TREATMENT OF VTE IN

DIFFERENT PATIENT PROFILES

David Jiménez, MD, PhD, FCCP

Ramón y Cajal Hospital, IRYCIS

Madrid, Spain

TREATMENT OF VTE IN DIFFERENT PATIENT PROFILES

David Jiménez, MD, PhD, FCCP

Ramón y Cajal Hospital, IRYCIS

Madrid, Spain

• Advisory board : Bayer HealthCare Pharmaceuticals; Boehringer

Ingelheim Pharmaceuticals; Bristol-Myers Squibb; Leo Pharma; ROVI;

Sanofi

• Lectures : Bayer HealthCare Pharmaceuticals; Boehringer Ingelheim

Pharmaceuticals; Bristol-Myers Squibb; Daiichi Sankyo; Leo Pharma;

ROVI; Sanofi

• Research funding : Sanofi; ROVI

Potential conflicts of interest

Cohen AT. Thromb Haemost 2007

Annual incidence of VTE

VTE incidence

PE is frequent in hospitalized patients

Fanikos J, Am J Med 2013

PE expenses

Case-fatality rate of PE

Cohen AT. Thromb Haemost 2007

Mortality from VTE

Annual burden of VTE in the US

100.000

200.000

300.000

400.000

500.000

600.000 543.000

87.000 64.000 53.0005.800

VTE Breastcancer

Prostatecancer

Caraccidents AIDS

Dea

ths

per

year

Cohen AT. Thromb Haemost 2007

VTE burden

47 EMERGENCY EMBOLECTOMIES

J Thorac Cardiovasc Surg 2005;129:1018 Courtesy, Samuel Z. Goldhaber

UpToDate 2006

Prophylaxis

Diagnosis

Treatment

Asymptomatic DVT

Death

PE

Post-thrombotic syndrome

Symptomatic DVT

Pulmonary hypertension

With the aim to reduce the burden of VTE

Patient

66-year-old female with acute PE

No comorbidities

HR 90/min SBP 120 mm Hg Saturation 93%

Would you treat this patient on an outpatient basis?

1. Yes

2. First, I would order a BNP testing

3. First, I would order an echocardiogram

4. First, I would order a troponin testing

Would you treat this patient on an

outpatient basis?

Pulmonary Embolism Severity Index

Aujesky D, AJRCCM 2005

OTPE trial

Outpatient

(n=171)

Inpatient

(n=168)

P*

N (%)

Recurrent VTE 1 (0.6) 0 0.011

Major bleeding

14 days 2 (1.2) 0 0.031

90 days 3 (1.8) 0 0.086

Overall

mortality

1 (0.6) 1 (0.6) 0.005

*Non-inferiority margin = 4% Aujesky D, Lancet 2011

OTPE trial

Outpatient

(n=171)

Inpatient

(n=168)

P

Length of hospital stay, days 0.5 3.9 <0.001

Readmissions, n 18 23 0.60

Emergency department visits, n 36 36 0.94

Primary-care doctor visits, n 202 216 0.67

Home nursing visits, n 348 105 0.53

Aujesky D, Lancet 2011

Simplified PESI

Jiménez D. Arch Intern Med 2010

Age > 80 1 point

Cancer 1 point

Cardiopulmonary disease 1 point

HB > 110/min 1 point

SBP < 100 mm Hg 1 point

O2 saturation < 90% 1 point

995 patients from a single centre

sPESI: validation

369 patients from 18 hospitals

(SWIVTER)

30-day all-cause mortality:

4.3%

Low-risk: 28.7%

Negative predictive value:

100% Spirk D, Thromb Haemost 2011

1. LMWH

2. UFH

3. Warfarin

4. Lytics

How would you treat this patient?

