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Management of Hypertension. Ghada A Bawazeer. MSc, Pharm.D ., BCPS Ibrahim Sales, Pharm.D . Assistant Professors- Clinical Pharmacy Dept College of Pharmacy Sept. 2013. Background. Most diagnoses occurring between the third and fifth decades of life.

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management of hypertension

Management of Hypertension

Ghada A Bawazeer. MSc, Pharm.D., BCPS

Ibrahim Sales, Pharm.D.

Assistant Professors-Clinical Pharmacy Dept

College of Pharmacy

Sept. 2013

  • Most diagnoses occurring between the third and fifth decades of life.
  • Hypertension accounts for significant morbidity and mortality
  • One billion individual suffer from hypertension worldwide ( 26%). WHO year 2000 estimation
  • Seven millions deaths/year are attributed to hypertension
  • Billions of dollars are spent annually in direct and indirect cost of hypertension
hypertension in saudi arabia
Hypertension in Saudi Arabia
  • Elkhalifaet al (2011): prevalence of HTN 26%
  • Alzahrani(2011): prehypertension 37%, hypertension 18%
  • Alshehri(2008): 57.8% in diabetic patients
bp control rate
BP Control Rate
  • National Health and Nutrition Examination Survey (NHANES), United States, 2003–2010
    • Controlled 46.5%
    • Uncontrolled 53.5%
          • Unaware 39.4%
          • Aware and not treated 15.8%
          • Aware and treated 44.8 %

Data from National Health & Nutrition Examination Survey (NHNES)

what is the recommendation for bp screening
What is the recommendation for BP screening?
  • NICE
  • No National policy in KSA

Age: >40 yrs

Recheck in 5 yrs if normal

Recheck freq if Pre–HTN

If > 180 / 110, treat now

Age:> 18 yrs

Every 2 yrs if normal

Recheck in 1 yr if Pre–HTN

Stage 1 - Confirm in 2 months

Stage 2 - Confirm in 1 month

If > 180 / 110, treat now

blood pressure classification 2007 european societies of htn and cardiology
Blood Pressure Classification:2007 European Societies of HTN and Cardiology

ISH according to NICE: SBP >160 and DBP <90 mm Hg

cardiovascular risk and blood pressure
Cardiovascular Risk and Blood Pressure
  • Strong correlation between BP and CV morbidity and mortality.
  • Risk increases
  • Patients with prehypertension
  • SBP vs DBP
  • Essential HTN
    • > 90% unknown causes
      • Genetics
      • monogenic and polygenic forms of BP dysregulation
        • Genes affect
          • sodium balance, urinary kallikrein excretion, nitric oxide release, excretion of aldosterone, and angiotensinogen
  • Secondary
    • <10% have identifiable causes
      • removing the offending agent (when feasible) or treating/correcting the underlying comorbid condition should be the first step in management.
  • A: Accuracy, Apnea, Aldosteronism ( )
  • B: Bruits, Bad Kidneys: RAS / Renal Parenchyma/
  • Pheochromocytoma
  • C: Cushings, Coarctation of Aorta, Catechol ( )
  • D: Drugs, Diet
  • E: Erythropoietin ( ), Endocrinopathies/
hypertension pathophysiology
Hypertension Pathophysiology
  • Multiple factors that control BP are potential contributing components in the development of essential hypertension:
    • Genetics
    • Cardiac output
    • Sodium regulation
    • RAAS system
    • Sympathetic drive
    • Peripheral resistance
    • Vascular endothelium and smooth muscle
    • Electrolyte

How much blood flow

How much resistance to blood flow


Cardiac Output


Total peripheral resistance (TRP)

  • Functional vascular constriction and/or Structural vascular hypertrophy
    • Excess stimulation of the RAAS
    • ↑ Sympathetic
    • Genetic alterations of cell membranes
    • Endothelial-derived factors
    • Hyperinsulinemia (metabolic syndrome)
  • Increase pre-load
    • Increased fluid volume
      • excess sodium intake
      • renal sodium retention
  • Venous constriction:
    • Excess stimulation of
      • RAAS
      • Sympathetic
neuro humoral mechanisms
Neuro-Humoral Mechanisms
  • Renin-Angiotensin-Aldosterone System (RAAS)
    • Very complex endogenous system
    • Controlled mainly by the kidney
      • Influences vascular tone and sympathetic nervous system activity
  • Sympathetic nervous system
diagnostic algorithm for hypertension
Diagnostic algorithm for hypertension


BP Measurement,

History and Physical examination


Urgency / Emergency

Hypertension Visit 2

Target Organ Damage

or Diabetes

or BP ≥ 180/110?


of HTN



BP: 140-179 / 90-109




(If available)

Home BPM

(If available)

criteria for the diagnosis of hypertension and recommendations for follow up

Office BP

ABPM (If available)

Home BPM

Hypertension visit 3

>160 SBP or >100 DBP


of HTN

Awake BP





Awake BP

>135 SBP or

>85 DBP or


>130 SBP or

>80 DBP

< 135/85


<160 / 100



Hypertension visit 4-5

>140 SBP or

>90 DBP


of HTN


of HTN

Continue to follow-up

Continue to follow-up


of HTN

Continue to follow-up

< 140 / 90

Criteria for the diagnosis of hypertension and recommendations for follow-up

BP: 140-179 / 90-109

Repeat Home BPM


< 135/85

Patients with high normal blood pressure (office SBP 130-139 and/or DBP 85-89) should be followed annually.

