Managing Multiple Medications in Patients with PAH ADAANI FROST, MD Director, Pulmonary Hypertension...

Managing Multiple Medications in Patients with PAH

ADAANI FROST, MDADAANI FROST, MDDirector, Pulmonary Hypertension Center

Professor of MedicineBaylor College of Medicine

Houston, Texas

2

Learning Objectives (CME, CE, CPE)

At the completion of this educational activity, participants should be able to:

�̶ Describe the common medications used in the treatment of PAH and their interactions with one-another

�̶ Describe common medications used in the management of patients’ other conditions – including underlying conditions leading to PAH

�̶ Discuss how medications used to treat underlying medical conditions may interact with PAH-specific medications

Managing Multiple Medications in PAH

4

Updated Definition of PAH

Adapted from Badesch DB, et al. J Am Coll Cardiol. 2009;54(suppl 1):S55–S66Adapted from McLaughlin VV, et al. Circulation. 2009;119(16):2250-2294.

Increased mean pulmonary arterial pressure (mPAP)*

>25 mm Hg at rest

Normal pulmonary capillary wedge pressure (PCWP)

<15 mm Hg

Increased pulmonary vascular resistance (PVR)†

>3 Wood units

Right Heart Catheterization Confirmed

* Normal resting mPAP = 8 – 20 mm Hg. † In ACCP/AHA expert consensus; in 4th World Symposium on PH, increased PVR given without a value. Significance of mPAP from 21 – 24 mm Hg unclear.

5

Issues in Managing PAH

Drug-drug interactions — PAH-specific medications — Other medications given for the medical management of PAH— Drugs prescribed for co-morbid conditions

Adverse effects Administration

— Ability to comply with prescribing instructions

Clinical experience and data evaluating use and order of multiple PAH-specific therapies

6

PAH-specific Therapies Approved for Use in the US

Endothelin Receptor Antagonists

Phosphodiesterase-type 5 Inhibitors

Prostanoids – Prostacyclin Analogs

Ambrisentan Sildenafil Epoprostenol (IV)

Bosentan Tadalafil Iloprost (inhaled)

Treprostinil (IV, SC, and inhaled)

FDA. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Search_Drug_Name. Accessed November 1, 2009.

7

REVEAL Database: Overall PAH-specific Therapy at Time of Enrollment

Adapted from: Badesch DB, et al. Chest. 2009. DOI 10.1378/chest.09-1140. E-pub ahead of print.

47.0% 49.0%

32.3%

9.7%

0%10%20%30%40%50%60%70%80%90%

100%

ERA PDE51 IV/SCProstacyclin

InhaledProstacyclin

N = 2438.

8

REVEAL Database: Monotherapy vs Combination Therapy at Time of Enrollment

Adapted from: Badesch DB, et al. Chest. 2009. DOI 10.1378/chest.09-1140. E-pub ahead of print.

21.1% 24.4%16.1%

5.8%7.4% 7.5% 4.8% 3.0%0.9%

11.1%17.1%18.5%

0%

20%

40%

60%

80%

100%

ERA PDE51 IV/SCProstacyclin

InhaledProstacyclin

Monotherapy Dual Combination Triple Combination

N = 2438.

9

Updated Guidelines: Inadequate Clinical Response to Initial PAH Therapy

Atrial septostomy and/or

Lung transplantation

Sequential Combination Therapy

Prostanoids

EndothelinReceptor

Antagonists

PDE5Inhibitors

Barst RJ, et al. J Am Coll Cardiol. 2009;54(suppl 1):S78-S84.

Failure to show improvement or deterioration with monotherapy

10

PAH-specific Therapy Principles – Oral Therapy

Drugs within a single class should not be combined Patients responding to but intolerant to drug within a

class may benefit from a trial of an alternate drug within the same class— Sildenafil ↔ tadalafil— Bosentan ↔ ambrisentan

Patients failing on monotherapy probably would not benefit from switching to alternative monotherapy within the same class— Expert-opinion recommends combination therapy

Barst RJ, et al. J Am Coll Cardiol. 2009;54(suppl 1):S78–S84.

