Benefits of Hypertension Control:

What Levels ? Which Drugs ?

Dr. Akshay MehtaNanavati Superspeciality Hospital

Asian Heart Institute

Mr X is 64 yr old with BP of 148/84 since last 6 months despite all life style measures. He has no other RF, CVD or TOD. His brother had a stroke at age 73 yrs. Should one start drug Rx ?

A. No, as per JNC VIII panel report B. Yes, as per other guidelinesC. Leave it to the patient

Hypertension Guidelines 2011- 2014

Lindholm LH, Carlberg B. HT News 2014, Opus 35

Blood pressure (in mm Hg)

NICE 2011

ESH/ESC 2013

2014 Hypertension guidelines, US

“JNC 8”

ASH /ISH 2014

Indian Guidelines -2013

Definition of Hypertension

≥140/90 and daytime ABPM (or home

BP) ≥135/85

≥140/90 Not addressed ≥140/90 > 140/90 mm Hg

Blood pressure targets

< 140/90 <140/90 < 60 y. <140/90 <140/90 (young and middle aged)

<140/90≥ 80 y. Elderly < 80

y.≥ 80 y. Elderly 140 – 145/90

< 150/90 SBP 140-150 ≥ 60 y. <150/90 < 150/90SBP <140 in fit patients

Elderly ≥ 80 y.SBP 140-150

Blood Pressure target in patients with diabetes mellitus

Not addressed

< 140/85

<140 /90 <140/90 <140/80

Published Online Journal of American Medical Association 18th Nov, 2013

• New relaxed drug Rx goals: BP < 150/90 if age 60+ years

BP < 140/90 if age < 60 years

The panel originally appointed by the NHLBI to review the evidence on treatment of hypertension

If you were to wake up in the morning and had to have either a

stroke or a heart attack, which one of the 2 would you like to have?

Adjusted risk of outcome events by achieved systolic blood pressure, divided in to deciles (grey bars).

Sleight P Eur Heart J Suppl 2009;11:F16-F18

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Risk of Hypertn

and Absolute

Benefits of Drug Therapy Increase With

Age

Wang J et al. Hypertension. 2005;45:907-913

So for b/w age 60yrs & 80yrs, stopping at SBP 150 goal is not a good idea

• If you want to prevent stroke • If you want to protect the >60 population, a large

high risk group most likely to be protected with goal below 140 mm Hg SBP

• Major trials show benefit with goal BP around 143 which is nearer 140 than 150

• Going to 140 mm Hg is safe

Problems with JNC VIII panel report

• Not sanctioned by the NHLBI• The panel’s report is now published in JAMA as a

stand-alone document • Prior guidelines based on the totality of evidence,

including observational studies, RCTs, and meta-analyses, as well as expert opinion

• JNC VIII panel depended only on specific RCTs which showed lack of definitive benefit for goal of 140

• But paradoxical that for young pts goal maintained at 140 despite NO evidence of benefit from RCT

A target of <150/90 mm Hg is recommended for patients >80 if it can be done safely

JNC VIII panel - Corollary Recommendation

• In the general population aged ≥60 years, if pharmacologic treatment for high BP results in lower achieved SBP (eg, <140 mm Hg) and treatment is well tolerated and without adverse effects on health or quality of life, treatment does not need to be adjusted.

JNC VIII Panel Goals for CKD & Diabetes

• In the population aged ≥18 years with chronic kidney disease (CKD), initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg or DBP ≥90 mm Hg and treat to goal SBP <140 mm Hg and goal DBP <90 mm Hg

• In the population aged ≥18 years with diabetes, initiate pharmacologic treatment to lower BP at SBP ≥140 mm Hg or DBP ≥90 mm Hg and treat to a goal SBP <140 mm Hg and goal DBP <90 mm Hg. (Expert Opinion – Grade E)

Achieved systolic blood pressure (SBP) values and reductions in cardiovascular (CV) events in trials of

antihypertensive treatment in diabetics.

