Management of HTN in DM

8/8/2019 Management of HTN in DM

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Dr Mohamed Al-AmeenDr Mohamed Al-AmeenNephrology& Transplantation SpecialistNephrology& Transplantation Specialist

KAAH&OCKAAH&OC


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IHD Mortality Rate in each age dacade vs HTNIHD Mortality

Rate in each age dacade vs HTN

HTN in DM:HTN in DM:FactsFactsManagement of Hypertension in Diabetics


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Management of Hypertension in Diabetics

Hypertension in DiabetesHypertension in Diabetes

Affecting 2060% of diabetics.

HTN is common in Diabetics vs in Non diabetics

1.5 to 3 times.

Prevalence


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WHOWHOFact SheetFact SheetWorldWorld KSAKSA

20002000 20302030 20002000 20302030

DMDM 171,000,000171,000,000 366,000,000366,000,000 890,000890,000 2,523,0002,523,000

USA:o ~ 60% of Diabetics are HTN.o14% of Af. Am. have HTN& DM

ADA 2005

Germany:o 50% of 1ry care pts have HTN.o 12% of all pts have HTN& DM.

Lehnert H et al. 2005Lehnert H et al. 2005

133,800,000 801,880NOW


Hypertension in DiabetesHypertension in DiabetesPrevalence


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Hypertension in DiabetesHypertension in Diabetes

Prevalence

WHOWHOFact SheetFact Sheet

WorldWorld KSAKSA

20002000 20302030 20002000 20302030

DMDM 171,000,000171,000,000 366,000,000366,000,000 890,000890,000 2,523,0002,523,000

USA:o ~ 60% of Diabetics are HTN.o14% of Af. Am. have HTN& DM

ADA 2005

Germany:o 50% of 1ry care pts have HTN.o 12% of all pts have HTN& DM.


133,800,000 801,880NOW


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Hypertensive Diabetics vs HypertensiveHypertensive Diabetics vs Hypertensive

non diabeticsnon diabetics Twice the risk of CVDTwice the risk of CVD

The greatest reduction in cardiovascularThe greatest reduction in cardiovascular

mortality occurs at achieving a diastolicmortality occurs at achieving a diastolic

blood pressure of < 80 mmHg and systolicblood pressure of < 80 mmHg and systolic

blood pressure to


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WHOWHOFact SheetFact Sheet WorldWorld KSAKSA20002000 20302030 20002000 20302030

DMDM 171,000,000171,000,000 366,000,000366,000,000 890,000890,000 2,523,0002,523,000

USA:o One in every four has HTN.o ~ 60% of Diabetics are HTN.

ADA 2005

Germany:o 50% of 1ry care pts have HTN.o 12% of all pts have HTN&DM.



HTN in DM:HTN in DM: PrevalencePrevalence

133,800,000 801,880NOW

Only 25 percent of patients with

hypertension have adequate control of their

blood pressure

The Third National Health and Nutrition Evaluation SurveyThe Third National Health and Nutrition Evaluation Survey

(NHANES III)(NHANES III)

About HTN in Diabetic Pts:About HTN in Diabetic Pts:

29% unaware about that diagnosis.29% unaware about that diagnosis. 43% untreated.43% untreated. 55% uncontrolled (140/90).55% uncontrolled (140/90). Only 12% had BP


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NEJM 2000; 342:905 Diabetes Care 2005; 28:310 Am J Kid Dis 2007; 49 (Suppl 2):S74

Type 1Type 1

( are Htn)( are Htn)

At Diagnosis: 20-40%At Diagnosis: 20-40%

With Microalbuminuria: 30-50%With Microalbuminuria: 30-50%

With Macroalbuminuria: 65-88%With Macroalbuminuria: 65-88%

Type 2Type 2

( are Htn)( are Htn)

At Diagnosis: 50%At Diagnosis: 50%

With Microalbuminuria: 80%With Microalbuminuria: 80%

With Macroalbuminuria: >90%With Macroalbuminuria: >90%

HTN in DM:HTN in DM:PrevalencePrevalenceManagement of Hypertension in Diabetics


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Diabetes Hypertension

HTN in DM:HTN in DM: PARTNERS IN CRIMEPARTNERS IN CRIME


HTNHTN vsvs No HTNNo HTN DMDM vsvs No DMNo DM

2.4x in DM2.4x in DM 2.0x in HTN2.0x in HTN

NEJM 2000; 342:905 Diabetes Care 2005; 28:310NEJM 2000; 342:905 Diabetes Care 2005; 28:310

M f H i i Di b i


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DM-2DM-2

DM-1DM-1




Cause:Cause: Mainly renoparenchymal and pointing to DNOnset:Onset: Typically with microalbuminuria American diabetic association, Diab Care 2004

Cause:Cause: Mainly Insulin Resistance as a facet of MS.

