Prospective, multicenter clinical trial comparing the M6-C compressible cervical disc with anterior cervical discectomy and fusion for the treatment of single-level degenerative cervical radiculopathy: 5-year results of an FDA investigational device exemption study.

BACKGROUND CONTEXT: Various total disc replacement (TDR) designs have been compared to anterior cervical discectomy and fusion (ACDF) with favorable short and long-term outcomes in FDA-approved investigational device exemption (IDE) trials. The unique design of M6-C, with a compressible viscoelastic nuclear core and an annular structure, has previously demonstrated favorable clinical outcomes through 24 months. PURPOSE: To evaluate the long-term safety and effectiveness of the M6-C compressible artificial cervical disc and compare to ACDF at 5 years. STUDY DESIGN: Prospective, multicenter, concurrently and historically controlled, FDA-approved IDE clinical trial. PATIENT SAMPLE: Subjects with one-level symptomatic degenerative cervical radiculopathy were enrolled and received M6-C (n=160) or ACDF (n=189) treatment as part of the IDE study. Safety outcomes were evaluated at 5 years for all subjects. The primary effectiveness endpoint was available at 5 years for 113 M6-C subjects and 106 ACDF controls. OUTCOME MEASURES: The primary endpoint of this analysis was composite clinical success (CCS) at 60 months. Secondary endpoints were function and pain (neck disability index, VAS), physical quality of life (SF-36, SF-12), safety, neurologic, and radiographic assessments. METHODS: Propensity score subclassification was used to control for selection bias and match baseline covariates of the control group to the M6-C subjects. Sixty-month CCS rates were estimated for each treatment group using a generalized linear model controlling for propensity score. RESULTS: At 5 years postoperatively, the M6-C treatment resulted in 82.3% CCS while the ACDF group showed 67.0% CCS (superiority p=.013). Secondary endpoints indicated that significantly more M6-C subjects achieved VAS neck and arm pain improvements and showed maintained or improved physical functioning on quality-of-life measures compared to baseline assessments. The M6-C group-maintained flexion-extension motion, with significantly greater increases from baseline disc height and disc angle than observed in the control group. The rates of M6-C subsequent surgical interventions (SSI; 3.1%) and definitely device- or procedure-related serious adverse events (SAE failure; 3.1%) were similar to ACDF rates (SSI=5.3%, SAE failure=4.8%; p>.05 for both). CONCLUSIONS: Subjects treated with the M6-C artificial disc demonstrated superior 5-year achievement of clinical success when compared to ACDF controls. In addition, significantly more subjects in the M6-C group showed improved pain and physical functioning scores than observed in ACDF subjects, with no difference in reoperation rates or safety outcomes.

Prospective, multicenter clinical trial comparing M6-C compressible six degrees of freedom cervical disc with anterior cervical discectomy and fusion for the treatment of single-level degenerative cervical radiculopathy: 2-year results of an FDA investigational device exemption study.

BACKGROUND CONTEXT: Various designs of total disc replacement (TDR) devices have been compared to anterior cervical discectomy and fusion (ACDF) with favorable outcomes in FDA-approved investigational device exemption trials. The design of M6-C with a compressible viscoelastic nuclear core and an annular structure is substantially different than prior designs and has previously demonstrated favorable kinematics and clinical outcomes in small case series. PURPOSE: To evaluate the safety and effectiveness of the novel M6-C compressible artificial cervical disc compared with ACDF for subjects with single-level degenerative cervical radiculopathy. STUDY DESIGN/SETTING: Prospective, multicenter, concurrently and historically controlled, FDA-approved investigational device exemption clinical trial. PATIENT SAMPLE: Subjects with one-level symptomatic degenerative cervical radiculopathy were enrolled and assigned to receive M6-C or ACDF. OUTCOME MEASURES: Pain and function (Neck Disability Index, VAS), quality of life (SF-36), safety, neurologic, and radiographic assessments of motion (both flexion extension and lateral bending) were performed. The primary clinical endpoint was composite clinical success (CCS) at 24 months. METHODS: Using propensity score subclassification to control for selection bias, 160 M6-C subjects were compared to a matched subset of 189 ACDF controls (46 concurrent and 143 historical controls). RESULTS: Both ACDF and M6-C subjects reported significant improvements in patient-reported outcomes at all time points over baseline. Overall SF-36 Physical Component Score and neck and arm pain scores were significantly improved for M6-C as compared to ACDF treatment. CCS and mean Neck Disability Index improvements were similar between M6-C and ACDF. Correspondingly, there were significantly fewer subjects that utilized pain medication or opioids following M6-C treatment at 24 months relative to baseline. Range of motion was maintained in subjects treated with M6-C. Subsequent surgical interventions, dysphagia rates, and serious adverse events were comparable between groups. CONCLUSIONS: M6-C treatment demonstrated both safety and effectiveness for the treatment of degenerative cervical radiculopathy. Treatment with M6-C demonstrated noninferiority for the primary endpoint, indicating a similar ability to achieve CCS at 24 months. However, for the secondary endpoints, M6-C subjects demonstrated significantly improved pain and function compared to ACDF subjects, while maintaining range of motion, improving quality of life, and decreasing analgesic and opioid usage at 2 years postoperatively relative to baseline.

Lipid-Lowering Efficacy of Ezetimibe in Patients with Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses.

INTRODUCTION: Patients with atherosclerotic cardiovascular disease (ASCVD), especially those with recent (< 1 year) acute coronary syndrome (ACS), are at high risk for recurrent cardiovascular events. This risk can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) levels. A comprehensive meta-analysis on the LDL-C-lowering efficacy of ezetimibe is lacking. This study attempts to address this gap. METHODS: A systematic literature review of randomized controlled trials evaluating the LDL-C-lowering efficacy of ezetimibe in the ASCVD population was conducted. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for publications from database inception to August 2018 and for conference abstracts from 2015 to August 2018. Meta-analyses were conducted to evaluate the LDL-C-lowering efficacy of ezetimibe in the ASCVD population and the recent ACS subgroup. RESULTS: In total, 12 studies were eligible for the meta-analyses. Treatment with combination ezetimibe plus statin therapy showed greater absolute LDL-C reduction than statin monotherapy (mean difference - 21.86 mg/dL; 95% confidence interval [CI] - 26.56 to - 17.17; p < 0.0001) after 6 months of treatment (or at a timepoint closest to 6 months). Similarly, in patients with recent ACS, combination ezetimibe plus statin therapy was favorable compared with statin monotherapy (mean treatment difference - 19.19 mg/dL; 95% CI - 25.22 to - 13.16; p < 0.0001). CONCLUSIONS: Ezetimibe, when added to statin therapy, provided a modest additional reduction in LDL-C compared with statin monotherapy. However, this may not be sufficient for some patients with ASCVD who have especially high LDL-C levels despite optimal statin therapy.