11

Pharmacokinetic Interactions Between PAH-specific Medications

Drug 1 Drug 2 Action

Ambrisentan None N/A

Bosentan Sildenafil Reduces sildenafil plasma concentrations 63%

Tadalafil Reduces tadalafil Cmax 27% at steady state

Sildenafil Bosentan Increases bosentan concentrations 50%

Tadalafil Bosentan Increases bosentan AUC <20%

Epoprostenol None N/A

Iloprost None N/A

Treprostinil None N/A

FDA. Package inserts for above products. Accessed at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Search_Drug_Name. Accessed November 1, 2009.

12

Bosentan-Sildenafil Pharmacokinetic Interactions

Sildenafil With and Without Bosentan Bosentan With and Without Sildenafil

Burgess G, et al. Eur J Clin Pharmacol. 2008;64(1):43–50.

Pla

sm

a C

on

ce

ntr

ati

on

(n

g/m

L)

1600

1400

1200

1000

800

600

400

200

00 1 2 3 4 5 6 7 8 9 10 11 12

Time (hr)

Bosentan + Placebo Day 10

Bosentan + Placebo Day 16

Sildenafil + Bosentan Day 10


Pla

sm

a C

on

ce

ntr

ati

on

(n

g/m

L)

600

00 2 4 6 8 10 12 14 16 18 20 22 24

Time (hr)

Sildenafil + Placebo Day 6

Sildenafil + Placebo Day 16



100

200

300

400

500

13

Bosentan-Tadalafil Pharmacokinetic Interactions

Tadalafil With and Without Bosentan Bosentan With and Without Tadalafil

Wrishko RE, et al. J Clin Pharmacol. 2008;48(5):610-618.

Bosentan + placebo

Bosentan + tadalafil

Day 10 Steady State Pharmacokinetics in Healthy Volunteers

Bo

se

nta

n P

las

ma

Co

nc

en

tra

tio

n (

ng

/mL

) 3000

0 3 6 9 12

Time (hr)

2000

1000

0

Tadalafil + placebo

Tadalafil + bosentan

Ta

da

lafi

l P

las

ma

Co

nc

en

tra

tio

n (

ng

/mL

) 1000

0 24 48 72 96

0

Time (hr)

500

14

No Pharmacokinetic Interactions Between Ambrisentan and Tadalafil

Spence R. CHEST 2008; October 25-30, 2008, Philadelphia, PA. Session AP2206.

N = 26, healthy volunteers.

-200

0

200

400

600

800

1000

1200

0 8 16 24 32 40 48 56 64 72

Time (hr)

Am

bris

enta

nC

once

ntra

ion

(ng/

mL)

-200

0

200

400

600

800

1000

1200

0 4 8 12 16 20 24

Day 1 (n = 23)

Day 9 (n = 23)

Inset: 0 - 24 hours

-200

0

200

400

600

800

1000

1200

0 8 16 24 32 40 48 56 64 72

Time (hr)

Am

bris

enta

nC

once

ntra

ion

(ng/

mL)

-200

0

200

400

600

800

1000

1200

0 4 8 12 16 20 24

Day 1 (n = 23)

Day 9 (n = 23)

Inset: 0 - 24 hour

-100

0

100

200

300

400

500

600

700

800

0 8 16 24 32 40 48 56 64 72 80 88 96

Time (hr)

Tad

ala

filC

on

ce

ntr

ati

on

(ng

/mL

)

-100

0

100

200

300

400

500

600

700

800

0 4 8 12 16 20 24

Day 1 (n = 24)Day 9 (n = 24)

Inset: 0 - 24 hours

Ambrisentan Tadalafil

Clinical Trial Data: Combination PAH Therapy

16

PACES: Sildenafil Added to Epoprostenol:Change from Baseline in 6-Minute Walk Distance

N=267; *P<0.01 versus placebo (ITT population).

