Masatoshi Minamisawa1,2, Brian Claggett1, Kota Suzuki1, Sheila M Hegde1, Amil M Shah1, Akshay S Desai1, Eldrin F Lewis3, Sanjiv J Shah4, Nancy K Sweitzer5, James C Fang6, Inder S Anand7, Eileen O'Meara8, Jean-Lucien Rouleau8, Bertram Pitt9, Marc A Pfeffer1, Scott D Solomon1, Orly Vardeny10. 1. Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (M.M., B.C., K.S., S.M.H., A.M.S., A.S.D., M.A.P., S.D.S.). 2. Department of Cardiovascular Medicine, Shinshu University Hospital, Matsumoto, Nagano, Japan (M.M.). 3. Stanford University Medical Center, CA (E.F.L.). 4. Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.). 5. University of Arizona, Tuscon (N.K.S.). 6. University of Utah School of Medicine, Salt Lake City (J.C.F.). 7. Minneapolis VA Hospital, MN (I.S.A.). 8. Montreal Heart Institute, Canada (E.O., J.-L.R.). 9. University of Michigan, Ann Arbor (B.P.). 10. Minneapolis VA Center for Care Delivery and Outcomes Research and University of Minnesota Medical School (O.V.).
Abstract
BACKGROUND: Polypharmacy is associated with a poor prognosis in the elderly, however, information on the association of polypharmacy with cardiovascular outcomes in heart failure with preserved ejection fraction is sparse. This study sought to investigate the relationship between polypharmacy and adverse cardiovascular events in patients with heart failure with preserved ejection fraction. METHODS: Baseline total number of medications was determined in 1758 patients with heart failure with preserved ejection fraction enrolled in the Americas regions of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist), by 3 categories: nonpolypharmacy (<5 medications), polypharmacy (5-9), and hyper-polypharmacy (≥10). We examined the relationship of polypharmacy status with the primary outcome (cardiovascular death, HF hospitalization, or aborted cardiac arrest), hospitalizations for any reason, and serious adverse events. RESULTS: The proportion of patients taking 5 or more medications was 92.5% (inclusive of polypharmacy [38.7%] and hyper-polypharmacy [53.8%]). Over a 2.9-year median follow-up, compared with patients with polypharmacy, hyper-polypharmacy was associated with an increased risk for the primary outcome, hospitalization for any reason and any serious adverse events in the univariable analysis, but not significantly associated with mortality. After multivariable adjustment for demographic and comorbidities, hyper-polypharmacy remained significantly associated with an increased risk for hospitalization for any reason (hazard ratio, 1.22 [95% CI, 1.05-1.41]; P=0.009) and any serious adverse events (hazard ratio, 1.23 [95% CI, 1.07-1.42]; P=0.005), whereas the primary outcome was no longer statistically significant. CONCLUSIONS: Hyper-polypharmacy was common and associated with an elevated risk of hospitalization for any reason and any serious adverse events in patients with heart failure with preserved ejection fraction. There were no significant associations between polypharmacy status and mortality.
BACKGROUND: Polypharmacy is associated with a poor prognosis in the elderly, however, information on the association of polypharmacy with cardiovascular outcomes in heart failure with preserved ejection fraction is sparse. This study sought to investigate the relationship between polypharmacy and adverse cardiovascular events in patients with heart failure with preserved ejection fraction. METHODS: Baseline total number of medications was determined in 1758 patients with heart failure with preserved ejection fraction enrolled in the Americas regions of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist), by 3 categories: nonpolypharmacy (<5 medications), polypharmacy (5-9), and hyper-polypharmacy (≥10). We examined the relationship of polypharmacy status with the primary outcome (cardiovascular death, HF hospitalization, or aborted cardiac arrest), hospitalizations for any reason, and serious adverse events. RESULTS: The proportion of patients taking 5 or more medications was 92.5% (inclusive of polypharmacy [38.7%] and hyper-polypharmacy [53.8%]). Over a 2.9-year median follow-up, compared with patients with polypharmacy, hyper-polypharmacy was associated with an increased risk for the primary outcome, hospitalization for any reason and any serious adverse events in the univariable analysis, but not significantly associated with mortality. After multivariable adjustment for demographic and comorbidities, hyper-polypharmacy remained significantly associated with an increased risk for hospitalization for any reason (hazard ratio, 1.22 [95% CI, 1.05-1.41]; P=0.009) and any serious adverse events (hazard ratio, 1.23 [95% CI, 1.07-1.42]; P=0.005), whereas the primary outcome was no longer statistically significant. CONCLUSIONS: Hyper-polypharmacy was common and associated with an elevated risk of hospitalization for any reason and any serious adverse events in patients with heart failure with preserved ejection fraction. There were no significant associations between polypharmacy status and mortality.
Authors: Robert L Page; Cindy L O'Bryant; Davy Cheng; Tristan J Dow; Bonnie Ky; C Michael Stein; Anne P Spencer; Robin J Trupp; JoAnn Lindenfeld Journal: Circulation Date: 2016-07-11 Impact factor: 29.690
Authors: Marc A Pfeffer; Brian Claggett; Susan F Assmann; Robin Boineau; Inder S Anand; Nadine Clausell; Akshay S Desai; Rafael Diaz; Jerome L Fleg; Ivan Gordeev; John F Heitner; Eldrin F Lewis; Eileen O'Meara; Jean-Lucien Rouleau; Jeffrey L Probstfield; Tamaz Shaburishvili; Sanjiv J Shah; Scott D Solomon; Nancy K Sweitzer; Sonja M McKinlay; Bertram Pitt Journal: Circulation Date: 2014-11-18 Impact factor: 29.690
Authors: Zachary A Marcum; Megan E Amuan; Joseph T Hanlon; Sherrie L Aspinall; Steven M Handler; Christine M Ruby; Mary Jo V Pugh Journal: J Am Geriatr Soc Date: 2011-12-08 Impact factor: 5.562
Authors: Bertram Pitt; Marc A Pfeffer; Susan F Assmann; Robin Boineau; Inder S Anand; Brian Claggett; Nadine Clausell; Akshay S Desai; Rafael Diaz; Jerome L Fleg; Ivan Gordeev; Brian Harty; John F Heitner; Christopher T Kenwood; Eldrin F Lewis; Eileen O'Meara; Jeffrey L Probstfield; Tamaz Shaburishvili; Sanjiv J Shah; Scott D Solomon; Nancy K Sweitzer; Song Yang; Sonja M McKinlay Journal: N Engl J Med Date: 2014-04-10 Impact factor: 91.245
Authors: Jasper Tromp; Li Shen; Pardeep S Jhund; Inder S Anand; Peter E Carson; Akshay S Desai; Christopher B Granger; Michel Komajda; Robert S McKelvie; Marc A Pfeffer; Scott D Solomon; Lars Køber; Karl Swedberg; Michael R Zile; Bertram Pitt; Carolyn S P Lam; John J V McMurray Journal: J Am Coll Cardiol Date: 2019-08-06 Impact factor: 24.094