m :HYPERTENSION TREATMENT
IN HIGH RISK PATIENTS Dr. H.M.EDIAL SANIF, SpJP m
Prevalence of hypertension in the adult US population :Prevalence of hypertension in the adult US population 76% 24% 44 000 000 hypertensive Americans Hypertensive Normotensive NHANES III, Burt et al (1995)
Slide 3 :Age (years) Prevalence of hypertension in the US adult
population by gender and age
(NHANES, phase1, 1988-1991)
Hypertension: treatment and control : % achieving BP control % of hypertensives taking medications 24% Controlled 53%
Taking medication 29% Not controlled Hypertension: treatment and control NHANES III, Burt et al (1995)
Slide 5 :HIPERTENSI PJK LVH L H F
Slide 6 :PJK ANTI OKSIDAN
ANTIPROLIFERASI
BLOK OKS.LDL
BLOK CA UPTAKE REGRESI PLAK
STABILISASI
ANTISPASME
DILATASI KORONER ATERO SKLEROTIK
Slide 7 :LVH 5 TH MENINGGAL 20 X LHF 12 X INFARK 50 X .. STROKE
Prevalence of hypertension in the adult US population :Prevalence of hypertension in the adult US population 76% 24% 44 000 000 hypertensive Americans Hypertensive Normotensive NHANES III, Burt et al (1995)
Slide 9 :Age (years) Prevalence of hypertension in the US adult
population by gender and age
(NHANES, phase1, 1988-1991)
Hypertension: treatment and control : % achieving BP control % of hypertensives taking medications 24% Controlled 53%
Taking medication 29% Not controlled Hypertension: treatment and control NHANES III, Burt et al (1995)
Slide 11 :HIPERTENSI PJK LVH L H F
Slide 12 :PJK ANTI OKSIDAN
ANTIPROLIFERASI
BLOK OKS.LDL
BLOK CA UPTAKE REGRESI PLAK
STABILISASI
ANTISPASME
DILATASI KORONER ATERO SKLEROTIK
Slide 13 :Atherosclerosis Cerebro
Vascular
Disease Severe
Heart Failure Peripheral
Vascular
Disease Coronary
Artery
Disease Myocardial
Infarction Moderate
Heart Failure Mild
Heart Failure Asymptomatic LV
Dysfunction PROGRESS SCAT
PART EUROPA
QUIET AIRE
PEACE
ISIS-4 SOLVD
SAVE
CONSENSUS
ELITE SOLVD
Progression from hypertension and CAD to heart failure: common comorbid risk factors :Progression from hypertension and CAD to heart failure: common comorbid risk factors Diabetes mellitus
Insulin resistance
Hyperlipidaemia
Renal dysfunction
Obesity
Cigarette consumption
Global burden of disease (WHO) :Global burden of disease (WHO) Leading causes of disease burden
Slide 16 :Hypertension prevalence, Awareness,
Treatment, and Control in Adults
United states, 1976-1994 Hypertension NHANES II NHANES III phase 1 NHANES III phase 2
(1976-1980) % (1988-1991) % (1991-1994) Awareness* 51 73 68.4
Treated 31 55 53.6
Controlled** 10 29 27.4 * Adults (ages 18-74)
** SBP < 140 mmHg and DBP < 90 mmHg The VI th JNC on detection, Evaluation, and treatment of high blood pressure, Arch Intern Med
Slide 17 :1940 : PENGOBATAN HIPERTENSI - Tensi Drop out (efek samping ) - Efek samping Drop out (mortalitas & morbiditas ) - Kerusakan organ target Otak
Ginjal
Jantung (mortalitas & morbiditas ) - Single dose - TP rasio > 50% (mortalitas & morbiditas ???) - SINDROMA METABOLIK
Slide 18 :Hypertension in practice 2nd, Beevers & MacGregor Hypertension Treatments Rules of Halves
RAS and Bradykinin System :RAS and Bradykinin System Inactive Peptida
Current Indications for ACE-Inhibitor :Current Indications for ACE-Inhibitor Hypertension
Heart Failure
Post M I
(Diabetic Nephropathy)
(Left Ventricular Dysfunction)
Slide 21 :Pleiotropic Cardiovascular Effects of ANGIOTENSIN Direct vasoconstriction
Sympathetic activation Endothelial
dysfunction Cell growth Na reabsorption
aldosterone Vasoconstriction Inflammation
cytokine
Superoxide Cardiac and
vascular
remodelling Volume ATHEROSCLEROSIS BlLOOD PRESSURE Angiotensin II
ANGIOTENSIN AND ATHEROSCLEROSIS :ANGIOTENSIN AND ATHEROSCLEROSIS Angiotensin involved in:
Endothelial dysfunction
Oxidized LDL production
Expression of adhesion and chemoattractant molecules
Macrophage activation and migration
Stimulates cytokine production
S.M. replication,hypertrophy and migration
Matrix expansion
Slide 23 :The Cardioprotective effect
* Restoration of heart function
* Improve impaired coronary circulation
* Reduce arrhythmia
* Prevent myocardial fibrosis, by ameliorating
vascular proliferation (remodelling)
The Properties of ACE - Inhibitors :The Properties of ACE - Inhibitors Hemodynamic effect