Zanchetti A Eur Heart J 2010;31:2837-2840Published on behalf of the European Society of Cardiology. All rights reserved. © The Author

2010. For permissions please email: journals.permissions@oxfordjournals.org

]able 1. Key studies on blood pressure targets in patients with chronic kidney disease

MDRD study REIN-2 AASK

Year of publication 1994 2005 2010

No. individuals included 840 338 1094

Cause of CKD Nondiabetic Nondiabetic 'Hypertensive'

Baseline kidney 33 (low BP target) 36 (low BP target) 46 (low BP target)

   function (ml/min) 32 (usual BP target) 34 (usual BP target) 45 (usual BP target)

Proteinuria at baseline 390 mg/day (low BP target) 2.8 g/day (low BP target) 80 mg/day (low BP target)

  310 mg/day (usual BP target) 2.9 g/day (usual BP target) 80 mg/day (usual BP target)

Target BP (mmHg) Low BP: MAP≤92 (≈125/75) Low BP:<130/80 Low BP: MAP≤92 (≈125/75)

  Usual BP: MAP≤107 (≈140/90) Usual BP: DBP<90 Usual BP: MAP≤102–107 (the latter ≈140/90)

Primary endpoint Rate of change in GFR ESRD Combination of doubling of serum creatinine, ESRD, and death

Satisfied with office BP ?What about other BP goals ?

Superiority of ambulatory BP for predicting CV death

Syst-Eur Study(Systolic hypertension in Europe Study)

Staessen JA et al. JAMA 1999;282:539-46

0.00

0.04

0.08

0.12

0.16

0.20

90 110 130 150 170 190 210 230Systolic blood pressure (mmHg)

2-ye

ars i

ncid

ence

of

card

iova

scul

ar e

ndpo

ints

Nighttime24-hDaytimeConventional

Other Goals to look at :More goals, better results !

• Out of office BP : -Nocturnal BP & Dip -BP variability –including morning surge -Masked hypertn• Rate of BP control• Lower limits of BP goals- J curve ?• Central aortic BP• Pulse wave velocity

What are the lower limits ?Is there a J curve ?

• No direct evidence

• Evidence from observational and post hoc analysis of trials like INVEST, HYVET, ON TARGET etc :

• 1. No J shaped relationship between systolic BP and adverse events

• 2. "     "                   " b/w BP and other organs such as brain, kidney etc

J curve in ON TARGET

Copyright © The American College of Cardiology. All rights reserved.

From: The J-Curve Between Blood Pressure and Coronary Artery Disease or Essential Hypertension: Exactly How Essential?

J Am Coll Cardiol. 2009;54(20):1827-1834. doi:10.1016/j.jacc.2009.05.073

Incidence of MI and Stroke Stratified by Diastolic Blood Pressure in the INVEST Study

Copyright © The American College of Cardiology. All rights reserved.

From: The J-Curve Between Blood Pressure and Coronary Artery Disease or Essential Hypertension: Exactly How Essential? J Am Coll Cardiol. 2009;54(20):1827-1834.

doi:10.1016/j.jacc.2009.05.073

Interaction of the J-Curve With Coronary RevascularizationPatients who were revascularized better tolerate a lower diastolic blood pressure (DBP) than those who were not.

There could be a J shaped relationship between DBP and cardiac events (MI) in elderly, having LVH and/or coronary heart disease (esp non revascularized), and wide pulse pressure. The critical DBP is 60 mm Hg.

Definitions of hypertension by office and out-of-office BP levels

Ambulatory BP targets : Heart Foundation

• • Daytime and night-time ABP “loads”* should be <20% above normal values.

• Mean day-time and night-time (sleep) ABP measurements should differ by >10%.

Which Drugs ?

All the following factors determine choice of initial drugs in hypertension

except :A. AgeB. Gender *C. RaceD. Presence of comorbid conditionsE. BMI (obesity)

Best drug(s) to initiate treatment with, in the young (<55)

• ACEI/ARB• BB• CCB• D

Young ElderlyRAAS

Na, Vol

WHY ?

ACEI/ARBOrBB

A or B

CCB or D

C or D

Gender

• No difference in drug Rx except :

• Pregnancy : M Dopa, α-BB, Hydralazine, BB, CCB

• Women of repro age : BB, α-BB

ACEI/ARB X X X

Race :

• In blacks : • Initial Rx should include CCB or D• In kidney disease ACE/ARB foll by C or D

Hypertn & Co morbid conditions

Hypertension and HF ARB or ACE inhibitor + BB + diuretic + AA

√ ×

• Obese individual

• Physically,mentally active • Resting tachycardia • Resting bradycardia • Postural hypotension

D, BB, A CCBACEI, CCB BB, CentrlBB, Diltia αBl, Amlo

Amlo, α Bl BB, DiltiaACEI/ARB Diu

√ ו Migraine• Asthma• Prostatism• Gout• Acute CVA

BBCCB (NDHP) BBαBB ARB Diu ACEI, BB, D Short actg DHPCCB

Drugs which activate the renin-angiotensin-aldosterone system (green) make it more susceptible to the action of drugs which

suppress the system (shown in red).