Narrow therapeutic window

Baker. J Manag Care Pharm 2009

Time in therapeutic range

Van Bladel ER. Thromb Res 2010

Outpatient therapy and OAC

LMWH vs. VKA

Jiménez D. BCF 2007

EventGroup LMWH

n= 181Group VKA

n= 199p

Recurrence 4 (2,2) 6 (3,0) 0,64

Death 6 (3,3) 11 (5,5) 0,20

Major bleeding 9 (5,0) 11 (5,5) 0,81

Composite endpoint 18 (9,9) 23 (12,7) 0,72

Length hospital stay 11 (9-13) 16 (14-18) 0,0001

Kearon C. Chest 2012

Once vs. twice daily regimen

Initial treatment with bemiparin

Kakkar VV. Thromb Haemost 2003

Bemiparin115 IU/kg every 24 hoursSubcutaneous injection

Hospitalizado

596 DVT patients

3-month follow-up

Home treatment Hospitalization

ESFERA trial

Santamaría A. Int J Clin Pract 2006

Home treatment

N = 434

Hospitalization

N = 149

P

PE 0 (0) 0.7 (1) 0.256

Recurrent VTE 0.5 (2) 0 (0) 0.554

Major bleeding 1.4 (6) 0 (0) 0.169

Death 1.2 (5) 0 (0) 0.227

Adverse events 5.1 (22) 7.4 (11) 0.196

Santamaría A. Int J Clin Pract 2006

ESFERA trial

Patient

66-year-old male with gastric cancer

Sudden onset of dyspnea

HR 115/min SBP 110 mm Hg Saturation 90%

Objective diagnosis of PE

How would you treat this patient?

1. VKA

2. LMWH

3. Rivaroxaban

4. Apixaban

How would you treat this patient?

Khorana A, J Clin Oncol 2009

Treatment in patients with cancer

Khorana A, J Clin Oncol 2009

Treatment in patients with cancer

Lee A, N Engl J Med 2003

Treatment in patients with cancer

Meyer G, Arch Intern Med 2002

Treatment in patients with cancer

ESFERA trial

601 patients with DVT w/wo PE

HOSPITALIZATION

OUTPATIENTREGIMEN

TREATMENT

BASELINE(month 0)

INTERMEDIATE (day 7 + 2)

FINAL (month 3)

FOLLOW-UP

• Combined incidence of DVT + PE + death at 3 months

• Major bleeding• Health

outcome measures

Bemiparin(5,000/7,500/

10,000 IU/day SC)

Santamaria A, Int J Clin Pract 2006

ESFERA trial

0.0471.7%0.4%Major bleeding

n.s.0%0%Recurrent DVT

n.s.0%0.4%Deaths related to VTE/bleeding

0.0482.6%0.4%Thrombocytopenia

n.s.0%0%PE

0.0326.0%1.8%Minor bleeding

P-valueBEMI/VKA

n = 116BEMI/BEMI

n = 279

Venous thromboembolism and bleeding depending on the drugadministered during secondary prevention (Days 1-98)

Santamaria A, Int J Clin Pract 2006

Patient (cont.)

66-year-old male with gastric cancer

Treatment with VKA

Worsening dyspnea and pleuritic chest pain

Objective diagnosis of recurrent PE

How would you treat this patient?

9% with LMWH

20% with VKA

Metastasis, younger age, short interval between VTE and cancer diagnosis (< 3 months)

Trujillo-Santos J, J Thromb Haemost 2008

Recurrent VTE on anticoagulation

PREPIC, Circulation 2005

Inferior vena cava filters

Hull RD, Am J Med 2006

Switch to LMWH

Retrospective study

70 patients with cancer and recurrent VTE while on LMWH or VKA

VKA: Switch to LMWH, LMWH: dose escalation

67% LMWH; 33% VKA

Carrier M, J Thromb Haemost 2009

Dose escalation

Patient

46-year-old female

Renal cell carcinoma

Staging CT scan: segmental PE

Should we treat this asymptomatic incidental thrombosis?

Incidental PE

UPE location 6-month survival Overall survival

HR (95% CI) P-value HR (95% CI) P-value

None1

(reference)

1

(reference)

Any1.97

(1.09-3.58)0.025

1.51

(1.01-2.27)0.048

Proximal2.28

(1.20-4.33)0.011

1.70

(1.06-2.74)0.027

Subsegmental0.80

(0.16-3.97)0.78

1.04

(0.44-2.39)0.92

O’Connell C, J Thromb Haemost 2011UPE, unsuspected PE

Incidental PE

Multivariate survival analysis revealed:

Overall HR 1.51 for UPE vs. matched controls (p=0.048)

HR 2.28 for proximal UPE at 6 months (p=0.01)

No significant impact of incidental ISSPE on survival

Results remained significant when:

Patients who did not receive anticoagulation (n=7 with proximal UPE)

were excluded

Controls with age outside of the 5-year restriction were excluded

Survival measured from date of malignancy diagnosis

O’Connell C, J Thromb Haemost 2011UPE, unsuspected PEISSPE, isolated subsegmental PE