Modulation of symphathetic activity
Improvement of endothelial function
Anti-atherogenic activity
Antiproliferative action
Antitrombotic effect Opie-L.Angiotensin Converting Enzyme Inhibitors, 1999
Slide 25 :Atherosclerosis Cerebro
Vascular
Disease Severe
Heart Failure Peripheral
Vascular
Disease Coronary
Artery
Disease Myocardial
Infarction Moderate
Heart Failure Mild
Heart Failure Asymptomatic LV
Dysfunction Risk Factors:
- Hypertension
- Dyslipidemia
RAS and Bradykinin System :RAS and Bradykinin System Inactive Peptida
Trend in ACE Inhibitors :Trend in ACE Inhibitors Timing of Administration Treatment Prevention After GISSI
ISIS
CONSENSUS AIRE
SAVE EUROPA
HOPE
QUIET Before
Prevalence of hypertension in the adult US population :Prevalence of hypertension in the adult US population 76% 24% 44 000 000 hypertensive Americans Hypertensive Normotensive NHANES III, Burt et al (1995)
Slide 29 :Age (years) Prevalence of hypertension in the US adult
population by gender and age
(NHANES, phase1, 1988-1991)
Hypertension: treatment and control : % achieving BP control % of hypertensives taking medications 24% Controlled 53%
Taking medication 29% Not controlled Hypertension: treatment and control NHANES III, Burt et al (1995)
Slide 31 :HIPERTENSI PJK LVH L H F
Slide 32 :PJK ANTI OKSIDAN
ANTIPROLIFERASI
BLOK OKS.LDL
BLOK CA UPTAKE REGRESI PLAK
STABILISASI
ANTISPASME
DILATASI KORONER ATERO SKLEROTIK
Slide 33 :LVH 5 TH MENINGGAL 20 X LHF 12 X INFARK 50 X .. STROKE
Prevalence of hypertension in the adult US population :Prevalence of hypertension in the adult US population 76% 24% 44 000 000 hypertensive Americans Hypertensive Normotensive NHANES III, Burt et al (1995)
Slide 35 :Age (years) Prevalence of hypertension in the US adult
population by gender and age
(NHANES, phase1, 1988-1991)
Hypertension: treatment and control : % achieving BP control % of hypertensives taking medications 24% Controlled 53%
Taking medication 29% Not controlled Hypertension: treatment and control NHANES III, Burt et al (1995)
Slide 37 :HIPERTENSI PJK LVH L H F
Slide 38 :PJK ANTI OKSIDAN
ANTIPROLIFERASI
BLOK OKS.LDL
BLOK CA UPTAKE REGRESI PLAK
STABILISASI
ANTISPASME
DILATASI KORONER ATERO SKLEROTIK
Slide 39 :LVH 5 TH MENINGGAL 20 X LHF 12 X INFARK 50 X .. STROKE
Slide 40 :Atherosclerosis Cerebro
Vascular
Disease Severe
Heart Failure Peripheral
Vascular
Disease Coronary
Artery
Disease Myocardial
Infarction Moderate
Heart Failure Mild
Heart Failure Asymptomatic LV
Dysfunction PROGRESS SCAT
PART EUROPA
QUIET AIRE
PEACE
ISIS-4 SOLVD
SAVE
CONSENSUS
ELITE SOLVD
Progression from hypertension and CAD to heart failure: common comorbid risk factors :Progression from hypertension and CAD to heart failure: common comorbid risk factors Diabetes mellitus
Insulin resistance
Hyperlipidaemia
Renal dysfunction
Obesity
Cigarette consumption
Global burden of disease (WHO) :Global burden of disease (WHO) Leading causes of disease burden
Slide 43 :Hypertension prevalence, Awareness,
Treatment, and Control in Adults
United states, 1976-1994 Hypertension NHANES II NHANES III phase 1 NHANES III phase 2
(1976-1980) % (1988-1991) % (1991-1994) Awareness* 51 73 68.4
Treated 31 55 53.6
Controlled** 10 29 27.4 * Adults (ages 18-74)
** SBP < 140 mmHg and DBP < 90 mmHg The VI th JNC on detection, Evaluation, and treatment of high blood pressure, Arch Intern Med
Slide 44 :1940 : PENGOBATAN HIPERTENSI - Tensi Drop out (efek samping ) - Efek samping Drop out (mortalitas & morbiditas ) - Kerusakan organ target Otak
Ginjal
Jantung (mortalitas & morbiditas ) - Single dose - TP rasio > 50% (mortalitas & morbiditas ???) - SINDROMA METABOLIK
Slide 45 :1940 : PENGOBATAN HIPERTENSI - Tensi Drop out (efek samping ) - Efek samping Drop out (mortalitas & morbiditas ) - Kerusakan organ target Otak
Ginjal
Jantung (mortalitas & morbiditas ) - Single dose - TP rasio > 50% (mortalitas & morbiditas ???) - SINDROMA METABOLIK
RAS and Bradykinin System :RAS and Bradykinin System Inactive Peptida
Current Indications for ACE-Inhibitor :Current Indications for ACE-Inhibitor Hypertension
Heart Failure
Post M I
(Diabetic Nephropathy)
(Left Ventricular Dysfunction)
