. As for intestinal metabolites, genetic prediction results suggested that for every 1 unit increase in betaine, the relative risk of heart failure and myocardial infarction increased by 1.4% and 1.7%, separately.ConclusionsThis study suggested new evidence of the relationship between gut microbiota and heart failure and its risk factors, which may shed light on designing microbiome- and microbiome-dependent metabolite interventions on heart failure and its risk factors in clinical trials in the future.

Real-World Clinical Experience of Semaglutide in Secondary Care Diabetes: A Retrospective Observational Study.

IntroductionThe glucagon-like peptide-1 receptor analogue (GLP-1RA) semaglutide is associated with improvements in glycaemia and cardiovascular risk factors in clinical trials. The aim of this study was to examine the real-world impact of semaglutide administered by injection in people with type 2 diabetes (T2D) across three secondary care sites in Wales.MethodsA retrospective evaluation of 189 patients with T2D initiated on semaglutide between January 2019 and June 2020 with at least one follow-up visit was undertaken.ResultsAt baseline, participants had a mean age of 61.1 years, mean glycated haemoglobin (HbA1c) of 77.8 mmol/mol (9.3%) and mean body weight of 101.8 kg. At 6 and 12 months of follow-up, mean HbA1c reductions of 13.3 mmol/mol (1.2%) and 16.4 mmol/mol (1.5%), respectively, were observed, and mean weight loss at 6 months was 3.0 kg (all p < 0.001). At 12 months, there were significant reductions in total cholesterol (0.5 mmol/L) and alanine transaminase (4.8 IU/L). Patients naïve to GLP-1RAs or with higher baseline HbA1c at baseline had greater glycaemic reductions, although clinically significant HbA1c reductions were also observed in those who switched from other GLP-1RAs, whose body mass index was < 35.0 and > 35.0 kg/m2 or who had lower baseline HbA1c. Semaglutide was generally well tolerated, although adverse-effects limited use in 18 patients (9.5%).ConclusionSemaglutide provided clinically and statistically significant reductions in HbA1c, body weight, lipids and liver enzymes.

Protocol for a randomized controlled trial to test the acceptability and adherence to 6-months of walnut supplementation in Chinese adults at high risk of cardiovascular disease

BackgroundConsumption of nuts improves cardio-metabolic risk factors in clinical trials and relates to lower risk of cardiovascular disease (CVD) in prospective observational studies. However, there has not been an adequately powered randomized controlled trial to test if nuts supplementation actually reduces incident CVD. In order to establish the feasibility of such a trial, the current study aimed to assess the acceptability and adherence to long-term nut supplementation amongst individuals at high CVD risk in China.MethodsThis protocol described a 6-month trial performed in Ningxia Province in China among participants with a history of CVD or older age (female ≥65 years, male ≥60 years) with multiple CVD risk factors. Participants were randomized to control (received non-edible gift), low dose walnut (30 g/d), or high dose walnut (60 g/d) groups in a 1:1:1 ratio. Walnuts were provided at no cost to participants and could be consumed according to personal preferences. Follow-up visits were scheduled at 2 weeks, 3 months and 6 months. The primary outcome was fasting plasma alpha linolenic acid (ALA) levels used as an indicator of walnut consumption. Secondary outcomes included self-reported walnut intake from the 24 h dietary recalls. The target sample size of 210 provided 90% statistical power with two-sided alpha of 0.05 to detect a mean difference of 0.12% (as percent of total fatty acid) in plasma ALA between randomized groups.ResultsTwo hundred and ten participants were recruited and randomized during October 2019. Mean age of participants was 65 years (SD = 7.3), 47% were females, and 94% had a history of CVD at baseline. Across the three study groups, participants had similar baseline demographic and clinical characteristics.DiscussionThis trial will quantify acceptability and adherence to long-term walnut supplementation in a Chinese population at high risk of CVD. The findings will support the design of a future large trial to test the effect of walnut supplementation for CVD prevention.Trial registrationNCT04037943Protocol version: v3.0 August 14 2019

The effect of almonds on vitamin E status and cardiovascular risk factors in Korean adults: a randomized clinical trial

