bp variability

Understated Concepts in Hypertension

Focus on BP Variability

Dr.N.PraveenFinal yr DM PG

Outline

• Hypertension and CV Risk: Where Do We Stand?

• Variability of BP and Cardiovascular Risk

• Key Considerations for Variability of BP

Hypertension and Cardiovascular Risk

Where Do We Stand?

BP Elevation Multiplication of CV Risk

• BP: Leading risk factor for Global

Burden of Disease (GBD, 2010)

• HT is associated with:

– 69% of first MIs

– 74% of cases of CHD

– 77% of first strokes

– 91% of cases of HF

Global Burden of Disease Study. Lancet 2012;380:2224-60Adapted from Thom T et al. Circulation. 2006;113:e85–e151.

BP=blood pressure; HTN=hypertension; MI=myocardial infarction; CHD=coronary heart disease; HF=heart failure.

Global burden of premature CVD

Globally, decreasing the prevalence of hypertension accounted for the largest risk reduction, followed by a reduction in tobacco smoking for men and obesity for women, but these results varied by region. The impact of meeting all risk factor targets on CVD mortality varied widely by region and sex.

Meta-analysis of 61 prospective, observational studies*

1 million adults

12.7 million person-years

*Epidemiologic studies, not clinical trials of HTN agents.BP, blood pressure; IHD, ischemic heart disease.Lewington S et al. Lancet 2002;360:1903-1913.

BP Reduction Is CriticalThe Lower, The Better

2 mm Hg decrease in mean SBP 10% reduction in

risk of stroke mortality

7% reduction in risk of IHD mortality

BENEFIT OF BP CONTROL

10 mm Hg lower systolic BP is associated with

• 50-60% lower risk of stroke death

• 40-50% lower risk of death – CAD

• 50% lower heart failure

GREATER BENEFIT IN OLDER AGES AND

AT HIGHER INITIAL BP READINGS

Hypertension in IndiaMet-analysis of 142 Studies (1950-2013)

• Overall Prevalence: 29.8%

Rural (%) Urban (%)

Prevalence 27.6 33.8

Awareness 25.3 42.0

Treatment 25.1 37.6

Control 10.7 20.2

Anchala R et al. J Hypertens. 2014 Jun;32(6):1170-7.

CSI CARDIAC PREVENT STUDY

• 21 states across India.(1,81,000)

• 36% population in hyderabad.(19,846)

• 25% are within the age group 31-45 yrs.

• 60% undiagnosed/unknown of hypertension.

• 42% not under control.

• 13% of deaths in CVD due to hypertension alone.

• MC profession affected is software professional.

• Average salt consumption >9-12g/day (recommended is 2-3

g/day)Venkat.S.Ram et al ,CSI PREVENT survey,2015

Blood Pressure MeasurementBeyond the Office Horizon

Certain Factors Independently Increase CV Risk, Beyond Clinical Blood Pressure

BP Variability

Masked HTCentral BP and Stiffness

Variability of BP and

Cardiovascular Risk

Prof. Gianfranco Parati, MD

What is BP Variability?

• BP normally fluctuates during day, can vary from day-to-day1

• Pronounced fluctuations in BP can occur over short / long-term

• Episodic Hypertension is common:2 o In TIA patients, 12% had stable HT, 69% had episodic HT

(some SBP readings ≤140 mmHg, some >140 mmHg)

• Self BP monitoring widely encouraged (ESC / JSH) 3

• BPV is difficult to measure in routine clinical practice: no clearly defined or widely adopted diagnostic definitions or treatment goals

1. Schillaci et al. Hypertension 2011;58:133-1352. Rothwell. Lancet 2010;375:938-948.3. Mancia et al. J Hypertension 2013;31:1281-1357

PHYSIOLOGICAL VARIATION IN BLOOD PRESSURE

BP REACTIVITY

• Defined as the response to environmental stressors,usually

quantiated as responses to standardized laboratory stressors.

• Hot reactors –individuals with increased reactivity.

• Difficult to quantitate – reactivity differs from stressor to stressor

and even upon retesting with same stressor.

• Suspected to be predictive of future development of

hypertension and CV risk – studies have not found this to be

true.

Blood pressure variability;how to deal? NR Rau,Medicine Update 2012Krantz et al ,Pschyol Bulletin 1984;96:435-464

BP LABILITY

• Characteristic of human BP.