Onset:Onset: with onset of Diabetes or may precede that by Ys. Ritz et al. J Int Med.2001;249: 215-223.

KidneyKidney

DiseaseDisease

KidneyKidney

DiseaseDisease

MetabolicMetabolic

SyndromeSyndrome

MetabolicMetabolic

SyndromeSyndrome

HTNHTNHTNHTN

M t f H t i i Di b ti


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Hypertensive patients without diabetes tend to be resistant to insulin

and are hyperinsulinaemic compared with normotensive controls.

Pollare T et al. Metabolism 1990, 39(2):167-174.

About 20% of patients with hypertension will develop type 2 diabetes

in a three year period. Bosch J et al. N Engl J Med 2006, 355(15):1551-1562.

Fasting glucose levels increase in older adults with hypertension

regardless of treatment type. BarzilayJ I et al. Arch Intern Med.2006;166:2191-2201

The RAS itself plays imp. role in thedevelopment of diabetes.

Over activity of RAS appears to be linked to

reduced insulin and glucose delivery to the

peripheral skeletal muscle and impaired glucosetransport and response to insulin signalling

pathways, thus increasing insulin resistance.Jandeleit-Dahm KA et al. J Hypertens 2005, 23(3):463-473.

Activation of a local pancreatic RAS, in

particular within the islets, may represent an

independent mechanism for the progression of

islet cell damage in diabetes.





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The risk of diabetes associated

with antihypertensive-drug therapy

appears to be explained by the

presence of hypertension.

Among the subjects who had

hypertension, the risk among those

not taking medication was similar to

that among those taking one or

more agents.

Among the subjects who were not

taking any antihypertensive

medication, the risk of diabetes

was much higher among

hypertensive Pts. than in non

hypertensive.

0

5

1 0

1 5

Chlorthalidone Amlodipine Lisinopril

11.6%

9.8%8.1%

ALLHAT: Incidence of New-Onset Diabetes at 4 Years

JAMA 2002;288:2981-2997

Role of Antihypertensive Drugs



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Taking a thiazide diuretic, ACETaking a thiazide diuretic, ACE

inhibitor, or CCB carry noinhibitor, or CCB carry no

greater risk for the subsequentgreater risk for the subsequentdevelopment of DM.development of DM.

DM was 28 percent more likelyDM was 28 percent more likely

to develop in subjects takingto develop in subjects taking

BB than in those taking noBB than in those taking no

medication.medication.

This adverse effect of BB mustThis adverse effect of BB must

be weighed against the provenbe weighed against the proven

benefits of this drug in reducingbenefits of this drug in reducing

the risk of cardiovascular eventsthe risk of cardiovascular events

Role of Antihypertensive Drugs



18/75AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 66, NUMBER 7 / OCTOBER 1, 2002

Diabetes and HTNDiabetes and HTNvsvs DiabetesDiabetes

Relative RiskRelative Risk

ofofComplicationsComplications

CHDCHD X 3.0X 3.0

StrokeStroke X 4.0X 4.0

RetinopathyRetinopathy X 2.0X 2.0

NephropathyNephropathy X 2.0X 2.0

NeuropathyNeuropathy X 1.6X 1.6

MortalityMortality X 2.0X 2.0

75% die from CVD75% die from CVD

NEJM 2005; 352:341





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Association between refractory hypertension and cardiometabolic risk

The HIPERFRE study, 2008

1,724 hypertensive patients, 35 physicians, 14 Primary Care Units

The HIPERFRE study, 2008

1,724 hypertensive patients, 35 physicians, 14 Primary Care Units





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D

EA

T

H

LDL=low-density lipoprotein; HDL=high-density lipoprotein; MI=myocardial infarction; CHD=congestive

heart failiure; HF=heart failure; ESRD=end-stage renal diseaseAdapted fromArch Intern Med. 2000; 160:1277-1283.

InsulinResistance Hyper-insulinemia

Triglycerides

LDL

HDL

Visceral Fat

Angiotensin II

SympatheticActivity

+ Hypertension

Diabetes

CHD

Stroke

MI

HF

ESRD

MetabolicSyndrome Morbid States





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Tight Glucose ControlTight Glucose Control

Tight BP ControlTight BP Control

**P < 0.05P < 0.05

-50 -

-40 -

-30 -

0 - StrokeAny DMEnd Point DM Death

MicrovascularComplications

Reduc t

ionin

Risk(%

)

UKPDS. BMJ. 1998:317;703-712.

-20 -

-10 -

Tight BP Control vs. Tight Glucose ControlTight BP Control vs. Tight Glucose Control

HTN in DM:HTN in DM: Effect of BP ControlEffect of BP Control




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Tight BP Control vs. Tight Glucose ControlTight BP Control vs. Tight Glucose Control

HTN in DM:HTN in DM: Effect of BP ControlEffect of BP Control

Tight BP Control Tight Glucose Control




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1.1. Measure BP properly.Measure BP properly.

