Summary Cardiotoxicity is a known risk of anthracycline treatment. However, the relative contribution of anthracyclines to the development of congestive heart failure (CHF), when included in a poly‐chemotherapy regimen, is unclear. We examined cardiotoxicity in adult patients with diffuse large B‐cell lymphoma and follicular lymphoma undergoing first‐line immunochemotherapy from 2000–2012. In total, 2440 patients without previous heart disease were identified from the Danish Lymphoma Registry, of which 1994 (81·7%) were treated with anthracycline‐containing chemotherapy [R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R‐CHOEP (R‐CHOP + etoposide)] and 446 (18·3%) were treated without anthracyclines (reference group). Compared to the reference group, the adjusted hazard ratio of CHF after 3–5 cycles of R‐CHOP/CHOEP was 5·0 [95% confidence interval (CI) 1·4; 18·5], 6 cycles 6·8 (95% CI 2·0; 23·3) and >6 cycles 13·4 (95% CI 4·0; 45·0). The cumulative 5‐year risk of CHF with all‐cause mortality as competing risk was 4·6% after 3–5 cycles of R‐CHOP/CHOEP, 4·5% after 6 and 7·9% after more than 6 cycles. Cumulative 5‐year risk for patients treated without anthracyclines was 0·8%. Using anthracyclines in first‐line lymphoma treatment increases risk of CHF in patients without previous history of heart disease. In particular, treatment with >6 cycles of R‐CHOP/CHOEP is associated with a significant increase in CHF rate.

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BackgroundTreatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels.MethodsThe effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2), the beta-fraction of the epithelial sodium channel (u-ENaCbeta), cyclic-AMP (u-cAMP), prostaglandin E2 (u-PGE2). Free water clearance (CH2O), fractional excretion of sodium (FENa), and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide.ResultsIbuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher.ConclusionDuring inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone systemTrial RegistrationClinical Trials Identifier: NCT00281762

An acute dose of AS decreased FE(Na) and DBP in healthy humans. The reduction in fractional urinary sodium excretion was very modest and transitory, and most likely secondary to the fall in diastolic blood pressure (DBP). However, renal haemodynamics, tubular function, vasoactive hormones and blood pressure were unchanged during short-term statin treatment in healthy man.