Impact of Blood Pressure The Importance of Achieving and Maintaining Target Goals

MBBS(Malaya); MRCP(UK); AdvMCard(UKM); CCMR(Germany); AM; FNHAM; FAsCC;FACC Consultant Cardiologist Serdang Hospital.

Dr Annuar Rapaee

PMPL000701MYSG201004

Lecture Outline:
Burden

of Hypertension What guidelines tell us ? Choosing the ideal blood pressure Impact of blood pressure treatment

Burden of Hypertension in Malaysia

PMPL000501MYSG201004

Prevalence of Hypertension in Malaysia

The prevalence of hypertension in Malaysians aged 30 years and above was 42.6% in 2006 Hypertension is a silent disease; 4.8 million individuals with hypertension in Malaysia, the majority of cases (64%) in the country remain undiagnosed.

Prevalence of Hypertension by Age and Gender

20 29

30 39

40 49

50 59

60 69

70

Age

Cardiovascular Disease Leading Cause of Global Mortality

Maternal and perinatal conditions Nutritional deficiencies Infectious and parasitic diseases Cancer Other non-infectious diseases Injuries Respiratory diseases

Respiratory infections

CV diseases

WHO World Health Report 2004

Global Mortality : Risk Factors

High blood pressure Tobacco High cholesterol Underweight Unsafe sex High BMI Physical inactivity Alcohol Indoor smoke from solid fuels Iron deficiency
0 1000 2000

High mortality, developing region Lower mortality, developing region Developed region
3000 4000 5000 6000 7000 8000

Attributable Mortality x 1000

Ezzati et al. Lancet. 2002;360:1347-1360

Cardiovascular Disease : Admission Government Hospital 1985 - 2000

Hypertensive Disease Ischaemic Heart Disease

Data from MOH,

Cerebrovascular Disease
Disease of Arteries, Veins, Lymphatic Vessels & Unspecified Disorders of the Circulatory System Rheumatic Fever & Rheumatic Heart Disease

Disease of Pulmonary Circulation & other Forms of Heart Disease

Cardiovascular Disease : Deaths Government Hospital 1985 - 2000

7812 7249 6574 6058 6205 5959 6221 6336 6475 6535 6352 6715 7496 7071 7307 7559

Data from MOH

The Cardiovascular Continuum

Remodelling MI Atherosclerosis & LVH

Ventricular Dilation CHF End-stage microvascular & heart disease

Risk eg Hypertension

Death

Adapted from Dzau et al.

Hypertension : Increased CV Risk

Coronary Disease
Biennial Age-Adjusted Rate per 1000

Stroke

Peripheral Artery Disease

Cardiac Failure

2 times

3 - 4 times

3 - 4 times

Framingham Heart Study

Kannel et al JAMA 1996

Risk of CV Events Increases with Diastolic BP Framingham study 38-year follow-up

Age-adjusted annual rate 50 Events in women Rate/1000 women 40 30 20 10 0 Percent of events 50 40 30 20 10 0

Events in men Rate/1000 men

20-74

75-84

85-94 DBP, mm Hg

95-104

105-160

Kannel. Am J Cardiol 2000

Risk of CV Events Increases with Systolic BP Framingham study 38-year follow-up

Age-adjusted annual rate 50 Events in women Rate/1000 women 40 30 20 10 0 Percent of events 50 40 30 20 10 0

Events in men Rate/1000 men

74-119

120-139

140-159 SBP, mm Hg

160-179

180-300

Kannel. Am J Cardiol 2000

Risks of Stroke and Coronary Heart Disease Increases with Diastolic BP

7 prospective observational studies Relative risk of stroke 4.00 2.00 1.00 0.50 0.25 76 84 91 98 105

Stroke

9 prospective observational studies Relative risk of CHD 4.00 2.00 1.00 0.50 0.25 76 84 91 98 105

CHD

Approximate mean DBP, mm Hg

MacMahon et al. Lancet 1990

CV risk Doubles with Each BP Rise of 20/10 mmHg

* Individuals aged 40-70 yrs, starting at BP 115/75

Lewington et al Lancet 2003

CV mortality risk 8 7 6 5 4 3 2 1 0 115/75

Coronary Artery Disease (CAD) is the Most Common Cause of Morbidity and Mortality in Patients with Hypertension