2.2. Define Hypertensive Patients.Define Hypertensive Patients.

3.3. Evaluate hypertensive Patients.Evaluate hypertensive Patients.4.4. TherapyTherapy

HTN in DM:HTN in DM:ManagementManagementManagement of Hypertension in Diabetics


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HTN in DM:HTN in DM: 1- Measure BP Properly1- Measure BP Properly

Joint National CommiteeJoint National Commitee

Caffeine, exercise, and smoking should be avoided

for at least 30 minutes prior to measurement.JNC-7




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HTN in DM:HTN in DM: 1- Measure BP Properly1- Measure BP Properly

Indications of Ambulatory BP monitoringIndications of Ambulatory BP monitoring

JNC-7




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High Normal BP and CVD Risk

HTN in DM:HTN in DM: 22-- Define Hypertensive PatientsDefine Hypertensive Patients

Joint National Committee 7 (JNC-7)Joint National Committee 7 (JNC-7)



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HTN in DM:HTN in DM:2-2- Define Hypertensive PatientsDefine Hypertensive PatientsSystolic or Diastolic Hypertension???????Systolic or Diastolic Hypertension???????

250

200

150

100

50

0


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Diastolic hypertension predominates before age 50,

either alone or in combination with SBP elevation.

Systolic hypertension increases with age, and above

50 years of age, systolic hypertension represents the

most common form of hypertension.

DBP is a more potent cardiovascular risk factor thanSBP until age 50; thereafter, SBP is more important.

DBP control rates exceeded 90 percent, but SBP

control rates were considerably less (6070 percent)

J Clin Hypertens 2002;4:393-404.Hypertension 2001;37:12-8.

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HTN in DM:HTN in DM:2-2- Define Hypertensive PatientsDefine Hypertensive Patients

Three-fourths of 1ry care physicians failed to initiate therapy if SBP 140-159.Three-fourths of 1ry care physicians failed to initiate therapy if SBP 140-159. Most physicians have been taught that the diastolic pressure is more importantMost physicians have been taught that the diastolic pressure is more important

than SBP and thus treat accordingly.than SBP and thus treat accordingly. Most primary care physicians did not pursue control to


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HTN in DM:HTN in DM:ManagementManagement



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3.3. Evaluate hypertensive Patients.Evaluate hypertensive Patients.4.4. Therapy:Therapy:

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Estimate CV Risk Factors.Estimate CV Risk Factors.

Diagnose Target Organ Damage.Diagnose Target Organ Damage.

Exclude Identifiable Causes of HTN.Exclude Identifiable Causes of HTN.Routine Laboratory work up with ECG,Routine Laboratory work up with ECG,

lipid profile and urinary albumin.lipid profile and urinary albumin.

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HTN in DM:HTN in DM:3- Evaluate3- Evaluate Hypertensive Pts.Hypertensive Pts.



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HTN*Age:

Older than 55 years for men

Older than 65 years for women

DM*

Abnormal Lipid Profile*:

Elevated LDL (or total) cholesterolLow HDL cholesterol*

Estimated GFR


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HeartLVH

Angina/prior MI

Prior coronary revascularization

Heart failure

BrainStroke or transient ischemic attack

Dementia

CKDPeripheral arterial disease

Retinopathy


Target Organ DamageTarget Organ Damage



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ABCD diagnosis of 2ry HTNABCD diagnosis of 2ry HTN

A:A: Accuracy, Apnea, AldosteronismAccuracy, Apnea, Aldosteronism

B:B: Bruit, Bad KidneyBruit, Bad KidneyC:C: Catecholamines, Coarctation,Catecholamines, Coarctation,

Cushing's S.Cushing's S.

D:D: Drugs, DietDrugs, Diet


Identifiable Causes of HTNIdentifiable Causes of HTN


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3.3. Evaluate hypertensive Patients.Evaluate hypertensive Patients.4.4. Therapy:Therapy:




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1.1. Blood Pressure GoalBlood Pressure Goal

2.2. Life Style ModificationLife Style Modification

3.3. Phamacological TherapyPhamacological Therapy

HTN in DM:HTN in DM:4- Therapy4- Therapy



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HOTHOT (Hypertension Optimal Treatment).(Hypertension Optimal Treatment).

ABCD-NTABCD-NT ((Appropriate Blood Pressure Control in Diabetes)Appropriate Blood Pressure Control in Diabetes)

UKPDSUKPDS (UK Prospective Diabetes Study)(UK Prospective Diabetes Study)

IDNTIDNT (Irbesartan in Diabetic Nephropathy(Irbesartan in Diabetic Nephropathy Trial)Trial)

INVEST (INVEST (International Verapamil-Trandolapril)International Verapamil-Trandolapril)

ADAADA (American Diabetic association)(American Diabetic association)

ISHIBISHIB (International Society of Hypertension in Blacks)(International Society of Hypertension in Blacks)

CHEPCHEP

(Canadian Hypertension Education Program)(Canadian Hypertension Education Program)

BHSBHS (British Hypertension Society)(British Hypertension Society)

JNC 7JNC 7 (Joint National Committee 7)(Joint National Committee 7)

HTN in DM:HTN in DM:4- Therapy4- TherapyGoal Blood PressureGoal Blood Pressure

Less Than 130/80



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National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis.National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis.2000;36(3):646-661.2000;36(3):646-661.

