Hypertension in patients at risk of cardiovascular disease:

The key role of patient compliance

Massimo Volpe, MD, FAHA, FESCUniversity of Rome “La Sapienza” Rome, Italy

Relevant disclosure of interest: Consultant to Daiichi Sankyo and the Menarini group

Hypertension in patients at risk of cardiovascular disease

• Case studies show how patients with multiple chronic conditions often require a high pill burden which can affect compliance

• Patient management remains a challenge

• Patient adherence has a big impact on the success of treatment

• For patients at CV risk, adherence is especially important:

– Higher risk greater need to reduce and control BP

– Concomitant diseases more treatments, more pills

– “Drugs don’t work if people don’t take them” (Former US Surgeon General C. Everett Koop)

• Effective treatments, including combinations, are now available

Factors behind poor BP control in hypertension

• Poor adherence to prescribed therapy

• Physician inertia

• Poor physician-patient communication

• Insufficient use of combination therapy

• Poor control of lifestyle measures (e.g. dietary habits, physical inactivity, smoking)

• Lack of practical and simple guidelines for management of hypertension

Volpe. Expert Rev CV Therapy 2010 Jun;8:811–20

For patients, adherence is complex and is influenced by several factors

Miller et al. J Clin Hypertens (Greenwich). 2010;12:328-34. Okken et al. Neth Heart J 2008;16:197-200. Nabi et al. J Hypertens 2008;26:2236-43. Barrier et al. Mayo Clin Proc 2003;78:211-4.

Betancourt et al. Curr Hypertens Rep 1999;1:482-8. Hassan et al. J Hum Hypertens 2006;20:23-9.Wang et al. J Gen Intern Med 2002;17:504-11.

Adherence Adherence

Depression

Younger age

Poor patient satisfaction

Medication barriers

Health beliefs

Motivation

Lack of sense of guilt, regret and shame

Type and delivery of educational materials

Adherence/compliance in hypertensive patients typically falls over time

Vrijens B et al. BMJ 2008;336:1114-7

Good adherence with antihypertensive therapy significantly improves BP control

Pat

ien

ts w

ith

BP

co

ntr

ol*

(%

)

Level of adherence

0

10

50

30

20

High(≥80%)

Medium(50–79%)

Low(<50%)

43

34 33

Odds ratio = 1.45p=0.026 (controlling for age, gender and

comorbidities)

40

BP goal: <140/90 mmHg (or <130/85 mmHg in patients with diabetes) Bramley et al. J Manag Care Pharm 2006;12:239–45

Good adherence is widely acknowledged to be important for better BP control

International guidelines point out that:

– adherence is a major factor in BP control

– improving adherence clearly has the potential to improve patients’ clinical outcomes

– monitoring patients’ adherence is an important clinical parameter

World Health Organization. 2003. http://www.who.int/chp/knowledge/publications/adherence_introduction.pdf.

Hill MN et al. J Clin Hypertens 2011;12:757-64.

There is a higher risk of first-ever acute CV events* in patients with low adherence

0.0

0.2

0.4

0.6

0.8

1.0

Adherence within 6 months after diagnosis

*Estimated by Cox proportional-hazards models, PDC: proportion of days coveredMazzaglia G et al. Circulation 2009;120:1598-605.

Low (PDC <40%)

High (PDC ≥80%)

0.87(0.73 – 1.03)

0.50(0.35 – 0.69)

Risk

of fi

rst a

cute

CV

even

t(h

azar

d ra

tio)

1.00

Medium (PDC 40–79%)

Good adherence is associated with lower risk of CHF, CAD and cerebrovascular events

Compared with patients with low (<80%) adherence, those with high (≥80%) adherence showed

Adherence calculated using medication possession ratio: total number of days supply of dispensed medication divided by duration of follow up

