The Value of Controlling Blood Pressure and Reducing Risk

1
The Value of Controlling Blood Pressure and
Reducing Risk

• Eva Lonn, MD, MSc, FRCPC, FACC
• Professor of Medicine, McMaster University

2
Risk of AMI associated with Risk Factors in the
Overall Population
Yusuf S et al. Lancet 2004364937-952
3
Risk of AMI associated with Risk Factors in the
Overall Population
4
INTERHEARTRisk of AMI with Multiple Risk
Factors
Smk
DM
HTN
ApoB/A
123
All 4
O
PS
All RFs
5
INTERHEART Association of Risk Factors with AMI
in Men Women (1)
Cases () 20.1 53.1 25.5 16.2 53.0 34.6 45.6
46.5
6
Relation of BP and Age to IHD Risk Meta-analysis
of 61 Observational Studies in 12.7 million
person-years
7
Relation of BP and Age to Stroke
Risk Meta-analysis of 61 Observational Studies
in 12.7 million person-years
8
Impact of High-Normal Blood Pressure on the Risk
of Cardiovascular Disease Framingham Study
Men
Women
High normal (130-139/85-89 mm Hg) Normal
(120-129/80-84 mm Hg) Optimal (lt120/80 mm Hg)
High normal (130-139/85-89 mm Hg) Normal
(120-129/80-84 mm Hg) Optimal (lt120/80 mm Hg)
10
Plt0.001
P0.01
8
6
Cumulative Incidence ()
Cumulative Incidence ()
4
2
0
0
2
4
6
8
10
12
14
0
2
4
6
8
10
12
14
Time (y)
Time (y)
Vasan et al. N Engl J Med. 20013451291-1297.
9
Global Risk

• Thresholds for BP and other risk
• factors need to be considered in the
• context of global risk

Wald NJ. BMJ 20033261-6
10
CVD Risk

• HTN prevalence 50 million people in the United
  States.
• The BP relationship to risk of CVD is continuous,
  consistent, and independent of other risk
  factors.
• Each increment of 20/10 mmHg doubles the risk of
  CVD across the entire BP range starting from
  115/75 mmHg.
• Prehypertension signals the need for increased
  education to reduce BP in order to prevent
  hypertension.

11
Benefits of Lowering BP
Average Percent Reduction Stroke incidence
3540 Myocardial infarction 2025
Heart failure 50
In stage 1 HTN and additional CVD risk factors,
achieving a sustained 12 mmHg reduction in SBP
over 10 years will prevent 1 death for every 11
patients treated.
12
Impact of Lifestyle Therapies on Blood Pressure
in Hypertensive Adults
Result of aggregate and metaanalyses of short
term trials. Miller ER et al. J Clin Hyper 1999
Nov/Dec191-8.
13
Lifestyle Therapies in Hypertensive Adults
Summary
14
BP-Lowering Treatment Trialists Collaboration
Stroke
CHD
A B C D E F G
A B C D E F G
1.50
Relative Risk of Stroke
1.25
1.00
Relative Risk of CHD
0.75
0.50
0.25
Systolic BP Difference Between Randomized Groups
(mm Hg)
Systolic BP Difference Between Randomized Groups
(mm Hg)
A CCB v placebo D ARB v
control G
ACEi v diuretic and BB
B ACEI v placebo E
ACEI v CCB
C more intense v less F
CCB v diuretic or BB
Blood Pressure Lowering Treatment Trialists
Collaboration. Lancet. 20033621527-1535.
15
BP-Lowering Treatment Trialists Collaboration
Heart Failure
1.50
1.25
1.00
Relative Risk of HF
0.75
0.50
A B C D
E F G
0.25
-10
-8
-6
-4
-2
0
2
4
Systolic BP Difference BetweenRandomized Groups
(mm Hg)
Blood Pressure Lowering Treatment Trialists
Collaboration. Lancet. 20033621527-1535.
16
BP-Lowering Treatment Trialists
CollaborationComparisons of Different Drug
Classes
Relative Risk
RR (95 CI)
BP Difference(mm Hg)
Major CV events
1.02 (0.98, 1.07)
2/0
ACEI vs D/BB
1.04 (0.99, 1.08)
1/0
CA vs D/BB
0.97 (0.95, 1.03)
1/1
ACEI vs CA
CV death
1.03 (0.95, 1.11)
ACEI vs D/BB
2/0
1.05 (0.97, 1.13)
CA vs D/BB
1/0
1.03 (0.94, 1.13)
ACEI vs CA
1/1
Total mortality
1.00 (0.95, 1.05)
ACEI vs D/BB
2/0
0.99 (0.95, 1.04)
CA vs D/BB
1/0
1.04 (0.98, 1.10)
1/1
ACEI vs CA
0.5
1.0
2.0
FavorsFirst Listed
FavorsSecond Listed
Blood Pressure Lowering Treatment Trialists
Collaboration. Lancet. 20033621527-1535.
17
BP-Lowering Treatment Trialists
CollaborationComparisons of Different Drug
Classes
RR (95 CI)
Relative Risk
BP Difference(mm Hg)
Stroke
1.09 (1.00, 1.18)
ACEI vs D/BB
2/0
0.93 (0.86, 1.01)
CA vs D/BB
1/0
1.12 (1.01, 1.25)
ACEI vs CA
1/1
Coronary heart disease
0.98 (0.91, 1.05)
ACEI vs D/BB
2/0
1.01 (0.94, 1.08)
CA vs D/BB
1/0
0.96 (0.88, 1.05)
ACEI vs CA
1/1
Heart failure
1.07 (0.96, 1.19)
ACEI vs D/BB
2/0
CA vs D/BB
1.33 (1.21, 1.47)
1/0
ACEI vs CA
0.82 (0.73, 0.92)
1/1
0.5
1.0
2.0
FavorsFirst Listed
FavorsSecond Listed
Blood Pressure Lowering Treatment Trialists
Collaboration. Lancet. 20033621527-1535.
18
Myth CCBs are Harmful CCBs Safe and Effective
BP Lowering Drugs
INSIGHT (n6,321)
INVEST (n22,576)
ALLHAT (n33,357)
CONVINCE (16,602)
Brown et al. Lancet 2000356366-72. ALLHAT
Research Group. JAMA 20022882981-97. Pepine C,
et al. JAMA 20032902805-16. Black H, et al.
JAMA 20032892073-82.
19
BP Lowering was not equal
20
ALLHAT Heart Failure
15
Amlodipine
12
Lisinopril
Chlorthalidone
9
Cumulative Event Rate,
6
3

• Excess early HF events
• Diuretic withdrawal
• BP differential
• Ascertainment of events
• (accuracy of diagnosis)
• No difference in HF deaths (Chlor 1.1 Lis 1.1)

0
1
2
3
4
5
6
7
Time to Event, y
No. at RiskChlorthalidone 15,255 14,528 13,898 13
,224 11,511 6369 3015 384 Amlodipine 9048 8535 818
5 7801 6785 3775 1780 210 Lisinopril 9054 8496 809
6 7689 6698 3789 1837 313
Heart failure was not a prespecified
endpoint.ALLHAT Collaborative Research Group.
JAMA. 20022882981-2997.
21
VALUE Systolic Blood Pressure in Study
Sitting SBP by Time and Treatment Group
155
Valsartan (N 7649)
Amlodipine (N 7596)
150
mmHg
145
140
135
1
24
48
2
3
4
6
12
18
30
36
42
54
60
66
Baseline
Months
(or final visit)
Difference in SBP Between Valsartan and Amlodipine
5.0
4.0
3.0
2.0
mmHg
1.0
0
1
24
48
2
3
4
6
12
18
30
36
42
54
60
66
1.0
Months
(or final visit)
Julius S et al. Lancet. June 2004363.
22
VALUE Analysis of Results Based on BP Control
at 6 Months
Pooled Treatment Groups
Odds Ratio

Fatal/Non-fatal cardiac events
0.75 (0.670.83)

Fatal/Non-fatal stroke
0.55 (0.460.64)

All-cause death
0.79 (0.710.88)
Myocardial infarction
0.86 (0.731.01)

Heart failure hospitalisations
0.64 (0.550.74)
0.4
0.6
0.8
1.0
1.2
1.4
Controlled patients (n 10755)
Non-controlled patients (n 4490)
Hazard Ratio 95 CI
SBP lt 140 mmHg at 6 months.
P lt 0.01.
Weber MA et al. Lancet. 2004363204749.
23
VALUE Analysis of Results Based on Immediate
Response
Pooled Treatment Groups
Odds Ratio
Fatal/Non-fatal cardiac events

0.88 (0.790.97)

Fatal/Non-fatal stroke
0.83 (0.710.98)

All-cause death
0.90 (0.810.99)
Myocardial infarction
0.89 (0.761.04)
Heart failure hospitalisations
0.87 (0.751.01)
0.4
0.6
0.8
1.0
1.2
1.4
Immediate responders (n 9336)
Non-immediate responders (n 5663)
Odds Ratio 95 CI
Those not on previous tx SBP ? 10 mmHg at one
month those on previous tx SBP baseline at
one month. P lt 0.05 P lt 0.01.
Weber MA et al. Lancet. 2004363204749.
24
Myth BP Lowering post Stroke is
HazardousPROGRESS Outcomes
n6,105
Total Stroke
Vascular Death
Nonfatal MI
0
-5
-10
9
-15
-20
Relative Risk Reduction
-25
-30
28 Plt0.0001
Avg BP decrease 9/4 mm Hg
-35
-40
38
PROGRESS Collaborative Group. Lancet.
20013581033-1041.
25
CHEP 2004 Treatment of Systolic-Diastolic
Hypertension without Other Compelling Indications
TARGET lt140/90 mmHg
Lifestyle modification therapy

• CONSIDER
• Nonadherence?
• Secondary HTN?
• Interfering drugs or lifestyle?
• White coat effect?

Dual CombinationCombine adjacent classes
Triple or Quadruple therapy
CHEP Canadian Recommendations for the Management
and Treatment of Hypertension. 2004
26
Combination Therapy Needed to Achieve Target DBP
Goals
Patients with diabetes or renal impairment
required an average of 3.2 BP medications to
reach lower BP goals
3
Bakris et al. Am J Kidney Dis 200036646-61
27
HOPE and EUROPA
20 15 10 5 0
20 16 12 8 4 0
HOPE
EUROPA
22

• Mean BP Lowering 3/2 mm Hg HOPE
• 5/2 mmHg
  EUROPA
• History of Hypertension HOPE 46
• 
  EUROPA 27
• Baseline BP HOPE 139/79 mmHg
• EUROPA 137/82 mmHg
  

Placebo
20
Placebo
Perindopril
Ramipril
RR 0.80 p0.0003
RR 0.78 p0.00001
0 500 1000 1500
0
2
3
4
5
1
Years
Days
28
ACTION Main Study Results

• Mean BP Lowering 6/3 mmHg
• History of Hypertension 52
• Baseline BP 138/80 mmHg

Per 100 patient/years
Poole-Wilson P et al. Lancet 2004364849-57.
29
PEACE Primary Outcomes
The PEACE Trial Investigators, N Engl J Med
20043512058-2068
30
ACE-I Reduced DM (2ndary Outcome)
31
ARBs Reduced DM (2ndary Outcome)
32
Hypertension Awareness, Treatment, and Control
Canada 1992
22 of Canadians 18-70 y have hypertension
9
Patients with diabetes Treated, controlled
Joffres et al. Canadian Heart Health Survey. Am
J Hypertension 2001141099-105.
33
Systolic BP of Patients With Hypertension
NHANES III
66 Not Meeting Goal
34 Meeting Goal
Population (millions)
80-90
101-110
121-130
141-150
161-170
181-190
201-210
221-230
241-250
Systolic BP Range (mm Hg)
Lapuerta. Am J Hypertens. 19991292A. Abstract
K030.
34
Obesity Prevalence Percent of Population With
BMI ?30 kg/m2
Year
BMIbody-mass index (wt/ht2). Kopelman. Nature.
2000404635-643.