Resistant HT

Resistant Hypertension-Resistant Hypertension-evaluation and managementevaluation and management

Resistant HTN-definitionResistant HTN-definition

BP > 140/90 inspite of three concurrent BP > 140/90 inspite of three concurrent antihypertensive drugs which also antihypertensive drugs which also includes a diuretic in routine patients and includes a diuretic in routine patients and

In diabetics and patient with CKD a BP > In diabetics and patient with CKD a BP > 130/80 is considered as resistant HTN130/80 is considered as resistant HTN

Resistant HTN-evaluationResistant HTN-evaluation

ComplianceCompliance Analgesics, appetite suppressants, Analgesics, appetite suppressants,

erythropoetinerythropoetin Renal artery stenosisRenal artery stenosis HyperaldosteronismHyperaldosteronism PheochromocytomaPheochromocytoma Thyroid diseaseThyroid disease Steroid intakeSteroid intake Salt intake,smokingSalt intake,smoking


Alchohol bingeAlchohol binge Nasal decongestantsNasal decongestants Cold and cough medicationsCold and cough medications Indigenous drugsIndigenous drugs Obesity-hypoventilationObesity-hypoventilation Renal parenchymal diseaseRenal parenchymal disease Polycystic kidneyPolycystic kidney Primary aldosteronismPrimary aldosteronism


Cushing’s diseaseCushing’s disease Pregnancy induced hypertensionPregnancy induced hypertension Coarctation of aortaCoarctation of aorta

Resistant hypertension-pseudoresistanceResistant hypertension-pseudoresistance

High office blood pressureHigh office blood pressure

Adequately controlled home blood Adequately controlled home blood pressurepressure

Role of ambulatory BP monitoringRole of ambulatory BP monitoring

25% of total deaths in India 25% of total deaths in India are related to are related to cardiovascular diseases (2.3 million deaths) cardiovascular diseases (2.3 million deaths)

It has been predicted that by 2020, there would It has been predicted that by 2020, there would be a be a 111% increase in cardiovascular deaths in 111% increase in cardiovascular deaths in India India ● This increase is much more than 77% for ChinaThis increase is much more than 77% for China

Cardiovascular Disease BurdenCardiovascular Disease BurdenIndian perspective Indian perspective

Gupta R. Journal of Human Hypertension (2004) 18, 73–78.

Cardiovascular Disease Burden ..rising trend in IHD!

Park K. Cardiovascular diseases: Park’s Textbook of PSM, 19th Ed, 2007:303

Cardiovascular Disease BurdenCardiovascular Disease BurdenHypertension shares Consistent relationship with CVD risk!Hypertension shares Consistent relationship with CVD risk!

2-3 million

4-3 million

7-8 million

16 million

PopulationAll cardiovascularHigh blood pressureHigh cholesterolOverweight and obesity

Mortality

Norman M Kaplan, Lionel H Opie Lancet 2006;367:168-76

Drop in SBP & DBP by 10- and 5 mm Hg respectively

reduces risk of mortality from IHD by 30%

Lewington 2002

Hypertension in IndiaControl remains suboptimal..

0

10

20

30

40

50

60

Awareness Treatment Control

Men Women

Zachariah et al. Ind Heart J 2003; 55:245-51

Kerala One third AWARE One fourth

TREATED

One tenth CONTROLLEDTotal

Hypertension in IndiaHypertension in IndiaControl remains suboptimal..Control remains suboptimal..

Hathial M. J Indian Med Assoc. 2007; 105 (7): 401-2, 404, 410.

An Indian survey conducted in hypertensive patients (n=3402) receiving antihypertensive medications showed prevalence of

Uncontrolled HT

% of uncontrolled hypertensive

patients

Despite the best of treatment care and drugs available,

Hypertension largely remains Uncontrolled!

Uncontrolled HypertensionComplications..

Risk Factors:Diabetes

Hypertension

Vascular Dysfunction

Vascular Disease

Tissue Injury(IHD, Stroke)

PathologicalRemodeling

Target OrganDysfunction (HF, Renal)

End-stageOrgan Failure

Death

Oxidative Stress / Oxidative Stress / EndothelialEndothelialDysfunctionDysfunction

Target OrganTarget Organ DamageDamage

Adapted from Dzau et al. Circulation. 2006;114:2850-2870.

MI: Myocardial infarctionHF: Heart failure

Uncontrolled Hypertension Uncontrolled Hypertension Contributing factors..Contributing factors..

