A post-marketing survey evaluating the safety and efficacy of a fixed-dose single-pill combination of cilnidipine and valsartan in patients with hypertension: Real-world JSH 2014 and 2019 implementations.

METHODS: : The home blood pressure control by a single-pill combination of cilnidipine and valsartan (HOPE-Combi) survey sought to evaluate the safety and efficacy of cilnidipine 10 mg/valsartan 80 mg single-pill combination (SPC of Cil/Val) treatment in patients with hypertension for over 12 months. Of 2622 subjects' data; we analyzed 2572 cases for safety and 2372 cases for efficacy. RESULTS: Adverse drug reaction (ADR) incidence rate was 3.77% (97 of 2572 patients). The frequency of ADRs did not differ between patients aged <75 years and those aged ≥75 years (3.70% vs. 3.93%, respectively); between patients with and without chronic liver disease (CLD; 6.44% vs. 3.54%, respectively); and between patients with and without chronic kidney disease (CKD; 5.26% vs. 3.59%, respectively). Office systolic blood pressure (BP) was reduced from 149.5 ± 19.6 mmHg to 133.5 ± 14.8 mmHg (-15.8 mmHg, P < .01); pulse rate was also reduced 75.5 ± 12.2 bpm to 73.5 ± 11.3 bpm (-1.8 bpm, P < .01) after 12 months. CONCLUSIONS: : The SPC of Cil/Val was safe and effective in treating BP of hypertensive patients in real-world settings.

Blood pressure control with cilnidipine treatment in Japanese post-stroke hypertensive patients: The CA-ATTEND study.

Blood pressure control is important in post-stroke hypertensive patients and antihypertensive treatment is recommended for such patients. Ca-channel blockers are recommended as the medications of choice for the treatment of post-stroke patients. Here, we report the results of a large-scale prospective post-marketing surveillance study of post-stroke hypertensive patients (n = 2667, male 60.4%, 69.0 ± 10.9 years) treated with cilnidipine, with regard to blood pressure control and adverse reactions. Cilnidipine treatment caused a decrease in both clinic and home blood pressures 2 months after the beginning of treatment, and the decreased blood pressure was maintained until the end of 12 months' observation. The proportion of patients in whom clinic blood pressure was well controlled (<140/90 mmHg) increased from 21.5% to 65.3% in cilnidipine treatment, with no differences in effectiveness among the various clinical subtypes of stroke. In total, 346 adverse events occurred, with an overall incidence of 8.9% (238 of 2667 patients). In the elderly group, specifically, a fall and a hip fracture each occurred in 1 (0.1%) patient. These results indicate that cilnidipine was effective in treating uncontrolled blood pressure and was well tolerated in Japanese post-stroke hypertensive patients in a real-world clinical setting.

[Results of a Drug Use Survey of Filgrastim Biosimilar 1(Filgrastim BS Syringe for Inj. "MOCHIDA"and "F")].

With the aim of evaluating the safety and efficacy of filgrastim biosimilar 1(Filgrastim BS syringe for Inj. "MOCHIDA"and "F"), we conducted a drug use results survey of this product for its indications, including mobilization of hematopoietic stem cells into peripheral blood and chemotherapy-induced neutropenia. Of the 518 cases enrolled between August 2013 and July 2015, 495 were selected to be subjects of our safety and efficacy evaluations. 37 cases (7.47%)experienced side effects, which were mainly lower back pain(19, 3.84%), fever(8, 1.62%)and bone pain(3, 0.61%). As for serious side effects, interstitial pneumonia was reported in 2 cases, but this disorder has already been ecognized as being associated with the use of filgrastim originator, and there were no reports of unknown side effects calling for immediate attention. In addition, we investigated hypersensitivity reactions(such as nettle rash and anaphylactic shock)and diminished drug effects, both of which are considered to be attributable to immunogenicity, and found that non-serious nettle rash was reported in 2 cases. However, there have been no reports of anaphylactic shock or diminished drug effects. The efficacy rate based on physicians' clinical observations was 97.98%. This study confirmed that there are no problems with the clinical use of filgrastim biosimilar 1.

Single-pill combination of cilnidipine, an l-/n-type calcium channel blocker, and valsartan reduces the day-by-day variability of morning home systolic blood pressure in patients with treated hypertension: A sub-analysis of the HOPE-combi survey.

