Download Days of a Heart Valve`s Life - CSHP-BC

Days of a
Heart Valve’s
Life
The pharmacist’s approach to valvular heart disease
Erica Wang BScPharm, PharmD, ACPR, BCPS
Clinical Pharmacy Specialist – Cardiac Surgery
St. Paul’s Hospital | Providence Health Care | Lower Mainland Pharmacy Services
CSHP-BC Clinical Symposium
Learning Objectives
• By the end of this 45-minute session, the audience should be able to:
– State the common causes of valvular heart disease
– List the complications of valvular heart disease
– Describe the hemodynamic consequences of valvular heart
disease
– Describe the indication for and alternatives of pharmacotherapy in
valvular heart disease, specifically in aortic stenosis, aortic
regurgitation, mitral stenosis and mitral regurgitation
– Describe the principles of pharmacotherapy after valve surgery
– State the antithrombotic recommendations for various prosthetic
valve replacements, including transcatheter valve implantation
– Explain when ASA should or should not be added to the vitamin K
antagonist in patients with prosthetic heart valves
18 September 2014
Outline
•
•
•
•
•
•
•
•
Valve anatomy and physiology
Diagnosis of VHD
Complications of VHD
Specific valve pathologies
– Aortic stenosis and regurgitation
– Mitral stenosis and regurgitation
Open heart surgery
Prosthetic heart valves
Anticoagulation
Controversies
Introduction
Guidelines and Resources
• 2014 AHA/ACC Valvular Heart Disease Guidelines
– Full: Circulation 2014;129(23):e521-643
– Executive Summary: Circulation. 2014;129(23):2440-92
• 2012 ESC Valvular Heart Disease Guidelines
– Eur Heart J 2012;33(19):2451-96
• 2012 CHEST Guidelines for Valvular Heart Disease
– CHEST 2012;141(2)(Suppl):e576S–e600S
• 2006 AHA/ACC Valvular Heart Disease Guidelines
– J Am Coll Cardiol 2006;48(3);e1-148
• Canadian Cardiovascular Pharmacist Network (CCPN)
Antithrombotic Guidelines Pocket Reference 2008
– http://ccpn.ca/docs/AntithromboticThrombolyticTxPocketcard.pdf
Figure: Number waiting for and completed open heart
surgeries in BC (CABG, valve, other)
• Valvular heart disease (VHD) affects > 100 million people worldwide
• In Canada, VHD is less common than other cardiac conditions like
CAD, HF, HTN
• The burden of VHD is increasing
– High incidence of rheumatic heart disease in developing
countries
– ↑ burden of degenerative valve disease in developed countries
– Patients with valve disease are living longer and diagnosis is
often made at an older age
• ↑ frequency of comorbidity, ↑ risk of intervention
– ↑ in previously operated patients who require re-operation
Eur Heart J 2003;24:1231–1243 | Lancet 2006;368:1005–1011
Lancet 2009; 374:565-76 | Cardiac Services BC Annual Report 2011
Cardiac Services BC Annual Report 2011
Heart Valve Anatomy
Valve Physiology
• Right Heart
– Tricuspid Valve
– Pulmonary Valve
• Left Heart
– Mitral Valve
– Aortic Valve
http://www.ssmhealth.com/heart/PublishingImages/heart.jpg
http://healthtopics.hcf.com.au/images/hcf/gifs/heart-valve-replacement.gif
Valve Function
Valve Pathology
• Valve does not open
– Stenosis
• Valve does not close
– Insufficiency
• Valve leaflets do
not close together
– Regurgitation
• Backward blood
flow
http://www.drugs.com/health-guide/images/205521.jpg
Diagnosis and Types of VHD
• Identification
– On physical exam (e.g. heart murmur)
– Symptoms (eg syncope, CP, SOB, ↓ exercise tolerance, HF)
• May not be recognized by the patient due to progressive
nature valve disease
– Incidental finding (e.g. chest imaging)
• Diagnosis
– Echo (TTE or TEE)
• Tricuspid valve regurgitation or stenosis
• Pulmonary valve regurgitation or stenosis
• Mitral regurgitation or stenosis
• Aortic regurgitation or stenosis
– Other: CXR, ECG, coronary angiogram, cardiac CT, cardiac
MRI
Circulation. 2014 Jun 10;129(23):e521-643
http://www.drugs.com/health-guide/images/205522.jpg
Valve Disease Classification