135/85

155/95

175/105

Blood pressure (mm Hg) * Individuals aged 40-70 years, starting at BP 115/75 mm Hg
Lewington et al. Lancet 2003 JNC VII. JAMA 2003

Hypertension Poorly Controlled Worldwide Percentage of Patients with Controlled BP (<140/90 mm Hg)

Belgium 25%

Canada 16%

China 3%

England 6%

France 33%

Italy 9%

Poland 4%

Russia 6%

Spain 16%

USA 24%

Erdine. European Society of Hypertension Scientific Newsletter 2000

Blood Pressure Control in Malaysia

Proportion of patients (%)

NHMS;1996 by MOH 21,000 subjects > 30yr - 33% HPT, only 23% on Rx and only 6% < 140/90 mmHg Manjung Hosp,Perak Hypertension Survey 2003 397 subjects, 98% > 30yr 22.9% HPT, 45% on Rx, 55% not aware and only 22.6% < 140/90 mmHg GHKL Physician clinic 2005 N=222 patients, 22.1% one drug,33.3% 2 drugs,34.2% 3 drugs, 8.1% 4 drugs. 10.8% BP<140/90mmHg and 89.2% >140/90mmHg.

The Rule of Halves *****

Only 1/2 have been diagnosed Only 1/2 of those diagnosed have been treated Only 1/2 of those treated are adequately controlled Thus, only 12.5% overall are adequately controlled

1999

Impact of Hypertension

HOT

Untreated or sub-optimally controlled hypertension leads to

increased cardiovascular, cerebrovascular and renal morbidity and mortality In persons older than 50 years, SBP > 140 mmHg is a much more important CVD risk factor than DBP Risk of CVD beginning at 115/75 mmHg doubles with each increment of 20/10 mmHg Individuals who are normotensive at age 55 have a 90% lifetime risk of developing hypertension

Clinical Practice Guidelines Management off Hypertension (3rd Edition Feb 2008) The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (August 2004)

Lecture Outline:
Burden

of Hypertension What guidelines tell us ? Choosing the ideal blood pressure Impact of blood pressure treatment

Blood Pressure has Multiple Regulatory Pathways

Patient 1 Patient 2 Patient 3

Sympathetic nervous system Renin-angiotensin system Total body sodium

B. Waeber, March 2007, with permission

Questions to be Answered
What is high blood pressure? Clinical evaluation - what should be done? Which factors influence prognosis? Do patients benefit from antihypertensive treatment?

CPG Management of Hypertension

CPG Management of Hypertension

Clinical Practice Guidelines Management off Hypertension (3rd Edition Feb 2008)

CPG Management of Hypertension

CPG Management of Hypertension

Clinical Practice Guidelines Management off Hypertension (3rd Edition Feb 2008)

JNC 7

JNC 7

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (August 2004)

JNC 7

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (August 2004)

UK NICE Guidelines for treatment of Hypertension June 2007

The update of the NICE guideline on hypertension in primary care was undertaken because recent large clinical outcome trials had provided new information about the pharmacological treatment of hypertension.

National Institute of Health and Clinical Excellence (NICE) NICE Clinical Guidelines (Published August 2004)

UK NICE Guidelines for treatment of Hypertension June 2007

According to the new NICE guidelines for treatment of hypertension of June 2006, calcium channel blockers or thiazide-type diuretics are now recommended for initial treatment in patients over 55 years of age and in black patients of all ages.

ACE-inhibitors or Angiotensin-II Receptor Antagonists (if ACE-inhibitors are not tolerated) are recommended for younger patients.
National Institute of Health and Clinical Excellence (NICE) NICE Clinical Guidelines (Published August 2004)

UK NICE Guidelines for treatment of Hypertension June 2007

Beta-blockers are no longer considered a preferred routine initial therapy in the general population, but are still to be considered as initial therapy in younger patients, e.g. those with increased sympathetic drive and those with intolerance or contraindications to ACE-inhibitors and angiotensin-II antagonists.