• No clear definition that differentiates normal from abnormal lability.

• Labile hypertension – widely used – lacks an accepted definition

and is more of a clinical impression rather than a specific

diagnosis.

• Patients experience transient but substantial increases in BP.

• Likely due to sympathetic activation.

• BP usually falls without intervention.

• Risk of hypertension in future but no role of pretreatment.

Types of BP VariabilityDeterminants and Prognostic Relevance

Pronounced fluctuations in BP can occur over short- and long-term observation periods

Parati et al. Nat Rev Cardiol 2013;10:143-155

BPV Differs in Extent Between Individuals

Rothwell PM. Lancet 2010;375:938-948

Patient 1 with lower BPV Patient 2 with higher BPV

Weeks

40

60

80

100

120

140

160

180

200

220

Blo

od p

ress

ure

(mm

Hg)

1 2 3

SBP

DBP

40

60

80

100

120

140

160

180

200

220

Blo

od p

ress

ure

(mm

Hg)

1 2 3Weeks

Higher mean BPoverall

24-hr BPV and TOD: Cross-sectional Evidence

Adapted from Parati et al. Nat Rev Cardiol 2013;10:143-155

24-hr BPV and TOD: 7.4 yrs Follow-up

Adapted from Parati et al. Nat Rev Cardiol 2013;10:143-155

BP Variability and CV Risk

Hansen TW, et al. Hypertension 2010;55:1049-1057.

Systolic Average Real Variability Incidence of Mortality and CV Events in 8,938 patients

BPV, blood pressure variability; CV, cardiovascular; NCV, non CV.

BP VariabilityHazard Ratio for Stroke

UK TIA aspirin trial

ASCOT previous

TIA; Atenolol

ASCOT previous

TIA; Amlodipine

ESPS-1 placebo group

Dutch TIA trial

Mean SBP 3.63 1.81 0.94 1.89 2.34

SD SBP adjusted for Mean SBP

4.84 4.29 4.39 1.78 3.35

CV SBP adjusted for Mean SBP

3.82 3.51 3.25 2.22 3.41

National Institute for Health and Clinical Excellence (NICE) Clinical Guideline 127. Available at: http://www.nice.org.uk/nicemedia/live/13561/56007/56007.pdf. Accessed Apr 23, 2015

Definitions of Hypertension Office and Out-of-office BP Levels (mmHg)

Clinic Daytime (ABPM / HBPM)

Nighttime (ABPM)

24-hour (ABPM)0

35

70

105

140

175

140 135120

130

90 8570

80

Systolic BP Diastolic BP

BP Measurement Category

Blo

od P

ress

ure

(mm

Hg)

ABPM: Ambulatory BP Monitoring; HBPM: Home BP MonitoringMancia et al. J Hypertension 2013;31:1281-1357. Franklin SS et al. Hypertension. 2015;65(1):16-20.

WHY / WHERE ARE WE MISSING ?

Identifying HypertensionCategories of Blood Pressure

Masked Hypertension

(≈ 70% ↑↑ CV risk)

Sustained Hypertension

Normotension White-coat Hypertension

Clinic BP

Out

of C

linic

BP

JSH. Hypertension Research. 2009;32:70-7.

Nocturnal Hypertension Nighttime BP ≥120/70 mmHg (ABPM)

• Normally BP ↓ses by 10-20% at night (Dipping)

• Non-dipping / Reverse Dipping:

✓↑ risk of organ damage (brain, heart, kidney)

✓↑ CV events and mortality

Range of BP Dipping Class<0% Reverse Dipping

≥0%, <10% Non-Dipping≥10%, <20% Dipping (Normal pattern)

≥20% Extreme Dipping


DIPPERS NON DIPPERS

Nocturnal HypertensionInfluencing Factors and Management

Factors Influencing Nighttime Hypertension

↑ Fluid volume Heart failure, renal insufficiency

Sleep disorders Sleep apnoea

Autonomic dysfunction Diabetes, orthostatic hypotension

Neuropsychiatric disorders

Depression, cognitive decline, cerebrovascular disease


Sleep-time BP: prognostic marker of type 2 diabetes and therapeutic target for preventionRamón C. Hermida, Diana E. Ayala , Artemio Mojón José R. Fernández

• We prospectively evaluated 2,656 Individuals without diabetes, 1,292 men and 1,364 women, 50.6 ± 14.3 years of age, with

baseline BP ranging from normotension to hypertension according to ABP criteria. At baseline and annually (more frequently

if hypertension treatment was adjusted based on ABP) thereafter, ABP and physical activity (wrist actigraphy) were

simultaneously monitored for 48 h to accurately derive the awake and asleep BP means.