• Classification of valve disease severity:
– Mild, moderate, severe
• Based on:
– Symptoms
– Echocardiography findings
• Valve anatomy
• Gradients: Pressure difference across the valve
• Valve area
– More applicable in valve stenosis
– Measured when the valve is open
– Hemodynamic complications
Circulation. 2014 Jun 10;129(23):e521-643
Complications of
Valvular Heart Disease
•
•
•
•
•
•
E.g. Survival in Aortic Stenosis
Symptoms
– Due to ↓ in cardiac output
HF
– With preserved EF
• ↓ in cardiac output, but LV
function and size remains
normal
– With ↓ EF and/or ↓ LV function
• Will occur over time if the
VHD remains untreated
AF
– Especially with mitral stenosis
Pulmonary hypertension
Stroke
Mortality
http://www.allinahealth.org/ahs/helpingyourheart.nsf/page/heart.png/$FILE/heart.png
Management Strategies
• Monitoring
– Asymptomatic valve disease
– Echo every 1-5 years
• Medical management
– For those awaiting surgical intervention
– Valve not amenable to surgical intervention
– Decreased life expectancy
• Valve repair or replacement
– Symptomatic or severe valve disease
– Reasonable life expectancy and quality of life
Specific Valve Pathologies
•
•
•
•
Aortic Stenosis (AS)
Aortic Regurgitation (AR)
Mitral Stenosis (MS)
Mitral Regurgitation (MR)
Circulation. 2014 Jun 10;129(23):e521-643
Aortic Valve
Aortic Stenosis
http://www.mountsinai.org/static_files/MSMC/Images/microsite/Interventional%20Cardiology%20Cath%20Lab/Enlarged%20Image%20Gallery/Aortic-Stenosis-lg.jpg
https://myhealth.alberta.ca/health/_layouts/healthwise/media/medical/hw/h9991304_001.jpg
https://science.nichd.nih.gov/confluence/download/thumbnails/35422393/aorticvalve2.jpg?version=1&modificationDate=1253127771000&api=v2
http://www.allinahealth.org/ahs/helpingyourheart.nsf/page/aortic_valve.png/$FILE/aortic_valve.png
Aortic Stenosis
•
•
AS and LV Remodeling
Most common type of VHD
Etiology
– Calcified disease of normal leaflet (80%)
• 2-7% in those > 65y; generally present when 70-80y
• Inflammatory condition similar to atherosclerosis
– Risk factors: older age, male, smoking, HTN, diabetes, LDL,
lipoprotein and CRP
– Calcified disease of bileaflet valve
• Present in 2% of population; present in 10% of 1st degree relatives
• More common in men; presents earlier (ie. 50-60y)
– Rheumatic: rare (except in India)
AS is a chronic, progressive condition with a long latency period
– Aortic sclerosis: leaflet thickening without obstruction (5% progress to AS)
– Mortality 15-50% over 5 years once symptomatic
•
Eur Heart J. 2012 Oct;33(19):2451-96
Circulation. 2014 Jun 10;129(23):e521-643
http://www.marvistavet.com/assets/images/aortic_stenosis.gif
Aortic Stenosis
Medical management
•
•
•
•
Aortic Regurgitation
Aortic valve replacement (AVR) is only definite therapy for AS
– Transcatheter aortic valve implantation (TAVI) may be considered for
those who are poor surgical candidates
No medical management improves survival in AS
Prevention and asymptomatic AS
– Treat HTN
• HTN is associated with 56% increase in ischemic events and 2x
increase in mortality
• No studies addressing specific antihypertensives
• In theory, ACEI or any afterload reducing agent should be beneficial
(reduce LV fibrosis)
– Statins have no benefit on the progression of AS
Awaiting surgical intervention
– Use vasodilators with caution (e.g. nitrates)
• Nitrates reduce preload
http://www.heart-valve-surgery.com/Images/aortic-valve-regurgitation-image.jpg
Eur Heart J. 2012 Oct;33(19):2451-96
Circulation. 2014 Jun 10;129(23):e521-643
Aortic Regurgitation
Medical Management
Aortic Regurgitation
• Having bicuspid AV ↑ risk of AR, aortic dilatation
and dissection
• 2 types: chronic and acute
• Etiology
– Primary disease of aortic valve or aortic root
• Calcified disease, annuloaortic ectasia
(root dilation due to HTN or aging),
Marfan’s syndrome, aortic dissection,