  • Blood pressure measurement
    • Based on average of > 2 accurate measurements taken during two or more clinical encounters
patient evaluation
Patient Evaluation
  • Routine Laboratory Tests :
      • Urinalysis
      • Blood chemistry (potassium, sodium and creatinine)
      • Fasting glucose
      • Fasting total cholesterol and high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglycerides
      • Standard 12-leads ECG
      • Microalbuminurea (if diabetic patient)
patient evaluation1
Patient Evaluation
  • Optional Laboratory Tests
    • Investigation in specific patient subgroups
      • For those with diabetes or chronic kidney disease: assess urinary albumin excretion, since therapeutic recommendations differ if proteinuria is present.
      • For those suspected of having an endocrine cause for the high blood pressure, or renovascular hypertension, see following slides.
      • Other secondary forms of hypertension require specific testing.
assess global cardiovascular risk in all hypertensive patients
Assess global cardiovascular risk in all hypertensive patients

91% of hypertensive patients have at least 1 additional risk factor

 Risk factors =  Global CV risk

Rantala A, et al. J Intern Med 1999;245;163-74. Wannamethee S, et al. J Hum Hypertens 1998;12;735-41

iii assessment of the overall cardiovascular risk
III. Assessment of the overall cardiovascular risk

Cardiovascular Risk Factors

  • Presence of Risk Factors
    • Increasing age
    • Male gender
    • Smoking
    • Family history of premature cardiovascular disease (age< 55 in men and < 65 in women)
    • Dyslipidemia
    • Sedentary lifestyle
    • Unhealthy eating
    • Abdominal obesity
    • Dysglycemia (diabetes, impaired glucose tolerance, impaired fasting glucose)
  • Presence of Target Organ Damage
    • Microalbuminuria or proteinuria
    • Left ventricular hypertrophy
    • Chronic kidney disease (glomerular filtration rate < 60 ml/min/1.73 m2)
  • Presence of atherosclerotic vascular disease
    • Previous stroke or TIA
    • Coronary Heart Disease
    • Peripheral arterial disease

CV Risk Factors that may alter thresholds and targets in the treatment of HTN

methods of risk assessment
Methods of Risk Assessment
  • Clinical impression
  • Risk factor counting
  • Risk calculation or equation tools
  • Framingham hard coronary heart disease (CHD)
  • SCORE Canada – Systematic Cerebrovascular and Coronary Risk Evaluation
  • Cardiovascular Age™
  • Others: see notes

Will be discussed in more details during PPL 3 and Dyslipidemia lecture

what is the optimal bp target in hypertensive patients
What is the optimal BP target in hypertensive patients?
  • Optimal goal of BP is still debatable
  • J-curve phenomena: not conclusive hypothesis
  • Current evidences have many limitations to conclusively support 140/90 or 130/80 in HTN without diabetes, or <130/80 in patients with diabetes, CKD
  • There is a trend towards better outcomes with the lower range
goals of therapy
Goals of Therapy
  • Patient-oriented outcome:
    • Reducing CV risk
    • reduce HTN-associated morbidity and mortality.
      • target-organ damage (e.g., CV events, cerebrovascular events, heart failure, kidney disease).
  • Surrogate
    • to achieve a desired target BP
        • a tool that clinicians use to evaluate response to therapy
        • Not a guarantee of prevention of hypertension-associated TOD
approach to treatment
Approach to Treatment
  • Lifestyle modification


  • Pharmacological therapy
lifestyle recommendations for prevention and treatment of hypertension
Lifestyle Recommendations for Prevention and Treatment of Hypertension

To reduce the possibility of becoming hypertensive,

Reduce sodium intake to less than 1500 mg/day

  • Healthy diet: high in fresh fruits, vegetables, low fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources, low in saturated fat, cholesterol and salt in accordance with Canada's Guide to Healthy Eating.
  • Regular physical activity: accumulation of 30-60 minutes of moderate intensity dynamic exercise 4-7 days per week in addition to daily activities; For non-hypertensive or stage 1 hypertensive individuals, the use of resistance or weight training exercise (such as free weight lifting, fixed-weight lifting, or handgrip exercise) does not adversely influence blood pressure.
  • Low risk alcohol consumption: (≤2 standard drinks/day and less than 14/week for men and less than 9/week for women)
  • Attaining and maintaining ideal body weight (BMI 18.5-24.9 kg/m2)
  • Waist Circumference: Men <102 cm Women <88 cm
  • Tobacco free environment
impact of lifestyle therapies on blood pressure in hypertensive adults
Impact of Lifestyle Therapies on Blood Pressure in Hypertensive Adults