National Institute of Health and Clinical Excellence (NICE) NICE Clinical Guidelines (Published August 2004)

UK NICE Guidelines for treatment of Hypertension June 2007

National Institute of Health and Clinical Excellence (NICE) NICE Clinical Guidelines (Published August 2004)

New (1999) WHO-ISH Definitions and Classification of BP Levels

Category Optimal BP Normal BP High-Normal Grade 1 Hypertension (mild) Subgroup: Borderline Grade 2 Hypertension (moderate) Grade 3 Hypertension (severe) Isolated Systolic Hypertension Subgroup: Borderline Systolic BP (mm Hg) <120 <130 130-139 140-159 140-149 160-179 >180 >140 140-149 Diastolic BP (mm Hg) <80 <85 85-89 90-99 90-94 100-109 >110 <90 <90

1999 WHO-ISH Hypertension Practice Guidelines for Primary Care Physicians

Clinical Evaluation - What Should Be Done?

Exclude secondary causes of hypertension To ascertain the presence or absence of target organ damage
disorders that affect risk factors, prognosis and guide treatment

To assess lifestyle and identify other cardiovascular risk factors or concomitant

Such information is obtained from adequate history, physical examination, laboratory investigations and other diagnostic procedures

Clinical Practice Guidelines Management off Hypertension (3rd Edition Feb 2008)

Clinical Evaluation - What Should Be Done?

Risk factors of CVD I. Used for risk stratification II.Other factors adversely influencing prognosis Target organ damage (TOD) Associated clinical conditions (ACC)
1999 WHO-ISH Hypertension Practice Guidelines for Primary Care Physicians

Which Factors Influence Prognosis?

Decisions should not be made on BP alone, but also on presence of other risk factors, target organ damage, and concomitant diseases, as well as on other aspects of patients personal, medical, social, economic, ethnic, and cultural characteristics

1999 WHO-ISH Hypertension Practice Guidelines for Primary Care Physicians

More Than 80% of Patients with Hypertension Have Additional Risk Factors
Hypertensive patients (%)
40 30 20 10
2 40 32

14

12

None

Additional risk factors

Mancia et al. J Hypertens 2004;22:51 7 Copyright 2004, with permission from Lippincott, Williams and Wilkins

Which Factors Influence Prognosis?

Risk Factors for CVD
Major Risk Factors
Hypertension Cigarette Smoking Central Obesity Physical Inactivity Dyslipidaemia Diabetes Mellitus Microalbuminurea Estimated GFR < 60 mL/min) Age (>55 years for men, >65 years for women) Family History of Premature Cardiovascular Disease (<55 years for men, <65 years for women)

Clinical Practice Guidelines Management off Hypertension (3rd Edition Feb 2008)

Which Factors Influence Prognosis?

Risk Factors for CVD
Target Organ Damage
Heart Left Ventricular Hypertrophy Angina or Prior Myocardial Infarction Prior Coronary Revascularization Brain Stroke or Transient Ischaemic Attack Chronic Kidney Disease Peripheral Arterial Disease Retinopathy

Clinical Practice Guidelines Management off Hypertension (3rd Edition Feb 2008)

Which Factors Influence Prognosis?

Associated Clinical Conditions (ACC)
Cerebrovascular Disease Ischaemic Stroke Cerebral Haemorrhage Transient Ischaemic Attack (TIA) Heart Disease Myocardial Infarction Angina Pectoris Coronary Revascularization Congestive Heart Failure

1999 WHO-ISH Hypertension Practice Guidelines for Primary Care Physicians

Which Factors Influence Prognosis?

Associated Clinical Conditions (ACC)
Renal Disease Diabetic nephropathy Renal Failure, Plasma Creatinine Concentration > 177 mmol/L (>2.0 mg/dL) Vascular Disease Dissecting Aneurysm Symptomatic Arterial Disease Advanced Hypertensive Retinopathy Haemorrhages or Exudates Papillpedema

1999 WHO-ISH Hypertension Practice Guidelines for Primary Care Physicians

Stratifying Risk Quantifying Prognosis

Clinical Practice Guidelines Management off Hypertension (3rd Edition Feb 2008)

Which Factors Influence Prognosis?

Typical 10 year risk of stroke or myocardial infarction

Low risk Medium risk High risk Very high risk = = = = <15 percent 15-20 percent 20-30 percent 30 percent or higher

1999 WHO-ISH Hypertension Practice Guidelines for Primary Care Physicians

Which Factors Influence Prognosis?