American Association of Clinical Endocrinologist, 2006American Association of Clinical Endocrinologist, 2006Target BP 1gmTarget BP 1gm

HTN in DM:HTN in DM:4- Therapy4- TherapyGoal Blood PressureGoal Blood Pressure Less Than 130/80

Can We Go to More Lower Target ?

IDNTJASN 2005;16(7):21702179



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Lowest Systolic Blood Pressure Is Associated with Stroke

inStages 3 to 4 Chronic Kidney Disease

J Am Soc Nephrol18: 960966, 2007

HR of Stroke vs SBP

Can We Go to More Lower Target ?

HTN in DM:HTN in DM:4- Therapy4- TherapyGoal Blood PressureGoal Blood Pressure Less Than 130/80

20,358 individuals studied, 1549 (7.6%) had CKD


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HTN in DM:HTN in DM:4- Therapy4- TherapyLife Style ModificationsLife Style Modifications


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InterventionIntervention TargetTarget

Reduce foods withReduce foods withadded sodiumadded sodium

< 2300 mg /day< 2300 mg /day

Weight lossWeight loss BMI


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HTN in DM:HTN in DM:4- Therapy4- TherapyLife Style Modifications:Life Style Modifications:DietaryDietary

Dietary Sodium

Less than 2300mg / day

(Most of the salt in food is hidden and comes fromprocessed food)

Dietary PotassiumIf required, daily dietary intake

>80 mmol

Calcium supplementation

No conclusive studies for hypertension

Magnesium supplementation

No conclusive studies for hypertension

High in fresh fruits

High in vegetables

High in low fat

dairy products

High in dietary andsoluble fibre

High in plant

protein

Low in saturatedfat and cholesterol Low in sodium


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Less than:Less than:

2,300 mg sodium (Na)2,300 mg sodium (Na)

100 mmol sodium (Na)100 mmol sodium (Na) 5,8 g of salt (NaCl)5,8 g of salt (NaCl)

1 teaspoon of table salt1 teaspoon of table salt

2,300 mg sodium = 1 level teaspoon of table salt

HTN in DM:HTN in DM:4- Therapy4- TherapyLife Style Modifications:Life Style Modifications:Daily SodiumDaily Sodium


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Exercise should be prescribed as adjunctive to pharmacological

therapy

Should be prescribed to reduce blood pressure

Type - Cardiorespiratory activity- Walking, jogging- Cycling- Non-competitive swimming

Time - 30-60 minutes

Intensity - Moderate

Frequency - Four to seven days per weekF

IT

T

HTN in DM:HTN in DM:4- Therapy4- TherapyLife Style Modifications:Life Style Modifications:Physical ActivityPhysical Activity


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Hypertensive and all patients

BMI over 25- Encourage weight reduction

- Healthy BMI: 18.5-24.9 kg/m2

Waist Circumference Men Women- Europid, Sub-Saharan African, Middle Eastern


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HTN in DM:HTN in DM:4- Therapy4- TherapyLife Style ModificationsLife Style Modifications

InterventionIntervention AmountAmount SBP/DBPSBP/DBP

Reduce foods with addedReduce foods with addedsodiumsodium

- 1800 mg sodium- 1800 mg sodium

hypertensivehypertensive-5.1 / -2.7-5.1 / -2.7

Weight lossWeight loss per kg lostper kg lost -1.1 / -0.9-1.1 / -0.9

Alcohol intakeAlcohol intake - 3.6 drinks/day- 3.6 drinks/day -3.9 / -2.4-3.9 / -2.4

Aerobic exerciseAerobic exercise 120-150 min/week120-150 min/week -4.9 / -3.7-4.9 / -3.7

Dietary patternsDietary patterns DASH dietDASH dietHypertensiveHypertensive

NormotensiveNormotensive-11.4 / -5.5-11.4 / -5.5

-3.6 / -1.8-3.6 / -1.8



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ACE inhibitors and ARBs are contraindicated in pregnancyACE inhibitors and ARBs are contraindicated in pregnancyand caution is required in prescribing to women of childand caution is required in prescribing to women of childbearing potential.bearing potential.

Use caution in initiating therapy with 2 drugs whereUse caution in initiating therapy with 2 drugs whereagressive blood pressure lowering is more likely or moreagressive blood pressure lowering is more likely or morepoorly tolerated (e.g. those with postural hypotension).poorly tolerated (e.g. those with postural hypotension).