Padwal R et al. CMAJ 2005;173;(7);749-751

general principles
General Principles
  • Use first line classes
    • ACE, ARB, CCB, Diuretics, BB
    • All classes demonstrated CV risk reduction benefits
      • Major determinant in reduction of Cardiovascular Risk is BLOODPRESSUREREDUCTION
  • recommend treatment with drugs taken only once a day.
  • recommend generic where appropriate and minimize cost.
II. Indications for PharmacotherapyUsual blood pressure threshold values for initiation of pharmacological treatment for hypertension

Lifestyle modification is recommended for all regardless of BP

TOD=target organ damage

target organ damage tod
Target Organ Damage (TOD)
  • Cerebrovascular disease
    • transient ischemic attacks
    • ischemic or hemorrhagic stroke
    • vascular dementia
  • Hypertensive retinopathy
  • Left ventricular dysfunction
  • Left ventricular hypertrophy
  • Coronary artery disease
    • myocardial infarction
    • angina pectoris
    • congestive heart failure
  • Chronic kidney disease
    • hypertensive nephropathy (GFR < 60 ml/min/1.73 m2)
    • albuminuria
  • Peripheral artery disease
    • intermittent claudication
    • ankle brachial index < 0.9
when to initiate drug therapy
When to initiate drug therapy?
  • Stage 1 HTN
    • No TOD, low CV risk
      • Life style modification (LS)
    • TOD, moderate-high risk
      • LS + drug therapy
  • Stage 2 HTN
    • LS + drug therapy
      • JNC 7 recommend 2 combination therapy as initial therapy
  • Isolated Systolic HTN
    • When BP >140/90 mm Hg
algorithm for treatment of htn
Algorithm for treatment of HTN

presence of compelling Indications

degree of BP elevation

iii treatment of adults with systolic diastolic hypertension without other compelling indications



III. Treatment of Adults with Systolic/Diastolic Hypertension WITHOUT Other Compelling Indications

TARGET <140/90 mmHg


Lifestyle modification






A combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >20 mmHg systolic or >10 mmHg diastolic above target

*BBs are not indicated as first line therapy for age 60 and above

ACEI, ARB and direct renin inhibitors are contraindicated in pregnancy and caution is required in prescribing to women of child bearing potential

iii considerations regarding the choice of first line therapy
III. Considerations Regarding the Choice of First-Line Therapy
  • ACEI, renin inhibitors and ARBs are contraindicated in pregnancy and caution is required in prescribing to women of child bearing potential.
  • BBs are not recommended as first line therapy for patients age 60 and over without another compelling indication.
  • Diuretic-induced hypokalemia should be avoided through the use of potassium sparing agents if required.
  • The use of dual therapy with an ACEI and an ARB should only be considered in selected and closely monitored people with advanced heart failure or proteinuric nephropathy.
  • ACEI are not recommended (as monotherapy) for black patients without another compelling indication.
does the cv benefits seen in allhat for chlortahlidone extend to hydrochlorothiazide
Does the CV benefits seen in ALLHAT for Chlortahlidone extend to hydrochlorothiazide?
  • Chlorthalidone is the diuretic that was use in most of the influential trials
  • It is 2X more potent in lowering BP on a mg-per-mg basis than HCTZ
  • HCTZ has not been as extensively studied in major long term hypertension clinical trials.
  • It is notdefinitively known if the clinical benefits of reducing CV morbidity and mortality that have been proven with chlorthalidone can be extrapolated to HCTZ.
  • In clinical practice, however, CV benefits in hypertension apply to all thiazide-type diuretics, and benefits are considered a class effect.
add on therapy for systolic diastolic hypertension without other compelling indications

1. Add-on Therapy

  • Nonadherence
  • Secondary HTN
  • Interfering drugs or lifestyle
  • White coat effect

2. Triple or Quadruple Therapy

Add-on Therapy for Systolic/Diastolic Hypertension without Other Compelling Indications

If partial response to monotherapy

If blood pressure is still not controlled, or there are adverse effects, other classes of antihypertensive drugs may be combined (such as alpha blockers or centrally acting agents).

iii summary treatment of isolated systolic hypertension without other compelling indications
III. Summary: Treatment of Isolated Systolic Hypertension without Other Compelling Indications

TARGET <140 mmHg, < 150 mmHg for age > 80 years

Lifestyle modification


Thiazide diuretic




*If blood pressure is still not controlled, or there are adverse effects, other classes of antihypertensive drugs may be combined (such as ACE inhibitors, alpha blockers, centrally acting agents, or nondihydropyridine calcium channel blocker).

