Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial / 中华心血管病杂志

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

Efficacy and safety of early initiation of sacubitril-valsartan therapy in patients with acute decompensated heart failure / 中华心血管病杂志

Objective: To assess the efficacy and safety of the initiation of sacubitril-valsartan （ARNI） therapy, as compared with ACEI therapy, after hemodynamic stabilization among patients hospitalized for acute decompensated heart failure （ADHF）. Methods: A total of 199 hospitalized patients for ADHF in our department from January 2017 to June 2019 were included in this retrospective analysis. According to the medication early after hemodynamic stabilization, patients were divided into ARNI group (n=92) and ACEI group (n=107). Among the included patients, 61 patients with newly diagnosed heart failure at the time of admission were also divided into ARNI group (n=30) and ACEI group (n=31) according to the applied medication. Clinical baseline data and follow-up results of enrolled patients were collected through the electronic medical records at admission, outpatient and telephone follow-up. The primary effectiveness observation index was left ventricular ejection fraction (LVEF) and left ventricular end diastolic dimension (LVEDD) measured by echocardiography; the secondary observation index was death from any causes and hospitalization for heart failure. Safety outcomes were the incidences of symptomatic hypotension, worsening renal function, hyperkalemia, and angioedema. Results: The clinical baseline characteristics were similar between ARNI group and ACEI group（all P>0.05）. The duration of follow up was (15.2±6.5) months in all patients enrolled, (12.3±5.0) months in ARNI group, and (18.2±6.5) months in ACEI group. At the end of follow-up, prevalence of an absolute LVEF increase of more than 5% was 48.9% (45/92) in ANRI group and 25.2% (27/107) in ACEI group (P=0.001). Percent of LVEF increase to more than 50% was 17.4% (16/92) in ANRI group and 3.7% (4/107) in ACEI group (P=0.001). Percent of patients with more than 10 mm LVEDD reduction was 14.1% (13/92) in ANRI group and 3.7% (4/107) in ACEI group (P=0.009). All-cause mortality rate was 5.7% (5/88) in ARNI group and 15.3% (13/85) in ACEI group (P=0.038). Rate of re-hospitalization due to heart failure was 50% (46/92) in ARNI group and 71% (76/107) in ACEI group（P=0.002）.The rates of symptomatic hypotension, worsening renal function, hyperkalemia, and angioedema were similar between ARNI group and ACEI group (all P>0.05). In patients with first diagnosed heart failure，percent of LVEF increase to more than 50% was 30% (9/30) in ANRI group and 6.5% (2/31) in ACEI group (P=0.017). Percent of more than 10 mm LVEDD reduction was 26.7%(8/30) in ANRI group and 3.2%(1/31) in ACEI group (P=0.012). Percent of an absolute LVEF increase of more than 5% was 53.3% (16/30) in ANRI group and 51.6% (16/31) in ACEI group (P=0.893). Re-hospitalization due to heart failure was 23.3% (7/30） in ARNI group and 73.3% (11/31) in ACEI group（P<0.01）. Rate of all-cause death tended to be lower in patients receiving ARNI (3.4% (1/29)) as compared to patients receiving ACEI (13.0% (3/23), P=0.197）. Conclusions: Among patients with heart failure with reduced ejection fraction hospitalized for ADHF, the initiation of ARNI therapy after hemodynamic stabilization is associated with a more significant improvement of cardiac remodeling and pump function than ACEI therapy and satisfactory safety. In ADHF patients with first diagnosed heart failure, initiation of ARNI therapy after hemodynamic stabilization can more effectively improve cardiac remodeling and pump function than treatment with ACEI.

