Geographic variations in the PARADIGM-HF heart failure trial

Abstract

AimsThe globalization of clinical trials has highlighted geographic variations in patient characteristics, event rates, and treatment effects. We investigated these further in PARADIGM-HF, the largest and most globally representative trial in heart failure (HF) to date.Methods and resultsWe looked at five regions: North America (NA) 602 (8%), Western Europe (WE) 1680 (20%), Central/Eastern Europe/Russia (CEER) 2762 (33%), Latin America (LA) 1433 (17%), and Asia-Pacific (AP) 1487 (18%). Notable differences included: WE patients (mean age 68 years) and NA (65 years) were older than AP (58 years) and LA (63 years) and had more coronary disease; NA and CEER patients had the worst signs, symptoms, and functional status. North American patients were the most likely to have a defibrillating-device (54 vs. 2% AP) and least likely prescribed a mineralocorticoid receptor antagonist (36 vs. 65% LA). Other evidence-based therapies were used most frequently in NA and WE. Rates of the primary composite outcome of cardiovascular (CV) death or HF hospitalization (per 100 patient-years) varied among regions: NA 13.6 (95% CI 11.7–15.7) WE 9.6 (8.6–10.6), CEER 12.3 (11.4–13.2), LA 11.2 (10.0–12.5), and AP 12.5 (11.3–13.8). After adjustment for prognostic variables, relative to NA, the risk of CV death was higher in LA and AP and the risk of HF hospitalization lower in WE. The benefit of sacubitril/valsartan was consistent across regions.ConclusionThere were many regional differences in PARADIGM-HF, including in age, symptoms, comorbidity, background therapy, and event-rates, although these did not modify the benefit of sacubitril/valsartan.Clinical trial registration URL http://www.clinicaltrials.gov. Unique identifier: NCT01035255.

Angiotensin Receptor Neprilysin Inhibitor in Japanese Patients With Heart Failure and Reduced Ejection Fraction ― Baseline Characteristics and Treatment of PARALLEL-HF Trial ―

“…16 In addition, a comparison with other randomized clinical trial and registry data for Japanese patients with HFrEF, revealed a similar trend of lower BP while receiving the standardof-care background HF therapies. 12, 13 Similarly, the lower rate of ischemic etiology for HF in PARALLEL-HF relative to that reported in PARADIGM-HF was in line with earlier observations from this geographic region.…”

“…In addition, enrolled patients were largely similar to those in PARADIGM-HF, including those of the Asia-Pacific subgroup of PARADIGM-HF previously reported in the subgroup analysis by Kristensen et al, which showed that sacubitril/valsartan was equally effective in reducing the risk of CV death and HF hospitalization compared with enalapril. 16 The results of PARALLEL-HF are expected by 2019 and will verify whether sacubitril/valsartan provides similar improvements in clinical outcomes in Japanese patients with HFrEF as has been observed in PARADIGM-HF.…”

“…8, 16 In PARALLEL-HF, most patients were in NYHA Class II, which was relatively higher than those reported in PARADIGM-HF, and the NT-proBNP levels were also relatively lower in PARALLEL-HF. However, it is also important to note that there was no difference in the mean proportion of patients with diabetes, which is one of the risk factors for poor outcomes in HFrEF patients, was higher in PARALLEL-HF compared with PARADIGM-HF; a similar trend was shown in the clinical trials and registries with Japanese HFrEF patients.…”

“…12, 13 Similarly, the lower rate of ischemic etiology for HF in PARALLEL-HF relative to that reported in PARADIGM-HF was in line with earlier observations from this geographic region. 12,13, 16 The 0.11 mEq/L (P<0.001). AEs occurred in 32 patients, but only 2 patients discontinued the run-in because of AE, and angioedema was not observed in any case.…”

Comparative Analysis of Hospital Pharmacotherapy of Chronic Heart Failure With Reduced Left Ventricular Ejection Fractions in 2009-2010 and 2014-2015

“…Например, по данным исследования PARADIGM-HF частота назначений антагонистов минералокорти-коидных рецепторов существенно отличалась в ре-гионе «Центральная/Восточная Европа -Россия» от регионов «Северная Америка» и «Западная Европа». В целом наиболее современная, основанная на доказа-тельствах терапия ХСН назначалась чаще в регионах «Северная Америка» и «Западная Европа» [8]. В ази-атском регистре ХСН было также обнаружено наличие региональных различий в терапии ХСН, при этом вы-явлено влияние на вероятность соблюдения рекомен-даций уровня дохода в том или ином регионе [9].…”