Background. Uncertainty regarding clopidogrel effectiveness attenuation due to a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. Objective. To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. Methods. We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least one of the clinical outcomes of interest (major adverse cardiovascular event (MACE), cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis, and/or did not report at least a 6-month follow up. Statistical and clinical heterogeneity were evaluated and hazard ratios (HRs) and 95% confidence intervals (CIs) for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. Results. We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized control trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. Patients were, on average, in their mid-60’s, male, and with an array of comorbidities including hyperlipidemia, diabetes, hypertension and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR 1.28; 95% CI 1.24–1.32), myocardial infarction (HR 1.51; 95% CI 1.40–1.62) and stroke (HR 1.46; 95% CI 1.15–1.86). Only one study reported on GI bleed and pooled analysis couldn’t be conducted. Statistical testing suggested heterogeneity among studies, but subgroup analysis did not reveal a clear source. Conclusions. Concomitant clopidogrel-PPI therapy following PCI appears to be significantly associated with adverse cardiovascular events. Our findings suggest clinical guidelines should caution against the use of concomitant therapy in this patient population, and further research on the effect of individual PPIs is needed.

No abstract

Aim: Utilize the Bucher indirect treatment comparison (ITC) method to compare valbenazine and deutetrabenazine efficacy using clinical trial data. Methods: Outcomes included mean change from baseline in Abnormal Involuntary Movement Scale (AIMS) total score, AIMS response (≥50% improvement), clinical global impression of change response (score ≤2) and safety outcomes. Data were pooled by trial and dose; outcomes were analyzed at multiple time points. Results: ITC of AIMS score improvement significantly favored valbenazine 80 mg/day at 6 weeks versus deutetrabenazine 36 mg/day at 8 weeks, while valbenazine 40 mg/day was statistically similar to all doses of deutetrabenazine at all time points. No significant differences between drugs were found in AIMS and clinical global impression of change responses and safety outcomes. Conclusion: In this ITC of pooled trial data, valbenazine was generally favorable over deutetrabenazine, although dose titration and equivalency should be considered when interpreting results.

No abstract

Abstract Background Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with antipsychotic use. Data from RE-KINECT, a real-world study of antipsychotic-treated outpatients, were analyzed to assess the effects of possible TD on patient health and social functioning. Methods Analyses were conducted in Cohort 1 (patients with no abnormal involuntary movements) and Cohort 2 (patients with possible TD per clinician judgment). Assessments included: EuroQoL’s EQ-5D-5L utility (health); Sheehan Disability Scale (SDS) total score (social functioning); patient- and clinician-rated severity of possible TD (“none”, “some”, “a lot”); and patient-rated impact of possible TD (“none”, “some”, “a lot”). Regression models were used to analyze the following: associations between higher (worse) severity/impact scores and lower (worse) EQ-5D-5L utility (indicated by negative regression coefficients); and associations between higher (worse) severity/impact scores and higher (worse) SDS total score (indicated by positive regression coefficients). Results In Cohort 2 patients who were aware of their abnormal movements, patient-rated TD impact was highly and significantly associated with EQ-5D-5L utility (regression coefficient: − 0.023, P < 0.001) and SDS total score (1.027, P < 0.001). Patient-rated severity was also significantly associated with EQ-5D-5L utility (− 0.028, P < 0.05). Clinician-rated severity was moderately associated with both EQ-5D-5L and SDS, but these associations were not statistically significant. Conclusions Patients were consistent in evaluating the impacts of possible TD on their lives, whether based on subjective ratings (“none”, “some”, “a lot”) or standardized instruments (EQ-5D-5L, SDS). Clinician-rated severity of TD may not always correlate with patient perceptions of the significance of TD.