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Influence of model-predicted rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome.

ABSTRACT: BACKGROUND:This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeutic drug monitoring might provide additional information regarding rivaroxaban dose, beyond what patient characteristics provide. METHODS:A post hoc exposure-response analysis was conducted using data from the phase III ATLAS ACS 2 Thrombolysis in Myocardial Infarction (TIMI) 51 study, in which 15,526 randomized ACS patients received rivaroxaban (2.5?mg or 5?mg twice daily) or placebo for a mean of 13?months (maximum follow up: 31?months). A multivariate Cox model was used to correlate individual predicted rivaroxaban exposures and patient characteristics with time-to-event clinical outcomes. RESULTS:For the incidence of myocardial infarction (MI), ischemic stroke, or nonhemorrhagic cardiovascular death, hazard ratios (HRs) for steady-state maximum plasma concentration (Cmax) in the 5th and 95th percentiles versus the median were statistically significant but close to 1 for both rivaroxaban doses. For TIMI major bleeding events, a statistically significant association was observed with Cmax [HR, 1.08; 95% CI, 1.06-1.11 (95th percentile versus median, 2.5?mg twice daily)], sex [HR, 0.56; 95% CI, 0.38-0.84 (female versus male)], and previous revascularization [HR, 0.62; 95% CI, 0.44-0.87 (no versus yes)]. CONCLUSIONS:The shallow slopes of the exposure-response relationships and the lack of a clear therapeutic window render it unlikely that therapeutic drug monitoring in patients with ACS would provide additional information regarding rivaroxaban dose beyond that provided by patient characteristics.

SUBMITTER: Zhang L

PROVIDER: S-EPMC6669848 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Influence of model-predicted rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome.

Zhang Liping L Yan Xiaoyu X Nandy Partha P Willmann Stefan S Fox Keith A A KAA Berkowitz Scott D SD Sharma Amarnath A Hermanowski-Vosatka Anne A Schmidt Stephan S Weitz Jeffrey I JI Garmann Dirk D Peters Gary G

Therapeutic advances in cardiovascular disease 20190101

<h4>Background</h4>This analysis aimed to evaluate the impact of rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome (ACS) and to determine whether therapeutic drug monitoring might provide additional information regarding rivaroxaban dose, beyond what patient characteristics provide.<h4>Methods</h4>A <i>post hoc</i> exposure-response analysis was conducted using data from the phase III ATLAS ACS 2 Thrombolysis in Myocardial I ...[more]

PMID: 31364490

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Project description:PurposeTo evaluate 1-year outcomes of the Investigational Vertebroplasty Safety and Efficacy Trial (INVEST), a blinded, randomized, controlled trial to investigate the effectiveness of percutaneous vertebroplasty in the treatment of osteoporotic vertebral compression fractures.Materials and methodsPatients were enrolled at 11 sites in the United States, the United Kingdom, and Australia by using an institutional review board-approved protocol and HIPAA compliance, and all patients provided written informed consent. Patients were randomized to undergo vertebroplasty or a control procedure. After 1 month, patients were allowed to cross over and undergo the alternate procedure. Coprimary outcomes were patient-reported function, measured with the modified Roland-Morris Disability Questionnaire (RDQ), and pain (on a scale of one to 10) at 1 year. Intention-to-treat (ITT) and as-treated (AT) analyses were used to compare outcomes.ResultsOne hundred thirty-one participants (68 in the vertebroplasty group and 63 in the control group) were included in the analyses. Patients in both groups showed improvements in pain and function at 1 year. In ITT analyses, patients randomized to vertebroplasty did not differ from control subjects in terms of RDQ results (difference, 1.37 points; 95% confidence interval [CI]: -0.88, 3.62; P = .231) but reported lower levels of pain (difference, 1.02 points; 95% CI: 0.04, 2.01; P = .042). Eleven of 68 patients who underwent vertebroplasty (16%) and 38 of 63 control subjects (60%) crossed over and elected to undergo the alternate procedure (P < .001). In AT analyses, patients treated with vertebroplasty did not differ from control subjects in terms of RDQ results (difference, 0.66 points; 95% CI: -1.98, 3.30; P = .625) or pain (difference, 0.85 points; 95% CI: -0.35, 2.05; P = .166).ConclusionVertebroplasty may provide a modest reduction in pain at 1 year compared with a control procedure; however, no difference in functional disability was observed. Clinical trial registration no. NCT00068822.

Dataset Information

Influence of model-predicted rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome.

Publications

Influence of model-predicted rivaroxaban exposure and patient characteristics on efficacy and safety outcomes in patients with acute coronary syndrome.

Similar Datasets

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