Slide 48 :Pleiotropic Cardiovascular Effects of ANGIOTENSIN Direct vasoconstriction
Sympathetic activation Endothelial
dysfunction Cell growth Na reabsorption
aldosterone Vasoconstriction Inflammation
cytokine
Superoxide Cardiac and
vascular
remodelling Volume ATHEROSCLEROSIS BlLOOD PRESSURE Angiotensin II
ANGIOTENSIN AND ATHEROSCLEROSIS :ANGIOTENSIN AND ATHEROSCLEROSIS Angiotensin involved in:
Endothelial dysfunction
Oxidized LDL production
Expression of adhesion and chemoattractant molecules
Macrophage activation and migration
Stimulates cytokine production
S.M. replication,hypertrophy and migration
Matrix expansion
Slide 50 :Pleiotropic Cardiovascular Effects of ANGIOTENSIN Direct vasoconstriction
Sympathetic activation Endothelial
dysfunction Cell growth Na reabsorption
aldosterone Vasoconstriction Inflammation
cytokine
Superoxide Cardiac and
vascular
remodelling Volume ATHEROSCLEROSIS BlLOOD PRESSURE Angiotensin II
Slide 51 :The Cardioprotective effect
* Restoration of heart function
* Improve impaired coronary circulation
* Reduce arrhythmia
* Prevent myocardial fibrosis, by ameliorating
vascular proliferation (remodelling)
The Properties of ACE - Inhibitors :The Properties of ACE - Inhibitors Hemodynamic effect
Modulation of symphathetic activity
Improvement of endothelial function
Anti-atherogenic activity
Antiproliferative action
Antitrombotic effect Opie-L.Angiotensin Converting Enzyme Inhibitors, 1999
Slide 53 :Atherosclerosis Cerebro
Vascular
Disease Severe
Heart Failure Peripheral
Vascular
Disease Coronary
Artery
Disease Myocardial
Infarction Moderate
Heart Failure Mild
Heart Failure Asymptomatic LV
Dysfunction PROGRESS SCAT
PART EUROPA
QUIET AIRE
PEACE
ISIS-4 SOLVD
SAVE
CONSENSUS
ELITE SOLVD
Korelasi Kepatuhan Pasien Dengan Frekuensi Pemberian Dosis Obat :Korelasi Kepatuhan Pasien Dengan Frekuensi Pemberian Dosis Obat Skaer TL et al. Clin Ther 1993; 15:905-911
Skaer TL et al. Curr Ther Res. 1993; 53:256-264
Categories of hypertensive end-organ damage : Origin Category
Brain Stroke (atherothrombotic or haemorrhagic)
Transient ischaemic attack
Periodic ischaemic spells
Multi-infarct dementia
Ocular fundus Keith-Wagener-Barker grade III–IV
Heart Sudden death
Myocardial infarction
Angina (including variant form)
Arrhythmias
Left ventricular hypertrophy
Heart failure Birkenhäger and de Leeuw (1992) Categories of hypertensive end-organ damage
Categories of hypertensive end-organ damage : Origin Category
Large arteries Loss of compliance
(Dissecting) aneurysm
Peripheral occlusive arterial disease
Kidney Nephrosclerosis Categories of hypertensive end-organ damage Birkenhäger and de Leeuw (1992)
Antihypertensive therapy and the prevention of cardiovascular complications :Antihypertensive therapy and the prevention of cardiovascular complications Cumulative incidence of cardiovascular complications in hypertensive
patients with diastolic blood pressure of 90–114 mmHg Complications with lethal outcome (%) All cardiovascular complications (%) Observation period (years) Observation period (years) 60
50
40
30
20
10
0 60
50
40
30
20
10
0 0 1 2 3 4 5 0 1 2 3 4 5 Control
Treated Veterans Administration Cooperative Study Group (1970)
Risk of coronary artery disease and heart failure according to hypertensive status in the Framingham study :Risk of coronary artery disease and heart failure according to hypertensive status in the Framingham study Kannel, Sorlie (1975) 300
200
100
0 p<0.01 Average annual
incidence (per 10 000) 39 71 129 158 101 245 Normotensive (<140/90 mmHg)
Borderline hypertensive
Hypertensive (>160/95 mmHg)
(men and women aged 45–74 years) Women Men CAD HF
Hypertension: treatment and control : % achieving BP control % of hypertensives taking medications 24% Controlled 53%
Taking medication 29% Not controlled Hypertension: treatment and control NHANES III, Burt et al (1995)
Slide 61 :HIPERTENSI PJK LVH L H F
Slide 62 :PJK ANTI OKSIDAN
ANTIPROLIFERASI
BLOK OKS.LDL
BLOK CA UPTAKE REGRESI PLAK
STABILISASI
ANTISPASME
DILATASI KORONER ATERO SKLEROTIK
Slide 63 :LVH 5 TH MENINGGAL 20 X LHF 12 X INFARK 50 X .. STROKE
Slide 64 :1940 : PENGOBATAN HIPERTENSI - Tensi Drop out (efek samping ) - Efek samping Drop out (mortalitas & morbiditas ) - Kerusakan organ target Otak