collagen vascular disease, syphilis
– Rheumatic disease
– Infective endocarditis (IE)
– Post-TAVI or valvuloplasty
• Once symptoms present, mortality is 10-20%
per year without surgery
Eur Heart J. 2012 Oct;33(19):2451-96
Circulation. 2014 Jun 10;129(23):e521-643
•
•
•
•
AR is a state of increased afterload, hence use afterload reducing agents
Chronic AR
– Treat HTN with preferably an ACEI/ARB
Acute AR
– Early surgery is superior to medical management
– May result in acute pulmonary edema and reduced cardiac output
– Use vasodilators and inotropes for short-term improvement of symptoms
– Avoid BB
• Blocks compensatory tachycardia and will reduce BP even further
Severe AR (not amenable to surgical intervention)
– ACEI/ARB and BB are reasonable if ↓ EF
• ACEI / ARB have been shown to reduce need for AVR,
hospitalization for HF and death from HF
Circulation. 2014 Jun 10;129(23):e521-643
Mitral Valve
Mitral Stenosis
http://www.heart-valve-surgery.com/Images/mitral-valve-annulus.jpg |
http://circ.ahajournals.org/content/120/13/1287/F1.large.jpg
http://www.merckmanuals.com/media/home/figures/CVS_stenosis_regurgitation_valves_b.gif
Mitral Stenosis
Mitral Stenosis
• Etiology
– Rheumatic heart disease (most common; in women)
– Calcification
• Survival in asymptomatic patients is generally up to 10
years
• Progression is highly variable with sudden deterioration
– Precipitated by pregnancy, AF or embolism
• LV function is generally normal
• Most common complication: AF
• Mainstay of therapy is valve replacement
– High operative mortality 3-10%
http://dokterpenulis.files.wordpress.com/2008/03/mitral-stenosis-lg.jpg
Eur Heart J. 2012 Oct;33(19):2451-96
Circulation. 2014 Jun 10;129(23):e521-643
Mitral Stenosis
Medical Management
• Diuretics or nitrates to relieve symptoms
• 40% of patients with MS will develop AF
– Anticoagulation regardless of CHADS2 score
• Mitral stenosis = “Valvular” AF
– HR control
• Patients with MS are at high risk of atrial arrhythmias
• In patients with NSR
– HR control if symptomatic with exercise
• Secondary prevention of Rheumatic fever
– For at least 10y or until patient is 40y (which ever is
longer)
– Pen G, Pen V, Sulfadiazine, Macrolide
Circulation. 2014 Jun 10;129(23):e521-643
Mitral Regurgitation
•
•
•
•
Primary MR
Secondary MR
Acute MR
Chronic MR
• 2nd most
common type of
VHD requiring
surgery
Eur Heart J. 2012 Oct;33(19):2451-96
http://mvpresource.com/wp-content/uploads/2014/03/What-Is-Mitral-Regurgitation.png
Mitral Regurgitation
Primary MR
•
•
•
•
Disruption to various parts of the mitral apparatus
Etiology
– Rheumatic (↓ incidence)
– Degenerative (myxomatous degeneration) or collagen vascular disease
– IE
– Trauma or radiation (e.g. chordae rupture)
Acute or chronic
– Acute: Leaflet perforation, chordae rupture, papillary muscle dysfunction
or rupture; may result in acute pulmonary edema
• Poorly tolerated, poor prognosis
– Chronic: may progress insidiously, causing LV dysfunction before
symptoms
High risk of mortality and morbidity
– 14% CV death, 22% all-cause death; 33% cardiac event
Mitral Regurgitation
Primary MR
•
•
Management strategy
– Replacement
– Repair
• Lower peri-op mortality, improved survival, better preservation of
post-op LV function, lower risk of long term morbidity
Medical management
– Reduce filling pressures with nitrates and diuretics
– Nitroprusside for reducing pre-load and afterload (↓ regurgitant fraction)
– Inotropes for hemodynamic support
– Medical therapy for systolic dysfunction if not a valve surgery candidate
and EF < 60% (BB, ACEI/ARB, aldosterone antagonists)
– BB improve surgical outcomes, delays onset of LV dysfunction, reverse
LV dysfunction
– No evidence for ACEI in chronic MR without HF
Eur Heart J. 2012 Oct;33(19):2451-96
Circulation. 2014 Jun 10;129(23):e521-643
Circulation. 2014 Jun 10;129(23):e521-643 | J Heart Valve Dis 1993;2:512-22.