Example 1:
65-year old man with diabetes, TIAs, and BP of 145/90 mm Hg will have annual risk of major CVD event 20 times greater than 40-year old man with same BP but without diabetes or history of CVD

Which Factors Influence Prognosis?

Example 2:
40-year old man with BP of 170/105 mm Hg will have risk of major CV event 2-3 times greater than man of same age with BP of 145/90 mm Hg and similar other risk factors

Lecture Outline:
Burden

of Hypertension What guidelines tell us ? Choosing the ideal blood pressure Impact of blood pressure treatment

HOT
The relationship between BP and risk of CVD events is continuous, consistent and independent of other risk factors. The higher the BP, the greater is the chance of heart attack, heart failure, stroke and kidney disease

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (August 2004)

HOT

What physicians do in regards to cardiovascular diseases is important

S Julius 1998

HOT
Treatment adaptation of hypertensive patients not on target Dose increase Addition Switch

Unchanged repeat

84%

Based on 7 246 treated hypertensive patients whose diastolic blood pressure was not on target in France, Germany, Italy, Spain and UK

S Julius 1998

Copyright 1992 CardioMonitor , Taylor Nelson Healthcare

Benefits of Lowering Blood Pressure

HOT

Antihypertensive therapy reduces the incidence of

Stroke by 35 40% Myocardial Infarction by 20 25% Heart Failure by >50%

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (August 2004)

Benefits of Lowering Blood Pressure

Antihypertensive therapy In patients with Stage 1 hypertension and additional CV risk factors, achieving 12mmHg reduction in SBP over 10 years Prevents 1 death for 11 patients treated In presence of CVD or target organ damage

HOT

Only 9 patients would require BP reduction to prevent 1 death

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (August 2004)

Goals of Therapy
JNC 7

HOT

The ultimate public health goal of Antihypertensive therapy is the reduction of cardiovascular and renal morbidity and mortality

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (August 2004)

Intensive BP Control Reduces CV Risk

Stroke Coronary Heart Disease Heart Failure Major CV Events CV Death Total Mortality
More Intensive BP Control Better

HOT

Less Intensive BP Control Better

0.5 Relative Risk (95% CIs)

BPLTTC Lancet 2003

1.0

1.25

HOT

Hypertension Optimal Treatment

A Landmark Study A 3.8-Year International Study Of 18,790 Patients Malaysia was one of the investigation centres
HOT Study, Hansson & Zanchetti, 1998)

Primary Analysis of the HOT Study

HOT

to assess the relationship between major cardiovascular

events and three target diastolic blood pressures (< 90, < 85 and < 80 mm Hg) during antihypertensive therapy

to assess the relationship between major cardiovascular

events and the diastolic blood pressure achieved during antihypertensive therapy antihypertensive therapy reduces cardiovascular events

to assess if low dose acetylsalicylic acid in addition to

HOT Study, Hansson & Zanchetti, 1998)

Randomization to Target
Randomisation to target blood pressure and ASA in the HOT Study ASA 90 mm Hg placebo ASA 85 mm Hg placebo ASA 80 mm Hg placebo

HOT

HOT Study, Hansson & Zanchetti, 1998)

Protocol of Antihypertensive Treatment

HOT

Step 1 5 mg felodipine Step 2 5 mg felodipine

+ low dose ACE inhibitor or -blocker + low dose ACE inhibitor or -blocker + high dose ACE inhibitor or -blocker + high dose ACE inhibitor or -blocker + low dose alternative addition or HCT

Step 3 10 mg felodipine Step 4 10 mg felodipine Step 5 10 mg felodipine

HOT Study, Hansson & Zanchetti, 1998)

Patients
Patient characteristics at randomisation, mean (SD)
90

HOT
DBP target group (mm Hg) 85 80 n=6264 n=6264 n=6262 53/47 53/47 53/47 61.5 (7.5) 61.5 (7.5) 61.5 (7.5) 28.4 (4.7) 28.5 (4.7) 28.4 (4.6) 105 (3.4) 105 (3.4) 105 (3.4) 89 (26) 89 (23) 89 (23) 1.0 (0.3) 1.0 (0.3) 1.0 (0.3) 6.0 (1.1) 6.1 (1.1) 6.1 (1.2) 233 (44) 235 (44) 234 (44) 12.8 (1.1) 12.7 (1.1) 12.7 (1.1)

