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2016 hope 3 cognitive outcomes slides

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HOPE-3 cognitive substudy

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2016 hope 3 cognitive outcomes slides

  1. 1. The Heart Outcomes Prevention Evaluation (HOPE) – 3 Trial: Cognitive & Functional Outcomes Jackie Bosch For the HOPE-3 Investigators Population Health Research Institute (PHRI), McMaster University and Hamilton Health Sciences, Hamilton, Canada Unrestricted grants from the Canadian Institutes of Health Research and AstraZeneca
  2. 2. Rationale • Cognitive impairment & dementia affect 5-7% of those over 60 years • Elevated BP associated with cognitive impairment • Statins linked to short term memory loss in observational studies, but not RCTs • The HOPE-3 study evaluated BP lowering & rosuvastatin use in 12,705 intermediate CV risk: – Statin reduced CV events by 25% in all – BP lowering reduced CV events by 24% only in those with hypertension • We evaluated the effect of these interventions on cognitive & functional decline
  3. 3. 3,086 ≥ 70 years 12,705 Randomized 219 Died 1,626 Completed baseline & study end questionnaire (76%) Cognitive Questionnaire Completion (Primary Outcome) 2,361 Completed baseline questionnaire Participants 70 years+ invited to complete questionnaires 2,142 Alive at study end
  4. 4. Pre-Stated Outcomes: Cognitive & Functional • Primary Outcome: Decline in processing speed (Digit Symbol Substitution Test [DSST]) • Secondary Outcomes • Decline in executive function (modified Montreal Cognitive Assessment [mMoCA]) • Increase in psychomotor speed (Trail Making Test Part B [TMT-B]) • Other Outcomes – Change in function (functional questions [EQ 5D]) – Study end: Standard Assessment of Global Activities in the Elderly [SAGE])
  5. 5. Baseline + Study End Baseline Only Age (yrs, SD) 74 (±3.5) 75 (±4.1) Female 59% 59% Hypertension 45% 45% Blood Pressure (mmHg) 140/79 139/79 LDL-Cholesterol (mg/dL) 127 128 Diabetes 6% 6% Education >12 years 24% 13% Ethnicity White Caucasian Latin American Chinese Other Asian 24% 36% 24% 13% 18% 54% 10% 10% Baseline Characteristics
  6. 6. SBP and LDL Changes by Treatment Group Years SystolicBloodPressure(mmHg) 0 1 2 3 4 5 6 7 120125130135140 Placebo Candesartan/HCTZ 0 Year 1 Year 3 Study End 8090100110120130 Placebo Rosuvastatin mean Δ BP= 6/2.9 mmHg mean Δ 24.9 mg/dl
  7. 7. Study End DSST Score 29.1 29.4 29.1 29.4 29.3 29.9 0 5 10 15 20 25 30 35 BP Pla Rosu Pla BP+Rosu Dbl Pla DSS Change in means: 0.1 P=0.86 Sensitivity analysis demonstrated similar results Change in means: -0.5 P=0.38 Change in means: -0.4 P=0.63
  8. 8. Change in Cognitive Outcome by Treatment Group 28 29 30 31 32 33 34 Basline Study End BP DSST BP Pla 8 9 10 11 12 Basline Study End BP mMoCA BP Pla 130 135 140 145 150 Basline Study End BP TMT-B BP Pla 28 29 30 31 32 33 34 Basline Study End BP DSST Rosu Pla 8 9 10 11 12 Basline Study End BP mMoCA Rosu Pla 130 135 140 145 150 Basline Study End BP TMT-B Rosu Pla BP Lowering Cholesterol Lowering
