Browsing by Author "Effron, Mark B"
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Item Open Access Comparing Inverse Probability of Treatment Weighting and Instrumental Variable Methods for the Evaluation of Adenosine Diphosphate Receptor Inhibitors After Percutaneous Coronary Intervention.(JAMA cardiology, 2016-09) Federspiel, Jerome J; Anstrom, Kevin J; Xian, Ying; McCoy, Lisa A; Effron, Mark B; Faries, Douglas E; Zettler, Marjorie; Mauri, Laura; Yeh, Robert W; Peterson, Eric D; Wang, Tracy Y; Treatment With Adenosine Diphosphate Receptor Inhibitors–Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) InvestigatorsIMPORTANCE:There is increasing interest in performing comparative effectiveness analyses in large observational databases, yet these analyses must adjust for treatment selection issues. OBJECTIVES:To conduct comparative safety and efficacy analyses of prasugrel vs clopidogrel bisulfate after percutaneous coronary intervention and to evaluate inverse probability of treatment weighting (a propensity score method) and instrumental variable methods. DESIGN, SETTING, AND PARTICIPANTS:This study used data from the Treatment With Adenosine Diphosphate Receptor Inhibitors-Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study. Included in the study were patients undergoing percutaneous coronary intervention for myocardial infarction, 26.0% of whom received prasugrel. The study dates were April 4, 2010, to October 31, 2012. EXPOSURES:Choice of initial antiplatelet agent (prasugrel or clopidogrel). MAIN OUTCOMES AND MEASURES:Safety and efficacy outcomes included 1-year composite major adverse cardiovascular events, moderate to severe bleeding, and stent thrombosis. Hospitalizations for pneumonia, bone fractures, and planned percutaneous coronary intervention were used as the falsification end points. RESULTS:The study cohort comprised 11 784 participants (mean [SD] age, 60.0 [11.6] years, and 28.0% were female). Using inverse probability of treatment weighting adjustment, prasugrel and clopidogrel had similar major adverse cardiovascular events (hazard ratio [HR], 0.98; 95% CI, 0.83-1.16) and bleeding outcomes (1.18; 0.77-1.80), but prasugrel had a lower rate of stent thrombosis (0.51; 0.31-0.85). Using instrumental variable methods, prasugrel use was associated with a lower rate of the major adverse cardiovascular event end point (HR, 0.68; 95% CI, 0.47-1.00) but nonsignificant differences in the rates of bleeding (0.95; 0.41-2.08) and stent thrombosis (0.67; 0.16-2.00). There was no significant treatment difference noted in any of the falsification end-point rates when analyses were performed using inverse probability of treatment weighting, although the bone fracture end point approached statistical significance. Nevertheless, a lower rate of pneumonia-related hospitalizations was noted in the prasugrel-treated patients when analyses were performed using instrumental variable methods. CONCLUSIONS AND RELEVANCE:Conclusions regarding the safety and efficacy of antiplatelet therapy varied depending on analytic technique, and none were concordant with the results from randomized trials. In addition, both statistical strategies demonstrated concerning associations when tested in the falsification analyses. A high level of scrutiny and careful attention to assumptions and validity are required when interpreting complex analyses of observational data.Item Open Access How Reliable are Patient-Reported Rehospitalizations? Implications for the Design of Future Practical Clinical Studies.(J Am Heart Assoc, 2016-01-25) Krishnamoorthy, Arun; Peterson, Eric D; Knight, J David; Anstrom, Kevin J; Effron, Mark B; Zettler, Marjorie E; Davidson-Ray, Linda; Baker, Brian A; McCollam, Patrick L; Mark, Daniel B; Wang, Tracy YBACKGROUND: Longitudinal clinical investigations often rely on patient reports to screen for postdischarge adverse outcomes events, yet few studies have examined the accuracy of such patient reports. METHODS AND RESULTS: Patients with acute myocardial infarction (MI) in the TRANSLATE-ACS study were asked during structured interviews at 6 weeks, 6 months, and 12 months postdischarge to report any rehospitalizations. The accuracy of patient-reported rehospitalizations within 1 year of postdischarge was determined