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PHARMACOTHERAPY
UPDATES
PRESENTATION ON
HYPERTENSION
By Salahadin A. (B.Pharm)
1
6/10/2022
HIWOT FANA COMPREHENSIVE
SPECIALIZED HOSPITAL
CLINICAL PHARMACY and DPIS
UNIT
Outline
 Introduction
 Epidemiology and pathophysiology
 Risk factors
 Signs and symptoms
 Classification
 Diagnosis
 Management of hypertension
 Life style modifications
 References
2
Introduction
 Arterial hypertension is the most frequent
modifiable risk factor associated with
cardiovascular morbidity and mortality .
Despite the widespread availability of proven
approaches to lower blood pressure (BP), i.e.
lifestyle modification and pharmacotherapy, in
many patients BP control to guideline
recommended targets is not achieved. Current
guidelines have recommended lowering SBP
in most patients (<65 years) to targets of 120–
130 mmHg. The treatment targets in patients
of older age and the neutral effects of lowering
BP ≤ 140/90 mmHg in these patients are
3
Epidemiology and
pathophysiology
 The Effect of systolic and diastolic blood pressure on
cardiovascular outcomes.
 High SBP and DBP associate with increased CV events.
However, it remained unclear whether either SBP or DBP
carries more prognostic information. This question was
addressed in a study, which evaluated data from an
integrated health care delivery system in the US. Between
2007 and 2016, more than 36 million office BP
measurements were analyzed from around 1.3 million
people. The study confirmed that both SBP and DBP
increased the risk of CV events such as myocardial
infarction and stroke. Elevated SBP had a greater
prognostic effect on stroke and myocardial infarction.
However, DBP influenced the prognosis independently of
4
Cont’d
 The 2017 American College of Cardiology and
American Heart Association Guidelines on the
management of hypertension revised the
definition of hypertension, which has been defined
as >130/>80 mmHg. Contrary, in the 2018
European Guidelines, the definition remained
unchanged (>140/>90 mmHg). Against this
background the prevalence of hypertension
according to the different definition criteria were
analyzed. The prevalence of hypertension
increased from 18.9% with a threshold of >140/90
mmHg to 43.5% with >130/80 mmHg. An SBP of
>130 mmHg was present in almost 50% of the
participants over the age of 60 years.
5
Cont’d
 Hypertension not only increases the risk of stroke,
myocardial infarction, and renal failure but also
appears to be associated with heart valve diseases
such as aortic valve stenosis and aortic valve
insufficiency. In a study from the UK, 5.4 million
patients with unknown CV disease or aortic valve
disease at baseline were examined and followed for
9.2 years. A total of 20,680 patients (0.38%) were
diagnosed with aortic valve stenosis and 6440
patients (0.12%) with aortic regurgitation. For each
increase of 20mmHg in SBP, the relative risk [RR] of
aortic valve stenosis increased by 41% (HR 1.41, 95%
CI 1.38–1.45), and 38% for aortic regurgitation (HR:
1.38, CI 1.31–1.45), respectively.
6
Cont’d
 The participants were recruited between 2006 and 2010. A
total of 130 gene variants were selected for the genetic
determination of hypertension. A total of 1491 (0.45%)
patients had aortic valve stenosis, 634 (0.19%) aortic
regurgitation and 1736 (0.53%) mitral regurgitation. With
each increase in SBP by 20 mmHg, the RR for aortic valve
stenosis increased by 3.3-fold (odds ratio [OR] 3.26; 95%
CI1.50–7.10, p=0.002), for aortic regurgitation by 2.5 (OR
2.59; 95% CI 0.75–8.92, p=0.13), and for mitral valve
regurgitation by 2.2 (OR 2.19; 95% CI 1.07–4.47, p=0.03),
respectively. An increase in SBP by 20mmHg was
associated with an almost 3-fold higher risk to develop any
of the three valvular diseases (OR 2.85; 95% CI 1.69–4.78,
p < 0.001). These data suggest that lifetime exposure to
elevated SBP appears to be associated with an increased
7
Risk factors
 Personal history of CVD (myocardial infarction,
heart failure [HF], stroke, transient ischemic
attacks [TIA], diabetes, dyslipidemia, chronic
kidney disease [CKD], smoking status, diet,
alcohol intake, physical activity, psychosocial
aspects, history of depression).
 Family history of hypertension, premature
CVD, (familial) hypercholesterolemia,
diabetes.
