Browsing by Author "Vaduganathan, Muthiah"

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    Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials
    (American Heart Association, 2023) Fletcher, Robert A.; Arnott, Clare; Rockenschaub, Patrick; Schutte, Aletta E.; Carpenter, Lewis; Vaduganathan, Muthiah; Agarwal, Rajiv; Bakris, George; Chang, Tara I.; Heerspink, Hiddo J. L.; Jardine, Meg J.; Mahaffey, Kenneth W.; Neal, Bruce; Pollock, Carol; Jun, Min; Rodgers, Anthony; Perkovic, Vlado; Neuen, Brendon L.; Medicine, School of Medicine
    Background: Sodium glucose cotransporter‐2 inhibitors reduce systolic blood pressure (SBP), but whether they affect SBP variability is unknown. There also remains uncertainty regarding the prognostic value of SBP variability for different clinical outcomes. Methods and Results: Using individual participant data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, we assessed the effect of canagliflozin on SBP variability in people with type 2 diabetes across 4 study visits over 1.5 years as measured by standard deviation, coefficient of variation, and variability independent of the mean. We used multivariable Cox regression models to estimate associations of SBP variability with cardiovascular, kidney, and mortality outcomes. In 11 551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (−0.25 mm Hg [95% CI, –0.44 to −0.06]), but there was no effect on coefficient of variation (0.02% [95% CI, –0.12 to 0.16]) or variability independent of the mean (0.08 U [95% CI, –0.11 to 0.26]) when adjusting for correlation with mean SBP. Each 1 standard deviation increase in standard deviation of SBP variability was independently associated with higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19 [95% CI, 1.02–1.38]) and all‐cause mortality (HR, 1.12 [95% CI, 1.01–1.25]), with consistent results observed for coefficient of variation and variability independent of the mean. Increases in SBP variability were not associated with kidney outcomes. Conclusions: In people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease, higher visit‐to‐visit SBP variability is independently associated with risks of hospitalization for heart failure and all‐cause mortality. Canagliflozin has little to no effect on SBP variability, independent of its established SBP‐lowering effect.
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    Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America
    (Elsevier, 2023) Bozkurt, Biykem; Ahmad, Tariq; Alexander, Kevin M.; Baker, William L.; Bosak, Kelly; Breathett, Khadijah; Fonarow, Gregg C.; Heidenreich, Paul; Ho, Jennifer E.; Hsich, Eileen; Ibrahim, Nasrien E.; Jones, Lenette M.; Khan, Sadiya S.; Khazanie, Prateeti; Koelling, Todd; Krumholz, Harlan M.; Khush, Kiran K.; Lee, Christopher; Morris, Alanna A.; Page, Robert L., II; Pandey, Ambarish; Piano, Mariann R.; Stehlik, Josef; Stevenson, Lynne Warner; Teerlink, John R.; Vaduganathan, Muthiah; Ziaeian, Boback; Writing Committee Members; Medicine, School of Medicine
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    Modifiability of Composite Cardiovascular Risk Associated With Chronic Kidney Disease in Type 2 Diabetes With Finerenone
    (American Medical Association, 2023) Agarwal, Rajiv; Pitt, Bertram; Rossing, Peter; Anker, Stefan D.; Filippatos, Gerasimos; Ruilope, Luis M.; Kovesdy, Csaba P.; Tuttle, Katherine; Vaduganathan, Muthiah; Wanner, Christoph; Bansilal, Sameer; Gebel, Martin; Joseph, Amer; Lawatscheck, Robert; Bakris, George L.; Medicine, School of Medicine