Diuretic-induced hypokalemia should be avoided through theDiuretic-induced hypokalemia should be avoided through theuse of potassium sparing agent if required.use of potassium sparing agent if required.

HTN in DM:HTN in DM:4- Therapy4- TherapyDrug Therapy: ConsiderationDrug Therapy: Consideration



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Monitor creatinine and potassium when combining KMonitor creatinine and potassium when combining Ksparing diuretics, ACE inhibitors and/or ARBs.sparing diuretics, ACE inhibitors and/or ARBs.

If Dihydropyridine CCB Chosen: Not to be used withoutIf Dihydropyridine CCB Chosen: Not to be used withoutACEi or ARB agents.ACEi or ARB agents.

If a diuretic is not used as first or second line therapy,If a diuretic is not used as first or second line therapy,triple drug therapy should include a diuretic, when nottriple drug therapy should include a diuretic, when notcontraindicated.contraindicated.

Short-acting dihydropyridine calcium antagonists shouldShort-acting dihydropyridine calcium antagonists shouldnot be used in IHD because of their potential to increasenot be used in IHD because of their potential to increaserisk of mortality, particularly in the setting of acuterisk of mortality, particularly in the setting of acutemyocardial infarctionmyocardial infarction




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Beta Blockers BBs less appealing as first-line agents for treatment of hypertension inBBs less appealing as first-line agents for treatment of hypertension in

patients with either type 2 or type 1 diabetes mellitus (grade A).patients with either type 2 or type 1 diabetes mellitus (grade A).

BBs, however, have proved effective in the management of the ischemicBBs, however, have proved effective in the management of the ischemic

and congestive cardiomyopathies that are more common in patients withand congestive cardiomyopathies that are more common in patients withdiabetes than in those without diabetes.diabetes than in those without diabetes.

Because the major adverse effects of BBs may be mediated byBecause the major adverse effects of BBs may be mediated byperipheral vasoconstriction and increasing insulin resistance, the use ofperipheral vasoconstriction and increasing insulin resistance, the use ofthe new third-generation BBs (such asthe new third-generation BBs (such asNebivololNebivolol) or drugs that block) or drugs that block

both a and b receptors (such asboth a and b receptors (such as CarvedilolCarvedilol) may prove to be particularly) may prove to be particularlybeneficial (grade A).beneficial (grade A).

These agents cause vasodilatation and an increase in insulin sensitivity.These agents cause vasodilatation and an increase in insulin sensitivity.

American Association of Clinical Endocrinologist, 2006




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Beta Blockers (cont.)Beta Blockers (cont.) Two drug combinations of beta blockers, ACE inhibitorsTwo drug combinations of beta blockers, ACE inhibitors

and ARBs have not been proven to have additiveand ARBs have not been proven to have additivehypotensive effects.hypotensive effects.

Therefore these potential two drug combinations should notTherefore these potential two drug combinations should notbe used unless there is a compelling (non blood pressurebe used unless there is a compelling (non blood pressurelowering) indication such as ischemic heart disease, postlowering) indication such as ischemic heart disease, postmyocardial infarction, congestive heart failure or chronicmyocardial infarction, congestive heart failure or chronickidney disease with proteinuria.kidney disease with proteinuria.

It is not recommended to combine a non dihydropyridineIt is not recommended to combine a non dihydropyridineCCB and a beta blocker to reduce the risk of bradycardia orCCB and a beta blocker to reduce the risk of bradycardia orheart block.heart block.



4 Th


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If Diuretic Chosen: (Preferred if no other

compelling indications):

Creatinine


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AASK MAP


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HTN in DM:HTN in DM:4- Therapy4- TherapyDrug Therapy: Compelling IndicationsDrug Therapy: Compelling Indications

Compelling Indications Initial Therapy Options

Heart failure Thiazide, BB, ACE-I, ARBs, Aldost. Ant.

Post MI BB, ACE-I, Aldost. Ant.

High CVD Risk Thiazide, BB, ACE-I, CCB

CKD ACE-I, ARBs

Recurrent Stroke Thiazide, ACE-I


4 Th4 Th


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HTN in DM:HTN in DM:4- Therapy4- TherapyADA GuidelinesADA Guidelines

SystolicSystolic DiastolicDiastolic

Goal (mmHg)Goal (mmHg)


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HTN in DM:HTN in DM:4- Therapy4- TherapyPractical ViewPractical View

1.1.Pts. At goal BP < 130 / 80.Pts. At goal BP < 130 / 80.