8
Signs and symptoms
 Symptoms/signs of
hypertension/coexistent illnesses:
 Chest pain
 shortness of breath
 palpitations
 claudication
 peripheral edema
 headaches, blurred vision
 nocturia, hematuria, dizziness.
9
Classification
 Primary Hypertension
 Most individuals with high BP (over 90%) have
essential or primary hypertension. Numerous
potential mechanisms have been identified that
contribute to the pathogenesis of essential
hypertension, so identifying the exact underlying
abnormality is not possible. Genetic factors may
play a role in the development of essential
hypertension by affecting sodium balance or other
BP regulating pathways.
10
Cont’d
 Secondary Hypertension
 Secondary hypertension, where either a comorbid
disease or a drug (or other product) is responsible
for elevating BP is much less common than
primary hypertension (up to 10%).1 In most of
these cases, renal dysfunction resulting from
severe chronic kidney disease (CKD) or
renovascular disease is the most common
secondary cause. Certain agents (drugs or other
products), either directly or indirectly, can
increase BP and cause or exacerbate
hypertension.
11
Cont’d
 Isolated systolic hypertension is considered
to be present when the blood pressure is
≥140/<90 mmHg.
 Isolated diastolic hypertension is
considered to be present when the blood
pressure is <140/≥90 mmHg.
12
Cont’d
 WHITE COAT HYPERTENSION — Many patients
are anxious when visiting the physician, leading to
an office blood pressure (BP) that may be
substantially higher than BP during normal daily
activities. The diagnosis of white coat
hypertension (also called isolated clinic or office
hypertension) is applied to patients with office
readings that average more than 140/90 mmHg
and reliable out of office readings that average
less than 140/90 mmHg. Having the BP in the
office taken by a nurse or technician, rather than
the physician, may minimize the white coat
effect.
13
Cont’d
 Hypertensive urgency — Severe
hypertension (as defined by a diastolic blood
pressure above 120 mmHg) in asymptomatic
patients is referred to as hypertensive urgency.
 A hypertensive emergency is defined as
severe hypertension that is associated with
acute end-organ damage.
 Specific clinical presentations of hypertensive
emergencies include:
14
Hypertensive emergency
 Hypertensive encephalopathy: Severe BP elevation
associated with lethargy, seizures, cortical blindness and
coma in the absence of other explanations.
 Malignant hypertension — Severe BP elevation
(commonly>200/120 mm Hg) associated with advanced
bilateral retinopathy (hemorrhages, cotton wool spots,
papilledema).
 Hypertensive thrombotic microangiopathy: Severe BP
elevation associated with hemolysis and thrombocytopenia in
the absence of other causes and improvement with BP-
lowering therapy.
 Other presentations of hypertensive emergencies include
severe BP elevation associated with cerebral hemorrhage,
acute stroke, acute coronary syndrome, cardiogenic
15
Drug induced hypertension
16
Cont’d
17
Cont’d
18
 When BP is evaluated using both office and
out-of officemeasurements (HBPM or ABPM),
patients are classified into four categories :
 Normotension (OBP and out-of-office BP not
elevated)
 Sustained hypertension (elevated OBP and out-
of-office BP)
 White coat hypertension (WCH) (elevated OBP
but not out-of-office BP)
 Masked hypertension (MH) (elevated out-of-
office but not OBP)
Cont’d
19
Diagnosis
20
Cont’d
21
Cont’d
22
Cont’d
23
Management of hypertension
 Most patients with hypertension require
lifelong medical therapy to achieve optimal BP
control. The 2018 European Guidelines
equally recommend five classes of
antihypertensive drugs; these include ACE
inhibitors (ACE-I),angiotensin receptor
blockers (ARB), beta blockers (BB), calcium
channel blockers (CCB), and diuretics
(thiazides and thiazide-like diuretics).
24
Cont’d
 Given the high rates of non-adherence to
antihypertensive medication, the treatment
regimen should be effective and above all
uncomplicated. Hence, the importance of
combination treatment is particularly
highlighted to improve adherence to therapy
and BP control. Therefore, the 2018 European
Guidelines recommend, especially in the
context of lower BP targets, to start
antihypertensive therapy with an initial dual
fixed-dose combination of ACE-I or ARB+CCB
or diuretic.
25
Cont’d
26
Cont’d
27
28
Cont’d
 These combinations should be the primary
therapy for most patients. Exceptions are
patients with grade 1 hypertension (especially
with SBP values <150 mmHg), low risk as well
as elderly (≥80 years of age) or frail patients. If
BP is not controlled with a two-drug
combination, it is recommended escalating to a
three-drug combination of ACE-I or
ARB+CCB+diuretic (i.e. a triple combination).