Ginjal
Jantung (mortalitas & morbiditas ) - Single dose - TP rasio > 50% (mortalitas & morbiditas ???) - SINDROMA METABOLIK
Slide 65 :1940 : PENGOBATAN HIPERTENSI - Tensi Drop out (efek samping ) - Efek samping Drop out (mortalitas & morbiditas ) - Kerusakan organ target Otak
Ginjal
Jantung (mortalitas & morbiditas ) - Single dose - TP rasio > 50% (mortalitas & morbiditas ???) - SINDROMA METABOLIK
RAS and Bradykinin System :RAS and Bradykinin System Inactive Peptida
Prevalence of hypertension in the adult US population :Prevalence of hypertension in the adult US population 76% 24% 44 000 000 hypertensive Americans Hypertensive Normotensive NHANES III, Burt et al (1995)
Slide 68 :Age (years) Prevalence of hypertension in the US adult
population by gender and age
(NHANES, phase1, 1988-1991)
Hypertension: treatment and control : % achieving BP control % of hypertensives taking medications 24% Controlled 53%
Taking medication 29% Not controlled Hypertension: treatment and control NHANES III, Burt et al (1995)
Slide 70 :HIPERTENSI PJK LVH L H F
Slide 71 :PJK ANTI OKSIDAN
ANTIPROLIFERASI
BLOK OKS.LDL
BLOK CA UPTAKE REGRESI PLAK
STABILISASI
ANTISPASME
DILATASI KORONER ATERO SKLEROTIK
Slide 72 :LVH 5 TH MENINGGAL 20 X LHF 12 X INFARK 50 X .. STROKE
Prevalence of hypertension in the adult US population :Prevalence of hypertension in the adult US population 76% 24% 44 000 000 hypertensive Americans Hypertensive Normotensive NHANES III, Burt et al (1995)
Slide 74 :Age (years) Prevalence of hypertension in the US adult
population by gender and age
(NHANES, phase1, 1988-1991)
Hypertension: treatment and control : % achieving BP control % of hypertensives taking medications 24% Controlled 53%
Taking medication 29% Not controlled Hypertension: treatment and control NHANES III, Burt et al (1995)
Slide 76 :HIPERTENSI PJK LVH L H F
Slide 77 :PJK ANTI OKSIDAN
ANTIPROLIFERASI
BLOK OKS.LDL
BLOK CA UPTAKE REGRESI PLAK
STABILISASI
ANTISPASME
DILATASI KORONER ATERO SKLEROTIK
Slide 78 :LVH 5 TH MENINGGAL 20 X LHF 12 X INFARK 50 X .. STROKE
Slide 79 :Atherosclerosis Cerebro
Vascular
Disease Severe
Heart Failure Peripheral
Vascular
Disease Coronary
Artery
Disease Myocardial
Infarction Moderate
Heart Failure Mild
Heart Failure Asymptomatic LV
Dysfunction PROGRESS SCAT
PART EUROPA
QUIET AIRE
PEACE
ISIS-4 SOLVD
SAVE
CONSENSUS
ELITE SOLVD
Progression from hypertension and CAD to heart failure: common comorbid risk factors :Progression from hypertension and CAD to heart failure: common comorbid risk factors Diabetes mellitus
Insulin resistance
Hyperlipidaemia
Renal dysfunction
Obesity
Cigarette consumption
Global burden of disease (WHO) :Global burden of disease (WHO) Leading causes of disease burden
Slide 82 :Hypertension prevalence, Awareness,
Treatment, and Control in Adults
United states, 1976-1994 Hypertension NHANES II NHANES III phase 1 NHANES III phase 2
(1976-1980) % (1988-1991) % (1991-1994) Awareness* 51 73 68.4
Treated 31 55 53.6
Controlled** 10 29 27.4 * Adults (ages 18-74)
** SBP < 140 mmHg and DBP < 90 mmHg The VI th JNC on detection, Evaluation, and treatment of high blood pressure, Arch Intern Med
Slide 83 :1940 : PENGOBATAN HIPERTENSI - Tensi Drop out (efek samping ) - Efek samping Drop out (mortalitas & morbiditas ) - Kerusakan organ target Otak
Ginjal
Jantung (mortalitas & morbiditas ) - Single dose - TP rasio > 50% (mortalitas & morbiditas ???) - SINDROMA METABOLIK
Slide 84 :1940 : PENGOBATAN HIPERTENSI - Tensi Drop out (efek samping ) - Efek samping Drop out (mortalitas & morbiditas ) - Kerusakan organ target Otak
Ginjal
Jantung (mortalitas & morbiditas ) - Single dose - TP rasio > 50% (mortalitas & morbiditas ???) - SINDROMA METABOLIK
RAS and Bradykinin System :RAS and Bradykinin System Inactive Peptida
Current Indications for ACE-Inhibitor :Current Indications for ACE-Inhibitor Hypertension
Heart Failure
Post M I
(Diabetic Nephropathy)
(Left Ventricular Dysfunction)
Slide 87 :Pleiotropic Cardiovascular Effects of ANGIOTENSIN Direct vasoconstriction
Sympathetic activation Endothelial
dysfunction Cell growth Na reabsorption
aldosterone Vasoconstriction Inflammation
cytokine