Mea

n C

han

ge

Fro

m B

asel

ine

(m)

Weeks0 4 8 12

16

*

Placebo

Sildenafil

-10

0

10

20

30

40

50

Simonneau G, et al. Ann Intern Med. 2008;149(8):521-530.

17

STEP: Add-on Inhaled Iloprost to Stable Bosentan Monotherapy

0

20

40

60

80

100

Pat

ien

ts (

%)

Improved 1 Class

34.4%

ClinicalDeterioration

6.0%

62.5%

N=67. Inhaled iloprost added to stable bosentan monotherapy for a mean of 17.6 to 18.8 months.94% of patients were NYHA class III at baseline.

IloprostPlacebo

McLaughlin VV, et al. Am J Respir Crit Care Med. 2006;174(11):1257-1263.

0%

15.2%

No Change

Change From Baseline in NYHA Class

91.0%

Worsened 1 Class

3% 0%

18

Efficacy of Prostanoid Add-onto Failing Oral PAH Therapy

Jacobs W, et al. J Heart Lung Transplant. 2009;28(3):280-284.

N=18. End observations completers only. 4 patients had died or were unable toperform 6-minute walk distance at study end.

Start Prostanoid

6MW

D

500

450

400

300

4m 4m Pr End obs

350

Baseline

+ 64 mP=0.003

Pre Post

19

Lack of Efficacy of Bosentan + Epoprostenol Combination Therapy (BREATHE-2)

Adapted from Humbert M, et al. Eur Respir J. 2004;24(3):353–359.

Placebo/epoprostenol (n=10) Baseline

Bosentan/epoprostenol (n=19) Baseline

Placebo/epoprostenol 16 Weeks

Bosentan/epoprostenol 16 Weeks

-40 0 40 80 1206MWD m

20

Tadalafil in PAH Associated with Collagen Vascular Disease

Girgis R. Presented at Chest 2009. Oct. 31 – Nov. 5, 2009. San Diego CA. #9099

6MWD at 16 Weeks

* P<0.05 vs placebo.Placebo (n = 16) vs 40 mg tadalafil (n = 17). From randomized dose-ranging trial, including 2.5, 10, 20, and 40 mg tadalafil.

Baseline 4 8 16

-30

-20

0

20

40

30

10

-10

12

PlaceboTadalafil 40 mg

Weeks

Ch

ang

e f

rom

bas

elin

e6M

WD

(m

)

*

*

^

21

Tadalafil in PAH – Change in 6MWD

Girgis R. Presented at Chest 2009. Oct. 31 – Nov. 5, 2009. San Diego CA. #9099

* P<0.05 vs placebo.Placebo (n = 56) vs 40 mg tadalafil (n = 50) of patients with IPAH/HPAH. From randomized dose-ranging trial, including 2.5, 10, 20, and 40 mg tadalafil.

^

4 8 12 16

PlaceboTadalafil 40 mg

Ch

ang

e F

rom

Bas

elin

e 6M

WD

(m

)

Weeks

IPAH

*

* *40

35

30

25

20

15

10

5

0

Baseline

Additional Pharmacotherapeutic Considerations with PAH

23

General Medical Care for PH

Diuretics— Drug choice is based on physician experience

Oral anticoagulants— Generally recommended for patients with IPAH in absence of

contraindications• Maintain INR of 1.5 to 2.5 (US guidelines)

Digoxin— Short-term IV therapy increases cardiac output; no long-term

data demonstrating efficacy in PAH

— Slows ventricular rate in patients with atrial fibrillation/flutter

Barst RJ et al. J Am Coll Cardiol. 2009;54(suppl 1):S78-S84. Galie N, et al. Eur Heart J. 2009;30(20):2493-2537.

24

Anticoagulation in PAH: Role of Thrombotic Arteriopathy

Adapted from Johnson SR, et al. Chest. 2006;130(2);545-552.