29
Cont’d
 If BP still remains uncontrolled, despite triple
therapy in sufficient doses, treatment should
be increased by addition of spironolactone 25–
50 mg or, if no tolerated, other diuretics such
as amiloride or higher doses of other diuretics,
a BB, or an alpha-blocker should be added.
Therapy with BB is recommended especially
for patients with cardiac comorbidities (heart
failure, angina pectoris postmyocardial
infarction, atrial fibrillation, or younger women).
30
Hydrochlorothiazide and the
increased the risk of cancer
31
 The warning published by the European Medicines Agency (EMA)
and the Federal Institute for Drugs and Medical Devices in Germany
regarding the potential risk of basal cell carcinoma (BCC) and
squamous cell carcinoma (SCC) of skin should be considered when
prescribing HCT-containing drugs.
 This letter was triggered by data from the Danish Cancer Registry
and the National Prescription Registry. These studies from Denmark
showed a cumulative dose-related relationship between HCT and
non-melanoma skin cancer (NMSC).
 The Danish study documented a dose dependent association
between HCT and the risk for BCC, ranging between 1.29 (95%CI
1.23–1.35) times for ≥50 g of HCT and 7.7 (95%CI 5.7–10.5) times
for ≥100 g of HCT for SCC.
 Chlorthalidone and indapamide are possible alternatives, but no
data are available on the potential risk for skin cancer of these
Valsartan recall
32
 The reason is the detection of a known carcinogen,
namely N-nitrosodimethylamine (NDMA), which can be
found in candesartan, irbesartan, losartan, olmesartan,
and valsartan.
 NDMA has been classified by the WHO International
Agency for Research on Cancer to be carcinogenic in
humans.
 If 100,000 patients would have received NDMA-
contaminated valsartan from Zhejiang Huahai
(manufacturing site where the highest levels of
contaminants were found) every day for 6 years in the
highest dose, it could result in 22 additional liver cancers
over the lifetime of these patients. The presence of
Life style modifications
33
Cont’d
34
References
 Hussam Al Ghorani etal. Hypertension trials
update journal of human hypertension Published
online: 12 January 2021
 2020 International Society of Hypertension Global
Hypertension Practice Guidelines
 2021European Society of Hypertension practice
guidelines for office and out-of-office blood
pressure measurement
 Dipiro pharmacotherapy 11th edition
 Uptodate
35
Thank you
36

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UPTODATE INFORMATION.pptx

  • 1. PHARMACOTHERAPY UPDATES PRESENTATION ON HYPERTENSION By Salahadin A. (B.Pharm) 1 6/10/2022 HIWOT FANA COMPREHENSIVE SPECIALIZED HOSPITAL CLINICAL PHARMACY and DPIS UNIT
  • 2. Outline  Introduction  Epidemiology and pathophysiology  Risk factors  Signs and symptoms  Classification  Diagnosis  Management of hypertension  Life style modifications  References 2
  • 3. Introduction  Arterial hypertension is the most frequent modifiable risk factor associated with cardiovascular morbidity and mortality . Despite the widespread availability of proven approaches to lower blood pressure (BP), i.e. lifestyle modification and pharmacotherapy, in many patients BP control to guideline recommended targets is not achieved. Current guidelines have recommended lowering SBP in most patients (<65 years) to targets of 120– 130 mmHg. The treatment targets in patients of older age and the neutral effects of lowering BP ≤ 140/90 mmHg in these patients are 3
  • 4. Epidemiology and pathophysiology  The Effect of systolic and diastolic blood pressure on cardiovascular outcomes.  High SBP and DBP associate with increased CV events. However, it remained unclear whether either SBP or DBP carries more prognostic information. This question was addressed in a study, which evaluated data from an integrated health care delivery system in the US. Between 2007 and 2016, more than 36 million office BP measurements were analyzed from around 1.3 million people. The study confirmed that both SBP and DBP increased the risk of CV events such as myocardial infarction and stroke. Elevated SBP had a greater prognostic effect on stroke and myocardial infarction. However, DBP influenced the prognosis independently of 4
  • 5. Cont’d  The 2017 American College of Cardiology and American Heart Association Guidelines on the management of hypertension revised the definition of hypertension, which has been defined as >130/>80 mmHg. Contrary, in the 2018 European Guidelines, the definition remained unchanged (>140/>90 mmHg). Against this background the prevalence of hypertension according to the different definition criteria were analyzed. The prevalence of hypertension increased from 18.9% with a threshold of >140/90 mmHg to 43.5% with >130/80 mmHg. An SBP of >130 mmHg was present in almost 50% of the participants over the age of 60 years. 5