Dual therapy

  • Nonadherence
  • Secondary HTN
  • Interfering drugs or lifestyle
  • White coat effect

Triple therapy

partial response
Partial response
  • Option 1: Increase the dose of the first agent, remember:
    • Dose response curves for efficacy are relatively flat
    • 80% of the BP lowering efficacy is achieved at half-standard dose
  • Option 2: Add another drug from the 1st line classes
    • Combinations of standard doses have additive blood pressure lowering effects.
combination therapy
Combination therapy
  • Most patients will require 2 or more agents to achieve BP control
  • Consider combination from among the first line drugs
  • Different possible combinations, consider patient factors and cost.
  • CHEP GL:
    • DHP-CCB + Diuretic
    • DHP-CCB + ACEI or ARB
    • DHP-CCB + BB
considerations when selecting a combination therapy
Considerations when Selecting a Combination Therapy
  • Use combination from first line classes
  • Many fixed-dose combination products are commercially available, consider patient factors and cost
    • some are generic
  • Most products contain a thiazide-type diuretic and have multiple dose strengths available.
  • Individual dose titration is more complicated with fixed-dose combination
considerations when selecting a combination t herapy
Considerations when Selecting a Combination Therapy
    • ACEI + ARB, not recommended (Grade A)
  • If a diuretic is not used as first or second line therapy, triple dose therapy should include a diuretic, when not contraindicated
  • If a BB was used initially, a CCB is preferred over thiazide-type diuretic, to reduce the person’s risk of developing diabetes.
  • Caution should be exercised in combining anon-DHP CCB and a BB to reduce the risk of bradycardia or heart block
considerations when selecting a combination t herapy1
Considerations when Selecting a Combination Therapy
  • Use caution in initiating therapy with 2 drugs in whom adverse events are more likely (e.g. frail elderly, those with postural hypotension or who are dehydrated).
choice of antihypertensive agent
Choice of antihypertensive agent

HTN with compelling indications:

choice of pharmacological treatment for hypertension
Choice of Pharmacological Treatment for Hypertension

Individualized treatment

  • Compelling indications:
    • Ischemic Heart Disease
    • Recent ST Segment Elevation-MI or non-ST Segment Elevation-MI
    • Left Ventricular Systolic Dysfunction
    • Cerebrovascular Disease
    • Left Ventricular Hypertrophy
    • Non Diabetic Chronic Kidney Disease
    • Renovascular Disease
    • Smoking
  • Diabetes Mellitus
    • With Nephropathy
    • Without Nephropathy
  • Global Vascular Protection for Hypertensive Patients
    • Statins if 3 or more additional cardiovascular risks
    • Aspirin once blood pressure is controlled
2013 canadian hypertension education program chep
2013 Canadian Hypertension Education Program (CHEP)

Important messages from past recommendations

  • Patients with diabetes are at high cardiovascular risk
  • Most patients with diabetes have hypertension
  • Treatment of hypertension in patients with diabetes reduces total mortality, myocardial infarction, stroke, retinopathy and progressive renal failure rates.
  • Treating hypertension in patients with diabetes reduces death and disability and reduces health care system costs
  • In diabetes, TARGET <130 systolic and <80 mmHg diastolic
  • If a patient has both diabetes and CKD, TARGET <130 systolic and <80 mmHg diastolic
  • The use of the combination of ACE inhibitor with an ARB should only be considered in selected and closely monitored people with advanced heart failure or proteinuric nephropathy.
xii treatment of hypertension in association with diabetes mellitus summary




XII. Treatment of Hypertension in association with Diabetes Mellitus: Summary

Threshold equal or over 130/80 mmHg and TARGET below 130/80 mmHg

A combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >20 mmHg systolic or >10 mmHg diastolic above target. Combining an ACEi and a DHP-CCB is recommended.

ACE Inhibitor

or ARB

1. ACE Inhibitor or ARB


2. DHP-CCB or Thiazide diuretic



> 2-drug combinations

Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB

Combinations of an ACEI with an ARB are specifically not recommended in the absence of proteinuria

More than 3 drugs may be needed to reach target values for diabetic patients

If Creatinine over 150 µmol/L or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired

accord study results and rationale for lack of impact on bp recommendations
ACCORD Study: Results and rationale for lack of impact on BP recommendations
  • Overall BP study was neutral with no benefit of systolic target < 120 mmHg vs < 140 mmHg for primary outcome, yet:
  • Power issue: Annual rate of primary outcome 1.87% in the intensive arm versus 2.09% in the standard arm vs 4%/year event rate projected during sample size calculations
  • Significant interaction between BP and glycaemia control studies such that those in usual care glycaemia group (A1c 7%+) had a significant improvement in primary outcome with lower BP target
  • Secondary outcome for stroke reduction showed a benefit for lower BP target (41% RRR)
  • Therefore no clear evidence supporting a change in BP targets for people with diabetes at this point