1.1. Monotherapy of drugs controls only 25% of patientsMonotherapy of drugs controls only 25% of patients

2.2. Concomitant risk factors – Type 2 DiabetesConcomitant risk factors – Type 2 Diabetes

3.3. Multi-Pill regimen leading to poor complianceMulti-Pill regimen leading to poor compliance

4.4. Side effects of conventional agents on higher dosesSide effects of conventional agents on higher doses

5.5. ‘‘Stringent’ BP goals to be achievedStringent’ BP goals to be achieved

Counter-regulatory mechanisms with monotherapy Counter-regulatory mechanisms with monotherapy

Uncontrolled Hypertension Uncontrolled Hypertension 1. Monotherapy with drugs1. Monotherapy with drugs

BP

Vasodilatation due to CCB or Diuretic

RAASActivation

RAAS blockade is the foundationof modern combination therapy

Combination with ARBs counters this mechanism

Uncontrolled Hypertension In IndiaUncontrolled Hypertension In India 1. Monotherapy or Combination therapy 1. Monotherapy or Combination therapy

Review of 42 trials shows combination of different Review of 42 trials shows combination of different classes results in classes results in 5 times greater BP reduction 5 times greater BP reduction

thereby reducing cardiovascular risk*thereby reducing cardiovascular risk*

*Wald DS. Am J Med 2009;122(3):290-300 ; Calhoun DA. Hypertension 2009: 54(1):32-39

%

%

ALLHAT shows

need for ≥3 drugswhen

continued on long-

term basis – Chrysant 2011

AAvoiding voiding CCardiovascular events through ardiovascular events through COMCOMbinationbination

therapy in therapy in PPatients atients LILIving with ving with SSystolic ystolic HHypertensionypertension

ACCOMPLISHACCOMPLISH

N ENGL J MED 359;23, DEC 2008

Uncontrolled Hypertension Uncontrolled Hypertension 1. Triple Drug Combination required..1. Triple Drug Combination required..

Patients often require several anti-hypertensivesPatients often require several anti-hypertensives

32

0

5

10

15

20

25

30

35

ACCOMPLISH

% Pts requiring ≥3 antihypertensives

%% pts

ACCOMPLISH: Avoiding Cardiovascular Events through COMmbination therapy in Patients Living wIth Systolic Hypertension

Chrysant SG. Postgraduate Medicine 2011;123(6):21-31

%

Uncontrolled Hypertension Uncontrolled Hypertension 2. Concomitant risk factors ..2. Concomitant risk factors ..

Diabetes Hypertension

HTN HTN vsvs No HTN No HTN DM DM vsvs No DM No DM

2.4x ↑ in DM2.4x ↑ in DM 2.0x ↑ in HTN 2.0x ↑ in HTN

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

Uncontrolled HypertensionUncontrolled Hypertension2. Concomitant risk factors..2. Concomitant risk factors..

Resistant HypertensionResistant Hypertension2. High incidence in Diabetics..2. High incidence in Diabetics..

Hathial M. J Indian Med Assoc. 2007; 105 (7): 401-2, 404, 410.

% of uncontrolled hypertensive

patients

An Indian survey conducted in hypertensive patients (n=3402) showed that amongst Diabetics (n=1435 patients), >80% pts had Uncontrolled BP

Guidelines recommend Target Goals of <130/80 mm Hg

Action to Control Cardiovascular Action to Control Cardiovascular Disease in Diabetes (Disease in Diabetes (ACCORDACCORD))

≈≈10,000 subjects with type 2 diabetes10,000 subjects with type 2 diabetes Double 2Double 22 design2 design

<130<130<120<120Systolic BPSystolic BP

StandardStandardIntensiveIntensive

<7.5%<7.5%<6%<6%HbAHbA1c1c goal goal

Anti-hypertensive therapy to achieve Target Goals in Anti-hypertensive therapy to achieve Target Goals in Intensive or Standard armsIntensive or Standard arms

NHLBI and ACCORD Study Web Site: http://www.nhlbi.nih.gov/new/press/03-02-20.htm. Accessed 10/22/04.

ACCORDACCORDHypertension controlled by Combination Hypertension controlled by Combination

therapy of antihypertensivestherapy of antihypertensives

77

0

20

40

60

80

ACCORD

% Pts requiring ≥3 antihypertensives% pts

ACCORD: Action to Control Cardiovascular Disease in Diabetes

%

The ACCORD Study Group . N Engl J Med 2010;362:1575-85

Resistant Hypertension Resistant Hypertension 3. Poor patient compliance..3. Poor patient compliance..

