1. The Relationship of Systolic and Diastolic Blood Pressure to Cardiovascular Disease Risk: Observational Data
The Relationship of Systolic and Diastolic Blood Pressure to Cardiovascular Disease Risk: Observational Data

2. Prevalence of Hypertension in the US
72 %
66 %
51 %
38 %
Percent hypertensive
18 %
Prevalence of Hypertension in the US
The prevalence of hypertension in a representative sample from the National Health and Nutritional Examination Survey (NHANES III, phases 1 and 2) reveals that approximately 25% of the US adult population has hypertension, and the prevalence of hypertension increases sharply with advancing age. NHANES III was a national examination study conducted in the US with the goals of: estimating the prevalence of selected diseases and risk factors; estimating population reference distributions of certain health parameters; documenting and investigating reasons for secular trends in selected diseases and risk factors; contributing to an understanding of disease etiology; and investigating the natural history of selected diseases. The NHANES III sample was selected from 81 counties between 1988 and 1994.
Reference:
The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 1997;157(21):
9 %
3 %
18-29
30-39
40-49
50-59
60-69
70-79
80+
Age
Based on NHANES III (phase 1 and 2)
Hypertension defined as blood pressure 140/90 mmHg or treatment
JNC-VI. Arch Intern Med. 1997;157:

3. Lifetime Risk of Developing Hypertension Beginning at Age 65
Men
Women
Risk of hypertension (%)
Lifetime Risk of Developing Hypertension Beginning at Age 65
Data from the Framingham Heart Study’s long-term follow-up indicate that the lifetime risk of developing hypertension is about 90 percent. The data are from a community-based prospective cohort study of 1,298 participants from the Framingham Heart Study who were between 55 and 65 years old and free of hypertension at baseline ( ). The residual life-time risk for developing hypertension (depicted above) was estimated for participants who reached the age of 65 free of hypertension.
Reference:
Vasan RS, Beiser A, Seshadri S et al. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA. 2002;287(8):
Years
Residual lifetime risk of developing hypertension among people with blood pressure <140/90 mmHg
Vasan RS, et al. JAMA. 2002; 287:
Copyright 2002, American Medical Association.

4. Mortality According to Blood Pressure in Men Age 50 to 69
Ratio (%) of actual to expected mortality
Mortality According to Blood Pressure in Men Age 50 to 69
Some of the earliest data on adverse consequences of hypertension come from the life insurance industry. This slide demonstrates rising mortality risk with increasing levels of systolic and diastolic blood pressure, but the slope of the increase is steeper for systolic blood pressure than for diastolic pressure. The number of entrants (insurance policies) in the Blood Pressure Study was close to 3,900,000.
Reference:
Society of Actuaries. Build and blood pressure study. Chicago; 1959.
Diastolic blood
pressure (mmHg)
Systolic blood pressure (mmHg)
Society of Actuaries. Blood Pressure Study, 1939.

5. Blood Pressure and Risk for Coronary Heart Disease in Men
Age 65-94
Age 65-94
Age-adjusted annual incidence of CHD per 1000
Age 35-64
Blood Pressure and Risk for Coronary Heart Disease in Men
Data from the Framingham Heart Study implicate rising systolic and diastolic blood pressure as risk factors for coronary heart disease. This is true for younger (yellow) and older (blue) age groups and for men and women (data not shown).
Reference:
The Framingham Study: an epidemiological investigation of cardiovascular disease. Section 34. Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Heart Study, 30-year follow-up. Bethesda, MD: National Heart, Lung, and Blood Institute, 1987.
Age 35-64
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
Based on 30 year follow-up of Framingham Heart Study subjects free of coronary heart disease (CHD) at baseline
Framingham Heart Study, 30-year Follow-up. NHLBI, 1987.

6. Risk of CHD Death According to SBP and DBP in MRFIT
Systolic blood pressure (SBP)
Diastolic blood pressure (DBP)
Relative risk of
CHD mortality
Risk of CHD Death According to SBP and DBP in MRFIT
With some 350,000 men screened from 1973 to 1975 and followed for major fatal outcomes, the Multiple Risk Factor Intervention Trial (MRFIT) has an enormously powerful database and permits a close look at the relationship of systolic blood pressure (SBP) and diastolic blood pressure (DBP), independently, to coronary heart disease (CHD) mortality risk. During 11.6 years of follow-up, there were 7,150 deaths due to CHD. Compared with subjects in the bottom decile of blood pressure (SBP <112; DBP <71), those at the top decile of the blood pressure distribution (SBP 151; DBP 98) were at markedly increased risk for death from CHD. The relationship of rising blood pressure to risk was continuous and graded, and was steeper for SBP compared with DBP. The average blood pressure levels of the MRFIT cohort were SBP 130 mmHg and DBP 84 mmHg. Optimal SBP, the level with the lowest death rate, was <120 mmHg.
Statistical significance between SBP and CHD, and DBP and CHD.
SBP: 3rd decile, P<0.05; 4th through 10th deciles, P<0.001.
DBP: 4th decile, P<0.01; 5th through 10th deciles, P<0.001.
Reference:
He J, Whelton PK. Elevated systolic blood pressure and risk of cardiovascular and renal disease: overview of evidence from observational epidemiologic studies and randomized controlled trials. Am Heart J 1999; 138 (3 Pt 2):211-9.
Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med 1993; 153 (5):
Decile 1 2 3 4 5 6 7 8 9 10
(lowest 10%)
(highest 10%)
<112 <71
>151 >98
SBP (mmHg)
DBP (mmHg)
CHD=coronary heart disease
He J, et at. Am Heart J. 1999;138:
Copyright 1999, Mosby Inc.

