Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome)

Aim To assess the benefit of short-term low molecular weightheparin nadroparin compared with unfractionated heparin in unstableangina or non-Q wave myocardial infraction patients and to determinewhether a longer, 2-week low molecular weight heparin regimenwould offer additional clinical benefit. Patients, Methods and Results This was a multicentre, prospective,randomized, double-blind study in three parallel groups, involving3468 patients. Patients received one of three treatment regimens:the unfractionated heparin group received an intravenous bolusof unfractionated heparin 5000IU, followed by an activated partialthromboplastin time adjusted infusion of unfractionated heparinfor 6±2 days; the nadroparin 6 group received an intravenousbolus of nadroparin 86 anti-Xa IU.kg^–1, followed by twicedaily subcutaneous injections of nadroparin 86 anti-Xa IU.kg^–1for6±2 days, and the nadroparin 14 group received an intravenousbolus of nadroparin 86 anti-Xa IU.kg^–1, followed by twicedaily subcutaneous injections of nadroparin 86 anti-Xa IU.kg^–1for14 days. No statistically significant differences were observedbetween the three treatment regimens with respect to the primaryoutcome (cardiac death, myocardial infarction, refractory angina,or recurrence of unstable angina at day 14). The absolute differencesbetween the groups in the incidence of the primary outcome were:–0·3% (P=0·85) for the nadroparin 6 groupvs the unfractionated heparin group and +1·9% (P=0·24)for the nadroparin 14 group vs the unfractionated heparin group.Furthermore, there were no significant intergroup differencesregarding any of the secondary efficacy outcomes. However, therewas an increased risk of major haemorrhages in the nadroparin14 group compared with unfractionated heparin (3·5% vs1·6%;P=0·0035). Conclusions Treatment with nadroparin for 6±2 days providessimilar efficacy and safety to treatment with unfractionatedheparin, for the same period, in the therapeutic managementof acute unstable angina or non-Q wave myocardial infarction,and may be easier to administer. A prolonged regimen of nadroparin(14 days) does not provide any additional clinical benefit.     

Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide

The aim was to determine the effects of dulaglutide, a synthetic once‐weekly, injectable human glucagon‐like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non‐fatal myocardial infarction or non‐fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all‐cause mortality. Follow‐up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle‐aged patient seen in general practice throughout the world.     

The DATAS rationale and design: a controlled, randomized trial to assess the clinical benefit of dual chamber (DDED) defibrillator.

Single chamber (SC) implantable cardioverter defibrillators (ICDs) have several limitations that might be relevant during follow-up, like atrial pacing requirements, inadequate therapies, sustained atrial tachyarrhythmias and difficulties to achieve an accurate diagnosis of the arrhythmia. Dual chamber (DC) ICDs offer an attractive and rational solution, although controversy remains if the costs and complexity of these devices offer a real clinical advantage. The Dual Chamber & Atrial Tachyarrhythmias Adverse Events Study (DATAS) was designed to analyze the ability of DC ICD, DDED, to reduce clinically significant adverse events compared with SC ICD in a non-selected population with conventional indications for ICD implantation. This is a prospective, multicentre, randomized, open labelled study, with three arms: two of them (simulated SC ICD and true DC ICD) cross-over, and the third (true SC ICD) parallels the other two. The composite primary end point comprises four Clinically Significant Adverse Events (CSAE): (1) all-cause mortality, (2) invasive intervention, hospitalization or prolongation of hospitalization due to cardiovascular cause, (3) inappropriate shocks, and (4) sustained symptomatic atrial tachyarrhythmias that (a) require urgent termination or (b) last more than 48h leading to therapeutic intervention. Secondary end points constitute each of the individual components of CSAE, cardiovascular status, quality of life and a detailed analysis of atrial and ventricular arrhythmias. To date (June 2003) there have been 343 patients enroled from 947 screened patients. The projected enrollment includes 360 patients and the conclusion of the study is expected at the beginning of 2005.     

Prevention of Syncope Trial (POST): a randomized clinical trial of beta blockers in the prevention of vasovagal syncope; rationale and study design.

