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.

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.