Multi-drug regimen required to control HT & other risk factorsMulti-drug regimen required to control HT & other risk factors Fixed –drug combination tablets reduces pill burden Fixed –drug combination tablets reduces pill burden to to

improve patient adherenceimprove patient adherence

Fung V. Clin Ther 2007;29(5):972-984

%

%

%

Resistant Hypertension Resistant Hypertension 4. Dose dependent side effects 4. Dose dependent side effects

Edema

Edema

Peripheral edema with CCBs Hypokalemia with Diuretics

* Relative to ACE-I after 1 y of treatment

0.5 1.0 2.0

Diuretics

βB

α-blockers

CCBs

ACE-Is

ARBs

1.83

1.64

1.23

1.08

1.00

0.92

- +Cause-specific HR (95% CI) for discontinuation*

Resistant Hypertension In IndiaResistant Hypertension In India4. ARBs ..ideal for Triple Drug therapy 4. ARBs ..ideal for Triple Drug therapy

Corrrao et al. J Hypertens. 2008;26:819–824.ARBs are safe & avoid Dose dependant Peripheral edema

or Hypokalemia with CCBs or Diuretics

29

CCB + ARB: The Synergies of Counter-Regulation (1)

SynergisticBP reduction

Complementaryclinical benefits

CCB Arteriodilation Peripheral oedema Effective in low-renin patients Reduces cardiac ischaemia

CCB RAS activation No renal or CHF

benefits

BP

Mistry et al. Expert Opin Pharmacother. 2006;7:575–581; Sica. Drugs. 2002;62:443–462; Quan et al. Am J Cardiovasc Drugs. 2006;6:103113.

30

CCB + ARB: The Synergies of Counter-Regulation (2)

ARB Venodilation Attenuates peripheral oedema Effective in high-renin patients No effect on cardiac ischaemia

ARB RAS blockade CHF and renal

benefits

Mistry et al. Expert Opin Pharmacother. 2006;7:575–581; Sica. Drugs. 2002;62:443–462; Quan et al. Am J Cardiovasc Drugs. 2006;6:103113.

SynergisticBP reduction

Complementaryclinical benefits

BP

CCB Arteriodilation Peripheral oedema Effective in low-renin patients Reduces cardiac ischaemia

CCB RAS activation No renal or CHF

benefits

31

Telmisartan Plus Amlodipine …

… as Initial Therapy

32

Telmisartan Plus Amlodipine Provides Consistent BP Reductions Across HTN Severities

-33.7-36.9

-47.5 -48.9

-60

-50

-40

-30

-20

-10

0160 – < 1701 190 – < 2002170 – < 1801 180 – < 1902

1. Littlejohn et al. J Clin Hypertens. 2009;11:207–213; 2. Neutel et al. J Clin Hypertens. 2010: In press; ASH 2010 poster presentation (LB-PO-10) & data on file

Moderate HTN Severe HTNBaseline SBP =

(n = 31) (n = 71)(n = 13) (n = 305)

Mea

n SB

P re

duct

ions

from

ba

selin

e (m

mH

g)

T80/A10 (n = 1361; n = 3792)

33

Telmisartan Plus Amlodipine Provides BP Reductions of ≥ 50 mmHg in Almost 50% of Patients With Severe HTN*

9.8

46.3

29.6

15.4

31.7

18.0

0

10

20

30

40

50

≥ 55 mmHg ≥ 60 mmHg≥ 50 mmHg

Mean SBP reductions from baseline*

Patie

nts

(%)

(n = 65) (n = 183) (n = 37) (n = 117) (n = 20) (n = 61)

A10 T80/A10

* Mean baseline BP = 185.4/103.2 mmHg

Neutel et al. J Clin Hypertens. 2010: In press; ASH 2010 poster presentation (LB-PO-10).

34

Telmisartan Plus Amlodipine Provides Consistently High BP Reductions in Hypertensive at-Risk Patients

-46.8 -46.6 -46.1 -47.5-43.2 -44.2

-60

-50

-40

-30

-20

-10

0

Diabetic1

Severe HTN ≥ 180/95 mmHg2

Obese BMI ≥ 30kg/m1

Metabolicsyndrome1*

(n = 62) (n = 175) (n = 36) (n = 100) (n = 30) (n = 379)

Elderly ≥ 65 y1 Black1

Mea

n SB

P re

duct

ions

from

ba

selin

e (m

mH

g)

Mean baseline BP = 185.4/103.2 mmHg* Diabetes, obesity (BMI 30kg/m2), and HTN

T80/A10

1. TEAMSTA Severe HTN study (data on file; Boehringer Ingelheim Pharmaceuticals, Inc); 2. Neutel et al. J Clin Hypertens. 2010: In press; ASH 2010 poster presentation (LB-PO-10).