Men/Women (%) Age (years) BMI (kg/m2) DBP (mm Hg) S-creatinine ( mol/l) (mg/100 ml) S-cholesterol (mmol/l) (mg/100 ml) Risk score*
* based on the WHO Monica project HOT Study, Hansson & Zanchetti, 1998)

Patients
Number of patient years in the HOT Study
Total Target 80 mm Hg Target 85 mm Hg Target 90 mm Hg ASA Placebo Lost patients 71 051 23 627 23 724 23 700 35 584 35 466 1 269 years years years years years years years

HOT

HOT Study, Hansson & Zanchetti, 1998)

DBP in HOT
Diastolic blood pressure in the HOT Study (% patients reaching target)
DBP (mm Hg) 105 100 95 90 85 80 0 0
HOT Study, Hansson & Zanchetti, 1998)

HOT

Target < 80 mm Hg Target < 85 mm Hg Target < 90 mm Hg

74 74 % % 60 60 % % 43 43 % %

80 80 % % 67% 67% 52% 52%

83% 83% 71% 71% 56% 56%

85% 85% 75% 75% 57% 57%

86 86 % % 75 75 % % 57 57 % %

86% 86% 73% 73% 55% 55%

12

24

36

Follow-up Final (months)

SBP in HOT
Systolic blood pressure in the HOT Study
SBP (mm Hg) 170 165 160 155 150 145 140 135 0 0 3 6 12 24 36

HOT

Target < 80 mm Hg Target < 85 mm Hg Target < 90 mm Hg

Follow-up Final (months)

HOT
Number of patients on Felodipine, ACE inhibitors, Beta-blockers and Diuretics (%)

3m Felodipine 96 ACE inhibitor 30 Beta-blocker 19 Diuretics 6

6m 91 36 23 10

12 m 24 m 36 m Final 88 38 25 14 85 40 27 18 82 41 28 20 78 41 28 22

HOT Study, Hansson & Zanchetti, 1998)

Side Effects
Patients reporting side effects (%) < 90 mm Hg Oedema peripheral Coughing Headache Flushing Dizziness Fatigue Impotence Dyspepsia Abdominal pain Hypotension
HOT Study, Hansson & Zanchetti, 1998)

HOT

< 85 mm Hg 13.9 4.7 4.1 3.2 2.8 1.7 1.3 1.6 1.2 1.0

< 80 mm Hg 14.4 5.1 4.7 3.2 3.3 2.4 1.5 1.5 1.1 1.2

13.9 3.8 4.4 3.1 2.2 1.7 1.4 1.5 1.3 0.7

Major CV Events
Estimated incidence of major CV events (95 % CI) in relation to achieved diastolic BP
Major CV events/1000 patient years
20 Minimum = 82.6 mm Hg 15

HOT

10

70

75

80

85

90

95

100

HOT Study, Hansson & Zanchetti, 1998)

105 mm Hg Mean DBP

Major CV Events
Risk of a major cardiovascular event reduced by 30% in the HOT Study
105 100 95 90 85 Achieved DBP 80 mm Hg

HOT

0 5 10 15 20 25

Optimal DBP reduction in the HOT Study

30 % risk reduction
HOT Study, Hansson & Zanchetti, 1998)

Major CV Events
Incidence of major CV events (95 % CI) in relation to achieved systolic BP
Major CV events/1000 patient years
20 Minimum = 138.5 mm Hg 15

HOT

10

0 120

130

140

150

160

170

180

HOT Study, Hansson & Zanchetti, 1998)

190 mm Hg Mean SBP

Major CV Events
Risk of a major cardiovascular event reduced by 22% in the HOT Study
170 160 150 140 130 Achieved SBP mm Hg

HOT

0 5 10 15 20 25

Optimal SBP reduction in the HOT Study

30 % risk reduction
HOT Study, Hansson & Zanchetti, 1998)

Major CV Events
All stroke in patients with IHD at randomisation in relation to target blood pressure groups
All stroke/1000 patient years 10 8 6 4 2 0 90
HOT Study, Hansson & Zanchetti, 1998)