• Results

During a 5.9-year median follow-up, 190 participants developed type 2 diabetes. The asleep systolic ABP mean was the most

significant predictor of new-onset diabetes in a Cox proportional-hazard model adjusted for age, waist circumference,

glucose, chronic kidney disease (CKD) and hypertension treatment.

Daytime clinic BP and awake or 48 h ABP mean had no predictive value when corrected by the asleep ABP mean. Analyses

of BP changes during follow-up revealed a 30% reduction in the risk of new-onset diabetes per 1-SD decrease in asleep

systolic ABP mean, independent of changes in clinic BP or awake or 48 h ABP means.

• Conclusions/interpretation

Sleep-time BP is a highly significant independent prognostic marker for new-onset diabetes. Alteration in sleep-time BP

regulation seems to precede, rather than follow, the development of new-onset diabetes. Most important, lowering asleep BP,

a novel therapeutic target requiring ABP evaluation, could be a significant method for reducing new-onset diabetes risk.

mailto:[email protected]

Sleep-time blood pressure

• value of using blood pressure to predict new-onset diabetes,

prospectively examining 2,656 individuals of varying blood

pressure levels who did not have diabetes at the beginning of

the study.

• After an average of 5.9 years of follow-up, 190 participants had

developed T2 DM.

• This first study suggested to the researchers that lowering

sleep-time blood pressure could be a novel method for

reducing the risk of new-onset diabetes.

MESSAGE

• Diabetes risk fell by 57% in patients taking

medication before bed

Morning Hypertension(surge)Early morning BP ≥135/85 mmHg (HBP / ABP)

Factors Influencing Morning Hypertension

Physiological BP surge ↑ Sympathetic, neuroendocrine activities

Associated conditions Stress, OSA, Drinking, Cold, Old age

Inadequate 24-hr control Loss of drug efficacy at night / over 24-hr

Patterns of Morning HT Clinical Outcomes

✓ Extension of nocturnal HT ✓ ↑ Cardiovascular risk

✓ ↑ BP Variability over 24-hr ✓ ↑ Occurrence of events

✓ Morning surge (rapid BP rise) ✓ Target organ damage


Morning BP Surge

Kario K, et al. J Cardiovasc Pharmacol 2003;42 Suppl 1:S87-S91.MBP, morning blood pressure.

Patients with sleep-trough surge of >55 mm Hg were classified in the MBP surge group

Central Blood PressureAorta as a Reservoir

Cavalcante JL et al. J Am Coll Cardiol. 2011 Apr 5;57(14):1511-22.

Factors Influencing Aortic Stiffness

• Hypertension

• Diabetes mellitus

• Atherosclerosis and Calcification

• Chronic Kidney Disease

• Aortic regurgitation; Valvular heart disease

• Hypertrophic cardiomyopathy

• Connective tissue disorders (Marfans, Ehlers Danlos)

Insults Resulting in Increasing Aortic Stiffness

Cavalcante JL et al. J Am Coll Cardiol. 2011 Apr 5;57(14):1511-22.

BP Variability is Related to Arterial Stiffness

Schillaci G et al. Hypertension. 2012 Aug;60(2):369-77.

AVERAGE REAL VARIABILITY

HOW TO TACKLE ?

Patients

Discontinue • Self-monitoring of BP

irregular therapy • Self-management by simple patient guidance system

• Establish patient population

• Strategic information

• Comprehensive intervention: Including message, reminder, BP self-monitoring, telephone follow-up, or working environment or pharmacy-based projects

Subject Phenomena Recommended improvements

■ Comprehensive BP management focusing on patients and combining doctors and communities

■ Poor compliance is a global problemo 1/3rd of patients will discontinue the initial therapy within 6 months after

treatment, and only one half of patients will continue treatment after 1 yearo Self-monitoring of BP is an important means of improving adherence

Mancia et al. J Hypertension 2013;31:1281-1357

2013 ESH / ESC Guidelines: Self-monitoring of BP: Key Component of BP Management

Home BP MonitoringJSH Recommendations, 2009

Is HBPM Equivalent to ABPM?