ACCORD study NEJM 2010

when would you consider bb
When would you consider BB?
  • Not first line therapy in uncomplicated HTN by almost all guidelines
  • Doesn’t reduce CV risk as does ACEI/ARB, CCB, diuretics in patients with only HTN.
  • Consider to use if compelling indication present (MI, CAD, HF)
  • those with an intolerance or contraindication to ACEI or ARBs, CCB
  • women of child-bearing potential
  • people with evidence of increased sympathetic drive.
  • Isolated systolic hypertension is common in the elderly
    • Treat similar to previous discussion
  • What about the very elderly?
  • Studies showed HTN in the very elderly (>80 yrs) should be treated
    • HYVET trial: reduced mortality at BP <150/90
  • What is the goal of BP in the very elderly?
    • Not clear
  • Use diuretics with caution: susceptible to volume depletion
  • Elderly patients are more sensitive to :
    • volume depletion and sympathetic inhibition than younger patients
      • orthostatic hypotension >> dizziness >> increase risk of falls
  • Use caution with diuretics, ACEI, and ARBs provide significant benefits and can safely be used in the elderly,
    • Start at low initial doses
  • Avoid centrally acting agents and alpha-blockers
patients susceptible to orthostatic hypotension
Patients susceptible to orthostatic Hypotension
  • Orthostatic Hypotension
    • SBP decrease of ↓ more than 20 mm Hg or DBP ↓more than 10 mm Hg when changing from supine to standing.
  • Risk factors: elderly, DM, severe volume depletion, baroreflex dysfunction, autonomic insufficiency, and use of venodilators
  • Start with low doses of the antihypertensive agent
htn pregnancy
HTN & Pregnancy
  • HTN in pregnancy major cause of maternal and neonatal morbidity and mortality.
  • Preeclampsia:
    • Elevated BP > 140/90 that appears after 20 weeks gestation accompanied by new-onset proteinuria (> 300 mg/24 hours). life-threatening complications for mother and fetus.
    • Definitive treatment of preeclampsia is Delivery
htn pregnancy1
HTN & Pregnancy
  • Eclampsia:
    • onset of convulsions in preeclampsia.
    • A medical emergency.
    • Treatment:
      • Delivery
      • restricting activity, bed rest, and close monitoring.
      • Antihypertensives prior to induction of labor if DBP is > 105 mm Hg with a target DBP of 95 to 105 mm Hg.
      • IV hydralazine (common), IV labetalol
      • Immediate-release oral nifedipine should not be used
htn pregnancy2
HTN & Pregnancy
  • Gestational hypertension:
    • New onset hypertension after mid-pregnancy, no proteinuria
  • chronic hypertension
    • elevated BP that is noted before the pregnancy began
    • Treatment:
      • consensus about most appropriate therapy in pregnancy is lacking
      • Methyldopa is still considered the drug of choice
      • Other agents are listed in table 19-7
htn reactive airway diseases
HTN & Reactive airway diseases
  • Cardioselective BB can be safely used in patients with Asthma or COPD and HTN (with compelling indication)
htn in patients with pad
HTN in Patients with PAD
  • noncoronary form of atherosclerotic vascular disease
  • Use ACEI
  • BB can be problematic in PAD, but not contraindicated in this group
  • Use BB with α and βand blcoking activity (carvedilol)
iv vascular protection for hypertensive patients statins
IV. Vascular Protection for Hypertensive Patients: Statins

In addition to current Canadian recommendations on management of dyslipidemia, statins are recommended in high-risk hypertensive patients with established atherosclerotic disease or with at least 3 of the following criteria:

• Male

• Age 55 or older

• Smoking

• Total-C/HDL-C ratio of 6 mmol/L or higher

• Family History of Premature CV disease


• ECG abnormalities

• Microalbuminuria or Proteinuria

ASCOT-LLA Lancet 2003;361:1149-58

iv vascular protection for hypertensive patients asa
IV. Vascular Protection for Hypertensive Patients: ASA

Consider low dose ASA

Caution should be exercised if BP is not controlled.

use of aspirin in patients with htn
Use of Aspirin in patients with HTN
  • Secondary Prevention

Daily low dose aspirin is established in the secondary prevention of cardiovascular disease

aspirin in patients with diabetes and htn
Aspirin in Patients with Diabetes and HTN

(ACCF/AHA Class III, Level of Evidence: C) (ADA Level of Evidence: C)

  • Low dose aspirin (75-162 mg) in Diabetic patients at increased CVD risk (10 year risk of CVD events over 10%) and not at increased risk for bleeding

(ACCF/AHA Class IIa, Level of Evidence: B) (ADA Level of Evidence: C)

  • Low dose ASA maybe considered in diabetics at intermediate CV risk

(ACCF/AHA Class IIb, Level of Evidence: C) (ADA Level of Evidence: E)

  • Do Not recommend low dose aspirin in patients at low risk. Potential Harm offset potential benefit

Circulation. 2010;121:2694-2701


High CV risk

  • Age M >50 , W >60
  • + one or more of:
  • Smoking
  • Hypertension
  • Dyslipidemia
  • FamHx of premature CVD
  • albuminuria
    • High risk of bleeding
  • history of previous GI bleeding or
  • PUD
  • concurrent use of medications that increase bleeding risk, such as NSAIDS or warfarin
  • Moderate CV risk
  • Younger patients
  • + one or more RF
  • Older patients with 10-year risk of 5-10%
  • Low CV risk
  • Age M <50 yr , W <60 yr. With no major additional
  • CVD risk factors;
  • 10-year CVD risk under 5%