BACKGROUND: Few therapies for vasovagal syncope have been proven effective. A large, placebo-controlled clinical trial of beta-blockers is needed. STRUCTURE OF STUDY: The Prevention of Syncope Trial (POST) is a multicentre, randomized, placebo-controlled, study of metoprolol in the prevention of vasovagal syncope. The primary hypothesis is that beta-blockers will increase the time to the first recurrence of syncope when compared with placebo. Patients will be randomized 1:1 to receive metoprolol or placebo, and followed for 1 year. The primary endpoint is the time to first syncope recurrence, and secondary endpoints include syncope frequency, presyncope, and quality of life. INCLUSION AND EXCLUSION CRITERIA: Patients are eligible if they have a positive tilt test and 3 syncopal spells preceding the tilt test. They are excluded if they have seizures or other causes of syncope; important heart disease; a contraindication to or need for beta blockers; a permanent pacemaker; a major noncardiovascular disease; or previous use of beta blockers at a dose greater than the equivalent of metoprolol 25mg twice daily for the purpose of suppressing vasovagal syncope. POWER CALCULATIONS: We assume a 40% risk of syncope in the control arm, an absolute reduction of 20% by metoprolol, and a dropout of 20%. Entry of 220 patients will result in an 80% chance of reaching a positive conclusion about beta-blocker therapy with 2p=0.05.     

Interleukin‐1 blockade in heart failure with preserved ejection fraction: rationale and design of the Diastolic Heart Failure Anakinra Response Trial 2 (D‐HART2)

Heart failure with preserved ejection fraction (HFpEF ) now accounts for the majority of confirmed HF cases in the United States. However, there are no highly effective evidence‐based treatments currently available for these patients. Inflammation correlates positively with adverse outcomes in HF patients. Interleukin (IL )‐1, a prototypical inflammatory cytokine, has been implicated as a driver of diastolic dysfunction in preclinical animal models and a pilot clinical trial. The Diastolic Heart Failure Anakinra Response Trial 2 (D‐HART2 ) is a phase 2, 2:1 randomized, double‐blind, placebo‐controlled clinical trial that will test the hypothesis that IL ‐1 blockade with anakinra (recombinant human IL ‐1 receptor antagonist) improves (1) cardiorespiratory fitness, (2) objective evidence of diastolic dysfunction, and (3) elevated inflammation in patients with HFpEF ( http://www.ClinicalTrials.gov NCT02173548 ). The co–primary endpoints will be placebo‐corrected interval changes in peak oxygen consumption and ventilatory efficiency at week 12. In addition, secondary and exploratory analyses will investigate the effects of IL ‐1 blockade on cardiac structure and function, systemic inflammation, endothelial function, quality of life, body composition, nutritional status, and clinical outcomes. The D‐HART2 clinical trial will add to the growing body of evidence on the role of inflammation in cardiovascular disease, specifically focusing on patients with HFpEF .     

Factors associated with failure to achieve a glycated haemoglobin target of <8.0% in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial

The aim of this study was to identify the clinical features of participants in the standard therapy arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) glycaemia trial who failed to reach the glycated haemoglobin (HbA1c) target. We analysed 4685 participants in the standard therapy arm, comparing participants who reached the HbA1c target of <8.0% with those whose HbA1c level was ≥8.0% 12 months after randomization. Baseline and 12‐month clinical characteristics were compared. At 12 months after randomization, 3194 participants had HbA1c <8.0% and 1491 had HbA1c ≥8.0%. Black race [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.61–0.89; p = 0.002], severe hypoglycaemia (OR 0.57, CI 0.37–0.89; p = 0.014) and insulin use (OR 0.51, CI 0.40–0.65; p < 0.001) were associated with failure to reach HbA1c goal at 12 months in the adjusted model. Even with free medications, free visits with clinicians and aggressive titration of medications, >30% of participants in the standard arm of the ACCORD trial had an HbA1c ≥8.0% at 1 year. Participants who were black, had severe hypoglycaemia and were on insulin were more likely to have an above‐target HbA1c concentration after 12 months on the standard protocol.     