We examined the effects of a fixed-dose single-pill combination of cilnidipine (10 mg), an L-/N-type calcium channel blocker, and valsartan (80 mg) (SPC of Cil/Val) on the day-by-day variability of morning home systolic blood pressure (MHSBP) in 616 patients with treated hypertension for 12 months as a sub-analysis of the HOPE-Combi survey, multicentral, post-marketing, and prospective observational survey. The SPC of Cil/Val was administrated once a day in the morning. The SPC of Cil/Val decreased the standard deviation (SD, from 6.3 ± 4.8 to 5.1 ± 3.8 mmHg, p < .01), coefficient of variation (from 4.3 ± 3.2 to 3.8 ± 2.9%, p < .05), average real variability (ARV, from 7.9 ± 6.6 to 6.3 ± 5.1 mmHg, p < .01), and the difference between maximum and minimum (MMD, from 11.9 ± 9.2 to 9.7 ± 7.2 mmHg, p < .01) of MHSBP. The variability of MHSBP increased with age; however, this was not increased in patients ≥70 years at the baseline. In elderly patients (≥70 years, N = 283), the SPC of Cil/Val decreased the SD (from 6.9 ± 5.6 to 5.6 ± 4.4 mmHg, p < .01), ARV (from 8.6 ± 7.7 to 6.9 ± 5.7 mmHg, p < .05), and MMD (from 13.2 ± 10.7 to 10.7 ± 8.3 mmHg, p < .01) of MHSBP at 12 months; the reduction in these MHSBP variability parameters was comparable to that in adults <70 years. These results suggest that the SPC of Cil/Val is effective in reducing day-by-day variability of MHSBP in elderly patients.

Single-pill combination of cilnidipine, an L-/N-type calcium channel blocker, and valsartan effectively reduces home pulse pressure in patients with uncontrolled hypertension and sympathetic hyperactivity: The HOPE-Combi survey.

The home blood pressure (BP) control by a single-pill combination of cilnidipine (an L-/N-type calcium channel blocker; CCB) and valsartan (HOPE-Combi) survey is a multicenter, post-marketing, prospective observational study of a single-pill combination of cilnidipine 10 mg and valsartan 80 mg (SPC of Cil/Val) in patients with uncontrolled hypertension. We examined the effects of the SPC of Cil/Val on morning home systolic BP (MHSBP) and morning home pulse pressure (MHPP) of 1036 patients with hypertension over 12 months. MHSBP decreased by 14.0 mm Hg (P < .01), and MHPP decreased by 6.6 mm Hg (P < .01). Moreover, morning home pulse rate (MHPR) decreased by 2.1 bpm (P < .01). A more progressive and greater decrease in MHSBP (-17.2 vs -10.3 mm Hg, P < .01) and MHPP (-7.6 vs -4.9 mm Hg, P < .01) was observed in patients with higher MHPR (≥70 bpm) than in those with lower MHPR (<70 bpm) over the treatment period. In particular, in patients with a wide MHPP (≥70 mm Hg), the difference in the MHPP reduction was greater in patients with higher MHPR than in those with lower MHPR (-17.9 vs -13.6 mm Hg, P < .01). These results suggested that the SPC of Cil/Val, which possesses the unique sympatholytic characteristics of an L-/N-type CCB, was particularly effective in patients with uncontrolled hypertension and sympathetic hyperactivity.

Effects of Cilnidipine, an L/N-Type Calcium Channel Blocker, on Carotid Atherosclerosis in Japanese Post-Stroke Hypertensive Patients: Results from the CA-ATTEND Study.

AIMS: Although several antihypertensive agents reduced the carotid intima-media thickness (IMT), it remains unclear whether those agents affect the interadventitial diameter (IAD). We aimed to examine whether cilnidipine, an L/N-type calcium channel blocker, reduced the common carotid IMT or IAD in post-stroke hypertensive patients. METHODS: The common carotid IMT and IAD were measured at the start of cilnidipine treatment and 12 months from that. The changes in the mean max-IMT or IAD between baseline and the 12-month follow-up were evaluated and compared between the thick group (max-IMT ≥1.1 mm) and the normal group (max-IMT ＜1.1 mm). RESULTS: A total of 603 post-stroke hypertensive subjects (mean age=69.3 yr, 378 males) were included in the analysis. At baseline, IAD was increased stepwise according to the value of max-IMT (p for trend ＜0.001). Among them, 326 subjects were followed up for 12 months. The mean max-IMT from baseline to 12 months did not change in the normal group (－0.01 mm, 95% confidence interval [CI] －0.03 to 0.01, n=170), whereas a significant reduction was observed in the thick group (－0.09 mm, 95% CI －0.13 to －0.05, n=156). The mean IAD was significantly reduced during the study period in the normal group (－0.14 mm, 95% CI －0.22 to －0.05) as well as in the thick group (－0.12 mm, 95% CI －0.21 to －0.03). CONCLUSIONS: Cilnidipine promoted the regression of common carotid IMT in post-stroke hypertensive patients, especially in the thick group. Cilnidipine also reduced the IAD in both normal and thick groups.