Circulation. 2010;121:2694-2701

resistant htn
Resistant HTN
  • patients who are uncontrolled (failure to achieve goal BP of <140/90 mm Hg, or lower when indicated) with the use of three or more drugs.
  • Causes:
  • Treatment
    • assure adequate diuretic therapy
    • appropriate use of combination therapies
    • use alternative antihypertensive agents when needed
hypertensive crisis
Hypertensive Crisis
  • presence of very elevated BP, typically greater than 180/120 mm Hg.
  • HTN Urgencies are not associated with acute or immediately progressing target-organ injury
  • HTN emergencies are associated with acute or immediately progressing target-organ injury
    • encephalopathy, intracranial hemorrhage, acute left ventricular failure with pulmonary edema, dissecting aortic aneurysm, unstable angina, and eclampsia or severe hypertension during pregnancy.
hypertensive urgency
Hypertensive Urgency
  • Don’t correct rapidly
  • Goal:
    • gradual reduction in BP to prevent cerebrovascular accidents, MI, and acute kidney failure.
  • adjusting maintenance therapy,
    • Add a new agent
    • and/or by increasing the dose of a present medication.
    • Use oral agents over a period of several hours to several days.
    • Reevaluate patient within and no later than 7 days (preferably after 1 to 3 days)
hypertensive emergency
Hypertensive Emergency
  • Require hospitalization and administration of parenteral therapy
  • See table 19-11
  • Goal:
    • a reduction in MAP of up to 25% within minutes to hours.
    • If the patient is then stable, BP can be reduced toward 160/100 to 160/110 mm Hg within the next 2 to 6 hours.
      • Rapid drops in BP may lead to end-organ ischemia or infarction.
    • If patients tolerate this reduction well, additional gradual reductions toward goal BP values can be attempted after 24 to 48 hours.
htn non adherence
HTN & Non-Adherence
    • 50% of patients with newly diagnosed hypertension are continuing treatment at 1 year
  • Identify potential barriers to adherence
    • Misunderstanding of Condition
    • Denial of illness / Asymptomatic
    • Lack of patient involvement in care plan
    • Unexpected adverse effects of medicine
    • Too many f/u visits, lab requests
    • Emphasis on PCMH Goals / Objectives
htn non adherence1
HTN & Non-Adherence
  • Assess adherence to pharmacological and non-pharmacological therapy at every visit
  • Teach patients to take their pills on a regular schedule associated with a routine daily activity e.g. brushing teeth.
  • Simplify medication regimens using long-acting once-daily dosing
  • Utilize fixed-dose combination pills
  • Utilize unit-of-use packaging e.g. blister packaging
htn non adherence2
HTN & Non-Adherence
  • Replacing multiple pill antihypertensive combinations with single pill combinations!
  • Encourage greater patient responsibility/autonomy in regular monitoring of their blood pressure
  • Educate patients and patients' families about their disease/treatment regimens verbally and in writing
  • Use an interdisciplinary care approach coordinating with work-site health care givers and pharmacists if available
monitoring therapeutic plan for patient with htn
Monitoring Therapeutic Plan for patient with HTN
  • Efficacy
    • BP: 2-4 weeks after initiation and each dose change
    • Once BP goal is reached: monitor BP q 3-6 months
    • Adherence at every visit, annual review of meds
  • Disease progression
    • Periodically ,
    • S&S of progressive hypertension-associated TOD
  • Toxicity:
    • See Table 19-8
monitoring therapeutic plan for patient with htn1
Monitoring Therapeutic Plan for patient with HTN
  • Patient Education on:
    • Home BP measurement:
      • educate patient to measure during the early morning hours for most days and then at different times of the day on alternative days of the week
    • Use of automated ambulatory BP monitoring
      • Currently used in situations such as suspected white coat hypertension.
  • Thiazides are more effective antihypertensives than loop diuretics in most patients
  • Loops are preferred in chronic kidney disease
  • High dietary sodium intake can blunt their effect
  • very effective in lowering BP when used in combination with most other antihypertensives
    • Additive/synergisticeffect
    • Counteract a compensatory increase in sodium and fluid retention may be seen with antihypertensive agents.
  • use usual doses to avoid adverse metabolic effects
  • Ideally, dose in the morning if given once daily and in the morning and late afternoon when dosed twice daily to minimize risk of nocturnal diuresis
  • chlorthalidone is approximately 1.5 times as potent as HCTZ; have additional benefits in osteoporosis; may require additional monitoring in patients with a history of gout or hyponatremia

Diuretics SE Profile:

  • Electrolyte imbalance:
    • Hypokalemia (more pronounced with loops)
    • Hypomagnesemia
    • Monitor closely especially in patients with LVH, coronary disease, on digoxin therapy >> serious cardiac arrhythmias
  • Hypercalcemia (loops: hypocalcemia)
  • sexual dysfunction
  • Metabolic disturbances:
    • Hyperuricemia
      • If gout occur in a patient who requires diuretic therapy, allopurinol can be given to prevent gout and will not compromise the antihypertensive effects of the diuretic
  • Hyperglycemia and dyslipidemia (more with TH-like)
    • usually are transient and often inconsequential.
  • Potassium-sparing diuretics can cause hyperkalemia
    • Avoid use with ACEI, ARB, direct renin inhibitor, K supplements
    • Eplerenone selective ARA, more hyperkalemia than spironolactone
diuretics interactions
Diuretics Interactions
  • Can be used safely with most agents
  • concurrent administration with lithium may result in increased lithium serum concentrations and can predispose patients to lithium toxicity.
thiazide induced hyperglycemia
Thiazide induced Hyperglycemia
  • Patients on thiazide-type diuretic therapy have a higher incidence of developing type 2 diabetes
  • Rational:
    • insulin utilization is linked to intracellular potassium. Hypokalemia predispose to largest increases in glucose concentrations. The potassium cut point at which this relationship appears is when serum potassium is less than 4.0 mEq/L.
thiazide induced hyperglycemia1
Thiazide induced Hyperglycemia
  • thiazide-type diuretics are NOT contraindicated in patients with diabetes, however , linicans should minimize hyperglycemia by:
    • use the lowest effective dose (e.g., hydrochlorothiazide 12.5 or 25 mg daily)
    • maintain serum potassium values between 4.0 and 5.0 mEq/L
    • Encourage lifestyle modification.
angiotensin converting enzyme inhibitors
Angiotensin Converting Enzyme Inhibitors
  • Has many evidence-based uses in patients with HTN and any compelling indications
  • Most ACEI can be dosed once daily in hypertension
    • Sometime, twice daily dosing is needed to maintain 24-hour effects with enalapril, benazepril, moexipril, quinapril and ramipril.
  • well tolerated
angiotensin converting enzyme inhibitors1
Angiotensin Converting Enzyme Inhibitors

ACEI Side Effects Profile

  • Hypotension:
    • starting dose should be reduced (almost by 50%) in patients at risk of hypotension (who are sodium or volume depleted, in heart failure exacerbation, very elderly, or on concurrent vasodilators or diuretics)
  • Start low and go slow
angiotensin converting enzyme inhibitors2
Angiotensin Converting Enzyme Inhibitors
  • Hyperkalemia
    • Risk factors: CKD, concomitant K-sparing diuretic, ARA, ARB, direct renin inhibitor and or K-supplements
    • Monitor K, creatinine values within 4 week, when starting or increasing the dose
angiotensin converting enzyme inhibitors3
Angiotensin Converting Enzyme Inhibitors
  • Acute kidney failure:
    • Risk factors: pre-existing kidney disease severe bilateral renal artery stenosis or severe stenosis in artery to solitary kidney
    • Slowly titrate the dose and monitor kidney function
    • Anticipate small increase in serum creatinine (MOA of the drug)
      • If more than 35% increase in Cr from baseline (< 3mg/dl) or absolute increase of >1 mg/dLyo may need to stop ACEI or reduce dose
angiotensin converting enzyme inhibitors4
Angiotensin Converting Enzyme Inhibitors
  • Angioedema
    • include lip and tongue swelling and possibly difficulty breathing. Serious cases, laryngeal edema and/or pulmonary symptoms
    • D/C ACEI and avoid future use
    • May use ARB
      • TRANSCEND study
angiotensin converting enzyme inhibitors5
Angiotensin Converting Enzyme Inhibitors
  • Persistent cough
    • In 20% of patients
    • Inhibition of bradykinin
    • Pregnancy:
      • major congenital malformations
      • do not use in pregnancy or in patients with a history of angioedema
angiotensin receptor blockers1
Angiotensin Receptor Blockers
  • Studies established that the CV event lowering benefits of ARB therapy are similar to ACE inhibitor therapy in hypertension.
    • ON-TARGET study
      • ACEI-based vs. ARB-based therapy vs. ACEI+ARB
      • No difference in 1 end point: CV death or hospitalization for heart failure
      • Combo regimen: no additional benefit and more SE
  • Comparable CV benefit as CCB-based therapy
angiotensin receptor blockers2
Angiotensin Receptor Blockers
  • Lowest incidence of SE
  • renal insufficiency
  • Hyperkalemia
  • Orthostatic hypotension.
  • Apply same precautions as with ACE inhibitors
  • should not be used in pregnancy
calcium channel blockers2
Calcium Channel Blockers
  • Two subclasses of CCBs:
    • DHP and non-DHP
      • pharmacologically very different
      • Antihypertensive effectiveness is similar
      • Different pharmacodynamic effects.
    • DHP studied in the ALLHAT study
    • Non-DHP
    • have additional benefits in patients with atrial tachyarrhythmia. Avoid in HF
calcium channel blockers3
Calcium Channel Blockers
  • CCB side effects profile
  • DHP:
    • Dizziness, flushing, headache, gingival hyperplasia, peripheral edema
    • mood changes
    • various gastrointestinal complaints.
    • Immediate release: reflex sympathetic stimulation
  • Non-DHP CCB:
    • anorexia, nausea, peripheral edema, and hypotension. Verapamil causes constipation in about 7% of patients., less with diltiazem
calcium channel blockers4
Calcium Channel Blockers
  • drug interactions
    • CYP450 A3A4 (diltiazem, verapamil)
    • Caution with: cyclosporine, digoxin, lovastatin, simvastatin, tacrolimus, theophylline
  • Caution with non-DHP & BB: risk of heart block
  • CCB Hepatic metabolism inhibited by grape fruit juice (~ 1 qt/d= 4cups)
ccb formaulations
CCB Formaulations
  • DHP:
    • Extended-release products are preferred for HTN
    • Immediate release DHP associated with an increased incidence of adverse CV effects
      • Not to be used in HTN
  • Non-DHP
    • SR formulation not AB rated by the FDA as interchangeable on mg-per-mg basis
      • Calan SR and Verelan
        • Different biopharmaceutical release mechanisms
      • Clinical significant: none
chronotherapeutic formulations
Chronotherapeutic formulations
  • Rational:
    • designed to target the circadian BP rhythm
    • blunting the early morning BP surge may result in greater reductions in CV events than conventional products in the morning.
    • Verapamil: Covera HS and Verelan PM, both dosed pm
    • Diltiazem: Cardizem LA, dosed am or pm
  • CONVINCE trial
    • Controlled ONsetVerapamil Investigation of Cardiovascular End-points
      • No difference in CV events compared to a thiazide-type diuretic–BB regimen
beta blockers2
Beta Blockers
  • Not a first line without compelling indications
  • Compelling indications :
    • Post-MI, coronary artery disease
    • left ventricular dysfunction and diabetes
    • BB based therapy is not associated with lower CV events
        • Possible explanation:
          • Most studies used atenolol
          • atenolol was used as once daily instead of twice daily (t1/2 is 6-7 hrs)
beta blockers3
Beta Blockers
  • All BB provide a similar degree of BP lowering
  • Different Pharmacodynamic properties:
    • Cardioselectivity
    • ISA
    • membrane-stabilizing effects
  • Cardioselective BB are preferred when treating HTN than nonselective BB
    • cardioselectivity is a dose-dependent phenomenon
beta blockers4
Beta Blockers
  • BB with ISA
    • do not appear to reduce CV events
    • resting heart rate, CO, and peripheral blood flow are not reduced
    • may increase risk post-MI or in those with coronary artery disease.
    • rarely used
  • All -blockers exert a membrane-stabilizing action on cardiac cells when large doses are given
    • Of value when BB are used as an antiarrhythmic agent.
beta blockers5
Beta Blockers
  • BB Pharmacokinetic differences
    • first-pass metabolism
    • route of elimination (renal vs. hepatic)
    • lipophilicity (more CNS SE)
    • serum half-lives.
beta blockers6
Beta Blockers
  • BB Side Effect Profile
    • Bradycardia
    • 2nd , 3rd heart block
    • Acute HF: if initial dose is high
    • Avoid abrupt cessation
      • abrupt discontinuation may present as tachycardia, sweating, and generalized malaise in addition to increased BP.
      • Taper gradually over 1 to 2 weeks
beta blockers7
Beta Blockers
  • Metabolic SE of BB
    • May increase serum cholesterol and glucose values
    • Transient , little clinical significance.
  • erectile dysfunction
  • Cold extremities
  • aggravate intermittent claudication or Raynaud phenomenon
aliskiren tekturna
Aliskiren (Tekturna®)
  • The first oral direct renin inhibitor
  • Block RAAS at point of activation

Nature Reviews Drug Discovery 7, 399-410 (May 2008)

aliskiren tekturna1
Aliskiren (Tekturna ®)
  • Approved in 2007 as mono and combination therapy
  • no long-term studies evaluating CV event reduction and significant drug cost compared to older generic agents with outcome data
  • Available products: single drug or combination with:
    • amlodipine
    • HCTZ
    • Valsartan: no longer marketed
    • triple combination tab with HCTZ and amlodipine
aliskiren tekturna2
Aliskiren (Tekturna ®)
  • Dose: 150-300 mg once daily
    • High fat meal decrease absorption
  • Side effects:
    • Similar to ACEI and ARB
      • Consider avoiding in women during childbearing years
    • Can cause diarrhea
    • Monitor K and serum Cr after initiation or titration of dose
    • Caution: angioedema
aliskiren tekturna3
Aliskiren (Tekturna ®)
  • ALTITUDE trial:
    • Trial was terminated early
    • Aliskiren added to ACEI or ARB therapy in patients with type 2 diabetes mellitus and renal impairment compared with a placebo add-on
    • An increase in nonfatal stroke, renal complications,
    • hyperkalemia, and hypotension and no apparent benefits among patients randomized to aliskiren group
  • FDA Black Box Warning:
    • Use in combination with ACEI or ARB in patients with diabetes or renal impairment (GFR<60 ml/min) should be avoided.

(Curr Drug Saf. 2012 Feb;7(1):76-85)