7. Risk of Stroke Death According to SBP and DBP in MRFIT
Systolic blood pressure (SBP)
Diastolic blood pressure (DBP)
Relative risk of stroke death
Risk of Stroke Death According to SBP and DBP in MRFIT
With some 350,000 men screened from 1973 to 1975 and followed for major fatal outcomes, the Multiple Risk Factor Intervention Trial (MRFIT) has an enormously powerful database and permits a close look at the relationship of blood pressure to stroke mortality. During 11.6 years of follow-up, there were 733 stroke deaths. There was an 8-fold gradient of risk across systolic blood pressure deciles and a 4-fold risk for diastolic blood pressure.
Statistical significance between SBP and stroke, and DBP and stroke.
SBP: 4th and 6th deciles, P<0.01; 7th through 10th deciles, P<0.001.
DBP: 7th through 9th deciles P<0.001; 10th decile P<0.001.
Reference:
He J, Whelton PK. Elevated systolic blood pressure and risk of cardiovascular and renal disease: overview of evidence from observational epidemiologic studies and randomized controlled trials. Am Heart J 1999; 138 (3 Pt 2):211-9.
Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med 1993; 153 (5):
Decile 1 2 3 4 5 6 7 8 9 10
(lowest 10%)
(highest 10%)
<112 <71
>151 >98
SBP (mmHg)
DBP (mmHg)
He J, et at. Am Heart J. 1999;138:
Copyright 1999, Mosby Inc.

8. Isolated Systolic Hypertension and CVD Risk in Framingham
2.5
ISH BP 160/<95 mmHg
BP <140/95 mmHg 82
2.4
Age-adjusted annual CVD event rate per 1000 43 33
Isolated Systolic Hypertension and CVD Risk in Framingham
In people over 60 years of age, isolated systolic hypertension (ISH) is the most common form of blood pressure elevation. These data from the Framingham Heart Study indicate that men and women with stage 2 or greater ISH (systolic blood pressure 160 mmHg when diastolic blood pressure was <95 mmHg) were at about a 2.5-fold risk for cardiovascular disease (P<0.001) over 24 months compared to those considered to have normal blood pressure (<140/95 mmHg). The population at risk were 1,687 men and 1,992 women from the Framingham cohort with SBP <160 mmHg in the first four biennial exams.
The Framingham Heart Study began in 1948 with an enrollment of 5,209 men and women, 30 to 62 years old, based on a two-thirds sample of the population of Framingham, Mass. After 30 years of follow-up, age-adjusted prevalence data showed 14.4% of the male population and 22.8% of females over age 65 to have ISH.
Reference:
Wilking SV, Belanger A, Kannel WB et al. Determinants of isolated systolic hypertension. JAMA. 1988; 260 (23): 18
Men
Women
CVD=cardiovascular disease ISH=isolated systolic hypertension
P<0.001 for difference between both men and women with ISH and blood pressure (BP) <140/95 mmHg
Wilking SV et al. JAMA. 1988;260:

9. The Relationship of Hypertension Treatment to CVD Risk Reduction: Introduction

10. Hypertension Treatment Effect Mirrors Observational Data
Incidence of cardiovascular disease
Treatment Effect
Hypertension Treatment Effect Matches Observational Data
Observational data indicate that risk for a variety of hypertension related outcomes rises with increasing levels of blood pressure. A key question to be answered in clinical trials is: To what extent does blood pressure treatment reduce the increase in cardiovascular disease risk associated with hypertension?
120
140
160
180
200
220
Systolic blood pressure (mmHg)

11. Landmark Clinical Trials Hypertension Treatment and Cardiovascular Disease Outcomes
1967 – VA Cooperative Study on DBP
1970 – VA Cooperative Study on DBP
1979 – HDFP
1980 – Australian Trial, Oslo Trial
1985 – MRC I, EWPHE
1991 – SHEP, STOP-Hypertension
1992 – MRC II in the elderly
1997 – Syst-Eur
2002 – LIFE
2002 – ALLHAT
Landmark Clinical Trials: Hypertension Treatment and Cardiovascular Disease Outcomes
A few of the many clinical trials in hypertension are shown on this slide. These trial results have changed our definition of hypertension and for ever altered our clinical management of patients with high blood pressure. Evolving national guidelines in the US and worldwide reflect the lessons learned and the evidence gathered from these and other landmark trials.
References:
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202 (11):
Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970; 213 (7):
Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA 1979; 242 (23):
The Australian therapeutic trial in mild hypertension. Report by the Management Committee. Lancet 1980; 1 (8181):
Helgeland A. Treatment of mild hypertension: a five year controlled drug trial. The Oslo study. Am J Med 1980; 69 (5):
Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med 1993; 153 (5):
MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party. Br Med J (Clin Res Ed) 1985; 291 (6488):
Amery A, Birkenhager W, Brixko P et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet 1985; 1 (8442):
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24):
Dahlof B, Lindholm LH, Hansson L et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991; 338 (8778):
Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ 1992; 304 (6824):
Staessen JA, Fagard R, Thijs L et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997; 350 (9080):