Superoxide Cardiac and
vascular
remodelling Volume ATHEROSCLEROSIS BlLOOD PRESSURE Angiotensin II
ANGIOTENSIN AND ATHEROSCLEROSIS :ANGIOTENSIN AND ATHEROSCLEROSIS Angiotensin involved in:
Endothelial dysfunction
Oxidized LDL production
Expression of adhesion and chemoattractant molecules
Macrophage activation and migration
Stimulates cytokine production
S.M. replication,hypertrophy and migration
Matrix expansion
Slide 89 :Pleiotropic Cardiovascular Effects of ANGIOTENSIN Direct vasoconstriction
Sympathetic activation Endothelial
dysfunction Cell growth Na reabsorption
aldosterone Vasoconstriction Inflammation
cytokine
Superoxide Cardiac and
vascular
remodelling Volume ATHEROSCLEROSIS BlLOOD PRESSURE Angiotensin II
Slide 90 :The Cardioprotective effect
* Restoration of heart function
* Improve impaired coronary circulation
* Reduce arrhythmia
* Prevent myocardial fibrosis, by ameliorating
vascular proliferation (remodelling)
The Properties of ACE - Inhibitors :The Properties of ACE - Inhibitors Hemodynamic effect
Modulation of symphathetic activity
Improvement of endothelial function
Anti-atherogenic activity
Antiproliferative action
Antitrombotic effect Opie-L.Angiotensin Converting Enzyme Inhibitors, 1999
Slide 92 :1940 : PENGOBATAN HIPERTENSI - Tensi Drop out (efek samping ) - Efek samping Drop out (mortalitas & morbiditas ) - Kerusakan organ target Otak
Ginjal
Jantung (mortalitas & morbiditas ) - Single dose - TP rasio > 50% (mortalitas & morbiditas ???) - SINDROMA METABOLIK
Slide 93 :1940 : PENGOBATAN HIPERTENSI - Tensi Drop out (efek samping ) - Efek samping Drop out (mortalitas & morbiditas ) - Kerusakan organ target Otak
Ginjal
Jantung (mortalitas & morbiditas ) - Single dose - TP rasio > 50% (mortalitas & morbiditas ???) - SINDROMA METABOLIK
Current Indications for ACE-Inhibitor :Current Indications for ACE-Inhibitor Hypertension
Heart Failure
Post M I
(Diabetic Nephropathy)
(Left Ventricular Dysfunction)
Slide 95 :Pleiotropic Cardiovascular Effects of ANGIOTENSIN Direct vasoconstriction
Sympathetic activation Endothelial
dysfunction Cell growth Na reabsorption
aldosterone Vasoconstriction Inflammation
cytokine
Superoxide Cardiac and
vascular
remodelling Volume ATHEROSCLEROSIS BlLOOD PRESSURE Angiotensin II
ANGIOTENSIN AND ATHEROSCLEROSIS :ANGIOTENSIN AND ATHEROSCLEROSIS Angiotensin involved in:
Endothelial dysfunction
Oxidized LDL production
Expression of adhesion and chemoattractant molecules
Macrophage activation and migration
Stimulates cytokine production
S.M. replication,hypertrophy and migration
Matrix expansion
Slide 97 :Pleiotropic Cardiovascular Effects of ANGIOTENSIN Direct vasoconstriction
Sympathetic activation Endothelial
dysfunction Cell growth Na reabsorption
aldosterone Vasoconstriction Inflammation
cytokine
Superoxide Cardiac and
vascular
remodelling Volume ATHEROSCLEROSIS BlLOOD PRESSURE Angiotensin II
Slide 98 :The Cardioprotective effect
* Restoration of heart function
* Improve impaired coronary circulation
* Reduce arrhythmia
* Prevent myocardial fibrosis, by ameliorating
vascular proliferation (remodelling)
Trend in ACE Inhibitors :Trend in ACE Inhibitors Timing of Administration Treatment Prevention After GISSI
ISIS
CONSENSUS AIRE
SAVE EUROPA
HOPE
QUIET Before
Slide 100 :Atherosclerosis Cerebro
Vascular
Disease Severe
Heart Failure Peripheral
Vascular
Disease Coronary
Artery
Disease Myocardial
Infarction Moderate
Heart Failure Mild
Heart Failure Asymptomatic LV
Dysfunction PROGRESS SCAT
PART EUROPA
QUIET AIRE
PEACE
ISIS-4 SOLVD
SAVE
CONSENSUS
ELITE SOLVD
Korelasi Kepatuhan Pasien Dengan Frekuensi Pemberian Dosis Obat :Korelasi Kepatuhan Pasien Dengan Frekuensi Pemberian Dosis Obat Skaer TL et al. Clin Ther 1993; 15:905-911
Skaer TL et al. Curr Ther Res. 1993; 53:256-264
Categories of hypertensive end-organ damage : Origin Category
Brain Stroke (atherothrombotic or haemorrhagic)
Transient ischaemic attack
Periodic ischaemic spells
Multi-infarct dementia
Ocular fundus Keith-Wagener-Barker grade III–IV
Heart Sudden death
Myocardial infarction
Angina (including variant form)
Arrhythmias
Left ventricular hypertrophy
Heart failure Birkenhäger and de Leeuw (1992) Categories of hypertensive end-organ damage