Measurement Method

Ambulatory (ABPM)

Home(HBPM)

Clinic (Office) Measurement

Supervision + - / + +

BP Patterns Daytime; Nighttime; 24 hr. Daytime only In clinic only

BP Variability 24 hr. (intraday);Visit-to-visit Day-to-day Visit-to-visit

Prediction of Outcome

Best; nighttime HT crucial

Superior to Clinic BPM

Standard measure

Guidance to Drug treatment

Most complete; 24 hr. control

Limited; better than Clinic BPM Limited and poor

Improving Compliance Maybe helpful Best evidence Minor influence

O'Brien E et al. J Hypertens. 2013 Sep;31(9):1731-68.

ABPM Recommended in High Risk Groups

✓ Ongoing antihypertensive treatment

✓ High-normal BP (130-139 / 85-89 mmHg)

✓ Smoking / DM / Obesity / Metabolic syndrome / CVD

✓ ↑sed drinking / stress / physical activity / heart rate

✓ Abnormal orthostatic changes in the BP

✓ Organ damage (LVH, ↑ carotid intima-media thickness)

Clinical Suspicion is Essential in these high-risk patients


Therapeutic Considerationsfor

Variability of BP

Guidelines on BPV

• NICE 20111

– Whatever the underlying mechanisms, SBP variability appears to be an important independent predictor of clinical outcomes

– BPV most effectively reduced by CCBs, closely followed by thiazide-type diuretics. Beta-blockers were the least effective and may actually increase blood pressure variability.

• ESC/ESH guidelines 20132

– Consideration should be given to the evidence that visit-to-visit BPV may be a determinant of CV risk, independently of the mean BP levels achieved during long-term treatment

– CV protection may be greater in patients with consistent BP control

1. National Institute for Health and Clinical Excellence (NICE) Clinical Guideline 127. Available at: http://www.nice.org.uk/nicemedia/live/13561/56007/56007.pdf. 2. Mancia G, et al. Eur Heart J 2013;34:2159-2219.

“Updated guidance recommends the best available evidence-based treatment options to suppress BPV in people with hypertension”

TRIAL EVIDENCE

CV Outcomes Relate to BPV and Antihypertensive Treatment

ASCOT-BPLA Trial1,3,4

▪ Lower risk of stroke with amlodipine vs atenolol

HR = 0.78 (0.67 ‒ 0.90)▪ Partly attenuated by adjusting for

mean systolic BPHR = 0.84 (0.72 ‒ 0.98)

▪ Abolished by adjusting for within-individual systolic BPV

HR = 0.99 (0.85 ‒ 1.16) ▪ Reduced daytime systolic BPV in

amlodipine group partly accounted for reduced risk of CV events, but reduced visit-to-visit clinic systolic BPV had a greater effect

MRC Trial1,2

▪ Temporal trends in BPV with atenolol correlated with trends in risk of stroke

▪ Risk of stroke higher with atenolol vs placebo over the first 2 years when systolic BPV was higher despite lower mean systolic BP

HR = 1.31 (0.81 ‒ 2.10) ▪ After 2 years when systolic BPV

no longer differed from placebo, but mean systolic BP was still reduced, the risk of stroke with atenolol was reduced

HR = 0.62 (0.40 ‒ 0.94)

1. Rothwell et al. Lancet Neurol 2010;9:469-48012. MRC Working Party. BMJ 1992;304:404-4123. Dahlof et al. Lancet 2005;366:895-9064. Poulter et al. Lancet 2005;366:907-913

ASCOT BPLAStudy Design and Treatment Algorithm

• Age 40 - 79 yrs with untreated / treated HT

• At least 3 additional CV risk factors (male sex, smoker, age 55 years, LVH, ischemic ECG abnormalities, T2DM, PVD, cerebrovascular disease, microalbuminuria or proteinuria, Total : HDL cholesterol ratio 6, family history)

• Total patients 19,257; median follow-up 5.5 yrs (106,153 pt-yrs of observation)

ASCOT BPLABP Reduction over Follow-up

Amlodipine-Based Regimen Better for Total CV End-points and Procedures

In All Patient Subgroups

Benefits Beyond BP Control?

Difference in SBP between treatment groups

• 2.7 mm Hg (average, throughout ASCOT BPLA)

Expected to generate a difference in outcomes of:

• 4 - 8% in coronary events

• 11 - 14% in strokes

Observed Difference in Outcomes is Greater than

Anticipated with BP Lowering Alone

SPRINT trial -RESULTS

• show a 12% reduction in the cardiovascular outcome

• 25% reduction in allcause mortality

• the full results are not yet available

• halted early (September 2015)

• clinical implications of this trial have not been determined

BP Variability and Stroke RiskEffect of Drug Classes on SBP Variability

Meta-analysis of 389 trials; ≈1 year of follow-up

Adapted from: Webb AJ et al. Lancet. 2010 Mar 13;375(9718):906-15.

↓ BP Variability with drug class ≡ ↓ Stroke Risk, independent of BP

Conduit Artery Function Evaluation (CAFE) Sub-study of ASCOT TRIAL

HEAD TO HEAD COMPARISON OF AMLODIPINE WITH OTHER

ANTIHYPERTENSIVES EFFECT ON BPV

Improved Long-term BPV with Amlodipine vs Other Antihypertensives

Wang JG, et al. J Am Soc Hypertens 2014. doi: 10.1016/j.jash.2014.02.004.ACEI, angiotensin-converting enzyme inhibitor; BPV, blood pressure variability; CI, confidence interview; SD, standard deviation.

SD-based BPV analysis (mm Hg) in individual studies and from a meta-analysis

Amlodipine vs Nifedipine GITS Effect on MBP Surge

• Open-label, controlled crossover study

• 40 patients with mild to moderate essential hypertension, receive amlodipine (5 mg/day) or nifedipine GITS (30 mg/day) for 12 weeks

• Evaluated reduction in ABPM with amlodipine and nifedipine GITS

Ferrucci A, et al. Clin. Drug Invest 1997;13(Suppl 1):67-72.

ABPM, Ambulatory BP monitoring; BP, blood pressure; BPV, BP variability; Gits, gastrointestinal therapeutic system; MBP, morning BP.

Changes in SBP with Amlodipine and Cilnidipine

24-hr SBP Daytime SBP Nighttime SBP Morning SBP-20

-16

-12

-8

-4

0

-14-16

-12-14

-11-13

-8.2-9.3

Amlodipine Cilnidipine24-hour ABPM Parameters

Redu

ction

in S

BP (m

m H

g)

Doses of Drugs Used in Study:Amlodipine: 2.5 to 5 mg OD (Less - than Maximum Anti-HT Dose)Cilnidipine: 10 to 20 mg OD (Maximum Anti-HT Dose)

BP Reductions from baseline were significant in both groups, nonsignificant between groups

Hoshide S et al. Hypertens Res. 2005 Dec;28(12):1003-8.

Changes in BP with Amlodipine and CilnidipineIndian Evidence

Daytime SBP Daytime DBP Nighttime SBP

Nighttime DBP

Morning SBP Morning DBP-18

-14

-11

-7

-4

0

-14

-8

-12

-6

-14

-5

-12

-8 -8

-4

-10

-4

Reduction in BP

Amlodipine Cilnidipine

Redu

ction

in S

BP (m

m H

g)

BP Reductions from baseline were significant in both groups

Zaman ZA et al. Int J Basic Clin Pharmacol 2013;2:160-4.

In Diabetic Hypertensives with Maximal RAS Blockade,Nebivolol Offered No Significant Advantage Over Metoprolol for Aortic BP

ALLHAT Trial Follow-upChlorthalidone, Amlodipine, Lisinopril Prevention of Fatal / Non-fatal Stroke

Yamal JM et al. J Am Soc Hypertens. 2014;8(11):808–819.

During trial, diuretic and CCB were superior to ACE-I

ALLHAT StudyUnexplained Observations

ALLHAT Investigators. Curr Hypertens Rep. 2003 Aug;5(4):293-4.