Relative risk of CHF

-11%(RR: 0.89; CI 0.80–

0.99)1

Relative risk of CAD

-10%(RR: 0.90; CI 0.84–0.95)2

Relative risk of CD

-22%(RR: 0.78; CI 0.70–0.87)3

1. Perreault et al. J Intern Med 2009;266:207-182. Perreault et al. Br J Clin Pharmacol 2010;69:74-84

3. Kettani et al. Stroke 2009;40:213-20

• 242,594 patients newly treated for hypertension during 2000-2001• No history of cardiovascular (CV) disease• Mean follow-up: 6 years• Analysis of hospitalisation for coronary or cerebrovascular disease

Persistence with antihypertensive treatment significantly reduces long-term CV risk

Ch

ang

e in

CV

ris

k (h

azar

d r

atio

)

RR: (95% CI 34-40%, p<0.0001)

–37%

0%

–25%

–50%

Continued useof therapy

Corrao et al. J Hypertens 2011;29:610-8

Factors behind poor BP control in hypertension

• Poor adherence to prescribed therapy

• Physician inertia

• Poor physician-patient communication

• Insufficient use of combination therapy

• Poor control of lifestyle measures (e.g. dietary habits, physical inactivity, smoking)

• Lack of practical and simple guidelines for management of hypertension

Volpe. Expert Rev CV Therapy 2010 Jun;8:811–20

Yes, decided to modify therapy

No modification of therapy

Clinical inertia is another major factor that influences BP control

42.4%

After 1 year, less than 50% of physicians decided to modify therapy even when BP control

was not achieved

The REassessment of Antihypertensive Chronic Therapy (REACT) study:•large observational (n=1482) assessment of hypertension management in Italy •patients managed in the same clinic on stable antihypertensive treatment for ≥1 year

Proportion of physicians who decided to modify therapy in patients with uncontrolled BP

57.6%

Volpe et al High Blood Press Cardiovasc Prev 2004;11:175–85

The Supporting Hypertension Awarenessand Research Europe-wide (SHARE) survey

• Anonymous* survey to assess challenges that European physicians face when trying to get patients to BP goal†

• May to December 2009

• 45 questions on several topics:

– factors that influence treatment choices

– opinions on different therapeutic approaches

– familiarity with and opinions about treatment guidelines and acceptable BP levels in hypertensive patients

*Physicians could input contact details at the end †BP goal (<140/90 mmHg, <130/80 mmHg for patients with co-morbidities or high CV risk) Redon et al J Hypertens 2011;29:1633–40

SHARE: physicians may lack confidence in measurements, or hesitate to reduce high SBP

0

1

2

3

4

5

110 120 130 140 150 160 170 180 190 200 210

Ph

ys

icia

n v

ote

s (

%/m

mH

g)

Systolic BP (mmHg)

BP level that physicians are

satisfied with (mean = 131.6 mmHg)

BP level that physicians are

concerned about (mean = 148.8 mmHg)

140

BP level at which physicians take

immediate action (mean = 168.2 mmHg)

Redon et al J Hypertens 2011;29:1633–40

Factors behind poor BP control in hypertension

• Poor adherence to prescribed therapy

• Physician inertia

• Poor physician-patient communication

• Insufficient use of combination therapy

• Poor control of lifestyle measures (e.g. dietary habits, physical inactivity, smoking)

• Lack of practical and simple guidelines for management of hypertension

Volpe. Expert Rev CV Therapy 2010 Jun;8:811–20

Ways to improve adherence/compliance

• Doctor-patient communication often appears inadequate, especially in general practice, and should be encouraged1

• Pill burden can be reduced by fixed-dose combination (FDC) therapy2

– Complicated treatment regimens contribute to poor compliance3

– Treatment simplification is a straightforward way to improve compliance

1. Volpe. High Blood Press Cardiovasc Prev 2008; 15: 63-73

2. Redon et al. J Hypertens Suppl 2008;26:S1–14

3. Burnier et al. Int J Clin Pract 2009;63:790–8

Physicians and patients can improve BP control and CV protection by working together