12. Relative Risk for Coronary Heart Disease
Odds ratios and 95% confidence intervals
Veterans Administration, 1967
Veterans Administration, 1970
Hypertension Stroke Study, 1974
USPHS Study, 1977
EWPHE Study, 1985
Coope and Warrender, 1986
SHEP Study, 1991
STOP-Hypertension Study, 1991
MRC Study, 1992
Syst-Eur Study, 1997
Total
Relative Risk for Coronary Heart Disease
This meta-analysis examines the relative risk for coronary heart disease (CHD) events in a variety of placebo control clinical trials. Although individual trials differed in the magnitude of risk reduction, the overall result was a 21% lower risk in total CHD in patients receiving active therapy compared with placebo (95% confidence intervals [CI] 10% to 31%; P<0.001). Fatal CHD was reduced 27% (95% CI 13% to 38%; P<0.001). Overall, 412 CHD events occurred in participants assigned to active treatment and 520 in those assigned to placebo. It should be noted, however, that among these 10 trials, the reduction in risk was only statistically significant for the SHEP study, in which CHD was reduced by 28% (95% CI 6% to 44%).
References:
He J, Whelton PK. Elevated systolic blood pressure and risk of cardiovascular and renal disease: overview of evidence from observational epidemiologic studies and randomized controlled trials. Am Heart J 1999; 138 (3 Pt 2):211-9.
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202 (11):
Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970; 213 (7):
Effect of antihypertensive treatment on stroke recurrence. Hypertension-Stroke Cooperative Study Group. JAMA 1974; 229 (4):
Amery A, Birkenhager W, Brixko P et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet 1985; 1 (8442):
Coope J, Warrender TS. Randomised trial of treatment of hypertension in elderly patients in primary care. Br Med J (Clin Res Ed) 1986; 293 (6555):
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24):
Dahlof B, Lindholm LH, Hansson L et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991; 338 (8778):
Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ 1992; 304 (6824):
Staessen JA, Fagard R, Thijs L et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997; 350 (9080):
0.79 (0.69 to 0.90)
0.5 1
1.5 2
Active treatment better than placebo
Active treatment worse than placebo
He J, et al. Am Heart J. 1999; 138:
Copyright 1999, Mosby, Inc.

13. Relative Risk for Stroke
Odds ratios and 95% confidence intervals
Veterans Administration, 1967
Veterans Administration, 1970
Hypertension Stroke Study, 1974
USPHS Study, 1977
EWPHE Study, 1985
Coope and Warrender, 1986
SHEP Study, 1991
STOP-Hypertension Study, 1991
MRC Study, 1992
Syst-Eur Study, 1997
Total
Relative Risk for Stroke
A similar analysis of stroke risk in this meta-analysis demonstrates a 37% lower risk of stroke in patients receiving active therapy vs. placebo (95% confidence interval [CI] 28% to 45%; P<0.001). Overall, there were 385 strokes in participants allocated to active treatment, and 596 in those assigned to placebo. Out of the 10 trials, the reduction in stroke was statistically significant in 6 of them.
References:
He J, Whelton PK. Elevated systolic blood pressure and risk of cardiovascular and renal disease: overview of evidence from observational epidemiologic studies and randomized controlled trials. Am Heart J 1999; 138 (3 Pt 2):211-9.
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202 (11):
Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970; 213 (7):
Effect of antihypertensive treatment on stroke recurrence. Hypertension-Stroke Cooperative Study Group. JAMA 1974; 229 (4):
Amery A, Birkenhager W, Brixko P et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet 1985; 1 (8442):
Coope J, Warrender TS. Randomised trial of treatment of hypertension in elderly patients in primary care. Br Med J (Clin Res Ed) 1986; 293 (6555):
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24):
Dahlof B, Lindholm LH, Hansson L et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet 1991; 338 (8778):
Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. BMJ 1992; 304 (6824):
Staessen JA, Fagard R, Thijs L et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet 1997; 350 (9080):
0.63 (0.55 to 0.72)
0.5 1
1.5 2
Active treatment better than placebo
Active treatment worse than placebo
He J, et al. Am Heart J. 1999; 138:
Copyright 1999, Mosby, Inc.

14. The Veterans Administration Cooperative Study on Antihypertensive Agents
The VA Cooperative Study on Antihypertensive Agents

15. The VA Cooperative Study, 1967
Cohort
143 men
Mean age
51 years
Eligibility
Diastolic BP mmHg
Design
Double blind; placebo control
Therapy
HCTZ, reserpine, hydralazine
Duration
1.5 years
BP change
-43/30 mmHg
The VA Cooperative Study, 1967
The VA Cooperative Study was begun at a time when it was not know whether hypertension therapy was beneficial, of no value, or possibly even harmful. Freis and his VA Cooperative Study Group colleagues designed the first adequately powered placebo-controlled, randomized clinical trial of drug treatment in patients with hypertension. Understandably, they selected patients with fairly severe hypertension—diastolic blood pressures of mmHg—for this landmark demonstration study. Active treatment included hydrochlorothiazide, reserpine, and hydralazine hydrochloride.
The study was terminated prematurely after only one and a half years because of clear evidence of benefit of treatment and excessive, rapid mortality in the placebo group. This landmark finding precluded any future placebo controlled trials in patients with severe hypertension.
Reference:
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202(11):
HCTZ=hydrochlorothiazide
VA Cooperative Study Group. JAMA. 1967;202:

16. Change in Systolic BP (mmHg) Change in Diastolic BP (mmHg)
The VA Cooperative Study, 1967: Change in Systolic and Diastolic Blood Pressure
Placebo
Placebo
Percent of patients
Percent of patients
Active drugs
Active drugs
The VA Cooperative Study, 1967: Change in Systolic and Diastolic Blood Pressure
Changes in blood pressure during treatment in the two study arms of the VA Cooperative Study are depicted above. Patients receiving placebo were far more likely to experience a rise in blood pressure and far less likely to have a reduction in blood pressure than those receiving active treatment. In those assigned to active therapy, blood pressure fell on average by 43/30 mmHg.
Reference:
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202(11):
-76
-60
-44
-28
-12 12 28
-76
-60
-44
-28
-12 12 28
Decrease (-)
(+) Increase
Decrease (-)
(+) Increase
Change in Systolic BP (mmHg)
Change in Diastolic BP (mmHg)
VA Cooperative Study Group. JAMA. 1967;202:
Copyright ©1967, American Medical Association.