35

Telmisartan/Amlodipine Provides 80% of its Maximum Effect After Just 2 Weeks of Treatment

Neutel et al. J Clin Hypertens. 2010: In press; ASH 2010 poster presentation (LB-PO-10).

A5 and T80/A5 for the first 2 weeks, then forced-titration to A10 and T80/A10, respectively; baseline BP = 185.4/103.2 mmHg

* Percentage of effect achieved after 2 weeks of treatment compared with end of study (Week 8)

Mea

n SB

P (m

mH

g)

Mean SBP reduction (mmHg)

185.4

137.9 Week 8

80%*

Week 2147.7

Baseline

–37.9 mmHg

–47.5 mmHg

T80/A10(n =379)

T80/A5(n = 405)

36


… 24-h ABPM

37

Telmisartan Plus Amlodipine Provides Superior 24-h ABPM Goal Rate Achievement (< 130/80 mmHg*) in > 82% of Patients

82.7

37.9

0

20

40

60

80

100

Patie

nts

achi

evin

g 24

-h

AB

PM g

oal*

(%)

* AHA criteria for 24-h BP goal

A10 T80/A10(n = 52)(n = 58)

p < 0.0001

Littlejohn et al. J Hypertens. 2008;26(suppl 1):S494; White et al. Blood Press Monit. 2010: In press.

38


… Safety and Tolerability

39

Telmisartan Plus Amlodipine Has a Safety and Tolerability Profile Similar to Placebo

4.3 4.3

2.2

10.9

0.6

1.9

1.3

2.2

1.3

6.0

7.8

1.1 1.1

1.8

3.0

4.7 4.8

0 0 0 0 0 0

0.90.91.3

2.2

1.41.11.1

0

2

4

6

8

10

12

Patie

nts

with

A

Es >

1%

inci

denc

e (%

) A mono (n = 319) T/A (n = 789)Placebo (n = 46)

Littlejohn et al. J Clin Hypertens. 2009;11:207–213.

Fatigue Oedema Sinusitis Naso-pharyn-

gitis

Upper respiratory

tract infection

Influenza Back pain

Dizzi-ness

Headache Peripheral oedema

40

Venous Fluid Leakage Induced by CCBs …

Arterialdilation(CCBs)

No venousdilation

Fluid leakage

Capillary bed

Opie et al. In: Opie LH, editor. Drugs for the Heart. 3rd ed. 1991:42–73; White et al. Clin Pharmacol Ther.1986;39:43–48; Gustaffson. J Cardiovasc Pharmacol. 1987;10:S121–S131.

Fluid leakage

Telmisartan significantly reduces peripheral oedema associated with Amlodipine

17.8

1.7

8.9

5.2

0

5

10

15

20

A10 T40/80+A5 T40/80+A10 T/A pooled

* p <0.05; † p <0.0001Littlejohn TW et al. J Clin Hypertension. 2009;11(4):207-213

Incidence of peripheral oedema (%)

†

†

*

42

Telmisartan Plus Amlodipine is Associated With Less Peripheral Oedema Compared With Amlodipine 10 mg

5.2

1.7

17.8

0

5

10

15

20

A10(n = 124)

T40–80+A5(n = 264)

Patie

nts

with

per

iphe

ral

oede

ma

(%)

T40–80+A5–A10(n = 543)

p < 0.0001

p < 0.0001

–90% –71%

Littlejohn et al. J Clin Hypertens. 2009;11:207–213.

43

Telmisartan + Amlodipine Data

Fast and superior BP reductions of > 31 mmHg (SBP) already after 1 week of treatment1

Up to 80% of maximum effect already after 2 weeks of treatment1

Consistent and strong BP reductions of up to 49.5 mmHg (SBP) across hypertension severities and a wide range of hypertensive at-risk (complex) patients1

SBP reduction of ≥ 50 mmHg in almost 50% of patients with baseline SBP ≥ 180 mmHg1

High BP response rates of up to 99.7% of patients1

Superior and dose dependent 24-h ABPM reductionsSuperior 24-h ABPM goal rate achievement (< 130/80 mmHg) of > 82%2,3

Superior efficacy and safety in patients not at goal with amlodipine4

A safety and tolerability profile similar to placebo, with up to 90% lower oedema rates compared with A10 monotherapy5

1. Neutel et al. J Clin Hypertens. 2010: In press; 2. White et al. Blood Press Monit. 2010: In press; 3. Littlejohn et al. J Hypertens. 2008;26(suppl 1):S494; 4. Neldam, Lang. J Clin Hypertens. 2009;11(Suppl s1):114 (P279); 5. Littlejohn et al.J Clin Hypertens 2009:11:207–213.