Prothrombotic state

Pulmonary arterial hypertension

Thrombotic arteriopathy

Abnormal hematologic parameters

25

Known Interactions of PAH-specific Medications with Oral Anticoagulants

Drug Interaction

Ambrisentan None

Bosentan Decreased the plasma concentrations of S-warfarin and R-warfarin by 29% and 38%, respectively

Sildenafil None

Tadalafil None

Epoprostenol Inhibits platelet aggregation. Potential to increase bleeding risk.

Iloprost Inhibits platelet function. Potential to increase bleeding risk.

Treprostinil Inhibits platelet aggregation. Potential to increase bleeding risk.

FDA. Package inserts for above products. Accessed at http://www.accessdata.fda.gov/ scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Search_Drug_Name. Accessed November 1, 2009.

26

Effects of Bosentan on Warfarin Pharmacokinetics

Weber C, et al. J Clin Pharmacol. 1999;39(8):847-854.

R-warfarin S-warfarin

N = 12 healthy male volunteers. Two-way crossover design.

Placebo

Co

nc

en

tra

tio

n (

µg

\L)

2000

0 24 48 72 96 120

Time (hr)

Bosentan

1500

1000

500

0

Placebo

Co

nc

en

tra

tio

n (

µg

\L)

2000

0 24 48 72 96 120

Time (hr)

Bosentan

1500

1000

500

0

27

Interactions of PAH-specific Medications with Digoxin

Drug Interaction

Ambrisentan None

Bosentan None

Epoprostenol Decreased digoxin oral clearance 15%

Iloprost None

Sildenafil None reported

Tadalafil None

Treprostinil None reported


28

PDE-5 Inhibitors: Comparison of Sildenafil and Tadalafil

Both agents act at same PDE5 binding site— Comparable mechanism of action, potencies, adverse effect

profiles

Tadalafil has longer elimination half-life— Once-daily versus three-times-daily dosing

Tadalafil Sildenafil

FDA. Package inserts for above products. Accessed at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Search_Drug_Name. Accessed November 1, 2009.

NH

H

H

N

NCH3

O

O

O

O

HN

N

N

HOOC

N

N

NCH3

CH3

CO2H

CO2H

OH

CO2H

O2S

CH2CH2CH3

CH3CH2O

O

29

PDE-5 Inhibitors: Important Class-related Drug-drug Interactions

Organic nitrates— Contraindicated in any form, due to risk of life-

threatening systemic hypotension Alpha blockers

— Potential for increased effects of alpha blockers used for systemic hypertension

• May result in dizziness or syncope Ritonavir and other CYP3A inhibitors

— Not recommended due to increased exposure to PDE5 inhibitor


30

PDE-5 Inhibitor Interaction with CYP3A4 Inhibitor

Example of PDE-5 inhibitor interaction with CYP3A4 inhibitors Co-administration dramatically increases plasma concentration

and AUC

Muirhead GJ, et al. Br J Clin Pharmacol. 2002;53(suppl 1):37S-43S.

Sil

den

afil

Pla

sm

a C

on

cen

trat

ion

(n

g/m

L-1)

1200

1100

1000

900

800

700

600

500

400

300

200

100

0

0 4 8 12 16 20 24

Time Post Dose (h)

31

ERAs: Comparison of Bosentan and Ambrisentan

Bosentan is sulfonamide— Metabolism is dependent on CYP450 enzyme system

• Inhibitors and inducers of CYP3A can impact bosentan clearance

Ambrisentan is propanoic acid derivative— Multiple clearance pathways

• Not CYP3A dependent— Ambrisentan has longer half-life

• Once-daily dosing

Bosentan Ambrisentan

NH

S

N

N

N

NH2O

H3C

H3C

CH

CH3

O

O

O O

O

N

COOH

NH3CO

CH3

CH3

O

32

Endothelin Receptor Antagonist Class Effects

Teratogenicity— Pregnancy is contraindicated with both

ambrisentan and bosentan• Use of bosentan requires non-hormonal contraceptives to

prevent pregnancy

Peripheral edema

33

Bosentan Contraindications Due to Drug-drug Interactions

Cyclosporin A— Steady-state bosentan concentrations increased 3-

to 4-fold

Glyburide— Increased risk of elevated liver aminotransferases— Use alternative glucose control agents

Bosentan full prescribing information. 2009.