17. The VA Cooperative Study, 1967: Assessable Morbid/Fatal Events
Placebo n=70
Active Rx* n=73
Accelerated hypertension 12
Stroke 4 1
Coronary event 2
CHF
Renal damage
Deaths
The VA Cooperative Study, 1967: Assessable Morbid/Fatal Events
During an average of 11 months of follow-up (2–16 months), far more hypertension-related events occurred in the placebo treated group than in those assigned to active therapy in the VA Cooperative Study. Most notable was the reduction in incidence of accelerated hypertension (12 vs 0).
Reference:
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202(11):
*P<0.001 active drug therapy vs placebo
VA Cooperative Study Group. JAMA. 1967;202:

18. The VA Cooperative Study, 1967: Conclusions
The actively treated group experienced a reduction in multiple hypertension-related endpoints
21 morbid/fatal events on placebo
1 morbid/fatal event on active therapy
The VA Cooperative Study, 1967: Conclusions
The VA Cooperative Study documented that treatment of severe diastolic hypertension could reduce risk for hypertension-related complications. Although the sample size was small and the follow-up was short, the risk for complications was exquisitely high and the design of the study was sufficiently rigorous to provide a definitive answer.
Reference:
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202(11):
VA Cooperative Study Group. JAMA. 1967;202:

19. The VA Cooperative Study, 1970
Cohort
380 men
Mean age
50 years
Eligibility
Diastolic BP mmHg
Design
Double blind; placebo control
Therapy
HCTZ, reserpine, hydralazine
Duration
5.5 years (mean=3.8 yrs)
BP change
Diastolic BP -19 mmHg
The VA Cooperative Study, 1970
The second VA Cooperative Study* involved longer-term follow-up of men with mild-to-moderate hypertension (diastolic blood pressure 90–114 mmHg). As anticipated, because of the lower risks associated with mild-to-moderate hypertension, the study sample was larger (n=380) and the follow-up far longer (mean 3.8 years) than in the earlier VA trial.
*this cohort and the severe hypertension cohort reported in 1967 were actually recruited simultaneously and subsequently separated.
References:
Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970; 213 (7):
Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 1967; 202(11):
VA Cooperative Study Group. JAMA. 1970;213:

20. The VA Cooperative Study, 1970: Assessable Morbid/Fatal Events
Placebo n=194
Active Rx* n=186
Accelerated hypertension 4
Stroke 20 5
Total coronary event 13 11
Fatal coronary event 6
Congestive heart failure
Renal damage 3
Deaths 19 8
The VA Cooperative Study, 1970: Assessable Morbid/Fatal Events
In the second VA Cooperative Study* of patients with mild-to-moderate hypertension, those randomized to active therapy experienced fewer morbid and fatal events than those receiving placebo. Most remarkable was the reduction in those on active therapy compared to placebo in stroke (5 vs 20 events, respectively) and congestive heart failure (0 vs 11 events, respectively).
*this cohort and the severe hypertension cohort reported in 1967 were actually recruited simultaneously and subsequently separated.
Reference:
Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970; 213 (7):
*P<0.001 active drug therapy vs placebo
VA Cooperative Study Group. JAMA. 1970;213:

21. The VA Cooperative Study, 1970: Conclusions
Active treatment reduced fatal and nonfatal endpoints
A subsequent analysis revealed that benefits were statistically significant only for those with baseline diastolic blood pressure mmHg
The VA Cooperative Study, 1970: Conclusions
In the second VA Cooperative Study* of patients with mild-to-moderate hypertension Freis and colleagues once again demonstrated the benefits of hypertension treatment. They extended the results of the first VA Cooperative Study to patients with less severe diastolic hypertension.
*this cohort and the severe hypertension cohort reported in 1967 were actually recruited simultaneously and subsequently separated.
Reference:
Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA 1970; 213 (7):
Effects of treatment on morbidity in hypertension. 3. Influence of age, diastolic pressure, and prior cardiovascular disease; further analysis of side effects. Circulation 1972; 45 (5):
VA Cooperative Study Group. Circulation. 1972; 45 (5):
VA Cooperative Study Group. JAMA. 1970;213:

22. The European Working Party on High Blood Pressure in the Elderly, 1985

23. The European Working Party on High Blood Pressure in the Elderly, 1985
Cohort
840; 30% men
Age
> 60 yrs old; mean 72 yrs old
Eligibility
Systolic BP 150239 mmHg; diastolic BP 90119 mmHg
Design
Double blind; placebo control
Therapy
HCTZ, triamterene
Duration
4.7 years
BP change
-21/10 mmHg at 5 years
The European Working Party on High Blood Pressure in the Elderly, 1985
By the mid-1980s a large body of evidence had accumulated to indicate that treatment of diastolic hypertension in middle-aged patients reduced morbidity and mortality from cardiovascular disease. There was relatively little information, however, about the impact of hypertension treatment in older patients.
The European Working Party on High Blood Pressure in the Elderly (EWPHE) enrolled 840 women and men >60 years old with combined systolic and diastolic hypertension (systolic BP 150239 mmHg; diastolic BP 90119 mmHg). The design was double blind, placebo controlled. Active therapy began with hydrochlorthiazide (HCTZ) and triamterene. The average blood pressure at baseline was 183/101 mmHg. At 5 years, there was a 21/10 mmHg difference in blood pressure between the two treatment arms.
Reference:
Amery A, Birkenhager W, Brixko P, Bulpitt C, Clement D, Deruyttere M, De Schaepdryver A, Dollery C, Fagard R, Forette F, et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet Jun 15;1(8442):
Amery A, et al. Lancet. 1985;1:

24. EWPHE Cardiovascular Mortality On-Treatment Analysis
Active (n=416)
Survival free of event (%)
Placebo (n=424)
EWPHE Cardiovascular Mortality On-Treatment Analysis
In patients in EWPHE on double blind treatment with active drug or placebo, cardiovascular mortality (-38%; P=0.023), depicted above, and cardiac mortality (-47%; P=0.048), favored the patients on active therapy. This slide shows survival free of cardiovascular death using an on-treatment analysis.
Reference:
Amery A, Birkenhager W, Brixko P, Bulpitt C, Clement D, Deruyttere M, De Schaepdryver A, Dollery C, Fagard R, Forette F, et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet Jun 15;1(8442): 1 3 6 2 4 5 7
Year of follow-up
EWPHE=European Working Party on High Blood Pressure in the Elderly
Amery A, et al. Lancet. 1985;1:
Reprinted with permission from Elsevier Science.

25. EWPHE Conclusions
Active treatment reduced cardiovascular (CV) mortality, largely due to a reduction in cardiac mortality
Older patients (>60 yrs old) with combined systolic and diastolic hypertension who received active therapy experienced 29 fewer CV events and 14 fewer CV deaths per 1,000 patient-years of treatment
EWPHE Conclusions
Active treatment in EWPHE reduced risk for fatal cardiovascular (CV) events, largely due to a reduction in cardiac events. Older patients with combined systolic and diastolic hypertension who received active therapy experienced 29 fewer CV events and 14 few CV deaths per 1,000 patient-years of treatment.
Reference:
Amery A, Birkenhager W, Brixko P, Bulpitt C, Clement D, Deruyttere M, De Schaepdryver A, Dollery C, Fagard R, Forette F, et al. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet Jun 15;1(8442):
EWPHE=European Working Party on High Blood Pressure in the Elderly
Amery A, et al. Lancet. 1985;1:

26. The Hypertension Detection and Follow-up Program, 1979

27. The Hypertension Detection and Follow-up Program, 1979
Cohort
10,940; 54% men; 44% black
Age
3069 yrs old; mean 50.8 yrs old
Eligibility
Diastolic BP  90 mmHg
Design
Stepped Care vs Referred Care
Therapy
Chlorthalidone (reserpine, methyldopa)
Duration
5 years
BP change
5 mmHg (Stepped Care vs Referred Care)
The Hypertension Detection and Follow-up Program, 1979
The Hypertension Detection and Follow-up Program (HDFP) was a study that compared a stepped-care (SC) blood pressure (BP) lowering program with referred care (RC) in over 10,000 men and women with diastolic hypertension of varying severity. The major aim of the study was to determine if more aggressive BP reduction, as compared with conventional treatment, could reduce major morbid and fatal outcomes. The study screened 158,906 people to identify and enroll the target sample. Once enrolled, patients were randomized to SC or RC treatment options.
The SC group was offered antihypertensive therapy in special centers and therapy was increased stepwise to achieve and maintain BP levels at or below the target level.* The SC therapy involved 4 steps.
Step 1. Prescription of the diuretic chlorthalidone (triamterene or spironolactone prescribed as supplementary or alternative);
Step 2. Addition of an antiadrenergic drug, preferably reserpine (methyldopa prescribed alternatively);
Step 3. Addition of the vasodilator hydralazine; and
Step 4. Addition of an antiadrenergic drug, guanethidine sulfate, with or without discontinuation of medication.
Patients in the RC group were referred to their “usual sources” for treatment.
Blood pressure remained consistently lower in the SC group, albeit on average only 5 mmHg lower. The study duration was 5 years.
*diastolic BP (DBP) <90 mmHg for those entering with DBP of 100 mmHg or already receiving antihypertensive therapy, and a 10 mmHg decrease for those entering with DBP 9099 mmHg.
Reference:
Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA 1979; 242 (23):
HDFP Cooperative Group. JAMA. 1979;242:

28. HDFP Mortality Rates Entire Cohort*
Referred Care
(n=5,456)
Cumulative mortality (%)
Stepped Care
HDFP Study Mortality Rates, Entire Cohort
In HDFP, overall, mortality was 17% lower in the SC group compared to the RC group (6.4% vs. 7.7%; P<0.01).
Reference:
Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA 1979; 242 (23):
(n=5,485) 1 2 3 4 5 6
Year of follow-up
HDFP=Hypertension Detection and Follow-up Program
HDFP Cooperative Group. JAMA. 1979;242:

29. HDFP Mortality Rates Diastolic BP 90104 mmHg*
Referred Care
Cumulative mortality (%)
(n=3,822)
Stepped Care
HDFP Study Mortality Rates, Diastolic BP 90–104 mmHg
In HDFP study participants with diastolic BP (DBP) 90104 mmHg at baseline, mortality was 20% lower with stepped care compared to referred care (5.9% vs. 7.4%; P<0.01). Within this cohort, there was a 22% reduction in mortality with DBP 90–94 mmHg, a 23% reduction with DBP 9599 mmHg, and a 14% reduction with DBP 100104 mmHg.
Reference:
Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA 1979; 242 (23):
(n=3,903) 1 2 3 4 5 6
BP=blood pressure
Year of follow-up
HDFP=Hypertension Detection and Follow-up Program
HDFP Cooperative Group. JAMA. 1979;242:

30. HDFP Conclusions
Overall, stepped care (SC) compared to referred care (RC) reduced total mortality by 17% (6.4 vs. 7.7%; P<0.01)
In patients with baseline diastolic blood pressure 90104 mmHg (n=7,725), mortality was reduced by 20% with SC vs. RC (5.9% vs. 7.4%; P<0.01)
Aggressive treatment of SC patients with the lowest baseline diastolic blood pressures (9094 and 9599 mmHg) reduced mortality
HDFP Study Conclusions
HDFP was the first study to demonstrate a reduction in mortality in response to more aggressive blood pressure treatment. Although the study was designed to mimic clinical practice, its lack of a placebo control may limit the ability to generalize the study findings.
Reference:
Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA 1979; 242 (23):
HDFP=Hypertension Detection and Follow-up Program
HDFP Cooperative Group. JAMA. 1979;242:

31. The Systolic Hypertension in the Elderly Program, 1991

32. The Systolic Hypertension in the Elderly Program, 1991
Cohort
4,736; 43% men
Age
 60 yrs old; mean 71.6 yrs old
Eligibility
Systolic BP 160219 mmHg and Diastolic BP <90 mmHg
Design
Double blind; placebo control
Therapy
Chlorthalidone (atenolol as step 2)
Duration
4.5 years
BP change
Systolic BP –12 mmHg
The Systolic Hypertension in the Elderly Program, 1991
The Systolic Hypertension in the Elderly Program (SHEP) was a clinical trial launched at a time when it was not know if treating older patients with isolated systolic hypertension (ISH) would be beneficial, harmful, or make no difference.
The study cohort consisted of nearly 5,000 men and women 60 years old with stage 2 or higher ISH. The design was randomized, double blind, placebo controlled. Active therapy began with the diuretic chlorthalidone; other drugs (or their placebo controls) could be added later as dictated by the blood pressure response to treatment.
Reference:
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24):
BP=blood pressure
SHEP Research Group. JAMA. 1991;265:

33. SHEP Change in Blood Pressure
Systolic BP
Diastolic BP
Placebo (n=2,371)
Placebo (n=2,371)
Change in BP (mmHg)
Active Rx (n=2,365)
SHEP Change in Blood Pressure
In the SHEP cohort, the mean blood pressure (BP) was 170/76 mmHg in both treatment arms at baseline. The systolic and diastolic BPs during follow-up are shown on this slide. For the actively treated group, the 5-year average systolic BP was 143 mmHg and the 5-year average diastolic BP was 68 mmHg. Blood pressure also declined in the placebo group, largely due to "drop in," which refers to patients who were assigned to placebo but were started on open label active therapy by their personal physicians. In the placebo group, the 5-year average systolic and diastolic BPs were 155 mmHg and 72 mmHg, respectively.
Reference:
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24):
Active Rx (n=2,365) 1 2 3 4 5 1 2 3 4 5
Years
Years
SHEP=Systolic Hypertension in the Elderly Program
BP=blood pressure
SHEP Research Group. JAMA. 1991;265:
Copyright ©1991, American Medical Association.

34. SHEP Average Blood Pressure During Follow-up
Blood pressure (mmHg)
SHEP Average Blood Pressure During Follow-up
Throughout the SHEP trial, the mean systolic BP in the active treatment group was substantially lower than at baseline, dropping almost 26 mmHg soon after the initiation of therapy.
Reference:
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24): 12 24 36 48 60
Months of follow-up
SHEP=Systolic Hypertension in the Elderly Program
SHEP Research Group. JAMA. 1991;265:
Copyright ©1991, American Medical Association.

35. SHEP Cumulative Stroke Rate
Placebo
(n=2,371)
Cumulative stroke rate
per 100 persons
Active Rx
(n=2,365)
SHEP Cumulative Stroke Rate
The SHEP primary endpoint was nonfatal or fatal stroke. The cumulative incidence of the primary endpoint is shown here for the two treatment arms. There was a gradual separation of the 2 groups in favor of active therapy. Overall, stroke risk was reduced by 36% in those assigned to active therapy (P=0.0003). The 5-year incidence of total stroke was 5.2 and 8.2 per 100 participants in the active treatment and placebo groups, respectively. The absolute benefit of treatment estimated at 5 years was 30 events per 1,000 participants.
Reference:
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24): 12 24 36 48 60 72
Months of follow-up
SHEP=Systolic Hypertension in the Elderly Program
SHEP Research Group. JAMA. 1991;265:
Copyright ©1991, American Medical Association.

36. SHEP Cardiovascular Disease Endpoints
Active Therapy vs. Placebo
Relative risk (95% CI)
0.87
0.63
0.68
0.75
0.46
SHEP Study Cardiovascular Disease Endpoints
In SHEP, not only was stroke risk reduced in those receiving active therapy, but risk for coronary heart disease (-25%), congestive heart failure (-54%), and cardiovascular disease (-32%) also were reduced. While the trend was in a favorable direction for deaths from any cause, the results for this endpoint were not statistically significant.
Reference:
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24):
Stroke
CHD
CHF
CVD
Death
CHD=coronary heart disease; CHF=congestive heart failure; CVD=cardiovascular disease
SHEP=Systolic Hypertension in the Elderly Program
SHEP Research Group. JAMA. 1991;265:

37. SHEP Conclusions
SHEP was the first clinical trial to demonstrate that reduction of blood pressure in patients with isolated systolic hypertension reduced cardiovascular (CV) mortality
The relative risk of stroke was reduced by 36% with therapy compared to placebo (P=0.0003)
The 5-year absolute benefits were a reduction in 30 strokes and 55 major CV disease events per 1,000 persons
SHEP Conclusions
In SHEP, older men and women with isolated systolic hypertension who received active treatment experienced fewer strokes and major cardiovascular disease events than those receiving placebo.
Reference:
Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991; 265 (24):
SHEP=Systolic Hypertension in the Elderly Program
SHEP Research Group. JAMA. 1991;265:

38. The Systolic Hypertension in Europe (Syst-Eur) Trial, 1997
The Systolic Hypertension in Europe Trial, 1997

39. The Systolic Hypertension in Europe Trial, 1997
Cohort
4,695; 67% women
Age
 60 yrs old
Eligibility
Systolic BP 160–219 mmHg and diastolic BP <95 mmHg
Design
Double blind; placebo control
Therapy
Nitrendipine (enalapril, HCTZ as Step 2)
Duration
Median 2 yrs (1-97 months)
BP difference
-10/5 mmHg
The Systolic Hypertension in Europe Trial, 1997
While the Systolic Hypertension in the Elderly Program (SHEP) had previously shown that treatment of isolated systolic hypertension (ISH) was beneficial, a study with a similar design was undertaken in Europe. The Systolic Hypertension in Europe (Syst-Eur) Trial enrolled nearly 5,000 older women and men with stage 2 or greater systolic hypertension and diastolic blood pressure (BP) <95. (SHEP used the more conventional definition of ISH, which required a diastolic BP <90 mmHg.) Like SHEP, Syst-Eur was randomized, double blinded, and placebo controlled. Unlike SHEP, a long-acting dihydropyridine calcium antagonist was used as initial therapy (and other drugs could be added as part of step 2 drug titration).
Reference:
Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O'Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997;350(9080):
Staessen JA, et al. Lancet. 1997;350:

40. Syst-Eur Mean Sitting Systolic Blood Pressure
Placebo (n=2,297)
Active treatment (n=2,398)
Systolic BP (mmHg)
P<0.001
Syst-Eur Mean Sitting Systolic Blood Pressure
In Syst-Eur, the mean sitting blood pressure at baseline was 174/86 mmHg for both the placebo and active treatment groups. For patients on active therapy, systolic blood pressures (BP) declined to values close to 150 mmHg. At median follow-up, 21.4% of patients in the placebo group and 43.5% in the active treatment group had reached the target for sitting systolic BP of <150 mmHg (P<0.001).
Reference:
Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O'Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997;350(9080): 1 2 3 4
Years since randomization
Syst-Eur=Systolic Hypertension in Europe Trial
Staessen JA, et al. Lancet. 1997;350:
Reprinted with permission from Elsevier Science.

41. Syst-Eur Mean Sitting Diastolic Blood Pressure
Diastolic BP (mmHg)
Placebo (n=2,297)
Syst-Eur Change Mean Sitting Diastolic Blood Pressure
At 2 years, sitting diastolic BP had fallen by a mean of 7 mmHg in the active therapy group and by 2 mmHg in the placebo goup in Syst-Eur. For patients on active therapy, diastolic BP declined to just under 80 mmHg.
Reference:
Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O'Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997;350(9080):
Active treatment (n=2,398) 1 2 3 4
Years since randomization
Syst-Eur=Systolic Hypertension in Europe Trial
Staessen JA, et al. Lancet. 1997;350:
Reprinted with permission from Elsevier Science.

42. Syst-Eur Primary Endpoint Fatal and Nonfatal Stroke
Placebo (n=2,297)
P=0.003
Active treatment (n=2,398)
Events per 100 patients
Syst-Eur Primary Endpoint Fatal and Nonfatal Stroke
The Syst-Eur primary endpoint was fatal and non-fatal stroke combined. Stroke occurred in 77 patients on placebo and 47 on active therapy. At the recommendation of the data safety and monitoring board the study was terminated prematurely because of a 42% reduction in stroke risk on active therapy.
Reference:
Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O'Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997;350(9080): 1 3 4 2
Years since randomization
Syst-Eur=Systolic Hypertension in Europe Trial
Staessen JA, et al. Lancet. 1997;350:
Reprinted with permission from Elsevier Science.

43. Syst-Eur Cardiovascular Disease Endpoints
Active therapy vs. placebo
14%
risk reduction (95% CI)
Percentage relative
30%
29%
31%
P<0.001
42%
P=0.003
Syst-Eur Cardiovascular Disease Endpoints
In addition to the sizable and significant reduction in stroke risk in Syst-Eur, declines of about 1/3 in cardiac endpoints (P=0.03), heart failure (P=NS), and myocardial infarction (P=NS) were observed in the active treatment group.
Reference:
Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O'Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997;350(9080):
Stroke MI
CHF
All CVD
Death
MI=myocardial infarction; CHF=congestive heart failure; CVD=cardiovascular disease
Syst-Eur=Systolic Hypertension in Europe Trial
Staessen JA, et al. Lancet. 1997;350:

44. Syst-Eur Conclusions
Older men and women with isolated systolic hypertension who received active treatment with a dihydropyridine calcium channel blocker experienced fewer strokes and cardiovascular disease (CVD) events than those receiving placebo.
Treatment of 1,000 patients for 5 years with this type of regimen could prevent 29 strokes or 53 major CVD endpoints.
Syst-Eur Conclusions
The conclusions of the Syst-Eur Trial were remarkably similar to those of SHEP. Older men and women primarily with isolated systolic hypertension who received active treatment experienced fewer strokes and cardiovascular disease (CVD) events than those receiving placebo. According to the findings in Syst-Eur, treatment of 1,000 patients for 5 years with this type of regimen could prevent 29 strokes or 53 major CVD endpoints.
Reference:
Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O'Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997;350(9080):
Syst-Eur=Systolic Hypertension in Europe Trial
Staessen JA, et al. Lancet. 1997;350:

45. The Australian National Blood Pressure (ANBP) Study, 1980

46. The Australian National Blood Pressure Study, 1980
Cohort
3,427; 80% men
Age
30–69 yrs old
Eligibility
Diastolic BP 95–109 mmHg
Design
Single blind; placebo control
Therapy
Chlorothiazide (methyldopa, beta blocker)
Duration
4 yrs
BP difference
-6 mmHg
The Australian National Blood Pressure Study, 1980
The Australian National Blood Pressure (ANBP) Study was a placebo controlled trial in patients 30–69 years old with diastolic blood pressure (BP) 95–109 mmHg. A total of 104,171 patients were screened, of whom 3,427 (3%) were eligible and enrolled. Active therapy began with chlorothiazide (500 mg daily) and methyldopa, propranolol, or pindolol could be added to achieve the diastolic BP goal of <90 mmHg (later reduced to <80 mmHg). Mean follow up was 4 years and the average difference in diastolic BP between the two groups was 6 mmHg.
Reference:
The Australian therapeutic trial in mild hypertension. Report by the Management Committee. Lancet 1980; 1 (8181):
The Australian Study Committee. Lancet. 1980;1:

47. The Australian Study Mean Diastolic Blood Pressure
pressure (mmHg)
The Australian Study Mean Diastolic Blood Pressure
In the ANBP study, mean screening seated diastolic blood pressure (BP) was ~100 mmHg in both the placebo and active treatment groups. During follow-up, however, mean diastolic BP was reduced to 93.5 mmHg for the placebo group and 88.3 for the active treatment group. Mean fall in diastolic BP was 12.2 for active treatment and 6.6 for placebo.
Reference:
The Australian therapeutic trial in mild hypertension. Report by the Management Committee. Lancet 1980; 1 (8181):
The Australian Study Committee. Lancet. 1980;1:

48. The Australian Study Incidence of Trial Endpoints (TEP)*
Intention-to-treat
Placebo (n=1,706)
Active (n=1,721)
No.
Rate
Total Fatal TEP 35
5.1 25
3.6
Cardiovascular 18
2.6 8
1.1‡
Non-cardiovascular 17
2.5
2.4
Non-fatal TEP
133
19.4
113
16.2
All TEP
168
24.5
138
19.7†
The Australian Study Incidence of Trial Endpoints
Both fatal and non-fatal trial endpoints (TEP) accumulated more quickly in the placebo group than in those assigned to active therapy in ANBP. Deaths and non-fatal events combined differed between the two groups (intention-to-treat analysis rates of 24.5 vs 19.7 per 1,000 patient years; P<0.05).
Reference:
The Australian therapeutic trial in mild hypertension. Report by the Management Committee. Lancet 1980; 1 (8181):
*Rates per 1,000 person-years exposure to risk.
†P< ‡P<0.025
The Australian Study Committee. Lancet. 1980;1:

49. The Australian Study Intention-to-Treat Trial Endpoints
No. of events
Placebo
n=1,706
Active
n=1,721
Ischemic heart disease
Fatal 11 5
Nonfatal myocardial infarction 22 28
Nonfatal other 76 65
Cerebrovascular events 6 3
Nonfatal
Hemorrhage or thrombosis 16 10
Transient cerebral ischemic attacks 9 4
Other fatal 18 17
Other nonfatal
The Australian Study Intention-to-Treat Trial Endpoints
Over 2/3 of ANBP trial endpoints were due to ischemic heart disease. There were about half the number of total cerebrovascular events in the active compared to the placebo group. The difference was significant for all cerebrovascular events (P<0.025) and for all non-fatal cerebrovascular events (P<0.05).
Reference:
The Australian therapeutic trial in mild hypertension. Report by the Management Committee. Lancet 1980; 1 (8181):
The Australian Study Committee. Lancet. 1980;1:

50. The Australian Study On-Treatment Trial Endpoints (TEP)
All TEP
P<0.01
Active (n=1,721)
Placebo (n=1,706)
Number of trial endpoints
All Fatal TEP
P<0.05
The Australian Study On-Treatment Trial Endpoints
The ANBP study on-treatment analysis results were statistically significant for all fatal trial endpoints (all fatal TEP) and for a pooled endpoint of non-fatal cardiovascular events plus deaths from any cause (all TEP). The differences were such that by on-treatment analysis there were 7 fewer TEPs, including 2 fewer deaths, per 1,000 person-years in the active group.
Reference:
The Australian therapeutic trial in mild hypertension. Report by the Management Committee. Lancet 1980; 1 (8181):
400
600
1200
1600
2000
Days in trial
The Australian Study Committee. Lancet. 1980;1:
Reprinted with permission from Elsevier Science.

51. The Australian Study Conclusions
The actively treated compared to placebo group experienced 30 fewer trial endpoints endpoints (P<0.05)
There was a significant reduction in mortality in the actively treated group, mostly due to a reduction in death from cardiovascular disease (P<0.025)
The Australian Study Conclusions
In the ANBP study, the actively treated compared to placebo group experienced fewer deaths and non-fatal events (intention-to-treat analysis rates of 24.5 vs 19.7 per 1,000 patient years; P<0.05).
Reference:
The Australian therapeutic trial in mild hypertension. Report by the Management Committee. Lancet 1980; 1 (8181):
The Australian Study Committee. Lancet. 1980;1: