The Impairment in Kidney Function in the Oral Anticoagulation Era. A Pathophysiological Insight.

The need for anticoagulation in patients with atrial fibrillation (AF) is fundamental to prevent thromboembolic events. Direct oral anticoagulants (DOACs) recently demonstrated to be superior, or at least equal, to Warfarin in reducing the risk for stroke/systemic embolism and preventing major bleeding and intracranial hemorrhages. The AF population often suffers from chronic kidney disease (CKD). Indeed, the relationship between AF and renal function is bidirectional: AF can trigger kidney failure, while kidney impairment can promote alterations able to enhance AF. Therefore, there are concerns regarding prescriptions of anticoagulants to patients with AF and CKD. The worsening in kidney function can be effectively due to anticoagulants administration. Warfarin has been recognized to promote acute kidney injury in case of excessive anticoagulation levels. Nevertheless, further mechanisms can induce the chronic worsening of renal function, thus leading to terminal kidney failure as observed in post-hoc analysis from registration trials and dedicated observational studies. By contrast, DOACs seem to protect kidneys from injuries more efficiently than Warfarin, although they still continue to play a role in promoting some kidney lesions. However, the exact mechanisms remain unknown. This narrative review aimed to discuss the influence of oral anticoagulants on renal impairment as well as to overview potential pathophysiological mechanisms related to this clinical complication.

Eligibility of outpatients with chronic heart failure for sodium-glucose co-transporter-2 inhibitors.

AIMS: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been shown to have a relevant role in the prevention of hospitalizations for heart failure and improvement in the life expectancy of patients with diabetes and outpatients with chronic heart failure (CHF) with reduced left ventricular ejection fraction, independently from the presence of type 2 diabetes mellitus (T2DM). The aim of our study was to evaluate in a real-world population the number of outpatients with CHF who meet the enrolment criteria of the main randomized controlled trials (RCT) published in the last 5 years and consequently identify the percentage of patients who could potential benefit from SGLT2i therapy. METHODS AND RESULTS: We retrospectively evaluated all consecutive outpatients referred for CHF. The diagnosis of T2DM was according to the latest European Society of Cardiology Guidelines. Clinical characteristics considered for the enrolment in the RCTs were recorded. We enrolled 515 patients, 384 (75%) of whom had a left ventricular ejection fraction (LVEF) ≤ 40%, 82 (16%) had pre-diabetes, and 187 (36%) had diabetes. Most of the patients with LVEF ≤ 40% met the criteria for the DAPA-HF trial (65%), and this percentage was even higher if the serum level of N-terminal pro-brain natriuretic peptide was not considered. A high percentage of patients with diabetes and LVEF > 40% met the criteria for the DECLARE (39%), CANVAS (47%), and EMPA-REG (30%) trials. Patients meeting the enrolment criteria of RCTs evaluating SGLT2i were also characterized by a high risk of heart failure events during follow-up. CONCLUSIONS: In spite of a low number of patients actually treated with SGLT2i, we observed that a high prevalence of patients with CHF met the clinical characteristics of RCTs that have demonstrated a beneficial effect of SGLT2i.

Baseline and incident hypochloremia in chronic heart failure outpatients: Clinical correlates and prognostic role.

BACKGROUND: Electrolyte serum disorders are associated with poor outcome in chronic heart failure. The aim of this study sought to identify the main driver of incident hypochloremia in chronic HF (CHF) outpatients and to determine the prognostic value of baseline and incident hypochloremia. METHODS: Consecutive CHF outpatients were enrolled and clinical, laboratoristic and echocardiographic evaluations were performed at baseline and repeated yearly in a subgroup of patients. Baseline and incident hypochloremia were evaluated. During an up to 5-year follow-up, all-cause mortality was the primary end-point for outcome. RESULTS: Among 506 patients enrolled, 120 patients died during follow-up. At baseline, hypochloremia was present in 10% of patients and it was associated with mortality at univariate (HR: 3.25; 95%CI: 2.04-5.18; p<0.001) and at multivariate analysis (HR 2.14; 95%CI: 1.23-3.63; p: 0.005) after correction for well-established CHF prognostic markers. Among patients with repeated evaluations and without baseline hypochloremia, in 13% of these, incident hypochloremia occurred during follow-up and furosemide equivalent daily dose was its first determinant (HR for 1 mg/die: 1.008; 95%CI: 1.004-1.013; p<0.001) at forward stepwise logistic regression analysis. Finally, incident hypochloremia was associated with mortality at univariate (HR: 4.69; 95%CI: 2.69-8.19; p<0.001) as well as at multivariate analysis (HR: 2.97; 95%CI: 1.48-5.94; p: 0.002). CONCLUSIONS: In CHF outpatients baseline and incident hypochloremia are independently associated with all-cause mortality, thus highlighting the prognostic role of serum chloride levels which are generally unconsidered. Future studies should evaluate if the strict monitoring and correction of hypochloremia could exert a beneficial effect on prognosis.

Mineralcorticoid Receptor Antagonist Withdrawal for Hyperkalemia and Mortality in Patients with Heart Failure.

BACKGROUND: Hyperkalemia is one of the most frequent side effects related to renin-angiotensin-aldosterone system (RAAS) inhibition, and can influence optimization of heart failure (HF) therapy. AIM: To evaluate the occurrence of hyperkalemia in a series of outpatients with chronic HF and its relationship with RAAS inhibitor therapy. METHOD: We evaluated consecutive outpatients with HF and a reduced left ventricular ejection fraction. The incidence of hyperkalemia and consequent changes in RAAS inhibitor therapy were evaluated for each patient. RESULTS: A history of hyperkalemia or at least 1 episode of hyperkalemia during follow-up was observed in 104 of 351 patients. Hyperkalemia mainly influenced mineralocorticoid receptor antagonist (MRA) therapy and, among patients with hyperkalemia, not taking MRA was associated with a greater risk of death on univariate analysis (HR = 6.39; 95% CI 2.76-14.79, p < 0.001) and multivariate analysis (HR = 5.24; 95% CI 1.87-14.72, p = 0.002) after correction for age, ischemic cardiomyopathy, diabetes, systolic arterial pressure, New York Heart Association class 3, left ventricular ejection fraction, presence of hyponatremia, glomerular filtration rate calculated by the EPI formula, and presence of N-terminal pro-B-type natriuretic peptide >1,000 pg/mL. CONCLUSION: The occurrence of hyperkalemia is common among outpatients with HF and it is the main cause of MRA withdrawal, which is associated with a worse prognosis. In this setting, the possibility of managing hyperkalemia using new classes of drugs could allow continuation of MRA therapy.