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Aims To investigate the impact of patiromer on the serum potassium level and its ability to enable specified target doses of renin–angiotensin–aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimization of the RAASi therapy [≥50% recommended dose of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist (MRA) spironolactone or eplerenone]. Specified target doses of the RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in the adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13–43) weeks, the adjusted mean change in potassium was +0.03 mmol/l in the patiromer group and +0.13 mmol/l in the placebo group [difference in the adjusted mean change between patiromer and placebo: −0.10 mmol/l (95% confidence interval, CI −0.13, 0.07); P < 0.001]. Risk of hyperkalemia >5.5 mmol/l [hazard ratio (HR) 0.63; 95% CI 0.45, 0.87; P = 0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P = 0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P < 0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P < 0.001) and total RAASi use score (win ratio 1.25, P = 0.048) favored the patiromer arm. Adverse events were similar between groups. Conclusion Concurrent use of patiromer and high-dose MRAs reduces the risk of recurrent hyperkalemia (ClinicalTrials.gov: NCT03888066). [ABSTRACT FROM AUTHOR]

Aim: Half of heart failure (HF) patients have chronic kidney disease (CKD) complicating their pharmacological management. We evaluated physicians' and patients' patterns of use of evidence‐based medical therapies in HF across CKD stages. Methods and results: We studied HF patients with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction enrolled in the Swedish Heart Failure Registry in 2009–2018. We investigated the likelihood of physicians to prescribe guideline‐recommended therapies to patients with CKD, and of patients to fill the prescriptions within 90 days of incident HF (initiating therapy), to adhere (proportion of days covered ≥80%) and persist (continued use) on these treatments during the first year of therapy. We identified 31 668 patients with HFrEF (median age 74 years, 46% CKD). The proportions receiving a prescription for angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor–neprilysin inhibitors (ACEi/ARB/ARNi) were 96%, 92%, 86%, and 68%, for estimated glomerular filtration rate (eGFR) ≥60, 45–59, 30–44, and <30 ml/min/1.73 m2, respectively; for beta‐blockers 94%, 93%, 92%, and 92%, for mineralocorticoid receptor antagonists (MRAs) 45%, 44%, 37%, 24%; and for triple therapy (combination of ACEi/ARB/ARNi + beta‐blockers + MRA) 38%, 35%, 28%, and 15%. Patients with CKD were less likely to initiate these medications, and less likely to adhere to and persist on ACEi/ARB/ARNi, MRA, and triple therapy. Among stoppers, CKD patients were less likely to restart these medications. Results were consistent after multivariable adjustment and in patients with HFmrEF (n = 15 114). Conclusions: Patients with HF and CKD are less likely to be prescribed and to fill prescriptions for evidence‐based therapies, showing lower adherence and persistence, even at eGFR categories where these therapies are recommended and have shown efficacy in clinical trials. [ABSTRACT FROM AUTHOR]

Aims In patients with current or a history of hyperkalaemia, treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) is often compromised. Patiromer, a novel potassium (K+) binder, may improve serum K+ levels and adherence to RAASi. Methods The DIAMOND trial will enroll ~820 patients with heart failure with reduced ejection fraction (HFrEF; ejection fraction =40%). Patients meeting the screening criteria will enter a single-blinded run-in phase where they will be started or continued on a mineralocorticoid receptor antagonist (MRA) titrated to 50mg/day and other RAASi therapy to =50% target dose, and patiromer. Patiromer will be titrated up to a maximum three packs/day (8.4 g/pack) to achieve optimal doses of RAASi without hyperkalaemia. The run-in phase will last up to 12weeks, following which patients will undergo double-blind randomization in a 1:1 ratio to receive either continued patiromer or placebo (patiromer withdrawal). The primary endpoint is the mean difference in serum K+ from randomization between patiromer and placebo arms. Secondary endpoints will include hyperkalaemia events with K+ value >5.5 mEq/L, durable enablement of MRA at target dose, investigator-reported adverse events of hyperkalaemia, hyperkalaemia-related clinical endpoints and an overall RAASi use score (using a 0-8-point scale) comprising all-cause death, occurrence of cardiovascular hospitalization or usage of comprehensive heart failure medication. Conclusion The DIAMOND trial is designed to determine if patiromer can favourably impact K+ control in patients with HFrEF with hyperkalaemia or a history of hyperkalaemia leading to RAASi therapy compromise, and in turn improve RAASi use. [ABSTRACT FROM AUTHOR]

Aims: Renin–angiotensin–aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID‐19). We investigated the association between use of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID‐19 hospitalization/death in a large nationwide population. Methods and results: Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020. COVID‐19 cases were defined based on hospitalization/death for COVID‐19. Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID‐19 in the overall population, and of all‐cause mortality in COVID‐19 cases. We performed consistency analysis to quantify the impact of potential unmeasured confounding. Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID‐19. After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID‐19 (odds ratio 0.86, 95% confidence interval 0.81–0.91) in the overall population, and with reduced mortality in COVID‐19 cases (hazard ratio 0.89, 95% confidence interval 0.82–0.96). MRA use was not associated with risk of any outcome. Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use. Conclusions: In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID‐19. [ABSTRACT FROM AUTHOR]