34

Bosentan Important Drug-drug Interactions

Hormonal contraceptives — Exposures decreased by bosentan— Nonhormonal birth control mandatory

Modest reduction in warfarin concentrations Ketoconazole increases bosentan concentrations by 2-fold

— No dose adjustment required, but potential for increased adverse effects

Rifampicin— 6-fold increase in initial bosentan trough levels, followed by

60% decrease in steady-state levels Tacrolimus

— Animal studies suggest increased bosentan levels. Use with caution

Bosentan full prescribing information. 2009.Wrishco RE, et al. J Clin Pharmacol. 2008;48(5):610-618.

35

Ambrisentan: Important Drug-drug Interactions

Cyclosporin A, rifampin, ritonavir— All may cause increase in ambrisentan exposure

Ambrisentan full prescribing information. 2007.

Managing PAH Co-morbid Conditions

37

REVEAL: Co-Morbidities in Patients With PAH

Badesch DB, et al. Chest. 2009. DOI 10.1378/chest.09-1140. E-pub ahead of print.

Dilated cardiomyopathyHistory of DVT

History of PERenal insufficiency

CirrhosisValvular heart disease

Non-skin cancerIschemic cardiovascular event

Diabetes mellitus (I and II)Thyroid disease

Sleep apneaObstructive airway disease

Clinical depressionRheumatoid arthritis

LupusOther

SclerodermaCVD/CTD

Obesity (BMI ≥30)Hypertension 40.2%

33.3%28.9%

17.0%11.2%

6.4%3.5%

25.2%21.9%

21.0%21.6%

12.0%9.3%

6.1%4.8%6.2%

4.5%6.9%

5.9%1.0%

38

REVEAL Registry: Commonly Used Medications in Patients With PAH

Badesch DB et al. Chest. 2009. DOI 10.1378/chest.09-1140. E-pub ahead of print.

ClopidogrelACE inhibitor

CorticosteroidsPsychotropics

Beta blockerStatin

Other anti-inflammatoryAspirin

Other antidepressantSSRI

Calcium channel blockerSynthetic thyroid

DigoxinOxygen

WarfarinDiuretic 69.3%

53.4%

40.3%

26.4%

20.6%

25.6%

19.4%

8.2%

15.7%

5.1%

16.1%

12.1%

10.3%

12.1%

11.3%

2.0%

39

Medical Management of PAH Associated with Systemic Sclerosis

No disease modifying therapy is approved for the treatment of systemic sclerosis— Immunosuppressants may be prescribed, but have

not been proven in clinical trials— Imatinib is currently being evaluated in clinical

trials

A wide range of medications are used to manage symptoms of systemic sclerosis

Zandman-Goddard G, et al. Clin Dev Immunol. 2005;12(3):165-173.

40

Therapeutic Approaches to Systemic Sclerosis

Organ Mechanism Treatment Examples

Skin Immunosuppression MethotrexateCyclosporin

Raynaud phenomenon

Vasodilation CCBs

Fibrosing alveolitis Immunosuppression Cyclophosphamide

GI Motility enhancers

PPIs

Octreotide

Omeprazole

Renal crisis Vasodilation ACE inhibitors

Zandman-Goddard G, et al. Clin Dev Immunol. 2005;12(3):165-173.

41

Raynaud Phenomenon Therapeutic Approaches And Their Potential Interaction with PAH Therapy

Drug/Drug Class Potential Interaction with PAH Therapy

CCBs Amlodipine-sildenafil co-administration results in additional decrease in supine BP

Alpha blockers Use with caution with PDE5 inhibitors

Glyceryl trinitrate

PDE5 inhibitor use contraindicated with all forms of nitrates

ACE inhibitors None noted

Serotonin antagonists

SSRIs may interfere with anticoagulation (warfarin) kinetics

Adapted from: Riemekasten G, et al. Rheumatology. 2006;45(suppl 3):iii49–iii51.Package Inserts.

