PHARMACOTHERAPY OF HYPERTENSION

Based on New Guidelines

Fariborz Nikaeen; MDInterventional cardiologist

2 november 2015

Prevalence of HypertensionAdults have elevated Blood Pressure

Patients with HTN

Diagnosed HTN 78%

Treated HTN 68%

Uncontrolled HTN 38%

Resistant HTN 9%

Patients with HTN

Diagnosed HTN

Treated HTN

Uncontrolled HTN

HTN=Hypertension

Only relying on manual office pressures misses out on white coat and masked hypertension

Manual Office BP mmHg

Am

bula

tory

BP m

mH

g

Hypertension

NormotensionWhite Coat Hypertension

Masked Hypertension

200

180

160

140

120

100100 120 140 160 180 200

135

2014

The prognosis of masked hypertension

Prevalence is approximately 10% in hypertensive patients.

0

5

10

15

20

25

30

35

Normal23/685

White coat24/656

Uncontrolled41/462

Masked236/3125

CV

eve

nts

per

100

0 p

atie

nt-y

ear

CV Events

Okhubo et al. J. Am. Coll. Cardiol. 2012;46;508-515

2014

What’s The Worst That Could Happen?

Importance OF HTN

• HTN is the most important modifiable CV risk factor

• HTN is the commonest cause of premature death

• HTN is the commonest cause of CKD & commonest cause of ESRD in elderly

• Continuum of increasing CV risk from SBP 115mmHg

• CV mortality doubles for every10/5 increase in BP>120/70

• High BP causes:

• 35% of all cardiovascular deaths

• 50% of all stroke deaths

• 25% of all CAD deaths

• 50% of all congestive heart failure

Benefits of Lowering BP

New Guidelines for Hypertension• National Institute for Health and Clinical Excellence

(NICE), 2011• Kidney Disease: Improving Global Outcome (KDIGO),

2012• European Society of Hypertension/European Society of

Cardiology, (ESH/ESC), 2013• American Diabetes Association (ADA), 2014• American Society of Hypertension and the International

Society of Hypertension (ASH/ISH), 2014• Eighth Joint National Committee (JNC8), 2014

JNC 82014 Evidence-Based Guideline for

the Management of

High Blood Pressure in Adults

JNC 8 (2014 Hypertension Guideline Management Algorithm)

1

JNC 8 (2014 Hypertension Guideline Management Algorithm)

2

JNC 8 2014 Hypertensionguideline

Goal BP and Initial Drug Therapy for Adults With Hypertension

Population Goal BP,mm Hg

Initial Drug Treatment Options

General ≥60 y <150/90 Nonblack: thiazide-type diuretic, ACEI, ARB, or CCBBlack: thiazide-type diuretic or CCB

General <60 y <140/90 Nonblack: thiazide-type diuretic, ACEI, ARB, or CCBBlack: thiazide-type diuretic or CCB

Diabetes <140/90 Thiazide-type diuretic, ACEI, ARB, or CCB

CKD <140/90 ACEI or ARB

Start one drug, titrate to maximum dose, and then add a second drug

Start one drug and then add a second drug before achieving maximum dose of the initial drug

Begin with 2 drugs at the same time, either as 2 separate pills or as a single pill combination

A

C

B

Strategies to Dose of Antihypertensive Drugs

Ratio of Incremental SBP lowering effect at “standard dose”– Combine or Double?

1.04 1

1.16

0.891.01

0.19 0.23 0.2

0.37

0.22

0

0.2

0.4

0.6

0.8

1

1.2

1.4

Thiazide β-blocker ACE-I CCB All

Combine Double

Incr

emen

al S

BP

red

uct

ion

rat

ioO

bse

rved

/Exp

ecte

d (

add

itiv

e)

BP lowering effects from antihypertensive drugs

Dose response curves for efficacy are relatively flat

80% of the BP lowering efficacy is achieved at half-standard dose

Combinations of standard doses have additive blood pressure lowering effects

key issues must be addressed during the initial office evaluation of a person with elevated BP readings:

1. Documenting that the BP is elevated 2. Defining the presence or absence of TOD related

to hypertension3. Screening for other CV risk factors that often accompany

hypertension4. Estimating the person’s absolute risk for CV and renal

disease

5. Assessing whether the person is likely to have an identifiable cause of HTN (secondary HTN) and should have further diagnostic testing to confirm or exclude that diagnosis

6. Obtaining data that may be helpful in the initial and subsequent choices for therapy.

GENERAL RULES1-Decrease CV mortality :ACEI ;ARBs, Diuretics, 2-Age:Elderly ,Middle age,Women at reproductive age3- Race/Ethnicity : Blacks,African-American ,whites,….4- Concomitant disease & Conditions: BPH,CRF,Asthma, …5- Compelling indications:Post MI,CKD , stroke,DM ,CHF, CAD,…6-Long acting Drugs : Patient compliance7-Start low (dosage)&go slow