2.2. Pts. with BP 130-139 / 80-89.Pts. with BP 130-139 / 80-89.

3.3. Pts. With BP 140 /90.Pts. With BP 140 /90.

1 32

WithoutCompelling

Indications

WithCompelling

Indications

WithCompelling

Indications

WithoutCompelling

Indications

WithCompelling

Indications

WithoutCompelling

Indications

LSM

Recheck each

isit

- LSM

- Recheck each

visit

- Treat CI

- LSM 3 m- if high BP

drug Therapyfor HTN

-LSM-Drug for HTN

-Drug for CI

-LSM

-Drug for HTN

- LSM- Drug combined

- Drug for CI

If BP 150/90 Start 2 drugs

CompellingIndications

Initial Therapy Options

Heart failure Thiazide, BB, ACE-I, ARBs,Aldost. Ant.

Post MI BB, ACE-I, Aldost. Ant.

High CVD Risk Thiazide, BB, ACE-I, CCB

CKD ACE-I, ARBs

Recurrent Stroke Thiazide, ACE-I

Algorithm for the Treatment of Hypertension in DMAlgorithm for the Treatment of Hypertension in DM


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ACE -ve or ARB (Or thiazide if no albuminuria or TOD)

Consider two-drug therapy if BPe 150/90 mmHg

140/90 Or albuminuria Or TOD

130/80 mmHg on two visits 1 month apart

130139/8089 No albuminuria, No TODLSM for 3 months

130/80 mmHg after 1 m

Add thiazide (or BID loop diuretic if cr 1.8

mg/dl or estimated GFR < ml/min/1.73m2)

Add nonDHP CCB (verapamil or diltiazem)

Substitute DHP CCB for nonDHP CCB

Add B-blockerAdd DHP CCB

Reassess for causes of resistant hypertension

Add blocker, hydralazine, clonidine Consider consultation.




Algorithm for the Treatment of Hypertension in DMAlgorithm for the Treatment of Hypertension in DM


4 Th4 Th


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In Type 2 patients: ACE-i or ARBs as a

first line.

In Type 1 patients: ACE-I is recommendedto reduce protein excretion

Consider the use of verapamil or diltiazem

in patients with proteinuria unable to

tolerate ACEi or ARBs.

BB is a potent antiproteinuric.

HTN in DM:HTN in DM:4- Therapy4- TherapyFor Pts. With Microalbuminuria or ProteinuriaFor Pts. With Microalbuminuria or Proteinuria

4 Th4 Th


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First-line agents include ACE inhibitors, ARBs, -First-line agents include ACE inhibitors, ARBs, -blockers, or diuretics. Additional drugs may be chosenblockers, or diuretics. Additional drugs may be chosenfrom these classes or another drug class.from these classes or another drug class.

In hypertensive patients with microalbuminuria or clinicalIn hypertensive patients with microalbuminuria or clinicalalbuminuria, an ACE inhibitor or an ARB should bealbuminuria, an ACE inhibitor or an ARB should bestrongly considered. If one class is not tolerated, thestrongly considered. If one class is not tolerated, theother should be substituted.other should be substituted.

In patients over age 55 years with hypertension orIn patients over age 55 years with hypertension oranother cardiovascular risk factor (history ofanother cardiovascular risk factor (history ofcardiovascular disease, dyslipidemia, microalbuminuria,cardiovascular disease, dyslipidemia, microalbuminuria,or smoking), an ACE inhibitor (if not contraindicated)or smoking), an ACE inhibitor (if not contraindicated)should be considered to reduce the risk ofshould be considered to reduce the risk of

cardiovascular events.cardiovascular events.

Drug Therapy: ConsiderationDrug Therapy: Consideration


4 Th4 Th


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In patients with a recent myocardial infarction, -In patients with a recent myocardial infarction, -

blockers, in addition, should be considered toblockers, in addition, should be considered to

reduce mortality.reduce mortality.

If ACE inhibitors or ARBs are used, monitorIf ACE inhibitors or ARBs are used, monitor

renal function and serum potassium levels.renal function and serum potassium levels.

In elderly hypertensive patients, blood pressureIn elderly hypertensive patients, blood pressureshould be lowered gradually to avoidshould be lowered gradually to avoid

complications.complications.

Drug Therapy: ConsiderationDrug Therapy: Consideration



4 Th4 Th


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HTN in DM:HTN in DM:4- Therapy4- TherapyACE-I + ARBs: Limited UtilityACE-I + ARBs: Limited Utility

Theoretically attractive: more complete RAAS blockadeTheoretically attractive: more complete RAAS blockade

Limited BP and CVD eventsLimited BP and CVD events vsvs ACE-I at max doseACE-I at max dose ONTARGET RCT: 25,620 with CVDONTARGET RCT: 25,620 with CVD StrokeStroke DMDM

RamiprilRamipril vsvs TelmisartanTelmisartan vsvs RRTTMinimalMinimal BP : 2.4/1.4 mm HgBP : 2.4/1.4 mm Hg

NoNo CVD events CVD events

MoreMore side effectsside effects

Albuminuria 30-40%Albuminuria 30-40% vsvs monoRx with ACE-I or ARBmonoRx with ACE-I or ARB