Significant reduction in AEs with Significant reduction in AEs with combination at starting dosagescombination at starting dosages

4. ARBs ..ideal for Combination therapy 4. ARBs ..ideal for Combination therapy

8-wk, randomized, double-blind clinical trial involving singlet or doublet therapy for Hypertension

Julian Segura. Integrated Blood Pressure Control 2011:4 27–34

JNC 7 guidelines 2003; ESH guidelines 2009; AHA Council statement 2007

< 140 / < 90 mm Hg in pts < 140 / < 90 mm Hg in pts with h/o of CVDwith h/o of CVD

< 130 < 130 //< 80 mm Hg for < 80 mm Hg for diabetics, CKDdiabetics, CKD

≤≤130/80 mmHg in pts with 130/80 mmHg in pts with h/o of CVDh/o of CVD

≤ ≤ 130 130 //< 80 mm Hg for < 80 mm Hg for diabeticsdiabetics

Resistant HypertensionResistant Hypertension5. Triple Drug therapy for ‘Stringent’ BP Goals5. Triple Drug therapy for ‘Stringent’ BP Goals

JNC - 7

International Guidelines and Clinical trials recommend BP levels of 130/80 mm Hg in most pts

Resistant Hypertension Resistant Hypertension ..Role of Triple Drug therapy ..Role of Triple Drug therapy

1.1. Monotherapy of drugs controls only 25% of patientsMonotherapy of drugs controls only 25% of patients● ALLHAT, SCOPE, ACCOMPLISH – ALLHAT, SCOPE, ACCOMPLISH – ≥3 antihypertensives often ≥3 antihypertensives often

requiredrequired

2.2. Concomitant risk factors – Type 2 DiabetesConcomitant risk factors – Type 2 Diabetes● ACCORD, IDNT – ACCORD, IDNT – benefits of combination therapybenefits of combination therapy

3.3. Multi-Pill regimen leading to poor compliance Multi-Pill regimen leading to poor compliance ● FDC tablets FDC tablets increase patient adherenceincrease patient adherence

4.4. Side effects of conventional agents on higher dosesSide effects of conventional agents on higher doses● COACHCOACH – side effects avoided with combination therapy – side effects avoided with combination therapy

5.5. ‘‘Stringent’ BP goals to be achievedStringent’ BP goals to be achieved● ESHESH (2009) and (2009) and AHA council AHA council (2007) guidelines for High-risk (2007) guidelines for High-risk

patientspatients

Need of Triple drug combination Need of Triple drug combination especially for..especially for..

Resistant HTN in Primary hypertensives Resistant HTN in Primary hypertensives or or

High-risk patientsHigh-risk patients

Ideal Triple drug therapy option for Ideal Triple drug therapy option for Resistant HypertensionResistant Hypertension

Telmisartan + Amlodipine + HCTZTelmisartan + Amlodipine + HCTZ

Telmisartan+ Amlodipine+ HCTZTelmisartan+ Amlodipine+ HCTZFor HypertensionFor Hypertension

12 Weeks Randomized, single blind study in patients with 12 Weeks Randomized, single blind study in patients with SBP 140 - 200 mmHg and DBP 90 - 120 mmHg (n= 220)SBP 140 - 200 mmHg and DBP 90 - 120 mmHg (n= 220)

Telmisartan (40 mg) + Amlodipine (5 mg) + HCT (12.5 mg) OD

Telmisartan (40 mg) + HCT (12.5 mg) OD

Group A Group B

Efficacy Parameter: 1.Effect on both SBP and DBP in sitting and supine position2.Quality of Life (QOL) questioner3.Safety parameters Follow-up: on week 1, 2, 4, 6, 8 and 10 for periodic efficacy and safety evaluations.