J Am Coll Cardiol. 2012;60:833-8. | J Am Coll Cardiol. 2002;40:149-54.
Mitral Regurgitation
Secondary (Functional) MR
•
•
•
•
•
•
•
Mitral Regurgitation
Secondary (Functional) MR
Also known as: ischemic MR
MV leaflets and chordae are structurally normal
MR caused by LV dysfunction (secondary to CAD, MI, cardiomyopathy)
Generally poor prognosis compared to primary MR
– Not improved by revascularization
Myocardial viability imaging should be performed pre-surgery
Operative mortality is higher
– Presence of comorbidities
– Repair yields better outcomes than replacement
• High risk of MR recurrence
Medical Management
– Treat LV dysfunction (ACEI/ARB, BB, aldosterone antagonists)
– Treat cause of LV dysfunction
Circulation. 2014 Jun 10;129(23):e521-643 | J Heart Valve Dis 1993;2:512-22.
J Am Coll Cardiol. 2012;60:833-8. | J Am Coll Cardiol. 2002;40:149-54.
http://www.mardil.com/wp-content/uploads/2011/02/NormalAbnormalFinal3.png
Open Heart Surgery
History
Basic Principles of
Medical Management in VHD
• Risk factor management
– Treat HTN, dyslipidemia, diabetes
• Treat the altered hemodynamics in each specific valve pathology
• Treat LV dysfunction if present
– Diuresis, ACEI/ARB, BB, aldosterone blockers
• Rheumatic fever prophylaxis
– Prompt treatment of streptococcal pharyngitis
• Infective endocarditis prophylaxis (for those with prosthetic heart
valves only)
– Oral health is key
• Vaccinations
– Influenza and pneumococcal
• Exercise
– Lack of studies in VHD
– May suggest regular aerobic exercise for select VHD patients
Circulation. 2014 Jun 10;129(23):e521-643
1895
1925
1960
1990s
2005
2013
First
Open
Heart
Surgery
First
Valve
Surgery
First
prosthetic
heart
valve:
StarrEdwards
cagedball
First offpump
open
heart
surgeries
First
transapical
valve in
Canada
First “tiara
device”
mitral
valve
Open Heart Surgery
Introduction
• Valve surgery is the mainstay of therapy for severe VHD
– 30% of VHD patients receive a prosthetic heart valve
• Over the last 50 years, there have been major advances in
surgical techniques and post-operative care for the VHD
patient
• Generally, the risk of mortality of severe VHD greatly
outweighs the risk of perioperative mortality
• In BC, 30-day adjusted mortality remains low compared to
society of thoracic surgeon (STS) reports
– Valve surgery: 2-3% (STS 3.4%)
– CABG + Valve surgery: 4-6% (STS 6.8%)
Open Heart Surgery
Operation
•
•
•
•
•
•
•
Sedation
Mechanical Ventilation
Sternotomy or thoracotomy
– Tranexamic acid
Cardiopulmonary bypass machine
– Heparinized circuit
• Protamine to reverse
– Fluids and blood products PRN
– Vasopressors (no inotropes)
Cardioplegia
– Potassium
– Hypothermia
Pre-, intra-, and post-op
transesophageal echo (TEE)
Chest tubes
Eur Heart J 2003;24:1231–1243. | Lancet 2006;368:1005–1011
Lancet 2009; 374:565-76. | Cardiac Services BC Annual Report 2011
http://mehmanesh.com/wp-content/uploads/2013/05/open-heart.png
Post Open Heart Surgery
Medical Management
Post-op Care
Inotropes and vasopressors
Diuresis
AF prophylaxis
Stress ulcer prophylaxis
DVT prophylaxis
Post-op complications
management
– Delirium
– Arrhythmias or heart block
– AKI
– Nausea and vomiting
– Bleeding
– Hyperglycemia
– Skin and soft tissue infection
• Home meds restarted
•
•
•
•
•
•
•
•
•
•
•
•
On Discharge
Diuresis
Change in antithrombotics
Change in BP meds
AF
– Treatment
– Prophylaxis
Change in diabetes meds
Stress ulcer prophylaxis
Bioprosthetic (1970)
Prosthetic Heart Valves
Types
Bioprosthetic
Brands: ATS Medical,
Carpentier-Edwards, Edwards,
Medtronic, St. Jude Medical,
Sorin
Mechanical
Brands: ATS Medical, Edwards,
Medtronic, On-X, Sorin, St Jude
Medical.
