Kalsium Antagonis pada Hipertensi

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Pemakaian kalsium antagonis dalam pengobatan hipertensi, semakin banyak diresepkan oleh dokter. Namun oleh karena terdapat beberapa jenis kalsium antagonis, maka diperlukan pengetahuan lebih mendalam agar pemilihan jenis kalsium antagonis tersebut tepat sasaran

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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

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