Aims: We assessed the interplay between hyperkalaemia (HK) and renin-angiotensin-aldosterone system inhibitor (RAASi) use, dose and discontinuation, and their association with all-cause or cardiovascular death in patients with chronic heart failure (HF). We hypothesized that HK-associated increased death may be related to RAASi withdrawal.Methods and Results: The ESC-HFA-EORP Heart Failure Long-Term Registry was used. Among 9222 outpatients (HF with reduced ejection fraction: 60.6%, HF with mid-range ejection fraction: 22.9%, HF with preserved ejection fraction: 16.5%) from 31 countries, 16.6% had HK (≥5.0 mmol/L) at baseline. Angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) was used in 88.3%, a mineralocorticoid receptor antagonist (MRA) in 58.7%, or a combination in 53.2%; of these, at ≥50% of target dose in ACEi: 61.8%; ARB: 64.7%; and MRA: 90.3%. At a median follow-up of 12.2 months, there were 789 deaths (8.6%). Both hypokalaemia and HK were independently associated with higher mortality, and ACEi/ARB prescription at baseline with lower mortality. MRA prescription was not retained in the model. In multivariable analyses, HK at baseline was independently associated with MRA non-prescription at baseline and subsequent discontinuation. When considering subsequent discontinuation of RAASi (instead of baseline use), HK was no longer found associated with all-cause deaths. Importantly, all RAASi (ACEi, ARB, or MRA) discontinuations were strongly associated with mortality.Conclusions: In HF, hyper- and hypokalaemia were associated with mortality. However, when adjusting for RAASi discontinuation, HK was no longer associated with mortality, suggesting that HK may be a risk marker for RAASi discontinuation rather than a risk factor for worse outcomes. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients.Methods and Results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P < 0.001) and there were no differences in causes of death. All-cause mortality and all-cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1-year all-cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years.Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF ≤45%. [ABSTRACT FROM AUTHOR]

Aims: In heart failure with reduced ejection fraction, drug and device therapy improve survival. We studied contemporary trends in utilization of evidence-based therapy and associated survival.Methods and Results: We studied 5908 patients with NYHA class II-IV heart failure, EF <30%, and duration of heart failure ≥6 months registered in the Swedish Heart Failure Registry between 2003 and 2012. Regression using generalized estimation equations was used to examine temporal trends in crude and risk-adjusted rates of utilization of evidence-based heart failure therapy and 30-day, 1-year, and 3-year survival. In 2003 vs. 2012, the risk-adjusted use of therapy and P-values for trends were as follows: renin-angiotensin system antagonists, 88% vs. 86% (P = 0.091); beta-blockers, 85% vs. 93% (P = 0.008); mineralocorticoid receptor antagonists, 53% vs. 42% (P < 0.001); CRT, 2.4% vs. 8.2% (P = 0.074); and implantable cardioverter-defibrillators, 4.0% vs. 10.7% (P = 0.004). During the same period, the risk-adjusted 30-day, 1-year, and 3-year survival was 92% vs. 94% (P = 0.532), 81% vs. 77% (P = 0.260), and 58% vs. 54% (P = 0.425), respectively.Conclusions: In this large nationwide registry, over the last decade the use of evidence-based drug therapy was high and remained stable over time, but, despite an increased use of device therapy, the absolute use was poor. This was associated with an absence of improvement in survival. The improvements in therapy and prognosis over the last generation may be levelling off, and efforts should be directed at improving implementation of evidence-based therapy. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions We explored timing, settings and predictors of angiotensin receptor–neprilysin inhibitor (ARNI) initiation in a large, nationwide cohort of patients with heart failure (HF) with reduced ejection fraction (HFrEF).Patients with HFrEF (ejection fraction <40%) registered in the Swedish HF Registry in 2017–2021 and naïve to ARNI were evaluated for timing and location of, and their characteristics at ARNI initiation. ARNI use increased from 8.3% in 2017 to 26.7% in 2021. Among 3892 hospitalized patients, 8% initiated ARNI in‐hospital or ≤14 days after discharge, 4% between 15 and 90 days, and 88% >90 days after discharge or never initiated. Factors associated with earlier initiation included follow‐up in specialized HF care, more severe HF, previous HF treatment use and higher income, whereas older age, higher comorbidity burden and living alone were associated with later/no initiation. Of 16 486 HFrEF patients, 8.1% inpatients and 5.9% outpatients initiated an ARNI at the index date. Factors associated with initiation in outpatients were overall consistent with those linked with an in‐hospital/earlier ARNI initiation; 4.9% of 10 209 with HF duration <6 months and 9.1% of 5877 with HF duration ≥6 months initiated ARNI. Predictors of ARNI initiation in HF duration <6 months were inpatient status, lower ejection fraction, hypertension, whereas previous angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker use was associated with less likely initiation. Discontinuation at 1 year ranged between 13% and 20% across the above‐reported analyses.In‐hospital and early initiation of ARNI are limited in real‐world care but still slightly more likely than in outpatients. ARNI were more likely initiated in patients with more severe HF, which might suggest its use as a second‐line treatment and only following worsening of clinical status. One‐year discontinuation rates were consistent regardless of the timing/setting of ARNI initiation. [ABSTRACT FROM AUTHOR]

In this article, the author reflects on a research related to role of hypertension leading to myocardial infarction, stroke, heart failure, renal failure and death. Topics discussed include factors contributing to increasing prevalence such as ageing population and rising obesity, association of ACE inhibitors towards increased risk of the primary outcome, and benefits of ACE inhibitors in heart failure and asymptomatic reduction in left ventricular ejection fraction.