Research Spotlight

Morvaridzadeh, M., Fazelian, S., Agah, S., Khazdouz, M., Rahimlou, M., Agh, F., Potter, E., Heshmati, S. and Heshmati, J. (2020). “Effect of ginger (Zingiber officinale) on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials.” Cytokine 135: 155224.

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The aim of this systematic review and meta-analysis was to investigate the efficacy of ginger supplementation on circulating levels of C-reactive protein (CRP), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), soluble intercellular adhesion molecule (sICAM), and interleukin-6 (IL-6) concentrations in randomized controlled trials (RCTs). The search included PubMed-Medline, EMBASE, Scopus, Web of Science and Cochrane Library databases to identify randomized clinical trials on the effect of ginger supplementation on circulation levels of CRP, hs-CRP, IL-6, sICAM, and TNF-α published up until February 1st, 2020. We did not restrict articles based on language of publication. Standard mean differences and 95% confidence intervals were calculated for net changes in inflammatory mediators using a random-effects model. Sixteen RCTs comprising 1010 participants were found to be eligible for this meta-analysis. There was a significant reduction of circulating CRP (SMD: -5.11, 95% CI: -7.91, -2.30, I(2) = 98.1%), hs-CRP (SMD: -0.88, 95% CI: -1.63, -0.12, I(2) = 90.8%) and TNF-α levels (SMD: -0.85, 95% CI: -1.48, -0.21, I(2) = 89.4%) following ginger supplementation. However, meta-analysis results did not show any significant impact of ginger supplementation on IL-6 (SMD: -0.45, 95% CI: -1.29, 0.38, I(2) = 89.2%), and sICAM levels (SMD: -0.05, 95% CI: -0.36, 0.26, I(2) = 00.0%). This systematic review and meta-analysis of RCTs demonstrates a significant impact of ginger in lowering circulating CRP, hs-CRP and TNF-α levels. Large-scale RCTs are still needed to draw concrete conclusions about the effect of ginger on other inflammatory mediators.

Akbari, A., Mobini, G.R., Agah, S., Morvaridzadeh, M., Omidi, A., Potter, E., Fazelian, S., Ardehali, S.H., Daneshzad, E. and Dehghani, S. (2020). “Coenzyme Q10 supplementation and oxidative stress parameters: a systematic review and meta-analysis of clinical trials.” Eur J Clin Pharmacol 76(11): 1483-1499.

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PURPOSE: Oxidative stress (OS) is associated with several chronic complications and diseases. The use of coenzyme Q10 (CoQ10) as an adjuvant treatment with routine clinical therapy against metabolic diseases has shown to be beneficial. However, the impact of CoQ10 as a preventive agent against OS has not been systematically investigated. METHODS: A systematic literature search was performed using the PubMed, SCOPUS, EMBASE, and Cochrane Library databases to identify randomized clinical trials evaluating the efficacy of CoQ10 supplementation on OS parameters. Standard mean differences and 95% confidence intervals were calculated for net changes in OS parameters using a random-effects model. RESULTS: Seventeen randomized clinical trials met the eligibility criteria to be included in the meta-analysis. Overall, CoQ10 supplementation was associated with a statistically significant decrease in malondialdehyde (MDA) (SMD – 0.94; 95% CI – 1.46, – 0.41; I(2) = 87.7%) and a significant increase in total antioxidant capacity (TAC) (SMD 0.67; 95% CI 0.28, 1.07; I(2) = 74.9%) and superoxide dismutase (SOD) activity (SMD 0.40; 95% CI 1.12, 0.67; I(2) = 9.6%). The meta-analysis found no statistically significant impact of CoQ10 supplementation on nitric oxide (NO) (SMD – 1.40; 95% CI – 0.12, 1.93; I(2) = 92.6%), glutathione (GSH) levels (SMD 0.41; 95% CI – 0.09, 0.91; I(2) = 70.0%), catalase (CAT) activity (SMD 0.36; 95% CI – 0.46, 1.18; I(2) = 90.0%), or glutathione peroxidase (GPx) activities (SMD – 1.40; 95% CI: – 0.12, 1.93; I(2) = 92.6%). CONCLUSION: CoQ10 supplementation, in the tested range of doses, was shown to reduce MDA concentrations, and increase TAC and antioxidant defense system enzymes. However, there were no significant effects of CoQ10 on NO, GSH concentrations, or CAT activity.

Azhar, A., Zaayman, M., Silfvast-Kaiser, A., Kivelevitch, D., Menter, A. and Paek, S.Y. (2020). “Ixekizumab in the treatment of moderate-to-severe plaque psoriasis: Patient adherence, satisfaction, and preferences.” Dermatol Ther Nov 1;e14486. [Online ahead of print.].

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Ixekizumab is a humanized monoclonal antibody that exhibits its immunomodulatory effects by binding to interleukin 17A (IL-17A), a proinflammatory cytokine. It was approved for the treatment of plaque psoriasis by the Food and Drug Administration in 2016. Ixekizumab has demonstrated superiority in clinical trials against etanercept, with no significant difference in the side effect profile. The chronicity of psoriasis requires continual treatment to achieve disease clearance. Many factors may affect adherence to treatment including patient satisfaction, patient preferences, medication cost, and medication side effects. Limited data on patient adherence, satisfaction, and preference exists in formal literature. Often, surrogate measures must be used to extrapolate information regarding these measures. In this narrative review, we describe patient adherence, satisfaction, and preferences via both direct and surrogate measures as they relate to ixekizumab treatment for moderate-to-severe plaque psoriasis.