  9. 9. BP Lowering in Key Subgroups -5 0 5 Cand/HCTZ better Placebo better Age-years <=72 (Mean=71.0) 72-75 (Mean=73.3) Overall P Trend >75 (Mean=78.1) 0.970 SBP-mmHg <=133.0 (Mean=123.8) 133.0-145.0 (Mean=139.1) >145.0 (Mean=156.3) 0.078
  10. 10. Rosuvastatin in Key Subgroups Mean Δ DSST for Combination Treatment: High SBP and High HDL Double Active Double Placebo p High SBP/High LDL -4.7 (22.6) -11.8 (16.5) 0.04 -5 0 5Rosu better Placebo better Overall Age-years <=72 (Mean=71.0) 72-75 (Mean=73.3) LDL-mg/dl <=112 (Mean=88.7) 112-140 (Mean=125.7) P Trend >75 (Mean=78.1) 0.800 >140 (Mean=164.9) 0.110
  11. 11. Treatment Effect by Length of Intervention Active Placebo Difference P (Trend) Mean (SD) Mean (SD) Mean (95% CI) 5 yrs -5.9 (19.8) -3.2 (18.0) -2.7 (-6.4,0.98) 5-5.5 yrs -9.7 (19.0) -6.7 (17.8) -3.0 (-6.6,0.63) 5.5-6.2 yrs -3.4 (19.3) -3.6 (21.1) 0.17 (-3.8,4.1) >6.2yrs -4.4 (14.4) -6.3 (15.7) 1.9 (-1.1,4.8) 0.036 BP Lowering No significant difference in effects of rosuvastatin by duration of treatment
  12. 12. Functional Outcomes by Treatment Group BP Pla P Ros Pla P New functional impairment (EQ-5D) 22% 22% 0.96 21% 23% 0.46 Overall function at study end (SAGE) Any functional impairment 59% 56% 0.19 57% 59% 0.89
  13. 13. Conclusions • HOPE-3 participants experienced cognitive and function decline over 5.6 years • BP lowering and rosuvastatin use did not significantly prevent cognitive or functional decline • Rosuvastatin had no adverse effect on cognitive function • Subgroup analyses: – Trend for benefit in those with highest baseline BP and LDL – Longer duration of blood pressure lowering associated with less cognitive decline – Both findings require further confirmation
  14. 14. Acknowledgements • Steering Committee: S. Yusuf, E. Lonn, A. Avezum, J. Bosch, I. Chazova, A. Dans, R. Diaz, G. Fodor, C. Held, P. Jansky, M. Keltai, K. Keltai, K. Khunti, J. Kim, L.A. Leiter, B.S. Lewis, L. Loss, L.S. Liu, P. Lopez-Jaramillo, P. Pais, A. Parkhomenko, R.J.G. Peters L.S. Piegas, J. Pogue*, C.M. Reid, K. Sliwa, W.D. Toff, J. Varigos, D. Xavier, K. Yusoff, J. Zhu • Data and Safety Monitoring Board: D. Sackett (Chair)*, D. DeMets (Chair), C. Baigent, C. Hennekens, J. Mancini • Event Adjudication: G. Dagenais (Chair), R. McKelvie (Co-Chair), N. Anderson, P. Magloire, M. Naufal, C. Morillo, L. Morillo, V. Pavlova, M. Rokoss, D. Sahlas, J Silva, B. Tsang, N. Yakubovich, P. Bogaty, Z. Punthakee, J. Wilkinson, Y. Liang, A. Avezum, P. Hildebrandt, M. Keltai, D. Halon, K. Yusoff, R.J.G. Peters, G. Fodor, C. Held, M. Corson, J. Mann, R. Hart, M. Sharma • Study Statisticians & Programmers: J. Pogue*, H. Jung, P. Gao, G. Wong, K.Balasubramanian, B. Swaminathan, R. Khatun, L. Dyal, C. Tang, A. Casanova. • Project Office: J. Bosch, J. Wilkinson, K. Kewell, A. Rathe, J. Castelli, J. Miller, A.Whate, K. Brettell, A. Rogge, C. Choppick, A. Kuptsova, S. Owens, S. MacRae, A. Mead,J. Gibson, N. Barkhordari, S. Chang, M. Hogge. * Deceased We thank all the investigator and study coordinators for their efforts We thank all participants for their selfless dedication

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