Categories of hypertensive end-organ damage : Origin Category
Large arteries Loss of compliance
(Dissecting) aneurysm
Peripheral occlusive arterial disease
Kidney Nephrosclerosis Categories of hypertensive end-organ damage Birkenhäger and de Leeuw (1992)
Antihypertensive therapy and the prevention of cardiovascular complications :Antihypertensive therapy and the prevention of cardiovascular complications Cumulative incidence of cardiovascular complications in hypertensive
patients with diastolic blood pressure of 90–114 mmHg Complications with lethal outcome (%) All cardiovascular complications (%) Observation period (years) Observation period (years) 60
50
40
30
20
10
0 60
50
40
30
20
10
0 0 1 2 3 4 5 0 1 2 3 4 5 Control
Treated Veterans Administration Cooperative Study Group (1970)
Risk of coronary artery disease and heart failure according to hypertensive status in the Framingham study :Risk of coronary artery disease and heart failure according to hypertensive status in the Framingham study Kannel, Sorlie (1975) 300
200
100
0 p<0.01 Average annual
incidence (per 10 000) 39 71 129 158 101 245 Normotensive (<140/90 mmHg)
Borderline hypertensive
Hypertensive (>160/95 mmHg)
(men and women aged 45–74 years) Women Men CAD HF
Progression from hypertension and CAD to heart failure: common comorbid risk factors :Progression from hypertension and CAD to heart failure: common comorbid risk factors Diabetes mellitus
Insulin resistance
Hyperlipidaemia
Renal dysfunction
Obesity
Cigarette consumption
Relative risk of coronary artery disease by increasing intensity of risk factors in men :Relative risk of coronary artery disease by increasing intensity of risk factors in men Hypertension
only Hypertension
+ hypercholesterolaemia
+ smoking Hypertension
+ hypercholesterolaemia Hypertension
+ hypercholesterolaemia
+ smoking
+ diabetes + LVH 50
40
30
20
10
0 Hypertension is defined as a SBP
of 150–160 mm Hg. Hypercholesterolaemia = serum cholesterol of 240–262 mg/dl and HDL cholesterol of 33–35 mg/dl. 6 13 19 44 10-year probability (%) Kannel (1992)
Progression from hypertension and CAD to heart failure: common comorbid risk factors :Progression from hypertension and CAD to heart failure: common comorbid risk factors Diabetes mellitus
Insulin resistance
Hyperlipidaemia
Renal dysfunction
Obesity
Cigarette consumption
Slide 109 :CLASSIFICATION OF BLOOD PRESSURE FOR ADULTS
AGE 18 YEARS OR OLDER Hypertension primer, 2nd edition, The essentials of high blood pressure, p. 275
Slide 110 :Components of CV risk stratification
In patients with hypertension TOD : Target Organ Damage; CCD: Clinical Cardiovascular Disease; MI: Myocardial infarction;
TIA : Transient Ischemic Attack; PAD : Peripheral S+Arterial Disease The VI th JNC on detection, Evaluation, and treatment of high blood pressure, Arch Intern Med
Slide 111 :RISK STRATIFICATIONS AND TREATMENT
( JNC VI, 1997 ) The VI th JNC on detection, Evaluation, and treatment of high blood pressure, Arch Intern Med
Slide 112 :Life style modifications
for Hypertension Prevention and Management Lose weight if over weight
Limit alcohol intake
Increase aerobic physical activity
Reduce sodium intake
Maintain adequate intake of dietary K, Ca, Mg
Stop Smoking
Reduce intake fat and cholesterol The VI th JNC on detection, Evaluation, and treatment of high blood pressure, Arch Intern Med
Slide 113 :Stratification of Risk
to Influence Treatment (WHO-ISH)
Management Strategy based on Risk Stratification :Management Strategy based on Risk Stratification WHO/ISH Hypertension Guidelines, 1999 Risk Stratification Absolute Risk* Treatment Low Risk <15% Observation before deciding whether to institute drug treatment Medium Risk 15-20% Monitor BP & other risk factors before deciding whether to institute drug treatment High Risk 20-30% Institute immediate drug treatment for HT, other risk factors, or conditions present Very High Risk >30% As for high-risk patients *risk of CV events over 10 years
Slide 115 :Vasoprotection
Ramipril
& the HOPE study Ramipril and Vasoprotection, slide 115
Slide 116 :Vitamin E in the prevention of CHD? Rationale for HOPE ACE inhibition in the prevention of:
- MI?
- Stroke?