Yeoh, S.E., Dewan, P., Desai, A.S., Solomon, S.D., Rouleau, J.L., Lefkowitz, M., Rizkala, A., Swedberg, K., Zile, M.R., Jhund, P.S., Packer, M. and McMurray, J.J.V. (2020). “Relationship between duration of heart failure, patient characteristics, outcomes, and effect of therapy in PARADIGM-HF.” ESC Heart Fail Oct 19. [Epub ahead of print].

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AIMS: Little is known about patient characteristics, outcomes, and the effect of treatment in relation to duration of heart failure (HF). We have investigated these questions in PARADIGM-HF. The aim of the study was to compare patient characteristics, outcomes, and the effect of sacubitril/valsartan, compared with enalapril, in relation to time from HF diagnosis in PARADIGM-HF. METHODS AND RESULTS: HF duration was categorized as 0-1, >1-2, >2-5, and >5 years. Outcomes were adjusted for prognostic variables, including N-terminal pro-brain natriuretic peptide (NT-proBNP). The primary endpoint was the composite of HF hospitalization or cardiovascular death. The number of patients in each group was as follows: 0-1 year, 2523 (30%); >1-2 years, 1178 (14%); >2-5 years, 2054 (24.5%); and >5 years, 2644 (31.5%). Patients with longer-duration HF were older, more often male, and had worse New York Heart Association class and quality of life, more co-morbidity, and higher troponin-T but similar NT-proBNP levels. The primary outcome rate (per 100 person-years) increased with HF duration: 0-1 year, 8.4 [95% confidence interval (CI) 7.6-9.2]; >1-2 years, 11.2 (10.0-12.7); >2-5 years, 13.4 (12.4-14.6); and >5 years, 14.2 (13.2-15.2); P < 0.001. The hazard ratio was 1.26 (95% CI 1.07-1.48), 1.52 (1.33-1.74), and 1.53 (1.33-1.75), respectively, for >1-2, >2-5, and >5 years, compared with 0-1 year. The benefit of sacubitril/valsartan was consistent across HF duration for all outcomes, with the primary endpoint hazard ratio 0.80 (95% CI 0.67-0.97) for 0-1 year and 0.73 (0.63-0.84) in the >5 year group. For the primary outcome, the number needed to treat for >5 years was 18, compared with 29 for 0-1 year. CONCLUSIONS: Patients with longer-duration HF had more co-morbidity, worse quality of life, and higher rates of HF hospitalization and death. The benefit of a neprilysin inhibitor was consistent, irrespective of HF duration. Switching to sacubitril/valsartan had substantial benefits, even in patients with long-standing HF.

Zannad, F., Ferreira, J.P., Pocock, S.J., Zeller, C., Anker, S.D., Butler, J., Filippatos, G., Hauske, S.J., Brueckmann, M., Pfarr, E., Schnee, J., Wanner, C. and Packer, M. (2020). “Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function: Insights from the EMPEROR-Reduced Trial.” Circulation Oct 23. [Epub ahead of print].

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Background: In EMPEROR-Reduced, empagliflozin reduced cardiovascular death or HF hospitalization, total HF hospitalizations, and slowed the progressive decline in kidney function in patients with HF and a reduced ejection fraction (HFrEF), with and without diabetes. We aim to study the effect of empagliflozin on cardiovascular and kidney outcomes across the spectrum of kidney function. Methods: In this pre-specified analysis, patients were categorized by the presence or absence of CKD at baseline (eGFR<60ml/min/1.73m(2) or UACR>300mg/g). The primary and key secondary outcomes were (1) a composite of cardiovascular death or HF hospitalization (primary outcome); (2) total HF hospitalizations, and (3) eGFR slope. The direct impact on kidney events was investigated by a prespecified composite kidney outcome (defined as a sustained profound decline in eGFR, chronic dialysis or transplant). The median follow-up was 16 months. Results: 3730 patients were randomized to empagliflozin or placebo, of whom 1978 (53%) had CKD. Empagliflozin reduced the primary outcome and total HF hospitalizations in patients with and without CKD: primary outcome HR=0.78 (95%CI=0.65-0.93) and HR=0.72 (95%CI=0.58-0.90), respectively; interaction P=0.63. Empagliflozin slowed the slope of eGFR decline by 1.11 (0.23-1.98) ml/min/1.73m(2)/year in patients with CKD and by 2.41 (1.49-3.32) ml/min/1.73m2/year in patients without CKD. The risk of the composite kidney outcome was reduced similarly in patients with and without CKD: HR=0.53 (95%CI=0.31-0.91) and HR=0.46 (95%CI=0.22-0.99), respectively. The effect of empagliflozin on the primary composite outcome and the key secondary outcomes was consistent across a broad range of baseline kidney function, measured by clinically relevant eGFR subgroups or by albuminuria, including patients with eGFR as low as 20 ml/min/1.73m(2). Empagliflozin was well tolerated in CKD patients. Conclusions: In EMPEROR-reduced, empagliflozin had a beneficial effect on the key efficacy outcomes and slowed the rate of kidney function decline in patients with and without CKD and regardless of the severity of kidney impairment at baseline. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03057977.