PurposeAlmonds have shown to beneficially modify some cardiovascular risk factors in clinical trials conducted in diverse ethnic populations but this relationship has never been tested in Koreans. Thus, we tested the impact of almonds consumed as a snack within the context of a typical Korean diet on cardiovascular risk factors.MethodsWe conducted a randomized, crossover trial in a free-living setting with a 2-week run-in period, two 4-week intervention phases, and a 2-week washout period between interventions. Eighty four overweight/obese participants (11 M/73 F; 52.4 ± 0.6 year; 25.4 ± 0.22 kg/m2) consumed either 56 g of almonds or isocaloric cookies daily for 4 weeks.ResultsMean % daily energy intake at baseline was 64.8, 21.3, and 14.9% from carbohydrate, fat, and protein, respectively. The addition of 56 g of almonds daily decreased carbohydrate energy to 55.0%, increased fat to 32.0%, and maintained protein at 14.7%. Consuming the almonds increased intake of MUFA by 192.3%, PUFA by 84.5%, vitamin E by 102.7%, and dietary fiber by 11.8% and decreased % energy from carbohydrate by 14.1%. Total caloric intake was increased by the almonds, but body weight, waist circumference, and body composition were not affected. Almonds in overweight and obese Korean adults decreased TC, LDL-C, and non-HDL-C by 5.5, 4.6, and 6.4%, respectively, compared to the cookie control (P ≤ 0.05). Almonds increased plasma α-tocopherol by 8.5% (P ≤ 0.05) from the baseline and tended to increase its value as compared to cookies (P = 0.055). Neither the almonds nor cookies altered plasma protein carbonyls, MDA or oxLDL. Of serum inflammatory markers, IL-10 was decreased by almond intake (P ≤ 0.05), and ICAM-1, IL-1β, and IL-6 tended to be lower with almonds, compared to the cookies.ConclusionsAlmonds at 56 g/day consumed as a snack favorably modified the Korean diet by increasing MUFA, PUFA, vitamin E, and dietary fiber intake and decreasing % energy intake from carbohydrate. Almonds also enhanced plasma α-tocopherol status and serum TC and LDL-C in overweight and obese Koreans. Thus, including almonds in typical Korean diets as a snack can help healthy overweight/obese individuals improve nutritional status and reduce their risk for CVD.

Baseline characteristics in stroke patients with atrial fibrillation: clinical trials versus clinical practice.

BackgroundWhen applying information gathered from medical research to the clinical setting, it is imperative that the sample of the investigated patients be representative of the clinical population. Because of this fact, it is necessary to closely examine the sample’s baseline characteristics in clinical trials.MethodsWe analysed baseline data of relevant trials investigating considerable proportions of patients with atrial fibrillation (AF) in the secondary stroke prevention: EAFT, SIFA, Active-W, BAFTA, RE-LY, AVERROES, ARISTOTLE and ROCKET AF. For comparing baseline data stroke patients with AF documented in a statutory stroke registry were considered. In a subgroup of patients (members of a large insurance) data on subsequent prescription for oral anticoagulants (oAK) were available.ResultsIn the stroke registry (n = 15,886) the mean age was higher than in the selected clinical trials (mean 77.7 versus 70–72 years). Among insurance members (n = 1,828), those with a prescription for oAK (n = 827) were older than patients recruited in clinical trials (mean 75.1 versus 70–72 years). Results also showed that the male sex was overrepresented in clinical trials (59–63% versus 46%). The distribution of vascular risk factors in recent clinical trials was comparable to proportions in the registry (hypertension: 77–85% versus 80%; diabetes mellitus: 20–26% versus 27%).ConclusionsThe majority of stroke patients with AF in the clinical setting are considerably older than those included in clinical trials. While the distribution of vascular risk factors in clinical trials corresponds to proportions observed in clinical practice, an overrepresentation of the male sex in clinical trials is evident.

Risk Factor Control for Coronary Artery Disease Secondary Prevention in Large Randomized Trials

This study evaluated data from 3 federally funded trials that focused on optimal medical therapy to determine if formalized attempts at risk factor control within clinical trials are effective in achieving guideline-driven treatment goals for diabetic patients with coronary artery disease (CAD). Despite clear evidence of benefit for CAD secondary prevention, the level of risk factor control in clinical practice has been disappointing. We obtained data from the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) diabetes subgroup, (n = 766 of 2,287), the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial (n = 2,368), and the FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900) to evaluate the proportion of patients achieving guideline-based, protocol-driven treatment targets for systolic blood pressure, low-density lipoprotein cholesterol, smoking cessation, and hemoglobin A1c. The primary outcome measure was the proportion of diabetic CAD patients meeting all 4 pre-specified targets at 1 year after enrollment. The pooled data include 5,034 diabetic patients. The percentages of patients achieving the 1-year low-density lipoprotein cholesterol targets compared with baseline increased from 55% to 77% in COURAGE, from 59% to 75% in BARI 2D, and from 34% to 42% in FREEDOM. Although similar improved trends were seen for systolic blood pressure, glycemic control, and smoking cessation, only 18% of the COURAGE diabetes subgroup, 23% of BARI 2D patients, and 8% of FREEDOM patients met all 4 pre-specified treatment targets at 1 year of follow-up. A significant proportion of diabetic CAD patients fail to achieve pre-specified targets for 4 major modifiable cardiovascular risk factors in clinical trials. We conclude that fundamentally new thinking is needed to explore approaches to achieve optimal secondary prevention treatment goals. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657) (Bypass Angioplasty Revascularization Investigation 2 Diabetes [BARI 2D]; NCT00006305) (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).