Transcatheter
- Transfemoral (AV)
- Transapical (AV, MV)
Brands: Edwards Sapien,
CoreValve, Sapien XT THV
Selection Criteria
Homograft
Xenograft
- Porcine valve
- Bovine pericardium
~10-20 year life span
Older patient
Not ideal to be on warfarin
More physiological
hemodynamics
Caged-ball
Tilting disc single leaflet
Bileaflet
Indefinite life span
Younger patient
Patient has another
indication for warfarin
Bovine pericardium
Porcine pericardium
Recommended in those who
are high risk surgical
candidates
Expected life expectancy >
12 months post-surgery
Eur Heart J. 2012 Oct;33(19):2451-96 | Circulation 1994;89:635-41 | Lancet 2009;374:565-76.
Transcatheter
Transcatheter Valves
Mechanical
Caged-ball (1960)
Tilting disc (1969)
Bileaflet (1977)
Lancet 2009;372:565-76 | http://img.medscape.com/pi/emed/ckb/clinical_procedures/79926-1889862-1971097-1972129.jpg
https://encrypted-tbn1.gstatic.com/images?q=tbn:ANd9GcR4bfMO0p97BSFFz-035ceLnzvqCuzPQmpC7T6w4YUT6jdsimAc
Anticoagulation in Prosthetic Valves
Goals of Therapy
Therapeutic Alternatives
• ASA
• Prevent thrombosis
– valve thrombosis (<2-4% per year)
– major embolism (<4-8% per year)
– total embolism (<9-18% per year)
• Prevent thromboembolic stroke
• Minimize bleeding
– <1 to 2% yearly
• Prevent mortality
– ↓ major embolism by 40%
– Total bleeding < 1% per year
• Warfarin
– ↓ major embolism by 75%
– Total bleeding 2% per year
• ASA + Warfarin
– ↓ major embolism by > 75%
– Total bleeding ~5% per year
Circulation 1994;89:635-41
Eur Heart J. 2012 Oct;33(19):2451-96
Circulation 1994;89:635-41
Approach to Anticoagulation in
Prosthetic Heart Valves
• Risk of thrombogenicity determines choice of antithrombotic
therapy
– Location of valve
• Mitral (2x) > Aortic
– Type of valve
• Mechanical (m) > Tissue (t)
– Mechanical: caged-ball (5x) > tilting disc > bileaflet
• Generation of valve
– Timing of valve replacement / repair
• Risk of thrombosis highest in first 3 months
– Presence of additional thromboembolism risk factors
J Am Coll Cardiol. 1995;25(5):1111-19| CHEST 2001; 119:220S-227S
Circulation 1994;89:635-41
Choice of Antithrombotic
Risk of
Thrombosis
Location
& Type
+
RF?
High
↓
↓
↓
↓
↓
↓
↓
↓
↓
↓
↓
Lower
MVR(m) or
AVR(m) –
Yes
AF
Enlarged left atria (>4.5-5cm in diameter)
Reduced EF
Hypercoagulable state
Hx thromboembolism
Atherosclerotic vascular disease
– Cerebrovascular disease
– Coronary artery disease
– Peripheral arterial disease
Duration
Indefinite
VKA to INR 3 + ASA
caged ball or
tilting disc
-
AVR(m) –
Yes
VKA to INR 3 + ASA
Indefinite
Indefinite
bileaflet
-
VKA to INR 2.5 + ASA
Indefinite
MVR(t) or
MV Repair
Yes
VKA to INR 2.5 + ASA
VKA x > 3 mos, ASA indefinitely
-
VKA to INR 2.5 + ASA
VKA x 3 mos, ASA indefinitely
MV Repair
or AVR(t)
Yes
VKA to INR 2.5 + ASA
VKA x > 3 mos, ASA indefinitely
-
(VKA to INR 2.5 x 3-6 mos)
ASA alone
ASA indefinitely
Eur Heart J. 2012 Oct;33(19):2451-96 | Circulation. 2014 Jun 10;129(23):e521-643 | CHEST 2012; 141(2)(Suppl):e576S–e600S
Additional Risk Factors (RF)
for Thrombosis
•
•
•
•
•
•
Antithrombotic
Recommendation
Adding ASA to VKA
Evidence for Adding ASA?
