Real-World Effectiveness and Tolerability of Tolvaptan in Patients With Heart Failure　― Final Results of the Samsca Post-Marketing Surveillance in Heart Failure (SMILE) Study ―

Abstract

Background:In Japan, tolvaptan is indicated for patients with heart failure and volume overload who have inadequate response to other diuretics. In contrast to the USA and Europe, tolvaptan can be used in Japan in patients with normal sodium levels. Methods and Results:In this multicenter, non-interventional, post-marketing surveillance study, prospective data from 3,349 patients treated with tolvaptan over a 5-year period were analyzed to identify benefits and risks. By Day 2 of treatment, 76.9% of evaluable patients had an increase in baseline 24-h urine volume (tolvaptan responders). Mean change in body weight was similar between 7.5 mg and 15 mg dosage groups (−3.6±3.9 kg and −3.7±4.0 kg, respectively). Improvement or disappearance rates for congestive symptoms from baseline to Day 14 ranged from 77.7% for lower limb edema to 51.1% for 3rd sound. Adverse drug reactions were reported in 18.1% of patients, most frequently thirst (8.4%). No case of central pontine myelinolysis was reported. All-cause mortality was significantly lower in patients with improved sodium concentration and increased 24-h urine volume. Conclusions:The effectiveness and safety of tolvaptan in real-world clinical settings was confirmed in this large-scale analysis. The 7.5-mg dose was equally as effective as the 15-mg dose and had a better safety profile. Improvements in all-cause mortality were suggested in tolvaptan responders.

Effects of Tolvaptan on Volume Overload in Patients with Heart Failure

“…21) Moreover, a postmarket surveillance in Japan (n = 1057) found that high doses of tolvaptan were a possible risk factor for hypernatremia (!150 mEq/L), and lower initial doses of tolvaptan were recommended. 32) Our subgroup analysis showed that the degree of change in serum sodium level was greater in the high-dose group. Hence, better strategies for optimizing doses of tolvaptan remain a challenge.…”

Update of acute and long-term tolvaptan therapy

“…The SMILE study, a post-marketing surveillance of tolvaptan, demonstrated from data of consecutive patients who had received tolvaptan between 2011 and 2015, that 43.6% of patients continued tolvaptan therapy for over two weeks in real-world clinical practice [3]. Also, 48.6% were aged over 80 years.…”

“…Almost half of the patients receiving tolvaptan therapy are aged over 80 years old [3] and we should understand the efficacy and safety of tolvaptan therapy in this population. The subanalysis of SMILE study demonstrated that the effectiveness of tolvaptan therapy in patients aged over 80 years old was similar to that in younger patients [21].…”

“…Many patients receiving tolvaptan therapy had renal dysfunction [3], which is associated with worse prognosis. Preservation of [ ( F i g .…”

“…considering the favorable clinical outcomes experienced by the clinicians [3]. Now is a time to review current accumulating evidence and update optimal therapeutic strategy in such expanded situations.…”