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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: [email protected]
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
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: [email protected]
]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
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
• 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
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.
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%.
All the following factors determine choice of initial drugs in hypertension
except :A. AgeB. Gender *C. RaceD. Presence of comorbid conditionsE. BMI (obesity)
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
√ ×
• 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 ?
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
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 ?
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