Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial.

BACKGROUND: Troponin changes over time have been suggested to allow for an early diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with troponin elevation may benefit of therapy with enalapril. It is unknown whether a preventive treatment with enalapril may further increase the benefit. METHODS: The International CardioOncology Society-one trial (ICOS-ONE) was a controlled, open-label trial conducted in 21 Italian hospitals. Patients were randomly assigned to two strategies: enalapril in all patients started before chemotherapy (CT; 'prevention' arm), and enalapril started only in patients with an increase in troponin during or after CT ('troponin-triggered' arm). Troponin was assayed locally in 2596 blood samples, before and after each anthracycline-containing CT cycle and at each study visit; electrocardiogram and echocardiogram were done at baseline, and at 1, 3, 6 and 12-month follow-up. Primary outcome was the incidence of troponin elevation above the threshold. FINDINGS: Of the 273 patients, 88% were women, mean age 51 ± 12 years. The majority (76%) had breast cancer, 3% had a history of hypertension and 4% were diabetic. Epirubicin and doxorubicin were most commonly prescribed, with median cumulative doses of 360 [270-360] and 240 [240-240] mg/m2, respectively. The incidence of troponin elevation was 23% in the prevention and 26% in the troponin-triggered group (p = 0.50). Three patients (1.1%) -two in the prevention, one in the troponin-triggered group-developed cardiotoxicity, defined as 10% point reduction of LV ejection fraction, with values lower than 50%. INTERPRETATION: Low cumulative doses of anthracyclines in adult patients with low cardiovascular risk can raise troponins, without differences between the two strategies of giving enalapril. Considering a benefit of enalapril in the prevention of LV dysfunction, a troponin-triggered strategy may be more convenient.

Antihypertensive effect of barnidipine 10 mg or amlodipine 5 to 10 mg once daily in treatment-naive patients with essential hypertension: A 24-week, randomized, open-label, pilot study.

BACKGROUND: Dihydropyridine calcium antagonists are largely employed for the treatment of hypertension, coronary heart disease, and heart failure. OBJECTIVE: The aim of our study was to compare the antihypertensive effect of the dihydropyridine calcium antagonists barnidipine and amlodipine. METHODS: This was a 24-week, randomized, open-label, pilot study. Consecutive treatment-naive patients with grade I or II essential hypertension (office sitting systolic blood pressure [BP] of 140-179 mm Hg and diastolic BP of 90-109 mm Hg) were enrolled. The primary end points were the effect of treatment with either barnidipine 10 mg or amlodipine 5 mg once daily on office and ambulatory BP, left ventricular mass index (LVMI), and markers of cardiac damage, serum procollagen type I C-terminal propeptide, and plasma amino-terminal pro-B-type natriuretic peptide concentrations. Patients were assessed at enrollment, and 12 and 24 weeks. During each visit, the prevalence of adverse events (AEs) was also monitored using spontaneous reporting, patient interview, and physical examination, the relationship to study drug being determined by the investigators. Compliance with treatment was assessed at each study visit by counting returned tablets. RESULTS: Thirty eligible patients (20 men, 10 women; mean [SD] age, 47 [12] years) were included in the study; all patients completed the 24 weeks of study treatment. Twelve weeks after randomization, 6 patients in the amlodipine group had their dose doubled to 10 mg due to inadequate BP control. Mean BP reductions at study end were not significantly different between the barnidipine and amlodipine groups (office BP, -10.3/-9.4 vs -16.6/-9.1 mm Hg; ambulatory BP, 9.4/6.4 vs 8.1/5.1 mm Hg). Reductions in LVMI and markers of cardiac damage were not significantly different between the 2 groups. Significantly more patients in the amlodipine group reported drug-related AEs compared with those in the barnidipine group (9 [60%] vs 2 [13%]; P < 0.05). CONCLUSION: In this small sample of treatment-naive hypertensive patients, the antihypertensive effect of barnidipine 10 mg once daily was not significantly different from that of amlodipine 5 to 10 mg once daily.