The most common adverse events
The most common adverse events in relation to udenafil treatment are headache and facial flushing; other possible adverse events are febrile sensation, dyspepsia, and visual disturbances. No severe adverse event related to udenafil has been reported thus far. The adverse event rate recorded in the present study is similar to that reported in other studies that used udenafil or other types of PDE-5 inhibitors. Patients with hypertension or lcz696 did not experience hemodynamic abnormalities or uncontrollable glucose levels. One case of vision abnormality associated with udenafil has been reported; however, the rate of udenafil-associated vision abnormality is lesser than the rate associated with sildenafil. In our study, none of the patients experienced abnormal vision. Two patients who discontinued the udenafil medication because of the adverse events did not experience severe adverse events. None of them required further treatment to resolve their symptoms.
Although this study was a randomized, double-blind, placebo-controlled trial, the limited number of patients from a single center and the use of a fixed dose of udenafil were the limiting factors in this study. The change of IIEF-5 score at the end of 12 weeks of treatment was affected by the type of anastomosis and was higher after colorectal anastomosis than after coloanal anastomosis. Patients with old age, neoadjuvant radiotherapy, and open operations showed a smaller variation (albeit without significance). These factors have been reported to be related with sexual function after rectal cancer surgery and, in our study, the level of anastomosis was the factor that exhibited the strongest relationship with the effect of the udenafil treatment. In addition, emotional factors, such as satisfaction with a relationship with a partner, may effect functional outcomes. However, we were not able to assess these subjective variables quantitatively. Thus, multi-institutional studies including a greater number of patients and the administration of various dosages of udenafil are needed in the future. One major limitation of this study was that we performed only a modified intention-to-treat analysis. Patients who completed all questionnaires could be assessed for functional change. During the early period of cancer surgery, the patients’ concentration to sexual function was not always possible. In future studies, our limitation should be considered to find more concrete result.
Background Heart failure (HF) is a growing socioeconomic concern worldwide. The prevalence of HF is estimated to be about 2-3%, and increases with age as high as 8.4%. HF with reduced ejection fraction (HFrEF) occupies about 50% of total HF population, and the mortality and morbidity are higher than in HF with preserved ejection fraction. Despite remarkable improvement in HF morbidity and mortality with the introduction of angiotensin converting enzyme inhibitors and/or β-blockers, continuous effort to developing innovative and novel therapeutic option has been made because there is considered to be still much room for additional reduction in morbidity and/or mortality. An impaired nitric oxide (NO) signaling pathway is commonly involved in a derangement of left ventricular (LV) hemodynamics, LV remodeling, and impairment of exercise capacity in HFrEF patients.5, 6 Dysregulation of NO pathway plays a central role in a rise of pulmonary vascular tone by disturbing pulmonary vascular smooth muscle function, leading to pulmonary hypertension (PHT), right ventricular (RV) dysfunction, exercise intolerance, and death.7, 8, 9, 10, 11 Hence, NO overproduction was suggested as a potentially effective therapeutic approach.5, 6 In this respect, inhibition of phosphodiesterase type 5 (PDE5) is a promising treatment target enhancing NO bioavailability in vivo by preventing the catabolism of cyclic guanine monophosphate (cGMP). Udenafil (Zydena®, Dong-A Pharmaceutical Company, Seoul, Korea) is a newly developed, long-acting PDE5 inhibitor, and has efficacy and safety profile comparable to other PDE5 inhibitors. Udenafil is similar to sildenafil in molecular structures, pulmonary selectivity, and its broad range of safety margin. Udenafil was reported to attenuate RV hypertrophy and fibrosis in a rat model of HFrEF. Apart from comparable efficacy and pharmacodynamics properties, udenafil is expected to be more advantageous over sildenafil in clinical use, in that its plasma half-life is much longer than that of sildenafil, by which patient compliance should be expected to increase with a resultant amelioration of prognosis.17, 18, 19 However, there were no clinical data available reporting therapeutic effects of udenafil on the LV hemodynamics, exercise performance, and pulmonary artery pressure in patients with HFrEF. Thus, these questions were evaluated in this randomized, double-blind, placebo-controlled trial.