Browsing by Author "O’Connor, Christopher M."

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    Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study
    (Elsevier, 2021) Felker, G. Michael; McMurray, John J. V.; Cleland, John G.; O’Connor, Christopher M.; Teerlink, John R.; Voors, Adriaan A.; Belohlavek, Jan; Böhm, Michael; Borentain, Maria; Bueno, Hector; Cole, Robert T.; DeSouza, Mary M.; Ezekowitz, Justin A.; Filippatos, Gerasimos; Lang, Ninian N.; Kessler, Paul D.; Martinez, Felipe A.; Mebazaa, Alex; Metra, Marco; Mosterd, Arend; Pang, Peter S.; Ponikowski, Piotr; Sato, Naoki; Seiffert, Dietmar; Ye, June; Emergency Medicine, School of Medicine
    Objectives: The primary objective was to identify well-tolerated doses of cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events. Background: Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects. Bristol-Myers Squibb-986231 (cimlanod) is an HNO donor being developed for acute heart failure (AHF). Methods: This was a phase IIb, double-blind, randomized, placebo-controlled trial of 48-h treatment with cimlanod compared with placebo in patients with left ventricular ejection fraction ≤40% hospitalized for AHF. In part I, patients were randomized in a 1:1 ratio to escalating doses of cimlanod or matching placebo. In part II, patients were randomized in a 1:1:1 ratio to either of the 2 highest tolerated doses of cimlanod from part I or placebo. The primary endpoint was the rate of clinically relevant hypotension (systolic blood pressure <90 mm Hg or patients became symptomatic). Results: In part I (n = 100), clinically relevant hypotension was more common with cimlanod than placebo (20% vs. 8%; relative risk [RR]: 2.45; 95% confidence interval [CI]: 0.83 to 14.53). In part II (n = 222), the incidence of clinically relevant hypotension was 18% for placebo, 21% for cimlanod 6 μg/kg/min (RR: 1.15; 95% CI: 0.58 to 2.43), and 35% for cimlanod 12 μg/kg/min (RR: 1.9; 95% CI: 1.04 to 3.59). N-terminal pro-B-type natriuretic peptide and bilirubin decreased during infusion of cimlanod treatment compared with placebo, but these differences did not persist after treatment discontinuation. Conclusions: Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period.
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    Geographical affiliation with top 10 NIH-funded academic medical centers and differences between mortality from cardiovascular disease and cancer
    (Elsevier, 2020-12) Angraal, Suveen; Caraballo, César; Kahn, Peter; Bhatnagar, Ambika; Singh, Bikramjot; Wilson, F. Perry; Fiuzat, Mona; O’Connor, Christopher M.; Allen, Larry A.; Desai, Nihar R.; Mamtani, Ronac; Ahmad, Tariq; Pediatrics, School of Medicine
    Community engagement and rapid translation of findings for the benefit of patients has been noted as a major criterion for NIH decisions regarding allocation of funds for research priorities. We aimed to examine whether the presence of top NIH-funded institutions resulted in a benefit on the cardiovascular and cancer mortality of their local population. METHODS AND RESULTS: Based on the annual NIH funding of every academic medical from 1995 through 2014, the top 10 funded institutes were identified and the counties where they were located constituted the index group. The comparison group was created by matching each index county to another county which lacks an NIH-funded institute based on sociodemographic characteristics. We compared temporal trends of age-standardized cardiovascular mortality between the index counties and matched counties and states. This analysis was repeated for cancer mortality as a sensitivity analysis. From 1980 through 2014, the annual cardiovascular mortality rates declined in all counties. In the index group, the average decline in cardiovascular mortality rate was 51.5 per 100,000 population (95% CI, 46.8-56.2), compared to 49.7 per 100,000 population (95% CI, 45.9-53.5) in the matched group (P = .27). Trends in cardiovascular mortality of the index counties were similar to the cardiovascular mortality trends of their respective states. Cancer mortality rates declined at higher rates in counties with top NIH-funded medical centers (P < .001). CONCLUSIONS: Cardiovascular mortality rates have decreased with no apparent incremental benefit for communities with top NIH-funded institutions, underscoring the need for an increased focus on implementation science in cardiovascular diseases.