Manish Maladkar et al.Open Journal of Internal Medicine, 2012, 2, 67-71

Telmisartan+ Amlodipine+ HCTZTelmisartan+ Amlodipine+ HCTZ RESULTSRESULTS

The Effect of Triple Drug Combination on SBP and DBP

Safety Evaluations: Both the treatments were tolerated well with few reports of adverse events. All the reported adverse events were of mild to moderate inten- sity and did not require any active management.

Conclusion: Telmisartan when combined with amlodipine and HCT showed better control of both SBP and DBP. Thus this combination may serve a potential role in achieving desired BP goals, in patients with essential hypertension, which are otherwise poorly managed by either monotherapy or dual drug therapy. At the same time studied triple drug combination exhibits comparable tolerability profile to that of dual drug combination.

Effect on Quality of Life (QOL): Both the treatments were associated with improved QOL.

Telmisartan+ Amlodipine+ HCTZTelmisartan+ Amlodipine+ HCTZ RESULTSRESULTS

Triple drug therapyTriple drug therapy..for ‘Early’control in ‘..for ‘Early’control in ‘Diabetics’Diabetics’

Diabetic subgroup analysedDiabetic subgroup analysed Treatment goal for BP was <130/80 mm HgTreatment goal for BP was <130/80 mm Hg Patients on Dual therapy shifted to Triple Patients on Dual therapy shifted to Triple

drug therapy after 4 weeksdrug therapy after 4 weeks Results for Triple drug combinationResults for Triple drug combination

● Greater change in BP (p<0.05)Greater change in BP (p<0.05)● More patients achieved treatment goals (p<0.05)More patients achieved treatment goals (p<0.05)● Most treatment-emergent adverse events were Most treatment-emergent adverse events were

mild to moderate in severitymild to moderate in severity

Chrysant SG. J Am Soc Hypertens 2012 Mar;6(2):132-41

Telmisartan Amlodipine HCTZTelmisartan Amlodipine HCTZrationale rationale

TelmisartanTelmisartan ARBARB Potent vasodilatorPotent vasodilator Long half-life of Long half-life of

24 h24 h Insurmountable Insurmountable

antagonism for 24 h antagonism for 24 h BP controlBP control

vasculoprotection vasculoprotection [NO][NO]

Dosage for HTNDosage for HTN● 40 to 80 mg 40 to 80 mg

AmlodipineAmlodipine Ca Channel blockerCa Channel blocker Potent vasodilatorPotent vasodilator Long half-life of Long half-life of

36-48 h36-48 h Excellent Excellent

antianginal agent.antianginal agent. vasculoprotection vasculoprotection

[NO][NO] ‘‘Diuretic’ propertyDiuretic’ property Dosage for HTNDosage for HTN

● 2.5 to 5 mg2.5 to 5 mg

HCTZ• Thiazide diuretic• Medium potency

diuretics acting by inhibiting the Na+/Cl- symporter in the DCT

• Long half life of upto 12 h

• Dosage for HTN– 12.5 to 25 mg

Telmisartan Amlodipine HCTZTelmisartan Amlodipine HCTZrationale rationale

TelmisartanTelmisartan Negligible side effectsNegligible side effects

● Safe coprescription Safe coprescription profileprofile

● Counters Renin rise Counters Renin rise due to Diuretic due to Diuretic properties of HCTZ & properties of HCTZ & Amlodipine Amlodipine

● Counteracts Counteracts hypokalemia of HCTZ hypokalemia of HCTZ by preventing by preventing aldosterone releasealdosterone release

● Potential to diminish Potential to diminish peripheral oedema by peripheral oedema by providing both arterial providing both arterial & venous & venous vasodilatation.vasodilatation.

● Lipid neutral Lipid neutral

AmlodipineAmlodipine Dose dependent Dose dependent

rise in side effectsrise in side effects● Peripheral edema Peripheral edema

, incidence , incidence doubles or triples doubles or triples with dosages of 5 with dosages of 5 to 10 mgto 10 mg

● Lipid neutralLipid neutral

HCTZ• Dose dependent rise

in side effects– Diabetogenic

effects with 25 mg– Hyperlipidemia– Hypokalemia

Resistant HTN-emerging RxResistant HTN-emerging Rx

Renal denervation therapyRenal denervation therapy

Resistant Hypertension-SummaryResistant Hypertension-Summary

Resistant HTN is commonResistant HTN is common

Detailed evaluation and investigation may Detailed evaluation and investigation may be requiredbe required

Proper management results in significant Proper management results in significant reduction in morbidity and mortalityreduction in morbidity and mortality

Documents

Resistant HT