Optimization of Evidence-Based Heart Failure Medications After an Acute Heart Failure Admission: A Secondary Analysis of the STRONG-HF Randomized Clinical Trial.

Importance: The Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies (STRONG-HF) trial strived for rapid uptitration aiming to reach 100% optimal doses of guideline-directed medical therapy (GDMT) within 2 weeks after discharge from an acute heart failure (AHF) admission. Objective: To assess the association between degree of GDMT doses achieved in high-intensity care and outcomes. Design, Setting, and Participants: This was a post hoc secondary analysis of the STRONG-HF randomized clinical trial, conducted from May 2018 to September 2022. Included in the study were patients with AHF who were not treated with optimal doses of GDMT before and after discharge from an AHF admission. Data were analyzed from January to October 2023. Interventions: The mean percentage of the doses of 3 classes of HF medications (renin-angiotensin system inhibitors, ß-blockers, and mineralocorticoid receptor antagonists) relative to their optimal doses was computed. Patients were classified into 3 dose categories: low (<50%), medium (≥50% to <90%), and high (≥90%). Dose and dose group were included as a time-dependent covariate in Cox regression models, which were used to test whether outcomes differed by dose. Main Outcome Measures: Post hoc secondary analyses of postdischarge 180-day HF readmission or death and 90-day change in quality of life. Results: A total of 515 patients (mean [SD] age, 62.7 [13.4] years; 311 male [60.4%]) assigned high-intensity care were included in this analysis. At 2 weeks, 39 patients (7.6%) achieved low doses, 254 patients (49.3%) achieved medium doses, and 222 patients (43.1%) achieved high doses. Patients with lower blood pressure and more congestion were less likely to be uptitrated to optimal GDMT doses at week 2. As a continuous time-dependent covariate, an increase of 10% in the average percentage optimal dose was associated with a reduction in 180-day HF readmission or all-cause death (primary end point: adjusted hazard ratio [aHR], 0.89; 95% CI, 0.81-0.98; P = .01) and a decrease in 180-day all-cause mortality (aHR, 0.84; 95% CI, 0.73-0.95; P = .007). Quality of life at 90 days, measured by the EQ-5D visual analog scale, improved more in patients treated with higher doses of GDMT (mean difference, 0.10; 95% CI, -4.88 to 5.07 and 3.13; 95% CI, -1.98 to 8.24 points in the medium- and high-dose groups relative to the low-dose group, respectively; P = .07). Adverse events to day 90 occurred less frequently in participants with HIC who were prescribed higher GDMT doses at week 2. Conclusions and Relevance: Results of this post hoc analysis of the STRONG-HF randomized clinical trial show that, among patients randomly assigned to high-intensity care, achieving higher doses of HF GDMT 2 weeks after discharge was feasible and safe in most patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03412201.

Effect of 3, 2-Drug Combinations of Antihypertensive Therapies on Blood Pressure Variability in Black African Patients: Secondary Analyses of the CREOLE Trial.

BACKGROUND: The effect of 3 commonly recommended combinations of anti-hypertensive agents-amlodipine plus hydrochlorothiazide (calcium channel blocker [CCB]+thiazide), amlodipine plus perindopril (CCB+ACE [angiotensin-converting enzyme]-inhibitor), and perindopril plus hydrochlorothiazide (ACE-inhibitor+thiazide) on blood pressure variability (V) are unknown. METHODS: We calculated the blood pressure variability (BPV) in 405 patients (130, 146, and 129 randomized to ACE-inhibitor+thiazide, CCB+thiazide, and CCB+ACE-inhibitor, respectively) who underwent ambulatory blood pressure monitoring after 6 months of treatment in the Comparisons of Three Combinations Therapies in Lowering Blood Pressure in Black Africans trial (CREOLE) of Black African patients. BPV was calculated using the SD of 30-minute interval values for 24-hour ambulatory BPs and for confirmation using the coefficient of variation. Linear mixed model regression was used to calculate mean differences in BPV between treatment arms. Within-clinic BPV was also calculated from the mean SD and coefficient of variation of 3 readings at clinic visits. RESULTS: Baseline distributions of age, sex, and blood pressure parameters were similar across treatment groups. Participants were predominately male (62.2%) with mean age 50.4 years. Those taking CCB+thiazide had significantly reduced ambulatory systolic and diastolic BPV compared with those taking ACE-inhibitor+thiazide. The CCB+thiazide and CCB+ACE-inhibitor groups showed similar BPV. Similar patterns of BPV were apparent among groups using within-clinic blood pressures and when assessed by coefficient of variation. CONCLUSIONS: Compared with CCB-containing combinations, ACE-inhibitor plus thiazide was associated with higher levels, generally significant, of ambulatory and within-clinic systolic and diastolic BPV. These results supplement the differential ambulatory blood pressure-lowering effects of these therapies in the CREOLE trial.

Disparities in clinical features and outcomes of peripartum cardiomyopathy in high versus low prevalent regions in Nigeria.

AIMS: The prospective, multicentre Peripartum Cardiomyopathy in Nigeria (PEACE) registry originally demonstrated a high prevalence of peripartum cardiomyopathy (PPCM) among patients originating from Kano, North-West Nigeria. In a post hoc analysis, we sought to determine if this phenomenon was characterized by a differential case profile and outcome among PPCM cases originating elsewhere. METHODS AND RESULTS: Overall, 199 (81.6%) of a total 244 PPCM patients were recruited from three sites in Kano, compared with 45 patients (18.4%) from 11 widely dispersed centres across Nigeria. Presence and extent of ventricular myocardial remodelling during follow-up, relative to baseline status, were assessed by echocardiography. During median 17 months follow-up, Kano patients demonstrated significantly better myocardial reverse remodelling than patients from other sites. Overall, 50.6% of patients from Kano versus 28.6% from other regions were asymptomatic (P = 0.029) at study completion, with an accompanying difference in all-cause mortality (17.6% vs. 22.2% respectively, P = 0.523) not reaching statistical significance. Alternatively, 135/191 (84.9%) of Kano patients had selenium deficiency (<70 µg/L), and 46/135 (34.1%) of them received oral selenium supplementation. Critically, those that received selenium supplementation demonstrated better survival (6.5% vs. 21.2%; P = 0.025), but the supplement did not have significant impact on myocardial remodelling. CONCLUSIONS: This study has shown important non-racial regional disparities in the clinical features and outcomes of PPCM patients in Nigeria, that might partly be explained by selenium supplementation.