Presentation Transcript

1. Regional Differences in Heart Failure Medication Changes During Acute Heart Failure Hospitalization: Findings From the PROTECT Trial

   Robert J. Mentz, Gad Cotter, John G. Cleland, Susanna R. Stevens, Karen Chiswell, Beth A. Davison, John R. Teerlink, Marco Metra, Adriaan A. Voors, Mona Fiuzat, Michael M. Givertz, Piotr Ponikowski, Barry M. Massie, and Christopher M. O'Connor
2. Background Clinical trials are increasingly conducted globally Shorten timelines Reduce costs Satisfy regulatory authorities Regional differences in CV trials – including HF Baseline patient characteristics Outcomes Specific reasons are uncertain Glickman SW, et al. NEJM 2009; Blair JE, et al. JACC2008
3. Unanswered Question Are there regional differences in medication changes during acute HF hospitalization? Hypothesis International differences exist in the use of HF medications Prior to admission During hospitalization At discharge (or Day 7)
4. PROTECT Trial Placebo-controlled, randomized trial of the adenosine antagonist rolofylline 2,033 patients Admitted with worsening HF & renal dysfunction Included patients regardless of LVEF Enrollment between 2007-2009 173 sites in 17 countries Neutral for primary endpoint of changes in symptoms and signs, clinical status and renal function through day seven Rolofylline: increased seizures and strokes Massie, BM et al. NEJM 2010
5. Methods We grouped countries into 6 regions based on international differences in CV clinical trials: North America Western Europe Eastern Europe Russia Israel Argentina In-hospital HF medication changes by region Mentz RJ, et al. Am Heart J 2012; 164(3): 303-12.
6. Enrollment 2033 patients 17 Countries & 173 Sites Russia = 14% N = 283 Western Europe = 19% N = 388 Eastern Europe = 33% N = 676 North America = 15% N = 313 Israel = 16% N = 318 Argentina = 3% N = 55
7. Country Contributions
8. Baseline Characteristics Results Presented as % or Median Value
9. 2 weeks prior to admission Baseline Medication Use (%) ArgIsr Russ East West NA ArgIsr Russ East West NA ArgIsr Russ East West NA ArgIsr Russ East West NA
10. Inpatient Medication Use (%) ArgIsr Russ East West NA ArgIsr Russ East West NA
11. Inpatient LOS & Diuretic Use ArgIsr Russ East West NA ArgIsr Russ East West NA ArgIsr Russ East West NA *Median Diuretic Dose (Furosemide Equivalent) through earliest of Day 7/Discharge
12. From 2 weeks prior to admission to discharge/day 7 Medication Changes: ACE/ARB 9% 14% 9% 18% 8% 72% 76% 77% 9% 12% 17% 16% 12% 69% 66% 13% 58% *Similar observations in those with documented HFrEF
13. Medication Changes: BB 11% 10% 16% 10% 15% 72% 75% 33% 45% 7% 8% 16% 10% 9% 8% 78% 72% 79%
14. Medication Changes: MRA 13% 53% 28% 34% 32% 43% 12% 37% 32% 19% 28% 47% 29% 53% 51% 13% 25% 20%
15. 30-days from Day 14 Visit (44 days post-randomization) Mortality or Hospitalization Multivariable Predictors Other multivariable predictors included: Hospitalization for HF past year, Pulse Pressure, BUN
16. Summary Differences in baseline characteristics across 6 regions Age, Gender, HF Etiology Blood pressure, Renal Function, CABG, ICDs Marked HF medication differences Beta-blockers at baseline MRAs at baseline & discharge Different inpatient strategies and LOS Inotropes, vasodilators, diuretic dosing Differential initiation of HF medications
17. Limitations Specific trial entry criteria Lack of consensus on grouping regions Relatively small regional sample sizes Sites were selected based on operational feasibility not epidemiology
18. Conclusions There were marked differences in patient characteristics across world regions World regions demonstrated differential use of HF medications at baseline with distinct inpatient management strategies and drug initiation These findings should be confirmed in other datasets and explored for a potential role in the differential outcomes across regions
19. Thank you
20. Mentors Christopher M. O’Connor G. Michael Felker Mona Fiuzat Statisticians Susanna Stevens Karen Chiswell Acknowledgements
21. Death or CV/Renal Hosp (60 d)
22. Outcome Event Rates by Region
23. Outcomes Adjusted for BUN, past hospitalization for heart failure, sodium, systolic blood pressure, ischemic heart disease, edema, albumin, creatinine, glucose, rales, BMI, ALT, age, NYHA class, respiratory rate, heart rate, and WBC count