    Importance: It is currently unclear whether chronic kidney disease (CKD)-associated cardiovascular risk in type 2 diabetes (T2D) is modifiable. Objective: To examine whether cardiovascular risk can be modified with finerenone in patients with T2D and CKD. Design, setting, and participants: Incidence rates from Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis (FIDELITY), a pooled analysis of 2 phase 3 trials (including patients with CKD and T2D randomly assigned to receive finerenone or placebo) were combined with National Health and Nutrition Examination Survey data to simulate the number of composite cardiovascular events that may be prevented per year with finerenone at a population level. Data were analyzed over 4 years of consecutive National Health and Nutrition Examination Survey data cycles (2015-2016 and 2017-2018). Main outcomes and measures: Incidence rates of cardiovascular events (composite of cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, or hospitalization for heart failure) were estimated over a median of 3.0 years by estimated glomerular filtration rate (eGFR) and albuminuria categories. The outcome was analyzed using Cox proportional hazards models stratified by study, region, eGFR and albuminuria categories at screening, and cardiovascular disease history. Results: This subanalysis included a total of 13 026 participants (mean [SD] age, 64.8 [9.5] years; 9088 male [69.8%]). Lower eGFR and higher albuminuria were associated with higher incidences of cardiovascular events. For recipients in the placebo group with an eGFR of 90 or greater, incidence rates per 100 patient-years were 2.38 (95% CI, 1.03-4.29) in those with a urine albumin to creatinine ratio (UACR) less than 300 mg/g and 3.78 (95% CI, 2.91-4.75) in those with UACR of 300 mg/g or greater. In those with eGFR less than 30, incidence rates increased to 6.54 (95% CI, 4.19-9.40) vs 8.74 (95% CI, 6.78-10.93), respectively. In both continuous and categorical models, finerenone was associated with a reduction in composite cardiovascular risk (hazard ratio, 0.86; 95% CI, 0.78-0.95; P = .002) irrespective of eGFR and UACR (P value for interaction = .66). In 6.4 million treatment-eligible individuals (95% CI, 5.4-7.4 million), 1 year of finerenone treatment was simulated to prevent 38 359 cardiovascular events (95% CI, 31 741-44 852), including approximately 14 000 hospitalizations for heart failure, with 66% (25 357 of 38 360) prevented in patients with eGFR of 60 or greater. Conclusions and relevance: Results of this subanalysis of the FIDELITY analysis suggest that CKD-associated composite cardiovascular risk may be modifiable with finerenone treatment in patients with T2D, those with eGFR of 25 or higher, and those with UACR of 30 mg/g or greater. UACR screening to identify patients with T2D and albuminuria with eGFR of 60 or greater may provide significant opportunities for population benefits.
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    Predictors of Post-discharge Mortality Among Patients Hospitalized for Acute Heart Failure
    (Radcliffe Cardiology, 2017-11) Chioncel, Ovidiu; Collins, Sean P.; Greene, Stephen J.; Pang, Peter S.; Ambrosy, Andrew P.; Antohi, Elena-Laura; Vaduganathan, Muthiah; Butler, Javed; Gheorghiade, Mihai; Emergency Medicine, School of Medicine
    Acute Heart Failure (AHF) is a " multi-event disease" and hospitalisation is a critical event in the clinical course of HF. Despite relatively rapid relief of symptoms, hospitalisation for AHF is followed by an increased risk of death and re-hospitalisation. In AHF, risk stratification from clinically available data is increasingly important in evaluating long-term prognosis. From the perspective of patients, information on the risk of mortality and re-hospitalisation would be helpful in providing patients with insight into their disease. From the perspective of care providers, it may facilitate management decisions, such as who needs to be admitted and to what level of care (i.e. floor, step-down, ICU). Furthermore, risk-stratification may help identify patients who need to be evaluated for advanced HF therapies (i.e. left-ventricle assistance device or transplant or palliative care), and patients who need early a post-discharge follow-up plan. Finally, risk stratification will allow for more robust efforts to identify among risk markers the true targets for therapies that may direct treatment strategies to selected high-risk patients. Further clinical research will be needed to evaluate if appropriate risk stratification of patients could improve clinical outcome and resources allocation.