How to combine drugs ?

The BHS recommendations forcombining BP lowering drugs

Which is a better combination with ACE I/ ARB ?

• CCB

• Diu

ACCOMPLISH TRIALC

umul

ativ

e ev

ent r

ate

HR (95% CI): 0.80 (0.72, 0.90)

20% Risk Reduction

Time to 1st CV morbidity/mortality (days)

p = 0

ACEI + HCTZ

ACEI + CCB650

526

.0002

INTERIM RESULTS Mar 08

‘ACCOMPLISH’ SUBANALYSIS Fat versus the thin !

• in patients treated with hydrochlorothiazide and benazepril, there was a 69% higher risk in the lean patients as compared to obese

• in people treated with amlodipine, this phenomenon not seen

• in lean pts, amlodipine was better and reduced the risk of cardiovascular death 38%, total stroke by 40%, and MI by more than 50%

• In obese patients diuretics - OK

NICEGUIDANCEAug 2011

When to Initiate Rx with Beta blockers?

• women of child-bearing potential • people with evidence of increased

sympathetic drive.• Co morbid conditions requiring BB If BB alone not effective add CCB or D ?

Best drug to reduce nocturnal BP

• ACEI/ARB

• BB

• CCB

• Diuretic √

Best drug to reduce BP variability

• ACEI/ARB

• BB

• CCB √

• D

Low-Dose Combination Rx Increased efficacy Fewer side-effects

WHEN indicated ?

Hypertension Guidelines 2011- 2014

Lindholm LH, Carlberg B. HT News 2014, Opus 35

Blood pressure (in mm Hg)

NICE 2011

ESH/ESC 2013

2014 Hypertension guidelines, US

“JNC 8”

ASH /ISH 2014

Indian Guidelines -2013

Definition of Hypertension

≥140/90 and daytime ABPM (or home

BP) ≥135/85

≥140/90 Not addressed ≥140/90 > 140/90 mm Hg

Blood pressure targets

< 140/90 <140/90 < 60 y. <140/90 <140/90 (young and middle aged)

<140/90≥ 80 y. Elderly < 80

y.≥ 80 y. Elderly 140 – 145/90

< 150/90 SBP 140-150 ≥ 60 y. <150/90 < 150/90SBP <140 in fit patients

Elderly ≥ 80 y.SBP 140-150

Blood Pressure target in patients with diabetes mellitus

Not addressed

< 140/85

<140 /90 <140/90 <140/80

Initiate drug therapy with two drugs

Not mentioned

In patients with markedly elevated BP

≥160/100 ≥160/100 > 160/100

All the following are sound combination of drugs except ?

A. ACEI +CCB B. CCB+BBC. ARB + DiuD. ACEI + ARB

Indian Hypertn Guidelines 2013

BP Goals :• 140/90 mm Hg in the young and middle aged• 140/80 mm Hg in diabetic patients • 130/85 mm Hg in pts who have survived stroke• 140-145/90 in elderly patients• Treatment of hypertension even in > 80 has been showed to

be beneficial and has been recommended.• A J shaped curve does exist specially for non revascularised

CAD patients and caution has been advocated in trying to lower blood pressure to low target levels specially in these patients.

Indian Hypertn Guidelines 2013• Which drugs : • Beta-blockers not first line agents and now recommended as

agents for use only in young or in hypertensives with specific indications.

• Diuretics are now considered at par with of ACEI’s or ARB’s and CCB and not

• as preferred agents as in previous guidelines.• Chlorthalidone is now available and shown to be better than

Hydrochlorothiazide and its usage is to be preferred.

Indian Hypertn Guidelines 2013• Which Drugs• When blood pressure is high by more than 20/10 mm of Hg

systolic and diastolic it is now recommended to start with a combination of drugs.

• Certain combinations have been shown to be better than others in recent trials. (Specially ACEI’s/ARB’s +CCB’s)

Take home messages :

• BP Goal : Office BP < 140/90 in all except age 80 & above

• Other Goals – more benefits : Out of office BP (esp noct BP, dip, variability, masked hypertn etc)

• Initiate Rx accrdg to age and co morbid conditions• Use physiologically sound combinations• Avoid severe diastolic hypotension esp in non

revascularized CAD pts