42

Ambrisentan Does Not Interfere With Pharmacokinetics of Omeprazole

Harrison B, et al. Am J Respir Crit Care Med. 2009;179:A3348.

0

Eth

iny l

Es t

rad

iol

Pla

sm

a C

on

cen

tra

tio

n (

pg

/mL

)

160

140

120

100

60

0

20

80

40

12 24 36

Ambrisentan, n=26

Ambrisentan + Omeprazole, n=7

180

Time (hours)

48

^

43

PAH and Co-morbid Diabetes

No data published on management of diabetes in patients with PAH

Bosentan and glyburide co-administration contraindicated due to increased risk of elevated liver transaminases— Use alternate forms of glycemic control

Bosentan full prescribing information. 2009.

44

SSRI Use in PAH and Co-morbid Clinical Depression: Antidepressant AND PAH Therapy?

Shah SJ, et al. Chest. 2009;136(3):694-700.

Cumulative hazard of death by SSRI use. Patients enrolled in PH observational database.

Cu

mu

lati

ve H

azar

d0.60

0 2 4 6 8

Time (years)

0.40

0.20

0.00

No SSRI

SSRI

No SSRI 473 306 212 135 71SSRI 69 35 23 14 8

Number at Risk:

45

Body Mass Index in PAH Varies by Etiology: Comparison of REVEAL and NHANES

Waxman AB. Presented at Chest 2009. Oct. 31 – Nov. 5, 2009. San Diego CA. #8573

N = 2,141 REVEAL subjects compared with age- and gender- matched controls from NHANES

REVEAL BMI, kg/m2

NHANES BMI, kg/m2 P value

28.3 28.2 0.37

29.1 28.1 <0.001

27.8 26.9 0.18

24.6 26.8 <0.001

27.5 28.7 <0.001

32.6 28.7 <0.001

26.7 28.7 0.045

29.2 28.9 0.70

Overall

IPAH

FPAH

CDH

CTD

Drugs & Toxins

HIV

PortoPH

REVEAL pts have lower BMI

REVEAL pts have higher BMI

REVEAL BMI – NHANES BMI

-6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6

46

Pathophysiology of Obesity-related Cardiomyopathy

In: Dela Cruz CS, et al. Clin Chest Med. 2009;30(3):509–523.

Excessive Adipose Tissue

OSA/OHS

Hypoxemia/Acidosis

Pulmonary ArterialHypertension

Pulmonary venousHypertension RV Failure

RV Hypertrophy and Enlargement

No Change in HR

Decreased SVR

LV Failure

Increase CirculatingBlood Volume

Increase LV Stroke Volume

Increased CO

LV Enlargement

Increased LV Wall Stress

Eccentric LV Hypertrophy

LV Diastolic & SystolicDysfunction

47

Therapy of PAH Related to Obesity-hypoventilation Syndrome

Obesity-hypoventilation syndrome (OHS) usually related to BMI >34 and daytime hypercapnia (PCO2 of ≥45 mm Hg)

Tracheostomy should be offered along with chronic outpatient mechanical ventilation— Nocturnal O2 supplementation, CPAP not adequate

therapy

Additional PAH-specific therapy may be added as needed

Alam S, et al. Clin Chest Med. 2007;28(1):91–115.

48

Modafinil Use in PAH Related to Obstructive Sleep Apnea

Indicated for reducing excessive sleepiness in narcolepsy, obstructive sleep apnea/hypoventilation syndrome (OSA/OHS), and shift work sleep disorder (SWSD)

Metabolism is via hepatic enzymes— Potential to inhibit CYP2C19, suppress

CYP2C9, and induce CYP3A4, CYP2B6, and CYP1A2

— Potential to interfere with S-warfarin metabolism

Modafinil prescribing information. 2007.

49

Use of PAH-specific Therapy in Patients with Portopulmonary Hypertension (PoPH)

Bosentan, but not iloprost, associated with improved clinical outcomes

Hoeper MM, et al. Eur Respir J. 2007;30(6):1096–1102.

