Browsing by Author "Stewart, Ralph AH"

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    ItemOpen Access
    Characterization of cardiovascular clinical events and impact of event adjudication on the treatment effect of darapladib versus placebo in patients with stable coronary heart disease: Insights from the STABILITY trial.
    (American heart journal, 2019-02) Held, Claes; White, Harvey D; Stewart, Ralph AH; Davies, Richard; Sampson, Shani; Chiswell, Karen; Silverstein, Adam; Lopes, Renato D; Heldestad, Ulrika; Budaj, Andrzej; Mahaffey, Kenneth W; Wallentin, Lars; STABILITY Investigators

    Background

    Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease.

    Methods

    Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results.

    Results

    In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03]).

    Conclusions

    The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication.
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    ItemOpen Access
    Six-minute walk distance after coronary artery bypass grafting compared with medical therapy in ischaemic cardiomyopathy.
    (Open heart, 2018-01) Stewart, Ralph AH; Szalewska, Dominika; Stebbins, Amanda; Al-Khalidi, Hussein R; Cleland, John GH; Rynkiewicz, Andrzej; Drazner, Mark H; White, Harvey D; Mark, Daniel B; Roy, Ambuj; Kosevic, Dragana; Rajda, Miroslaw; Jasinski, Marek; Leng, Chua Yeow; Tungsubutra, Wiwun; Desvigne-Nickens, Patrice; Velazquez, Eric J; Petrie, Mark C
    In patients with ischaemic left ventricular dysfunction, coronary artery bypass surgery (CABG) may decrease mortality, but it is not known whether CABG improves functional capacity.To determine whether CABG compared with medical therapy alone (MED) increases 6 min walk distance in patients with ischaemic left ventricular dysfunction and coronary artery disease amenable to revascularisation.The Surgical Treatment in Ischemic Heart disease trial randomised 1212 patients with ischaemic left ventricular dysfunction to CABG or MED. A 6 min walk distance test was performed both at baseline and at least one follow-up assessment at 4, 12, 24 and/or 36 months in 409 patients randomised to CABG and 466 to MED. Change in 6 min walk distance between baseline and follow-up were compared by treatment allocation.6 min walk distance at baseline for CABG was mean 340±117 m and for MED 339±118 m. Change in walk distance from baseline was similar for CABG and MED groups at 4 months (mean +38 vs +28 m), 12 months (+47 vs +36 m), 24 months (+31 vs +34 m) and 36 months (-7 vs +7 m), P>0.10 for all. Change in walk distance between CABG and MED groups over all assessments was also similar after adjusting for covariates and imputation for missing values (+8 m, 95% CI -7 to 23 m, P=0.29). Results were consistent for subgroups defined by angina, New York Heart Association class ≥3, left ventricular ejection fraction, baseline walk distance and geographic region.In patients with ischaemic left ventricular dysfunction CABG compared with MED alone is known to reduce mortality but is unlikely to result in a clinically significant improvement in functional capacity.NCT00023595.
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    ItemOpen Access
    The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation.
    (European heart journal, 2016-05) Hijazi, Ziad; Lindbäck, Johan; Alexander, John H; Hanna, Michael; Held, Claes; Hylek, Elaine M; Lopes, Renato D; Oldgren, Jonas; Siegbahn, Agneta; Stewart, Ralph AH; White, Harvey D; Granger, Christopher B; Wallentin, Lars; ARISTOTLE and STABILITY Investigators

    Aims

    Atrial fibrillation (AF) is associated with an increased risk of stroke, which is currently estimated by clinical characteristics. The cardiac biomarkers N-terminal fragment B-type natriuretic peptide (NT-proBNP) and cardiac troponin high-sensitivity (cTn-hs) are independently associated with risk of stroke in AF. Our objective was to develop and validate a new biomarker-based risk score to improve prognostication of stroke in patients with AF.

    Methods and results

    A new risk score was developed and internally validated in 14 701 patients with AF and biomarkers levels determined at baseline, median follow-up of 1.9 years. Biomarkers and clinical variables significantly contributing to predicting stroke or systemic embolism were assessed by Cox-regression and each variable obtained a weight proportional to the model coefficients. External validation was performed in 1400 patients with AF, median follow-up of 3.4 years. The most important predictors were prior stroke/transient ischaemic attack, NT-proBNP, cTn-hs, and age, which were included in the ABC (Age, Biomarkers, Clinical history) stroke risk score. The ABC-stroke score was well calibrated and yielded higher c-indices than the widely used CHA2DS2-VASc score in both the derivation cohort (0.68 vs. 0.62, P < 0.001) and the external validation cohort (0.66 vs. 0.58, P < 0.001). Moreover, the ABC-stroke score consistently provided higher c-indices in several important subgroups.

    Conclusion

    A novel biomarker-based risk score for predicting stroke in AF was successfully developed and internally validated in a large cohort of patients with AF and further externally validated in an independent AF cohort. The ABC-stroke score performed better than the presently used clinically based risk score and may provide improved decision support in AF.

    Clinicaltrials gov identifier

    NCT00412984, NCT00799903.