Parameter OutcomeBP Reduction Equivalent Reduction in SBP and DBP, and

control of BP through study period

Proteinuria Reduction Significantly Superior with Hydrochlorothiazide, relative to Amlodipine

Delay in Progression of CKD

Significantly Superior with Amlodipine, relative to Hydrochlorothiazide

ACCOMPLISH Trial2nd Add-on Antihypertensive Class

ACCOMPLISH Trial: Effect of Drug Combinations on CKD Outcomes

Study Groups:• Benazepril plus Amlodipine (5,744 patients)• Benazepril plus Hydrochlorothiazide (5,762 patients)Mean follow-up: 2.9 years

Bakris GL et al. Lancet. 2010;375(9721):1173-81.

ACCOMPLISH TrialDelay of CKD Progression

Significantly Superior With Amlodipine

Bakris GL et al. Lancet. 2010;375(9721):1173-81.

N Engl J Med 2008;359:2417-28

ACCOMPLISH TrialCardiovascular Events

However, the reduction in BPV by amlodipine was significantly associated with the reduction in BP (P0.006) and the reduction in HR variability (P0.02), whereas the corresponding reduction by indapamide sustained release was only associated with the reduction in HR variability at night (P0.004). IIn summary, 3-month amlodipine or indapamide sustained release treatment was associated with a significant reduction in BPV, and the mechanism of those reductions was possibly attributable to lowering BP or ameliorating the autonomic nervous system regulation or both. The combination of the 2 agents might help to optimize such properties.

PLEIOTROPIC EFFECTS OF AMLODIPINE

Benefits Beyond BP ControlAmlodipine’s Chemical Structure and Pleiotropic Effects

Anti-atherogenesis; Plaque stabilization

• ↓ Platelet aggregation (↓ p-selectin levels)

• Antioxidant action

• ↓ smooth muscle cell proliferation

• Remodeling of atherosclerotic membrane structure

• ↑ endothelial nitric oxide production

Mason RP et al. Atherosclerosis. 2002; 165:191-199. Tiryaki O et al. Clin Exp Hypertens. 2012;34(2):145-52. Umemoto S et al. Hypertens Res. 2006 Mar;29(3):179-86. Pitt B et al. Circulation 2000;102:1503-10. Jorgensen B et al. J Am Coll Cardiol 2000;35:592-9. Nissen SE et al. JAMA. 2004 Nov 10;292(18):2217-25.

Meta-analysis (87,257 patients): Amlodipine and CV Outcomes“Amlodipine reduced the risk of total cardiovascular events as well as all-cause mortality compared with non-CCB-based regimens, indicating its benefit for high-risk cardiac patients.”

Lee SA et al. Korean J Intern Med. 2014 May;29(3):315-24.

SYNERGISM

Synergism Between RAS Inhibitors and Amlodipine

• CCBs are usually combined with an ACEI or an ARB that target the renin-

angiotensin system1

– ACEI or ARB is favorable since they can be used at higher doses to increase efficacy

without compromising tolerability2

• ARB-based combinations may be more desirable than ACEI-based combinations

due to their superior tolerability3

• The use of CCB/ARB combinations has been shown to be ‘capable of most

effectively reducing even severe hypertension’3

1. Mancia G, et al. Eur Heart J 2013;34:2159-2219. 2. Kreutz R. Vasc Health Risk Manag 2011;7:183-192. 3. Erdine S. Ther Adv Cardiovasc Dis 2012;6:31-44.

Anchored drug to target BPV control:

Amlodipine

ARB?

ACEI?+ OR

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BPV, BP variability; CCB, calcium channel blocker.

Antihypertensive Drugs and CombinationsControl of BP Variability

Telmisartan / Amlodipine combination

(all doses)

Telmisartan 80mg

Amlodipine 10mg

Valsartan 160mg

Ramipril 10mg

Placebo-1.5

-0.5

0.5

-1.06

-0.05

-1.37

0.45 0.47

0.24

-0.82

-0.16

-0.54 -0.59

0.27

0.05

24-hour BPV Daytime BPV Nighttime BPV

Mea

n R

educ

tion

in B

P V

aria

bilit

y (S

D)

SD: Standard DeviationN = 10 studiesParati G et al. J Hypertens. 2014 Jun;32(6):1326-33.

Summary

• BPV control should be considered as a goal to guide choice

of initial antihypertensive treatments

• MBP should be monitored as it is a potential marker for

BPV

• CCBs are the antihypertensive class of choice for BPV

control

• Among CCBs, amlodipine as initial monotherapy has

proven efficacy in reducing BPV and MBP surge

• Synergism between long acting CCBs and ARBs

Thank You

bp variability

Education