? Effects on ESRD?? Effects on ESRD? NKF, 2007:NKF, 2007: considerconsiderif albumin/cr > 500 mg/g on monoRxif albumin/cr > 500 mg/g on monoRx

NEJMNEJM2008; 358:15472008; 358:1547 AmAm JJKidKidDisDis 2007; 49(Suppl 2):S742007; 49(Suppl 2):S74


4 Th4 Th


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Increased HTN control

Reduced hypokalemia

Cardioprotective Available as a generic medication

Increased adherence

HTN in DM:HTN in DM:4- Therapy4- TherapyACE-I + HCTZ: Excellent 1ACE-I + HCTZ: Excellent 1stst line agentline agent


4 Th4 Th


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Consider continuing the ACE-I: 38-55% Likelihood the cough will resolve.

Consider changing the time of administration or lowering the dose

Consider antitussives or lozenges while waiting for symptom toresolve.

Consider switching to a 2nd ACE-I: Effective for 1 in 10 patients

Consider using a different drug class: Diuretic, beta-blocker or calcium channel blocker

If an ACE-I is indicated because of comorbid conditions (e.g. DM,HF,CKD) an ARB (i.e. LOSARTAN) can be used as an alternative

HTN in DM:HTN in DM:4- Therapy4- TherapyACE-I CoughACE-I Cough


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ACE-I or ARBs may causeACE-I or ARBs may cause

Hyperkalemia:Hyperkalemia:1.1. Avoid other medications that causeAvoid other medications that cause

hyperkalemia (K suppl, NSAIDs, Cox2hyperkalemia (K suppl, NSAIDs, Cox2inhibitors, K sparing diuretics).inhibitors, K sparing diuretics).

2.2. Evaluate causes of hyperkalemia.Evaluate causes of hyperkalemia.

3.3. Treat hyperkalemia with diuretics.Treat hyperkalemia with diuretics.

4.4. Continuo ACE-I or ARBs if K < 5.5 mmol/l.Continuo ACE-I or ARBs if K < 5.5 mmol/l.

Monitor GFRMonitor GFR1.1. If GFR >30% within 4 weeks, evaluate.If GFR >30% within 4 weeks, evaluate.

2.2. Continuo ACE-I or ARBs if GFR < 30% fromContinuo ACE-I or ARBs if GFR < 30% frombaseline over 4 months.baseline over 4 months.

HTN in DM:HTN in DM:4- Therapy4- TherapyACE-I or ARBs and HyperkalemiaACE-I or ARBs and Hyperkalemia


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HTN in DM:HTN in DM:4- Therapy4- TherapyResistant HypertensionResistant Hypertension

Anti Hypertensive DrugsAnti Hypertensive Drugs


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ClassClass Drug (Trade Name)Drug (Trade Name) Usual Dose Range in MG/Usual Dose Range in MG/DAYDAY

Thiazide diureticsThiazide diuretics Chlorothiazed (Diuril)Chlorothiazed (Diuril)

Chlorthalidone (generic)Chlorthalidone (generic)

Hydroclorothiazide (Microzide, HydroHydroclorothiazide (Microzide, HydroDIURIL)DIURIL)

Polythiazide (Renese)Polythiazide (Renese)

Indapamide (Lozol)Indapamide (Lozol)

Metalozol (Mykrox)Metalozol (Mykrox)

Metalazone (zaroxolyn)Metalazone (zaroxolyn)

125-500125-500

12.5-2512.5-25

12.5-5012.5-50

2-42-4

1.25-2.51.25-2.5

0.5-1.00.5-1.0

2.5-52.5-5

Loop diureticsLoop diuretics Bumetanide (bumex)Bumetanide (bumex)

Furosemide (Lasix)Furosemide (Lasix)

Torsemide (Demadex)Torsemide (Demadex)

0.5-20.5-2

20-8020-80

2.5-102.5-10

Potassium-sparingPotassium-sparing

diureticsdiuretics

Amiloride (Midamor)Amiloride (Midamor)

Triamtrene (Dyrenium)Triamtrene (Dyrenium)

5-105-10

50-10050-100

Aldosterone receptorAldosterone receptorblockersblockers

Eplernone ( Inspra)Eplernone ( Inspra)

Spironolactone (Aldactone)Spironolactone (Aldactone)

50-10050-100

25-5025-50




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ACE InhibitorsACE Inhibitors Benazepril (Lotensin) captoprilBenazepril (Lotensin) captopril(capoten)(capoten)

Enalapril (vasotec)Enalapril (vasotec)

Fosinopril (monopril)Fosinopril (monopril)

Lisinopril (prinivil, zestril)Lisinopril (prinivil, zestril)

Moexipril (Univasc)Moexipril (Univasc)

Perindopril (Accupril)Perindopril (Accupril)

Quinapril (Accupril)Quinapril (Accupril)