  • 6. Cont’d  Hypertension not only increases the risk of stroke, myocardial infarction, and renal failure but also appears to be associated with heart valve diseases such as aortic valve stenosis and aortic valve insufficiency. In a study from the UK, 5.4 million patients with unknown CV disease or aortic valve disease at baseline were examined and followed for 9.2 years. A total of 20,680 patients (0.38%) were diagnosed with aortic valve stenosis and 6440 patients (0.12%) with aortic regurgitation. For each increase of 20mmHg in SBP, the relative risk [RR] of aortic valve stenosis increased by 41% (HR 1.41, 95% CI 1.38–1.45), and 38% for aortic regurgitation (HR: 1.38, CI 1.31–1.45), respectively. 6
  • 7. Cont’d  The participants were recruited between 2006 and 2010. A total of 130 gene variants were selected for the genetic determination of hypertension. A total of 1491 (0.45%) patients had aortic valve stenosis, 634 (0.19%) aortic regurgitation and 1736 (0.53%) mitral regurgitation. With each increase in SBP by 20 mmHg, the RR for aortic valve stenosis increased by 3.3-fold (odds ratio [OR] 3.26; 95% CI1.50–7.10, p=0.002), for aortic regurgitation by 2.5 (OR 2.59; 95% CI 0.75–8.92, p=0.13), and for mitral valve regurgitation by 2.2 (OR 2.19; 95% CI 1.07–4.47, p=0.03), respectively. An increase in SBP by 20mmHg was associated with an almost 3-fold higher risk to develop any of the three valvular diseases (OR 2.85; 95% CI 1.69–4.78, p < 0.001). These data suggest that lifetime exposure to elevated SBP appears to be associated with an increased 7
  • 8. Risk factors  Personal history of CVD (myocardial infarction, heart failure [HF], stroke, transient ischemic attacks [TIA], diabetes, dyslipidemia, chronic kidney disease [CKD], smoking status, diet, alcohol intake, physical activity, psychosocial aspects, history of depression).  Family history of hypertension, premature CVD, (familial) hypercholesterolemia, diabetes. 8
  • 9. Signs and symptoms  Symptoms/signs of hypertension/coexistent illnesses:  Chest pain  shortness of breath  palpitations  claudication  peripheral edema  headaches, blurred vision  nocturia, hematuria, dizziness. 9
  • 10. Classification  Primary Hypertension  Most individuals with high BP (over 90%) have essential or primary hypertension. Numerous potential mechanisms have been identified that contribute to the pathogenesis of essential hypertension, so identifying the exact underlying abnormality is not possible. Genetic factors may play a role in the development of essential hypertension by affecting sodium balance or other BP regulating pathways. 10
  • 11. Cont’d  Secondary Hypertension  Secondary hypertension, where either a comorbid disease or a drug (or other product) is responsible for elevating BP is much less common than primary hypertension (up to 10%).1 In most of these cases, renal dysfunction resulting from severe chronic kidney disease (CKD) or renovascular disease is the most common secondary cause. Certain agents (drugs or other products), either directly or indirectly, can increase BP and cause or exacerbate hypertension. 11
  • 12. Cont’d  Isolated systolic hypertension is considered to be present when the blood pressure is ≥140/<90 mmHg.  Isolated diastolic hypertension is considered to be present when the blood pressure is <140/≥90 mmHg. 12
  • 13. Cont’d  WHITE COAT HYPERTENSION — Many patients are anxious when visiting the physician, leading to an office blood pressure (BP) that may be substantially higher than BP during normal daily activities. The diagnosis of white coat hypertension (also called isolated clinic or office hypertension) is applied to patients with office readings that average more than 140/90 mmHg and reliable out of office readings that average less than 140/90 mmHg. Having the BP in the office taken by a nurse or technician, rather than the physician, may minimize the white coat effect. 13
  • 14. Cont’d  Hypertensive urgency — Severe hypertension (as defined by a diastolic blood pressure above 120 mmHg) in asymptomatic patients is referred to as hypertensive urgency.  A hypertensive emergency is defined as severe hypertension that is associated with acute end-organ damage.  Specific clinical presentations of hypertensive emergencies include: 14