HOT

p=0.046 for trend

85

80 Target DBP mm Hg

Conclusion

HOT

The blood pressure of treated patients is far from being

normotensive pressure

Every effort should be made at achieving target blood The effective lowering of blood pressure in the HOT Study
was associated with a low rate of major CV events

Conclusion

HOT

The greatest reduction in major CV events was achieved by

lowering DBP to an optimal level of 83 mm Hg

The greatest reduction of major CV events was achieved by

lowering SBP to an optimal level of 139 mm Hg

Further reduction below this level was safe In patients with IHD a J-shaped relationship was not found
between the target blood pressure groups and major CV events

The Felodipine Event Reduction (FEVER) Study:

A randomized long-term placebo-controlled trial in Chinese hypertensive patients

Journal of Hypertension 2005, 23:21572172

Objective
Compare the incidence of stroke & other CV events in
hypertensive patients receiving a low-dose diuretic and calcium antagonist combination with those receiving lowdose diuretic monotherapy

Assess the effects of a small BP difference at achieved

levels lower than those achieved in previous placebocontrolled trials.

FEVER Study Design

Investigator designed, prospective, multicentre, double blind, randomized, place
controlled, parallel-group trial Endpoint Driven 9800 Chinese patients were enrolled Hypertensive patients With at least one event* or one risk factor+ Followed up at 3 months intervals for an average of 40 months

*myocardial infarction or stroke beyond the previous 6 months; stable angina or clinical evidence of coronary heart disease, congestive heart failure NYHA class II; peripheral arterial disease; transient ischaemic attack +male sex;current smoking of more than one cigarette per day during at least 1 year; total serum cholesterol 5.7 mmol/l, 220 mg/dl, within the previous year or lipid-lowering treatment; diabetes mellitus; left ventricular hypertrophy by Sokolow and Lyon electrocardiographic voltage criteria; proteinuria dip stick or higher; body mass index > 27 kg/m2

Treatment Flow Chart

Study Endpoints
Primary Endpoint
Time to first stroke

Prespecified Secondary Endpoints

All cardiovascular events All cardiac events Death from any cause

Recruitment

Baseline Patient Characteristics

Difference in Blood Pressure

Reduction of 4.2/2.1 mmHg in the felodipine group

Primary Outcome 27% RR in All Strokes

Lower incidences of CV events among felodipine patients

Secondary Outcomes 27% RR in total cardiovascular events

Secondary Outcomes 31% RR in all cause death

Other Observations 32% RR in coronary events

Other Observations 33% RR in cardiovascular death

Felodipine ER was Well-Tolerated

Adverse events reported during treatment

Discussion
The FEVER study shows that in Chinese hypertensive patients
receiving a small dose of the diuretic hydrochlorothiazide (12.5 mg once a day) the addition of a small dose of the calcium antagonist felodipine (5 mg once a day), instead of placebo, is accompanied by a further SBP/DBP decrease of 4/2 mmHg (despite a more frequent add-on therapy in the placebo group

Discussion
Marked reductions in fatal and non-fatal stroke (27%, P = 0.001), total cardiovascular events (27%, P < 0.001), total cardiac events (34%, P 0.012), coronary events (32%, = 0.024), c cardiac failure (30%, NS), death by any cause(31%, = 0.006), cardiovascular death (17%, P = 0.019), and cancer (36%, P = 0.017).

Relevant Clinical Conclusions FEVER

Even a small difference in SBP/DBP, amounting to
approximately 4/2 mmHg, can be associated with substantial reductions in the incidence of most types of cardiovascular events in Chinese hypertensive patients

Relevant clinical conclusions FEVER

It substantiates and supports guidelines recommendations, and
indicates that even small differences in the control of SBP just below and just above the 140 mmHg goal (and DBP just below and above 85 mmHg) are accompanied by substantial differences in outcomes. SBP and DBP values achieved in the felodipine group of FEVER closely correspond to the SBP/DBP values of 138.5/82.6 mmHg (138.1/82.3 mmHg) indicated as optimal blood pressures in the HOT study

Relevant Clinical Conclusions FEVER

FEVER shows the benefits of treating hypertension with a lowdose combination of antihypertensive agents

The results of FEVER directly show that adding a low

dihydropyridine dose to a low-dose thiazide diuretic further reduces blood pressure and cardiovascular outcomes

HOT

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