A positive, optimistic, motivated perception of

hypertension and its management was

associated with higher probability of having

controlled BP and lower SBP measures in patients

P for trend = 0.01

Poorly motivated

Slightly motivated

Intermediate Motivated Highly motivated

31.7%32.2% 32.2%

35.3%

41.7%

French cross-sectional, observational study2022 hypertensive patients followed by 347 general practitioners & 210 cardiologists

Consoli et al. J Hypertens 2010;28:1330–9

Factors behind poor BP control in hypertension

• Poor adherence to prescribed therapy

• Physician inertia

• Poor physician-patient communication

• Insufficient use of combination therapy

• Poor control of additional risk factors (e.g. obesity, physical inactivity, smoking)

• Lack of practical and simple guidelines for management of hypertension

Volpe. Expert Rev CV Therapy 2010 Jun;8:811–20

Use of antihypertensive polytherapy among all hypertension visits in which a drug was reportedly prescribed

Perc

enta

ge o

f anti

hype

rten

sive

dr

ug v

isits

0

10

20

30

40

50

60

70

Diuretic-BB

Diuretic-ACEI/ARB

Diuretic-CCB

BB-CCB ACEI/ARB-CCB

ACEI/ARB-BB

Anycombination

Antihypertensive drug combinations

1993

1998

2004

≥3 classes

2 classes

Ma J et al. Hypertension 2006;48:846-852

Combination therapy gives the increased efficacy that many patients need to achieve BP control

Doubling the dose of one drug (from standard to twice standard dose)

Incr

emen

tal

SB

P r

ed

uct

ion

rat

io o

f o

bse

rved

to

exp

ecte

d a

dd

itiv

e ef

fect

s

1.0

0.8

0.6

0.4

0.2

0

1.2

1.4

Thiazide Beta blocker ACEI CCB All classes

Adding a drug from another class

ACEI, angiotensin-converting enzyme inhibitor; CCB, calcium channel blocker

0.190.23

0.20

0.37

1.04 1.00

0.89 1.01

0.22

1.16

Wald et al. Am J Med 2009;122:290 – 300

Some patients need to combine more than two drugs to achieve BP control

• ..in no less than 15–20% of hypertensive patients, BP control cannot be achieved by a two-drug combination.1

• This is reflective of many patients in a clinical setting requiring more than two drugs

• When three drugs are required, the most rational combination appears to be a blocker of the renin– angiotensin system, a calcium antagonist, and a thiazide diuretic at low doses

Mancia et al. J Hypertens 2009;27:2121–58

-8.7

-16.5

-23.6-25.0

-20.0

-15.0

-10.0

-5.0

0.0

One drug Two drugs Three drugsR

ed

uct

ion

in S

BP

(m

mH

g)

Adding a third drug further increases efficacy of combination therapy

Law et al. BMJ 2009;338:b1665

++ AMLAML

Guidelines recommend single-pill fixed-dose combinations (FDCs)

Whenever possible, fixed dose (or single pill) combinations should be preferred, because simplification of treatment carries advantages for compliance to treatment

This new therapeutic option can improve hypertension treatment outcomes

HCTZHCTZ++ ++ AMLAML AMLAMLARBARB

ARBARB

• Poor adherence and clinical inertia contribute to low BP control rates

• Physician/ patient communication can improve BP control

• Good adherence lowers BP and significantly reduces the risk of cardiac & cerebrovascular events

• Single pill combination therapy may increase adherence in hypertension

Summary

Summary and perspectives

• We have the opportunity to challenge the position of cardiovascular disease as Europe’s Number One Killer

• BP control rates must improve and making greater use of combination therapy is central to achieving this goal

• Lack of adherence has a major negative impact on BP control but can be addressed

• Fixed dose combinations like those based upon olmesartan give us the chance to improve adherence and BP control and should allow us to aim for far higher BP goal rates than at present

70%Objective

New Mission of the Società Italiana dell’Ipertensione Arteriosa (SIIA)

2012 - 2015

Volpe M. High Blood Press Cardiovasc Prev 2012;19(1): in press