- Diabetes complications? Ramipril and Vasoprotection, Part 1, slide 116 Need direct confirmation of these therapeutic benefits in a large-scale, randomised, prospective trial
Slide 117 :Does the addition of ramipril and/or vitamin E to the ongoing medication of a broad range of 'high-risk' patients with preserved left ventricular function reduce cardiovascular morbidity and mortality? HOPE - aim Ramipril and Vasoprotection, Part 2, slide 117
Slide 118 :HOPE - inclusion criteria Eligible: Men and women
Age ³ 55 years
History of CVD (coronary artery disease, stroke, peripheral vascular disease) or
Diabetes plus at least 1 other CV risk factor:
- Hypertension
- Total cholesterol > 5.2 mmol/L
- HDL cholesterol 0.9 mmol/L
- Microalbuminuria
- Current smoking Ineligible: HF or low EF (< 0.40)
Uncontrolled hypertension
Recent MI or stroke (< 1 month)
Use of/hypersensitivity to ACE inhibitors or vitamin E
Overt nephropathy Ramipril and Vasoprotection, Part 2, slide 118
Slide 119 :HOPE - design Study design: Randomised, double-blind, 2 X 2 factorial Follow-up: 4.5 years (visits at 6 months) Study sample: 10,576 patients
- 1035 (subsequently excluded)
9541 patients Randomisation: Ramipril 10 mg/day n = 4645
Placebo (i.e. no ramipril) n = 4652
Total n = 9297*
and
Vitamin E 400 IU/day n = 4761
Placebo (i.e. no vitamin E) n = 4780
Total n = 9541 *Excludes 244 patients randomised to low-dose ramipril (2.5 mg/day) in SECURE substudy Ramipril and Vasoprotection, Part 2, slide 119
Slide 120 :HOPE – endpoints Outcome measures: Primary
- Composite of MI/stroke/CV death
(+ separate analysis of each) Data analysis: Intention-to-treat
Stratified due to factorial design Secondary and others
- Total mortality
- Revascularisation
- Worsening angina/unstable angina (including hospitalisations)
- HF (including hospitalisations)
- Cardiac arrest
- Onset of new diabetes
- Diabetes complications Ramipril and Vasoprotection, Part 2, slide 120
Slide 121 :Variable Ramipril (n = 4645) Placebo (n = 4652) Men/women 3366 (72%)/1279 (28%) 3451 (74%)/1201 (26%)
Age (years)* 66 ± 7 66 ± 7 *[mean ± S.D.] HOPE (ramipril) - baseline characteristics SBP/DBP (mm Hg)* 139 ± 20/79 ± 11 139 ± 20/79 ± 11
Heart rate (beats/min)* 69 ± 11 69 ± 11
BMI (kg/m2)* 28 ± 4 28 ± 4 History of CAD 3691 (79.5%) 3786 (81.4%)
- MI 2410 (51.9%) 2482 (53.4%)
- Stable AP 2544 (54.8%) 2618 (56.3%)
- Unstable AP 1179 (25.4%) 1188 (25.5%)
- CABG 1192 (25.7%) 1207 (25.9%)
- PTCA 853 (18.4%) 806 (17.3%)
Stroke or TIA 500 (10.8%) 513 (11.0%)
PVD 1966 (42.3%) 2085 (44.8%)
Hypertension 2212 (47.6%) 2143 (46.1%)
Diabetes 1808 (38.9%) 1769 (38.0%)
Current smokers 645 (13.9%) 674 (14.5%) Elevated total cholesterol level 3036 (65.4%) 3089 (66.4%)
Low HDL cholesterol level 842 (18.1%) 881 (18.9%)
LVH 379 (8.2%) 406 (8.7%)
MA 952 (20.5%) 1004 (21.6%) Ramipril and Vasoprotection, Part 2, slide 121
Slide 122 :Medication Ramipril Placebo
(n = 4645) (n = 4652) Beta-blockers 1820 (39.2%) 1853 (39.8%)
Acetylsalicylic acid or other
antiplatelet agents 3497 (75.3%) 3577 (76.9%)
Hypolipidaemic drugs 1318 (28.4%) 1340 (28.8%)
Diuretics 713 (15.3%) 706 (15.2%)
Calcium-channel blockers 2152 (46.3%) 2228 (47.9%) HOPE (ramipril) – concomitant medications Patients were already medically well-managed according to their underlying disease Ramipril and Vasoprotection, Part 2, slide 122
Slide 123 :SBP/DBP (mm Hg)
Baseline 1 month 2 years Final visit Placebo 139/79 137/78 138/78 139/77 HOPE (ramipril) - BP Ramipril 139/79 133/76 135/76 136/76 Extremely small decrease in BP in the ramipril group (3/3 mmHg) and even less in the placebo group (0/2 mmHg) Ramipril and Vasoprotection, Part 2, slide 123
Slide 124 :Ramipril p < 0.001 HOPE (ramipril) – primary outcomes (I) Placebo Ramipril and Vasoprotection, Part 2, slide 124
Primary Endpoint - Risk Reduction All differences p < 0.001 :Primary Endpoint - Risk Reduction All differences p < 0.001
Relative Risk ReductionStroke and MI according to SBP decrease :Relative Risk ReductionStroke and MI according to SBP decrease
Hypertensive versus normotensive patientsRelative Risk Reduction :Hypertensive versus normotensive patientsRelative Risk Reduction
Slide 128 :HOPE (ramipril) – onset of new diabetes Ramipril and Vasoprotection, Part 2, slide 128
Slide 129 :HOPE (ramipril) - subgroup analysis (I) No. of Incidence of MI, RR on ramipril
patients stroke or CV death (95% CI)