using claims-based medical bill validation as the reference standard. The cumulative incidence of rehospitalizations was compared when identified by patient report versus medical bills. Patients were categorized by the accuracy in reporting events (accurate, under-, or over- reporters) and characteristics were compared between groups. Among 10 643 MI patients, 4565 (43%) reported 7734 rehospitalizations. The sensitivity and positive predictive value of patient-reported rehospitalizations were low at 67% and 59%, respectively. A higher cumulative incidence of rehospitalization was observed when identified by patient report versus medical bills (43% vs 37%; P<0.001). Overall, 18% of patients over-reported and 10% under-reported the number of hospitalizations. Compared with accurate reporters, under-reporters were more likely to be older, female, African American, unemployed, or a non-high-school graduate, and had greater prevalence of clinical comorbidities such as diabetes and past cardiovascular disease. CONCLUSIONS: The accuracy of patient-reported rehospitalizations was low with patients both under- and over-reporting events. Longitudinal clinical research studies need additional mechanisms beyond patient report to accurately identify rehospitalization events. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01088503.Item Open Access Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.(The New England journal of medicine, 2021-08-04) REMAP-CAP Investigators; ACTIV-4a Investigators; ATTACC Investigators; Goligher, Ewan C; Bradbury, Charlotte A; McVerry, Bryan J; Lawler, Patrick R; Berger, Jeffrey S; Gong, Michelle N; Carrier, Marc; Reynolds, Harmony R; Kumar, Anand; Turgeon, Alexis F; Kornblith, Lucy Z; Kahn, Susan R; Marshall, John C; Kim, Keri S; Houston, Brett L; Derde, Lennie PG; Cushman, Mary; Tritschler, Tobias; Angus, Derek C; Godoy, Lucas C; McQuilten, Zoe; Kirwan, Bridget-Anne; Farkouh, Michael E; Brooks, Maria M; Lewis, Roger J; Berry, Lindsay R; Lorenzi, Elizabeth; Gordon, Anthony C; Ahuja, Tania; Al-Beidh, Farah; Annane, Djillali; Arabi, Yaseen M; Aryal, Diptesh; Baumann Kreuziger, Lisa; Beane, Abi; Bhimani, Zahra; Bihari, Shailesh; Billett, Henny H; Bond, Lindsay; Bonten, Marc; Brunkhorst, Frank; Buxton, Meredith; Buzgau, Adrian; Castellucci, Lana A; Chekuri, Sweta; Chen, Jen-Ting; Cheng, Allen C; Chkhikvadze, Tamta; Coiffard, Benjamin; Contreras, Aira; Costantini, Todd W; de Brouwer, Sophie; Detry, Michelle A; Duggal, Abhijit; Džavík, Vladimír; Effron, Mark B; Eng, Heather F; Escobedo, Jorge; Estcourt, Lise J; Everett, Brendan M; Fergusson, Dean A; Fitzgerald, Mark; Fowler, Robert A; Froess, Joshua D; Fu, Zhuxuan; Galanaud, Jean P; Galen, Benjamin T; Gandotra, Sheetal; Girard, Timothy D; Goodman, Andrew L; Goossens, Herman; Green, Cameron; Greenstein, Yonatan Y; Gross, Peter L; Haniffa, Rashan; Hegde, Sheila M; Hendrickson, Carolyn M; Higgins, Alisa M; Hindenburg, Alexander A; Hope, Aluko A; Horowitz, James M; Horvat, Christopher M; Huang, David T; Hudock, Kristin; Hunt, Beverley J; Husain, Mansoor; Hyzy, Robert C; Jacobson, Jeffrey R; Jayakumar, Devachandran; Keller, Norma M; Khan, Akram; Kim, Yuri; Kindzelski, Andrei; King, Andrew J; Knudson, M Margaret; Kornblith, Aaron E; Kutcher, Matthew E; Laffan, Michael A; Lamontagne, Francois; Le Gal, Grégoire; Leeper, Christine M; Leifer, Eric S; Lim, George; Gallego Lima, Felipe; Linstrum, Kelsey; Litton, Edward; Lopez-Sendon, Jose; Lother, Sylvain A; Marten, Nicole; Saud Marinez, Andréa; Martinez, Mary; Mateos Garcia, Eduardo; Mavromichalis, Stavroula; McAuley, Daniel F; McDonald, Emily G; McGlothlin, Anna; McGuinness, Shay P; Middeldorp, Saskia; Montgomery, Stephanie K; Mouncey, Paul R; Murthy, Srinivas; Nair, Girish B; Nair, Rahul; Nichol, Alistair D; Nicolau, Jose C; Nunez-Garcia, Brenda; Park, John J; Park, Pauline K; Parke, Rachael L; Parker, Jane C; Parnia, Sam; Paul, Jonathan D; Pompilio, Mauricio; Quigley, John G; Rosenson, Robert S; Rost, Natalia S; Rowan, Kathryn; Santos, Fernanda O; Santos, Marlene; Santos, Mayler O; Satterwhite, Lewis; Saunders, Christina T; Schreiber, Jake; Schutgens, Roger EG; Seymour, Christopher W; Siegal, Deborah M; Silva, Delcio G; Singhal, Aneesh B; Slutsky, Arthur S; Solvason, Dayna; Stanworth, Simon J; Turner, Anne M; van Bentum-Puijk, Wilma; van de Veerdonk, Frank L; van Diepen, Sean; Vazquez-Grande, Gloria; Wahid, Lana; Wareham, Vanessa; Widmer, R Jay; Wilson, Jennifer G; Yuriditsky, Eugene; Zhong, Yongqi; Berry, Scott M; McArthur, Colin J; Neal, Matthew D; Hochman, Judith S; Webb, Steven A; Zarychanski, RyanBackground
Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.Methods
In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.Results
The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.Conclusions
In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).Item Open Access Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.(The New England journal of medicine, 2021-08-04) ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators; Lawler, Patrick R; Goligher, Ewan C; Berger, Jeffrey S; Neal, Matthew D; McVerry, Bryan J; Nicolau, Jose C; Gong, Michelle N; Carrier, Marc; Rosenson, Robert S; Reynolds, Harmony R; Turgeon, Alexis F; Escobedo, Jorge; Huang, David T; Bradbury, Charlotte A; Houston, Brett L; Kornblith, Lucy Z; Kumar, Anand; Kahn, Susan R; Cushman, Mary; McQuilten, Zoe; Slutsky, Arthur S; Kim, Keri S; Gordon, Anthony C; Kirwan, Bridget-Anne; Brooks, Maria M; Higgins, Alisa M; Lewis, Roger J; Lorenzi, Elizabeth; Berry, Scott M; Berry, Lindsay R; Aday, Aaron W; Al-Beidh, Farah; Annane, Djillali; Arabi, Yaseen M; Aryal, Diptesh; Baumann Kreuziger, Lisa; Beane, Abi; Bhimani, Zahra; Bihari, Shailesh; Billett, Henny H; Bond, Lindsay; Bonten, Marc; Brunkhorst, Frank; Buxton, Meredith; Buzgau, Adrian; Castellucci, Lana A; Chekuri, Sweta; Chen, Jen-Ting; Cheng, Allen C; Chkhikvadze, Tamta; Coiffard, Benjamin; Costantini, Todd W; de Brouwer, Sophie; Derde, Lennie PG; Detry, Michelle A; Duggal, Abhijit; Džavík, Vladimír; Effron, Mark B; Estcourt, Lise J; Everett, Brendan M; Fergusson, Dean A; Fitzgerald, Mark; Fowler, Robert A; Galanaud, Jean P; Galen, Benjamin T; Gandotra, Sheetal; García-Madrona, Sebastian; Girard, Timothy D; Godoy, Lucas C; Goodman, Andrew L; Goossens, Herman; Green, Cameron; Greenstein, Yonatan Y; Gross, Peter L; Hamburg, Naomi M; Haniffa, Rashan; Hanna, George; Hanna, Nicholas; Hegde, Sheila M; Hendrickson, Carolyn M; Hite, R Duncan; Hindenburg, Alexander A; Hope, Aluko A; Horowitz, James M; Horvat, Christopher M; Hudock, Kristin; Hunt, Beverley J; Husain, Mansoor; Hyzy, Robert C; Iyer, Vivek N; Jacobson, Jeffrey R; Jayakumar, Devachandran; Keller, Norma M; Khan, Akram; Kim, Yuri; Kindzelski, Andrei L; King, Andrew J; Knudson, M Margaret; Kornblith, Aaron E; Krishnan, Vidya; Kutcher, Matthew E; Laffan, Michael A; Lamontagne, Francois; Le Gal, Grégoire; Leeper, Christine M; Leifer, Eric S; Lim, George; Lima, Felipe Gallego; Linstrum, Kelsey; Litton, Edward; Lopez-Sendon, Jose; Lopez-Sendon Moreno, Jose L; Lother, Sylvain A; Malhotra, Saurabh; Marcos, Miguel; Saud Marinez, Andréa; Marshall, John C; Marten, Nicole; Matthay, Michael A; McAuley, Daniel F; McDonald, Emily G; McGlothlin, Anna; McGuinness, Shay P; Middeldorp, Saskia; Montgomery, Stephanie K; Moore, Steven C; Morillo Guerrero, Raquel; Mouncey, Paul R; Murthy, Srinivas; Nair, Girish B; Nair, Rahul; Nichol, Alistair D; Nunez-Garcia, Brenda; Pandey, Ambarish; Park, Pauline K; Parke, Rachael L; Parker, Jane C; Parnia, Sam; Paul, Jonathan D; Pérez González, Yessica S; Pompilio, Mauricio; Prekker, Matthew E; Quigley, John G; Rost, Natalia S; Rowan, Kathryn; Santos, Fernanda O; Santos, Marlene; Olombrada Santos, Mayler; Satterwhite, Lewis; Saunders, Christina T; Schutgens, Roger EG; Seymour, Christopher W; Siegal, Deborah M; Silva, Delcio G; Shankar-Hari, Manu; Sheehan, John P; Singhal, Aneesh B; Solvason, Dayna; Stanworth, Simon J; Tritschler, Tobias; Turner, Anne M; van Bentum-Puijk, Wilma; van de Veerdonk, Frank L; van Diepen, Sean; Vazquez-Grande, Gloria; Wahid, Lana; Wareham, Vanessa; Wells, Bryan J; Widmer, R Jay; Wilson, Jennifer G; Yuriditsky, Eugene; Zampieri, Fernando G; Angus, Derek C; McArthur, Colin J; Webb, Steven A; Farkouh, Michael E; Hochman, Judith S; Zarychanski, RyanBackground
Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.Methods
In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.Results
The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.Conclusions
In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT02735707, and NCT04359277.).