Advanced oxidation protein products promote expression of stromal-cell derived factor-1alpha of ECV304 cells through ERK signal pathway / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of advanced oxidation protein products (AOPP) on expressions of stromal cell-derived factor-1alpha (SDF-1alpha) in ECV304 cells and the signal pathway that mediated the effects.</p><p><b>METHODS</b>AOPP-BSA was made from bovine serum albumin (BSA) and sodium hypochlorite. After treated with AOPP-BSA of different concentrations (50, 100, 200 micromol/L), the expressions of SDF-1alpha mRNA in ECV304 cells were measured by reverse transcription-polymerase chain reaction (RT-PCR) and the expressions of SDF-1alpha protein and the levels of phosphorylated extracellular signal-regulated kinase (ERK) in ECV304 cells were analyzed by Western blot. In inhibition test, U0126, the special inhibitor of ERK of different concentrations (0.1, 1, 10 rmol/L) were added into ECV304 cells culture media for 1 hour, then the cells were treated with AOPP-BSA for 24 hours, at last the protein levels in supernatant were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>AOPP-BSA obviously promoted the expressions of SDF-1alpha mRNA and increased the levels of SDF-1beta protein of ECV304 cells in dose-dependent manner (all P < 0.01), after 15 minutes treated with 200 micromol/L AOPP-BSA, the levels of phosphorylated ERK of ECV304 cells increased significantly (P < 0.01). When the ERK pathway was blocked by U0126, the promoting effects of AOPP-BSA on expressions of SDF-la protein in ECV304 cells were significantly inhibited in dose-dependent manner (P < 0.05).</p><p><b>CONCLUSION</b>AOPP induced the expression of SDF-la of ECV304 cells, ERK signal pathway is an important pathway that mediated the effects.</p>

Comparison on efficacy and safety between domestic levosimendan versus dobutamine for patients with acute decompensated heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of domestic levosimendan versus dobutamine for patients with acute decompensated heart failure (ADHF).</p><p><b>METHODS</b>ADHF patients from 8 medical centers were recruited in this multicenter, blind, positive-controlled, randomized study and received 24 h intravenous levosimendan (n = 114) or dobutamine (n = 114) therapy. SWAN-GANZ catheter was performed in patients with pulmonary capillary wedge pressure (PCWP) ≥ 15 mm Hg (1 mm Hg = 0.133 kPa) and cardiac index (CI) ≤ 2.5 L·min(-1)×m(-2) (n = 39 each).</p><p><b>RESULTS</b>Compared with baseline level, LVEF increased [(31.56 ± 9.69)% vs. (28.44 ± 7.08)%, P < 0.01] at 24 h in both groups. LVEF increase at 24 h was similar between two groups [(3.11 ± 6.90)% vs. (3.00 ± 6.63)%, P > 0.05]. The PCWP decrease at 24 h was significantly greater in levosimendan group than in dobutamine group [(-8.90 ± 7.14) mm Hg vs. (-5.64 ± 6.83) mm Hg, P = 0.04]. Decrease in NT-proBNP at 3 days was also more significant in levosimendan group than in dobutamine group [the percentage change compared to baseline: (-22.36 ± 38.98)% vs. (-8.56 ± 42.42)%, P < 0.01]. Dyspnea improvement at 24 h was more significant in levosimendan group than in dobutamine group. The incidences of adverse reactions and events were similar between two groups.</p><p><b>CONCLUSION</b>LVEF improvement is similar between dobutamine and domestic levosimendan while greater decreases in PCWP and NT-proBNP are achieved with domestic levosimendan in patients with ADHF.</p>

Clinical observation on isolated electroacupuncture for treatment of peripheral facial paralysis / 中国针灸

<p><b>OBJECTIVE</b>To study on therapeutic effect of isolated electroacupuncture on peripheral facial paralysis.</p><p><b>METHODS</b>One hundred cases were randomly divided into an observation group of 60 cases and a control group of 40 cases. The observation group were treated by isolated electroacupuncture and the control group by normal electroacupuncture. Jiache (ST 6), Yangbai (GB 14), Dicang (ST 4), Xiaguan (ST 7), Fengchi (GB 20) and Hegu (LI 4) were selected and same drugs were administrated in the two groups. Then their therapeutic effects were observed.</p><p><b>RESULTS</b>Forty-five cases were cured, 11 cases were markedly effective and 4 cases improved with an effective rate of 100.0% in the observation group, and corresponding figures were 26, 2 and 10 cases, and 95.0% in the control group, the observation group being better than the control group (P < 0.01).</p><p><b>CONCLUSION</b>Isolated electroacupuncture has a significant therapeutic effect on facial paralysis, being better than that of normal electroacupuncture.</p>