31 consecutive patients with Child class A or B cirrhosis and severe PoPHtreated for up to 3 yrs with either inhaled iloprost or bosentan

1.0

0.8

0.6

0.4

0.2

0.0

Ove

rall

Su

rviv

al

50

Use of PAH-specific Therapy in PoPH

ERAs (ambrisentan and bosentan) recommended only in patients with mild liver disease— Avoid with moderate or severe liver disease

PDE5 inhibitors (tadalafil and sildenafil) may be used in mild-to-moderate liver disease— Neither has been studied in severe liver disease

Riley TR 3rd, et al. Am Fam Physician. 2001;64(10):1735-1740.


51

Use of Beta-blockers in PoPH

Nonselective beta blockers or isosorbide mononitrate may be provided to prevent variceal bleeding in patients with cirrhosis— Beta blockers worsen hemodynamics and exercise

capacity in PoPH

Beta blockers + CYP3A4 inhibitors may increase AUC or decrease clearance of PDE5 inhibitors— All nitrates are contraindicated with PDE5 inhibitors

Galie N, et al. Eur Heart J. 2009;30(20):2493-2537.


Adherence to Therapy*

* Note: Heart failure literature accessed as surrogate for PAH. PAH-specific data on

adherence to therapy is lacking.

53

Managing Polypharmacy: Adherence to Therapy

Nonadherence to medication regimens is common, even in severe illness

In heart failure patients, >88% adherence rates associated with better outcomes

Lack of adherence to cyclosporin regimen associated with late acute organ rejection

Riegel B, et al. Circulation. 2009;120(12):1141-1163.

54

Three-times Daily vs Once-daily Dosing Intervals and Adherence to Chronic Therapy

Adapted from: Saini SD, et al. Am J Manag Care. 2009;15(6):e22-e33.

Diabetes

Migraine

Chronic Diseases

Hypertension

Epilepsy

Heart Failure

Adherence (%)

TID

QD

0 10 20 30 40 50 60 70 80 90 100

55

Depression as Barrier to Self-care in Heart Failure

Depression and depressive symptoms are independently associated with hospitalization and mortality in persons with heart failure

Depressive symptoms predict worse health status, and physical and social functioning, symptom burden, and QOL

Depression is associated with nonadherence to medications, decreased participation in exercise, lower adherence to diet recommendations, and lower rates of smoking cessation in patients with coronary disease


56

Clinical Anxiety and Self-care in Heart Failure


9.0%

14.0%

34.0%Taking all medications as prescribed

Daily monitoring of weight as recommended

Daily monitoring of symptoms of heart failure as

recommended

Complementary Alternative Medicine (CAM)

58

Use of Complementary/Alternative Medical Regimens

National Health Interview Survey (2002) N = 10,572 with cardiovascular disease 36% had used CAM (excluding prayer) in the

previous 12 months Most common types of CAM

— Herbal products (18%)— Mind-body therapies (17%)

Yeh GY, et al. Am J Cardiol. 2006;98(5):673-680.

59

Commonly Used Herbal/Complementary Medications in Cardiovascular Disease

34.0%

23.0%

22.0%

22%

20%

13%

12%

12%

11%

10%

Yeh GY, et al. Am J Cardiol. 2006;98(5):673-680.

n = 1816

Soy supplements

Peppermint

Ginger supplements

Fish oils/omega fatty acids

St. John’s wort

Glucosamine

Ginkgo biloba

Ginseng

Garlic supplements

Echinacea

60

Summary/Conclusions

PAH is rarely an isolated condition Managing patients with PAH must be

considered within the context of managing other co-morbid conditions

Drug-drug interactions should be considered when initiating or altering PAH-specific therapy

Adherence to medication regimens and barriers to adherence should also be considered

Patients may self-medicate with herbal products and should be appropriately counseled

Managing Multiple Medications in Patients with PAH ADAANI FROST, MD Director, Pulmonary Hypertension...

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