Ramipril (Altace)Ramipril (Altace)Trandolapril(Mavik)Trandolapril(Mavik)

10-4010-40

25-10025-100

2.5-402.5-4010-4010-40

10-4010-40

7.5-307.5-30

4-84-8

10-4010-40

2.5-202.5-20

1-41-4

Angiotensin IIAngiotensin II

AntagonistsAntagonists

Candesartan (Atacand)Candesartan (Atacand)

Eprosartan (Teveltan)Eprosartan (Teveltan)

Irbesartan (Avapro)Irbesartan (Avapro)

Losartan (Cozaar)Losartan (Cozaar)

Olmesartan (Benicar)Olmesartan (Benicar)

Telmisartan (Micardis)Telmisartan (Micardis)

Valsartan (Diovan)Valsartan (Diovan)

8-328-32

400-800400-800

150-300150-300

25-10025-100

20-4020-40

20-8020-80

80-32080-320




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Beta-BlockersBeta-Blockers Atenolol (Tenormin)Atenolol (Tenormin)

Betaxolol (Kerlone)Betaxolol (Kerlone)

Bisoprolol (zebeta)Bisoprolol (zebeta)Metoprolol (lopressor)Metoprolol (lopressor)

Metoprolol extended releaseMetoprolol extended release(Toprol XL)(Toprol XL)

Nadolol (Corgard)Nadolol (Corgard)

Propranolol (Inderal)Propranolol (Inderal)

Propranolol long-acting (InderalPropranolol long-acting (InderalLA)LA)

Timolol (Blocadren)Timolol (Blocadren)

25-10025-100

5-205-20

2.5-102.5-1050-10050-100

50-10050-100

40-12040-120

40-16040-160

60-18060-180

20-4020-40

Beta-Blockers with intrinsicBeta-Blockers with intrinsicsypathomimetic activitysypathomimetic activity

Acebutolol (Sectral)Acebutolol (Sectral)

Penbutolol (Levatol)Penbutolol (Levatol)

Pindolol (generic)Pindolol (generic)

200-800200-800

10-4010-40

10-4010-40

Combined Alpha and beta-Combined Alpha and beta-blockersblockers

Carvedilol (Coreg)Carvedilol (Coreg)

Labetalol (Normodyne)Labetalol (Normodyne)

12.5-5012.5-50

200-800200-800




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Calcium channel blockers-Calcium channel blockers-non Dihydropyridinesnon Dihydropyridines

Diltiazem extended releaseDiltiazem extended release

(cardizem CD, Dilacor XR, Tiazac) Diltiazem(cardizem CD, Dilacor XR, Tiazac) Diltiazem

extended release (Cardizem LA)extended release (Cardizem LA)Verapamil immediate release (calan, isoptin)Verapamil immediate release (calan, isoptin)

Verapamil long acting (calan SR,Verapamil long acting (calan SR,

Isoptin SR)Isoptin SR)

Verapamil Coer (Covera HS, Verelan PM)Verapamil Coer (Covera HS, Verelan PM)

180-420180-420

120-540120-540

80-32080-320

120-360120-360

120-360120-360

Calcium Channel Blockers -Calcium Channel Blockers -DihydropyridinesDihydropyridines

Amlodipine ( Norvasc )Amlodipine ( Norvasc )

Felodipine (plendil)Felodipine (plendil)

Isradipine (Dynaciric CR)Isradipine (Dynaciric CR)

Nicardipine sustained release (Cardene SR)Nicardipine sustained release (Cardene SR)

Nifedipine long-acting (Adalat CC, procardia XL)Nifedipine long-acting (Adalat CC, procardia XL)

Nisoldipine (Sular)Nisoldipine (Sular)

2.5-102.5-10

2.5-202.5-20

2.5-102.5-10

60-12060-120

30-6030-60

10-4010-40




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Alpha- BlockersAlpha- Blockers Doxazosin ( Cardura)Doxazosin ( Cardura)

Prazosin (minipress)Prazosin (minipress)

Terazosin (Hytrin)Terazosin (Hytrin)

1-161-16

2-202-20

1-201-20

Central alpha-agonistsCentral alpha-agonists

and other centrally actingand other centrally actingdrugsdrugs

Clonidine (Catapres)Clonidine (Catapres)

Clonidine patch (catapres-TTS)Clonidine patch (catapres-TTS)Methyldopa (Aldomet)Methyldopa (Aldomet)

Resrpine (generic)Resrpine (generic)

Guanfacine (generic)Guanfacine (generic)

0.1-0.80.1-0.8

0.1-0.30.1-0.3

250-1000250-1000

0.05-0.250.05-0.25

0.5-20.5-2

Direct VasodilatorsDirect Vasodilators

Hydralazine (Apresoline)Hydralazine (Apresoline)

Minoxidil (Loniten)Minoxidil (Loniten) 25-10025-100

2.5-802.5-80



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Management of HTN in DM

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