on placebo (%) Overall 9297 17.8 CVD 8162 18.7 No CVD 1135 10.2 Diabetes 3577 19.8 No diabetes 5720 16.5 Age < 65 yr 4169 14.2 Age 65 yr 5128 20.7 Men 6817 18.7 Women 2480 14.4 Hypertension 4355 19.5 No hypertension 4942 16.3 0.6 0.8 1.0 1.2 Ramipril and Vasoprotection, Part 2, slide 129 Ramipril was beneficial in all subgroups analysed
Slide 130 :HOPE (ramipril) - subgroup analysis (II) No. of Incidence of MI, RR on ramipril
patients stroke or CV death (95% CI)
on placebo (%) History of CAD 7477 18.6 No history of CAD 1820 14.2 Prior MI 4892 20.9 No prior MI 4405 14.2 Cerebrovascular disease 1013 25.9 No cerebrovascular disease 8284 16.7 PVD 4051 22.0 No PVD 5246 14.3 MA 1956 26.4 No MA 7341 15.4 Ramipril was beneficial in all subgroups analysed Ramipril and Vasoprotection, Part 2, slide 130
Slide 131 :Outcome Incidence in patients without renal insufficiency (n = 8307)
All Placebo Ramipril Hazard ratio
(%) group (%) group (%) (95% CI) Outcomes in patients
without renal insufficiency Primary Outcome 15.1 16.9 13.4 0.79 (0.70-0.88) MI * 10.5 11.5 9.4 0.81 (0.70-0.93)
Stroke 4.0 4.7 3.3 0.69 (0.55-0.86)
CV death 6.6 7.4 5.8 0.78 (0.66-0.93)
All death 10.6 11.1 10.0 0.90 (0.79-1.03) Hosp. For HF 2.9 2.9 2.9 1.03 (0.80-1.33)
Revascularization 16.9 18.1 15.6 0.87 (0.78-0.97) Annals of internal medicine vol 134; number 8 p. 633 * : Fatal and non fatal
Slide 132 :Outcome Incidence in patients with renal insufficiency (n = 980)
All Placebo Ramipril Hazard ratio
(%) group group (%) (95% CI) Outcomes in patients
with renal insufficiency Primary Outcome 22.2 25.5 9.3 0.80 (0.59-1.090) MI * 16.3 18.9 14.0 0.78 (0.54-1.11)
Stroke 5.0 5.9 4.1 0.83 (0.44-1.56)
CV death 11.4 14.7 8.5 0.59 (0.39-1.56)
All death 17.8 22.5 13.4 0.59 (0.42-0.83) Hosp. For HF 6.0 8.1 4.1 0.56 (0.30-1.06)
Revascularization 19.6 20.2 19.1 0.96 (0.70-1.33) Annals of internal medicine vol 134; number 8 p. 633
Slide 133 :Outcome Incidence in patients with a creatinine clearance
< 65 mL/min (n = 3394)
All Placebo Ramipril Hazard ratio
(%) group (%) group (%) (95% CI) Outcomes in patients
with creatinine clearance < 65ml/min Primary Outcome 18.5 21.2 15.9 0.75 (0.64-0.89) MI * 12.5 14.3 10.7 0.74 (0.61-0.91)
Stroke * 5.2 6.2 4.1 0.69 (0.49-0.91)
CV death 9.4 11.2 7.6 0.67 (0.53-0.85)
All death 14.8 16.6 13.0 0.80 (0.67-0.96) Hosp. For HF 4.5 5.0 4.1 0.82 (0.59-1.14)
Revascularization 16.9 18.0 15.9 0.89 (0.75-1.05) Annals of internal medicine vol 134; number 8 p. 634 * : Fatal and non fatal
Slide 134 :Outcome Incidence in patients with a creatinine clearance
> 65 mL/min (n = 5888)
All Placebo Ramipril Hazard ratio
(%) group (%) group (%) (95% CI) Outcomes in patients
with creatinine clearance > 65ml/min Primary Outcome 14.4 15.8 12.9 0.80 (0.70-0.92) MI * 10.3 11.1 9.4 0.83 (0.71-0.98)
Stroke * 3.5 4.1 2.9 0.71 (0.54-0.94)
CV death 5.8 6.3 5.2 0.81 (0.65-1.01)
All death 9.3 9.8 8.8 0.90 (0.76-1.07) Hosp. For HF 2.5 2.6 2.4 1.00 (0.72-1.39)
Revascularization 17.2 18.4 16.1 0.88 (0.78-1.00) Annals of internal medicine vol 134; number 8 p. 634 * : Fatal and non fatal
Slide 135 :BLOOD PRESSURE TARGET (WHO-ISH, 1999) 140 / 90 130 / 85 (Diabetes Melitus, young adult) 130 / 80 (Proteinuria) 125 / 75 (Proteinuria > 1 gram/day)
Slide 136 :HOPE : Risk Reduction
(ACE Inhibitors vs Placebo) HOPE Study Investigators. N Eng J Med 200;242:145-155
Effect of ramipril on degree of albuminuria(MicroHOPE) :Effect of ramipril on degree of albuminuria(MicroHOPE) Lancet 2000;355:235-239
Slide 138 :Hypertension Recommendations for Treatment of Hypertension CARDIOVASCULAR
DISEASE ISCHEMIA
blocker
ACE Inhibitors
Non DHP CCA ELDERLY
(Isolated Systolic HT)
Diuretic
DHP CCA
( long acting ) UNCOMPLICATED
( no comorbid condition)
Diuretic
blocker DIABETES
ACE Inhibitor
Diuretic
Non DHP CCA
blocker HYPERLIPIDEMIA
ACE Inhibitor
CCA
blocker
Vasodilators
Low Dose Diuretics MICRO
ALBUMINURIA
( non Diabetic )
( not as good an indicator of progression to ESRD as it is in DM )
ACE Inhibitor BENIGN PROSTATIC HYPERTROPHY
1 blocker
(improve symptoms by reducing symphatetic tone of bladder) HEART FAILURE
ACE Inhibitor
Loop Diuretic
Amlodipine
Carvedilol
ARBs
Conclusions :Conclusions Risk reduction in sub-populations on primary endpoint:
< 65 years: 18% p = 0.001
> 65 years: 25% p = 0.00001
Hypertensive: 25% p = 0.0001
Non-hypertensive: 19% p = 0.001
CAD patients: 20% p = 0.01
PVD patients: 25% p = 0.0001
Slide 140 :Terima Kasih
TRIATEC
RAMIPRIL1.25;2.5;, 5 & 10 mg TRIATEC 10 MG