The Heart Outcomes Prevention Evaluation (HOPE) 3 Trial Eva Lonn, - - PowerPoint PPT Presentation

▶
the heart outcomes prevention evaluation hope 3 trial
SMART_READER_LITE
LIVE PREVIEW

The Heart Outcomes Prevention Evaluation (HOPE) 3 Trial Eva Lonn, - - PowerPoint PPT Presentation

Aug 02, 2023 26 likes •238 views

The Heart Outcomes Prevention Evaluation (HOPE) 3 Trial Eva Lonn, Jackie Bosch, Salim Yusuf For the HOPE-3 Investigators Population Health Research Institute, (PHRI) McMaster University and Hamilton Health Sciences, Hamilton, Canada

slide-1
SLIDE 1

The Heart Outcomes Prevention Evaluation (HOPE) – 3 Trial

Eva Lonn, Jackie Bosch, Salim Yusuf

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

slide-2
SLIDE 2

Unique Aspects of HOPE-3

  • BP lowering trial with wide range of BP entry

criteria

  • Cholesterol lowering treatment based on risk
  • pposed to baseline LDL or HDL measurement
  • Diverse population

4

slide-3
SLIDE 3

Years Cumulative Hazard Rates

0.0 0.02 0.04 0.06 0.08 0.10 1 2 3 4 5 6 7

6356 6272 6200 6103 5968 4969 2076 522 6349 6270 6198 6096 5967 4970 2075 488

  • No. at Risk

Cand + HCTZ

Placebo

Placebo Candesartan + HCTZ HR (95% CI) = 0.95 (0.81-1.11) P-value = 0.51

CV Death, MI, Stroke, Cardiac Arrest, Revascularization, Heart Failure

14

slide-4
SLIDE 4

CV Death, MI, Stroke, Cardiac Arrest, Revasc, HF

0.5 1.0 2.0

Candesartan + HCTZ Better Placebo Better

3.5 4.6 7.5 1.25 (0.92-1.70) 1.02 (0.77-1.34) 0.76 (0.60-0.96) 0.009 HR (95% CI) P Trend

Prespecified Subgroups: By Thirds of SBP

SBP Mean ≤131.5 131.6-143.5 >143.5 Diff 6.1 5.8 5.6 Cutoffs 122 138 154 Placebo Event Rate% 17

slide-5
SLIDE 5

Meta analysis of BP Lowering Trials in DM

Results by Baseline Levels

Brunström & Carlberg, BMJ 2016

slide-6
SLIDE 6

BP Lowering Arm: Conclusions

  • Fixed dose combination of Candesartan 16 mg +

HCTZ 12.5 mg/day reduced BP by 6.0/3.0 mmHg, but did not reduce CV events

  • CV events were significantly reduced in the

highest third of SBP – SBP >143.5 mmHg, mean 154 mmHg

  • Results were neutral in the middle third, and

trended towards harm in the lowest third of SBP

  • Treatment increased lightheadedness, but not

syncope or renal dysfunction

19

slide-7
SLIDE 7

Cholesterol Lowering Arm Results

Jackie Bosch

20

slide-8
SLIDE 8

Unique Aspects of Cholesterol Lowering Arm

  • No entry criteria based on lipid level
  • No routine monitoring
  • No dose titration
  • Low dose of rosuvastatin
slide-9
SLIDE 9

Cholesterol Lowering: Outcomes

Outcome Rosuvastatin N (%) Placebo N (%) HR (95% CI)

p

Co-Primary 1 235 (3.7) 304 (4.8) 0.76 (0.64-0.91) 0.002 Co-Primary 2 277 (4.4) 363 (5.7) 0.75 (0.64-0.88) 0.0004 Secondary 1 306(4.8) 393 (6.2) 0.77 (0.66-0.89) 0.0006 CV Death 154 (2.4) 171 (2.7) 0.89 (0.72-1.11) 0.31 MI 45 (0.7) 69 (1.1) 0.65 (0.44-0.94) 0.02 Stroke 70 (1.1) 99 (1.6) 0.70 (0.52-0.95) 0.02 CV Hosp. 281 (4.4) 369 (5.8) 0.75 (0.64-0.88) 0.0003

22

slide-10
SLIDE 10

CV Death, MI, Stroke, Cardiac Arrest, Revasc, Heart Failure

Years

Cumulative Hazard Rates

0.0 0.02 0.04 0.06 0.08 0.10 1 2 3 4 5 6 7

Placebo Rosuvastatin

HR (95% CI) = 0.75 (0.64-0.88) P-value = 0.0004

6361 6241 6039 2122 6344 6192 5970 2073 Rosuva Placebo

23

slide-11
SLIDE 11

HOPE-3 & Other Studies of LDL Lowering and CVD

slide-12
SLIDE 12

Cholesterol Lowering: Conclusions

  • Rosuvastatin 10mg/day reduced:

– LDL-C by 34.6 mg/dl (0.9 mmol/l; i.e. 27% in LDL-C) – CVD by 25%

  • Consistent benefits regardless of:

– LDL-C – SBP – Risk – CRP – Ethnicity

  • Excess in muscle pain/weakness (reversible) and

perhaps cataract surgery

  • No excess in rhabdomyolysis, myopathy or new diabetes 27
slide-13
SLIDE 13

Combined BP & Cholesterol Lowering vs Double Placebo

Salim Yusuf

28

slide-14
SLIDE 14

Unique Aspects of BP & Chol Lowering

  • First formal testing of polypill concept on clinical

events

  • Demonstrates that the concept is valid in

people with elevated BP; in others there is no benefit

slide-15
SLIDE 15

CV Death, MI, Stroke, Cardiac Arrest, Revasc, Heart Failure

Years Cumulative Hazard Rates 0.0 0.02 0.04 0.06 0.08 0.10 1 2 3 4 5 6 7

Combination Double Placebo HR (95% CI) = 0.72 (0.57-0.89) P-value = 0.0030

3180 4 3063 1057 3181 3061 1045 3176 3040 1019 3168 3035 1030 Combination Rosuvastatin Candesartan/HCTZ Double Placebo

32

slide-16
SLIDE 16

RRR of Combination and Each Intervention vs Double Placebo

Overall

RRR

0% 10% 20% 30% 40% 50%

28% 26% 6% Combo Rosuva Only Cand + HCTZ Only

34

Co-Primary 2

RRR

0% 10% 20% 30% 40% 50%

40% 20% 24% Combo Rosuva Only Cand+HCTZ Only Highest Third of SBP

0% 10% 20% 30% 40% 50%

19% 31%

  • 8%

Combo Rosuva Only Cand + HCTZ Only

Lower Two Thirds of SBP

slide-17
SLIDE 17

Clinical Implications

  • Statins beneficial in intermediate-risk individuals

without CVD

  • BP lowering benefits only those with elevated BP
  • Combined BP & cholesterol lowering:

– Leads to a 40% risk reduction in hypertensives (benefits from both BP lowering and statin)

  • In others, 30% RRR from statin alone
  • Pragmatic strategy:

– No Lipid or BP entry criteria or targets – No Dose titration – Infrequent safety monitoring Strategy used in HOPE-3 is simple, safe and effective and widely applicable

37

slide-18
SLIDE 18

Back up

slide-19
SLIDE 19

5 yr Risk <11% (6.5%) 11-15% 15-21% >21% Overall SBP 155 159 162 165 158

BP Lowering by CV Risk

BPLTC Lancet 2014

  • Active. Control BP Diff HR (95%CI)
slide-20
SLIDE 20

1st & Recurrent CV Events

147 159 188 205 50 100 150 200 250 300 350 N EVENTS First Event 2+ Events Total Events HR: 0.65 P Value: 0.0003 First Event HR: 0.72 P Value: 0.0012 96 53 57 48

Dbl Active Rosuva Only Cand + HCTZ Dbl Plac Only

slide-21
SLIDE 21

NNT Combination vs Double Placebo: Recurrent CV Events (Secondary)

Overall 30 Upper 1/3rd 16 Lower 2/3rd 41