  • 15. Hypertensive emergency  Hypertensive encephalopathy: Severe BP elevation associated with lethargy, seizures, cortical blindness and coma in the absence of other explanations.  Malignant hypertension — Severe BP elevation (commonly>200/120 mm Hg) associated with advanced bilateral retinopathy (hemorrhages, cotton wool spots, papilledema).  Hypertensive thrombotic microangiopathy: Severe BP elevation associated with hemolysis and thrombocytopenia in the absence of other causes and improvement with BP- lowering therapy.  Other presentations of hypertensive emergencies include severe BP elevation associated with cerebral hemorrhage, acute stroke, acute coronary syndrome, cardiogenic 15
  • 18. Cont’d 18  When BP is evaluated using both office and out-of officemeasurements (HBPM or ABPM), patients are classified into four categories :  Normotension (OBP and out-of-office BP not elevated)  Sustained hypertension (elevated OBP and out- of-office BP)  White coat hypertension (WCH) (elevated OBP but not out-of-office BP)  Masked hypertension (MH) (elevated out-of- office but not OBP)
  • 24. Management of hypertension  Most patients with hypertension require lifelong medical therapy to achieve optimal BP control. The 2018 European Guidelines equally recommend five classes of antihypertensive drugs; these include ACE inhibitors (ACE-I),angiotensin receptor blockers (ARB), beta blockers (BB), calcium channel blockers (CCB), and diuretics (thiazides and thiazide-like diuretics). 24
  • 25. Cont’d  Given the high rates of non-adherence to antihypertensive medication, the treatment regimen should be effective and above all uncomplicated. Hence, the importance of combination treatment is particularly highlighted to improve adherence to therapy and BP control. Therefore, the 2018 European Guidelines recommend, especially in the context of lower BP targets, to start antihypertensive therapy with an initial dual fixed-dose combination of ACE-I or ARB+CCB or diuretic. 25
  • 28. 28
  • 29. Cont’d  These combinations should be the primary therapy for most patients. Exceptions are patients with grade 1 hypertension (especially with SBP values <150 mmHg), low risk as well as elderly (≥80 years of age) or frail patients. If BP is not controlled with a two-drug combination, it is recommended escalating to a three-drug combination of ACE-I or ARB+CCB+diuretic (i.e. a triple combination). 29
  • 30. Cont’d  If BP still remains uncontrolled, despite triple therapy in sufficient doses, treatment should be increased by addition of spironolactone 25– 50 mg or, if no tolerated, other diuretics such as amiloride or higher doses of other diuretics, a BB, or an alpha-blocker should be added. Therapy with BB is recommended especially for patients with cardiac comorbidities (heart failure, angina pectoris postmyocardial infarction, atrial fibrillation, or younger women). 30
  • 31. Hydrochlorothiazide and the increased the risk of cancer 31  The warning published by the European Medicines Agency (EMA) and the Federal Institute for Drugs and Medical Devices in Germany regarding the potential risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of skin should be considered when prescribing HCT-containing drugs.  This letter was triggered by data from the Danish Cancer Registry and the National Prescription Registry. These studies from Denmark showed a cumulative dose-related relationship between HCT and non-melanoma skin cancer (NMSC).  The Danish study documented a dose dependent association between HCT and the risk for BCC, ranging between 1.29 (95%CI 1.23–1.35) times for ≥50 g of HCT and 7.7 (95%CI 5.7–10.5) times for ≥100 g of HCT for SCC.  Chlorthalidone and indapamide are possible alternatives, but no data are available on the potential risk for skin cancer of these
  • 32. Valsartan recall 32  The reason is the detection of a known carcinogen, namely N-nitrosodimethylamine (NDMA), which can be found in candesartan, irbesartan, losartan, olmesartan, and valsartan.  NDMA has been classified by the WHO International Agency for Research on Cancer to be carcinogenic in humans.  If 100,000 patients would have received NDMA- contaminated valsartan from Zhejiang Huahai (manufacturing site where the highest levels of contaminants were found) every day for 6 years in the highest dose, it could result in 22 additional liver cancers over the lifetime of these patients. The presence of
  • 35. References  Hussam Al Ghorani etal. Hypertension trials update journal of human hypertension Published online: 12 January 2021  2020 International Society of Hypertension Global Hypertension Practice Guidelines  2021European Society of Hypertension practice guidelines for office and out-of-office blood pressure measurement  Dipiro pharmacotherapy 11th edition  Uptodate 35