Rationale,design, and baseline characteristics of the Salt Substitute in India Study (SSiIS): The protocol for a double‐blinded,randomized‐controlled trial

Reduced‐sodium, added‐potassium salt substitutes have favorable effects on blood pressure, but have not been tested in India. The Salt Substitute in India Study (SSiIS) is a double‐blinded, randomized‐controlled trial designed to investigate the effects of reduced‐sodium, added‐potassium salt substitution to replace usual cooking salt use and blood pressure (BP) among hypertensive patients in rural India. The primary objective is to assess effects on systolic blood pressure at 3 months. The secondary objectives are to determine effects on diastolic blood pressure, urinary sodium, and potassium levels, and to determine acceptability of the intervention. Eligible individuals received usual salt (100% sodium chloride) or salt substitute (70% sodium chloride and 30% potassium chloride) to replace all salt required for cooking and seasoning in the household. A total of 502 participants aged ≥18 years with a history of hypertension were successfully recruited and randomized in a 1:1 ratio to intervention or control, between November 2019 and January 2020. Mean blood pressure at baseline was 133.5/83.6 mm Hg and 96% were using one or more blood pressure‐lowering medications. The overall mean average 24‐hour urinary sodium excretion was 2825 (SD, 1166) mg/L, which corresponds to a urinary salt excretion of 10.4 g/d. Baseline findings suggest sodium intake in this population significantly exceeds World Health Organization recommendations. The SSiIS trial has successfully recruited participants and is well placed to determine whether salt substitution is an effective means of lowering blood pressure for rural Indian patients with hypertension.     

Upfront VIP‐reinforced‐ABVD (VIP‐rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS‐LTP95

Peripheral T‐Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B‐cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front‐line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d’Etude des Leucémies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP‐reinforced‐ABVD; VIP‐rABVD) and compared it to CHOP/21 as front‐line treatment in non‐cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2‐year event‐free survival (EFS) rate. Secondary objectives were to compare the response rate, overall survival, and toxicities as well as identify prognostic factors. Eighty‐eight patients were identified between 1996 and 2002 . Both arms were well balanced for patients’ characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2‐year EFS. Anaplastic large cell lymphoma type and Ann Arbor stage I–II were identified as two independent favourable prognostic factors influencing survival. VIP‐rABVD was not superior to CHOP/21 in terms of EFS as first‐line treatment of PTCL, confirming that CHOP/21 remains the reference regimen in these lymphomas.     

The effects of the Dietary Approaches to Stop Hypertension (DASH) diet on metabolic risk factors in patients with chronic disease: A systematic review and meta-analysis of randomized controlled trials

AimsThe DASH diet was designed for helping control of blood pressure but, fortunately, it can also be prescribed for many other chronic conditions. The current study intended to assess the potential effects of DASH diet on metabolic risk factors in patients with chronic disease.Data synthesisWe carried out a systematic literature search for RCTs from inception until July 2020. A total of 54 clinical trials were included in the final analysis. Compared to control groups, a significant lower effect of the DASH diet was noted for body weight (−1.59 kg; p < 0.001), BMI (−0.64 kg/m²; p < 0.001), and WC (−1.93 cm; p < 0.001) as well as for SBP (−3.94 mmHg; p < 0.001) and DBP (−2.44 mmHg; P < 0.001). The DASH diet significantly decreased TC (−5.12 mg/dl; p = 0.008) and LDL-C levels (−3.53 mg/dl; p = 0.041), but not HDL-C (0.30 mg/dl; p = 0.510), TG (−4.22 mg/dl; p = 0.067), and VLDL-C (−2.16 mg/dl; p = 0.062). No significant effect of the DASH diet was noted for blood glucose (−0.38 mg/dl; p = 0.216), insulin (−0.03 μIU/mL; p = 0.817), HOMA-IR (−0.15; p = 0.132), and CRP (−0.33 mg/l; p = 0.173).ConclusionsThe DASH diet is a feasible approach to weight loss and to control blood pressure and hypercholesterolemia.