2003 Cochrane review of 11
RCTs (N=2428) in prosthetic
valve patients found that
adding ASA to OAC vs OAC
alone:
– ↓ mortality (RR 0.58, 95%
CI 0.4-0.86)
– ↓ thromboembolism (RR
0.42, 95% CI 0.21-0.81)
– ↑ bleeding (RR 1.44, 95%
CI 1-2.08)
• Adding low dose ASA
(<100mg) did not ↑ bleeding
in this population
•
•
•
•
•
Add ASA
Additional risk factors for thrombosis:
– AF
– Hypercoagulable state (e.g.
thrombophilias)
– Low EF
– Vascular disease (e.g. CAD)
– Hx embolism (e.g. VTE)
Do not Add ASA
Elderly (>80 years)
Hx recent or severe bleeding (e.g. GIB)
Other risk factors for bleeding
– Abnormal renal or liver function
– Other medications that ↑ bleeding risk
CHEST 2012; 141(2)(Suppl):e576S–e600S
NEJM 1993; 329:524-29 | J Am Coll Cardiol 2000;35:739-46 | CDSR 2003;4:CD003464
Anticoagulation in AVR(t)
without additional thromboembolic risk factors
•
•
•
2014 AHA guidelines recommend VKA x 3-6 months then ASA
– 2008 AHA, 2012 ESC, 2012 CHEST: ASA alone
– 2012 ESC: VKA x 3 months then ASA
Aramendi et al. 2005
– P, R, OL, N=191 with bioprosthetic valves (94% AVR(t))
– triflusal 600mg daily vs. acenocoumarol (INR 2-3) x 3 mos
– Outcome: Thromboembolism, hemorrhage, valve-related death at
180d = NSS
Merie et al. 2012
– Retrospective cohort (Danish Registry), N=4075 AVR(t)+CABG, no
previous indication for warfarin, no POAF
– ASA, VKA, ASA + VKA, no ASA or VKA x 6.6y
• Analyses done on VKA+ASA vs. ASA or No antithrombotic
(N=2278+916 vs. N=181+700)
• VKA x 30-89d, 90-179d, 180-364d, 365-729d, 730d
– Outcomes: ↓stroke, ↓ thromboembolism, ↓ bleeding, ↓ CV death
J Am Coll Cardiol. 1995;25(5):1111-19 | Eur J Cardiothorac Surg 2005;27(5):854-60
JAMA. 2012;308(20):2118-25
JAMA. 2012;308(20):2118-25
Anticoagulation in
Mitral Valve Repair
Merie et al. 2012
• Bottom line: Use low-dose ASA alone in AVR(t) with no
additional risk factors for thrombosis
• There is controversy about the optimal antithrombotic in mitral
valve repair
– ASA + Warfarin x 3 months, then ASA alone
– Warfarin x 3 months, then ASA
– ASA
• Observational studies demonstrate that risk of
thromboembolism and bleeding are both low
– Thromboembolism 0.4-3% per patient year
– Bleeding 0.3-0.8% per year
– Confounded by 1/3 of patients developing AF during first 3
months
Interact Cardiovasc Thorac Surg 2006;5:761-6.
JAMA. 2012;308(20):2118-25
Anticoagulation in
Mitral Valve Repair
Antithrombotics in
Transcatheter Valves
•
•
•
http://www.mitralvalverepair.org/images/surgery/figure8.jpg
http://www.thechristhospital.com/upload/images/Departments/Heart%20and%20Vascular/MV_with_System_high%20res.jpg
St. Paul’s Hospital first pioneered the transfemoral and transapical
approaches for TAVI in 2005
– > 200 TAVIs have been completed since
Major complications: stroke, bleeding, hypotension, conduction
disturbances, AF, AKI, vascular injury, anemia, paravalvular leak
– Stroke rates and bleeding rates > 15% at 30d, which are independent
risk factors for mortality
Antithrombotic alternatives
– ASA 50-100mg daily + clopidogrel 75mg daily x 3-6 months then ASA
indefinitely (guideline recommended)
• 2 RCTs and 1 prospective observational trial
– ASA alone
– ASA + warfarin
– Clopidogrel + warfarin
– Warfarin alone
Cardiology Clinics 2013;31:607-18| JACC Cardiovasc Interv 2014;7:152-3 | Catheter Cardiovasc Interv 2011;78:457-67
Eurointervention 2010;5:666-72 | CHEST 2012; 141(2)(Suppl):e576S–e600S
Investigational
Transcatheter Valves
Bridging of Anticoagulation
•
•
•
•
•
Bridging ↑ risk of bleeding; unknown whether the ↑ risk of bleeding is off-set
by the benefits of ↓ thrombosis
Bridging is not required for procedures that are low risk of bleeding (e.g.
dental extractions); warfarin should be continued
2012 CHEST recommends bridging for risk of thrombosis 5 to > 10% yearly
– Any MVR(m), bileaflet AVR(m) with AF, cage-ball or tilting disc AVR(m),
any AVR and recent CVA (<6 months), AF with Rheumatic valve disease
Pre-op: stop warfarin x 3-5 days, LMWH bridging
Post-op management varies
– Bridging depends on the risk of bleeding from the surgery
• Heterogeneous definitions exist depending on type of surgery
– Post open heart surgery (OHS)
• Generally risk of bleeding > thrombosis post-OHS
• Do not bridge with LMWH; low target IV heparin protocol to start
POD 1-3
CHEST 2012;141(2)(Suppl):e326S-e350s
J Am Coll Cardiol 2012;60:483-92
Novel Oral Anticoagulants
(NOACs) in Prosthetic Heart Valves
• Studies with NOACs in AF excluded patients with valvular heart
disease (e.g. mitral stenosis) and prosthetic heart valves
• Dabigatran is contraindicated in those with mechanical valves
– RE-ALIGN Trial prematurely terminated
• Phase II, Dabi in mechanical valves
• Unknown if Factor Xa Inhibitors provide adequate anticoagulation
– Ongoing: Rivaroxaban in mechanical AVR (NCT02128841)
• Lack of evidence in bioprosthetic valves or valve repairs
– Possible NOAC use in AF and AVR(t)
• AVR(t) is the least thrombogenic prosthetic valve
– Low dose ASA daily
• Select surgeons have been recommending ASA + warfarin x
3 months then resume NOAC
Prosthetic Heart Valves
Limitations of the Literature
• Small sample size, non-randomized trials
– Observational trials or case series
• Risk of thrombosis comes from studies with 1st generation
valves
– For newer valves, company may conduct biased in-house
studies and make recommendations
• Heterogeneous valve types (AV and MV) studied with different
baseline thrombosis or bleeding risks
• Target INRs, frequency of INR checks, TTR infrequently
reported
• Other risks of thrombosis or bleeding poorly document or
uncontrolled for
• Advances in surgical techniques and post-surgical care will
affect thrombosis and bleeding outcomes
Eur J Cardiothorac Surg 2005;27(5): 854-860.
General Pharmacotherapeutic
Approach to the VHD Patient
•
•
Pre-surgical intervention
– Mild to moderate (watch and wait)
• Risk factor management
• Educate patient on important signs and symptoms
– Moderate to severe (surgery is imminent)
• Support hemodynamics with pharmacotherapy specific to the
pathophysiology
• Stop anticoagulation in preparation for surgery
Post-surgical intervention
– Re-evaluate need for pre-op medical management medications
– Treat LV dysfunction if present
– Assess need for anticoagulation and duration
– Risk factor management
– Minimize risk for infective endocarditis
• Recommend routine dental care
• Antibiotic prophylaxis for dental procedures in those with prosthetic
heart valves
Summary
• Valvular heart disease encompasses many valvular
pathologies
• Making pharmacotherapeutic decisions in VHD is complex
• Pharmacotherapy has a distinct role in the overall
management of VHD patients
• Choice of antithrombotic to balance the risks of thrombosis
and bleeding takes into account a variety of factors
• Novel surgical techniques (e.g. TAVI) will pose new
therapeutic challenges
• The pharmacist can play an important role in optimizing
pharmacotherapy wherever the patient may be in their
valvular heart disease journey