Treatment of Hypertension

CONSIDER

• Nonadherence• Secondary HTN• Interfering drugs or

lifestyle• White coat effect

Dual Combination

Triple Therapy

Lifestyle modification

Thiazidediuretic ACEI Long-acting

CCB

TARGET <140/90 mmHg For age<60 & <150/90 mmHg For age ≥60

ARB

Initial therapy

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

Treatment of Isolated Systolic Hypertension

CONSIDER

• Nonadherence• Secondary HTN• Interfering drugs or

lifestyle• White coat effect

Thiazide Amlodipin

Dual therapy

Triple therapy

Lifestyle modificationtherapy

ARB orACEI

TARGET : SBP <140 mmHg, for age<60 yr SBP< 150 mmHg for age > 60 years

*If blood pressure is still not controlled, or there are adverse effects, other classes of antihypertensive drugs may be combined

Choice of Pharmacological Treatment for Hypertension

• Compelling indications:• Stable IHD• Recent ST Elevation-MI or non-ST Elevation-MI• LV Systolic Dysfunction• Cerebrovascular Disease• Non Diabetic CKD

• Diabetes Mellitus• With Nephropathy• Without Nephropathy

Treatment of HTN in Patients with Stable IHD

• Caution should be exercised when combining (Verapamil Or Diltiazem) +beta-blocker• If abnormal systolic left ventricular function: avoid (Verapamil or Diltiazem)• Dual therapy with an ACEI +ARB are not recommended in the absence of refractory CHF• The combination of an ACEi and CCB is preferred

1. Beta-blocker2. Long-acting CCBStable angina

ACEI are recommended for most patients with established CAD*

ARBs are not inferior to ACEI in IHD

Short-actingnifedipine

Treatment of HTN in Patients with Recent STEMI or NSTEMI

Amlodipine*(Avoid diltiazem, verapamil)

Beta-blocker +ACEI (or ARB)Recent

myocardialinfarction

CHF?

NO

YES

Long-acting CCB

If beta-blocker contraindicated( Asthma, COPD, Heart Block,….) or not effective

*

Treatment of HTN with LV Systolic Dysfunction

If additional therapy is needed:• Diuretic (Thiazide for hypertension; Loop for volume control Or eGFR,30cc/min) • Spironolactone : for CHF NYHA-FC II-IV or post MI (clinical HF Or LVEF<40% Or DM)

SystolicLV

dysfunction

• ACEI(or ARB)+Beta blocker (carvedilol Or metoprolol)

Up titrate doses of ACEI or ARB

If ACEI and ARB are contraindicated: Hydralazine + Isosorbide dinitrate

If additional antihypertensive therapy is needed:

• ACEI / ARB Combination• Amlodipine

Verapamil Diltiazem

Treatment of HTN in Association With StrokeAcute Stroke: Onset to 72 Hours

Treat extreme BP elevation (systolic > 220 mmHg, diastolic > 120 mmHg)

by 15-25% over the first 24 hour with gradual reduction after.

Acute ischemic

Stroke

Avoid excessive lowering of BP which can exacerbate ischemia

Strongly consider blood pressure reduction in all patients after the acute phase of stroke or TIA .

Target BP < 140/90 mmHg

An ACEI / diuretic combination is preferred

StrokeTIA

Combinations of an ACEI with an ARB are not recommended

Treatment of HTN in Association With StrokeAcute Stroke: After72 Hours

Treatment of HTN in Patients with Non Diabetic CKD

Chronic kidney disease and proteinuria *

ACEI(or ARB)±Diuretic(Thiazide Or Loop)

Combination with other agents

Target BP: < 140/90 mmHg

* albumin:creatinine ratio [ACR] > 30 mg/mmol or urinary protein > 500 mg/24hr

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

Combinations of a ACEI and a ARB are specifically not recommended in the absence of proteinuria

Treatment of Hypertension in association with Diabetes

Mellitus

Treatment of HTN in DM without CKDThreshold ≥130/80 mmHg and Target below 130/80 mmHg

*Combinations of an ACEI with an ARB are specifically

not recommended

If eGFR <30 ml/min, a Furosemide should be substituted for a thiazide

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

DIABETESwith

Nephropathy

ACE Inhibitoror ARB

IF ACEI and ARB are contraindicated or not tolerated, SUBSTITUTE: • Long-acting CCB• Thiazide

Addition of one or more ofLong-acting CCB or Thiazide

3 - 4 drugs combination may be needed

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

Treatment of HTN in DM +CKD

•The use of the combination of ACE inhibitor with an ARB should only be considered in selected and closely monitored Patients with Refractory CHF or Marked proteinuria.