Adherence and discontinuation of optimal heart failure therapies according to age: a Danish nationwide study

Background: Guideline‐recommended disease‐modifying pharmacological therapies for heart failure (HF) with reduced ejection fraction are underutilized, particularly among elderly patients. We studied the association of age in adherence and discontinuation of angiotensin‐converting enzyme inhibitors/angiotensin‐II receptor blockers (ACEi/ARB), β‐blockers (BB), and mineralocorticoid receptor antagonists. Methods and Results: Patients with a first heart failure diagnosis who had initiated ACEi/ARB and BB within 120 days of presentation were included from nationwide registries and divided into 3 age groups: <65 years (reference), 65 to 79, and ≥80. One‐year median proportions of daily target doses were calculated. Adherence was estimated by the proportion of days covered. The 5‐year risk of discontinuation was assessed with the Aalen‐Johansen estimator. Discontinuation rates were evaluated using Multivariable Cox regression. Twenty‐nine thousand four hundred eighty‐two patients were included. Advancing age was associated with lower median proportions of daily target doses and adherence (ACEi/ARB 79.1%, 77.5%, and 69.4%; BB 79.1%, 78.6%, and 73.8%), in the <65, 65 to 79, and ≥80 age groups, respectively. Age ≥80 was associated with higher discontinuation rates (cumulative incidence, ACEi/ARB 41%, 44%, and 51%; BB 38%, 35%, and 39%; hazard ratio, ACEi/ARB 1.60 [95% CI, 1.51–1.69]; BB 1.33 [95% CI, 1.25–1.41]). The risk of mineralocorticoid receptor antagonists discontinuation differed little with age (50%, 54%, and 56%), although mineralocorticoid receptor antagonists initiation in the most elderly was less frequent (33%, 33%, and 22%). Conclusions: In a nationwide cohort of patients with heart failure, advanced age was associated with lower proportions of daily target doses, lower adherence, and higher discontinuation rates of ACEi/ARB and BBs. Focus on treatment adherence and optimal dosages among elderly patients with heart failure could improve outcomes

Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention. FUNDING: British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7

Left ventricular function, congestion, and effect of empagliflozin on heart failure risk after myocardial infarction

Background Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). Objective To evaluate the association between left ventricular ejection fraction (LVEF), congestion, or both on outcomes and the impact of empagliflozin in reducing HF risk post-MI. Methods In the EMPACT-MI trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF&lt;45%, congestion, or both to empagliflozin 10 mg daily or placebo and followed for a median of 17.9 months. Results Among 6522 patients, the mean baseline LVEF was 41%+9%; 2648 patients (40.6%) presented with LVEF&lt;45% alone, 1483 (22.7%) presented with congestion alone, and 2181 (33.4%) presented with both. Among patients in the placebo arm, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (hazard ratio [HR] 1.49; 95%CI, 1.31-1.69; P&lt;0.0001), first HF hospitalization (HR, 1.64; 95%CI, 1.37-1.96; P&lt;0.0001), and total HF hospitalizations (rate ratio [RR], 1.89; 95%CI, 1.51-2.36; P&lt;0.0001). Presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR 1.52, 1.94, and RR 2.03, respectively). Empagliflozin reduced the risk for first (HR 0.77, 95%CI 0.60-0.98) and total (RR 0.67, 95%CI 0.50-0.89) HF hospitalization, irrespective of LVEF or congestion or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. Conclusions In patients with AMI, severity of LV dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion