APPENDIX 5
Memorandum by Sanofi-aventis group (VT
8)
1. INTRODUCTION
AND CONTEXT
1.1 The sanofi-aventis group is the world's
3rd largest pharmaceutical company, ranking number 1 in Europe.
Backed by a world-class R&D organisation, sanofi-aventis is
developing leading positions in seven major therapeutic areas:
cardiovascular disease, thrombosis, oncology, diabetes, central
nervous system, internal medicine, vaccines.
1.2 Sanofi-aventis manufacture and market
the drug, enoxaparin (Clexane). Enoxaparin is a type of heparin
known as "low molecular weight heparin", which has anti-thrombotic
activity because of its capacity to inhibit clotting activity
in the body.
1.3 Enoxaparin is licensed throughout the
world for both the prevention "thromboprophylaxis" and
treatment of thrombosis.
1.4 Enoxaparin is the most widely prescribed
anticoagulant of its type and has been used in more than 130 million
people in 96 countries, including more than 470,000 patients in
the United Kingdom in 2000.
2. VENOUS THROMBOEMBOLISM—THE
DISEASE
2.1 Venous thromboembolism (VTE) is a common
medical condition caused by the formation of blood clots that
partially or completely block a vein.
2.2 The most common form is deep vein thrombosis
(DVT), which occurs when blood clots form in the deep veins of
the body, usually of the legs. DVT partially or completely blocks
veins and disrupts the normal flow of blood back to the heart.
2.3 Parts of the clot may break off and
lodge in the arteries that supply the lungs forming a "pulmonary
embolus" (PE). A PE is a medical emergency that can cause
irreversible damage to the lungs and which, when it occurs, frequently
results in death.
2.4 DVT and PE occur frequently in people
with certain risk factors (particularly those who are hospitalised).
Identification of these risks allows us to put in place preventative
mechanisms to stop them occurring. At present too little attention
is paid to prevent DVT and PE from occurring in those at risk.
3. VENOUS THROMBOEMBOLISM—A
PUBLIC HEALTH
PROBLEM
3.1 Robust clinical data confirm that VTE
is a major public health problem. New cases of DVT occur at a
rate of about 1 per 1,000 of the population1 and new cases of
non-fatal PE presenting to hospital occur at about 0.5 cases per
1,0002. In the UK this equates to approx. 59,000 new cases of
DVT and 29,500 new cases of non-fatal PE per year.
3.2 45% of patients presenting with PE die
within 30 days3.
3.3 In addition to those patients presenting
to hospital with PE it has been estimated that PE may account
for rates of sudden death at up to 0.40 per 1000 population4 equating
to over 24,000 deaths per year in the UK.
3.4 As outlined in the Confidential Enquiry
into Maternal Deaths 2000-2002 thromboembolism is the single biggest
killer of pregnant women.
3.5 Each year more people will suffer VTE-related
mortality than composite mortality associated with breast cancer,
AIDS and traffic accidents.
3.6 In addition to sudden death, there are
other significant long-term complications associated with DVT
and PE, which cause substantial illness and suffering.
3.7 Patients who survive a PE may go on
to develop chronic pulmonary hypertension, a serious and frequently
fatal complication caused by obstruction of the pulmonary blood
vessels by blood clots. This complication is more common than
had been thought, with almost 4% of PE patients developing the
condition within two years with only 30% surviving for five years5.
3.8 Approximately 50% of persons who develop
a DVT will go on to develop a PE and the initial diagnosis of
DVT is often missed6.
3.9 Patients who suffer an episode of DVT
are at risk of developing long-term complications in the form
of post-thrombotic syndrome, a painful, unpleasant and potentially
disabling condition often resulting in the development of leg
ulcers, which are persistent and difficult to heal. A recent study
has shown that over 20% of patients who suffer venous thromboembolism
will develop post-thrombotic syndrome within 10 years7.
3.10 Recent estimates of the total direct
cost burden of VTE management on UK secondary care services are
in the region of £340 million per annum. Indirect costs may
increase the cost burden to in excess of £500 million.
4. VENOUS THROMBOEMBOLISM—PATIENTS
AT RISK
4.1 VTE can occur suddenly and without warning
in any individual, but certain risk factors have been clearly
identified which place patients at high risk of developing the
condition.
4.2 Public awareness of VTE has been increased
by media coverage of "traveller's thrombosis", but the
role of travel in the development of VTE is both equivocal and,
if present, small.
4.3 The risk of developing DVT after hip
replacement surgery has been estimated to be as high as 50% of
patients when thromboprophylaxis is not used. The use of appropriate
thromboprophylaxis (such as low molecular weight heparin) can
reduce this risk to between 10 and 15% of patients.
4.4 The risk of developing DVT in certain
patients immobilised with a medical illness is similalrly high,
with approx. 40-50% of patients admitted with stroke or myocardial
infarction developing detectable venous thrombosis. A recent trial
has shown that even "moderate risk" medical patients
admitted to hospital have a 15% chance of developing detectable
venous thrombosis after 14 days8. The use of appropriate thromboprophylaxis
(such as low molecular weight heparin) can reduce this risk to
5% of patients.
4.5 The recent Government response to the
Select Committee report on "Air travel and health" reported
a detailed and accepted list of risk factors for VTE.
— Immobilisation for a day or more.
— Increased clotting tendency.
— Recent major surgery/injury, especially
to lower limbs (eghip replacement) or abdomen.
— Inherited or acquired impairment
of blood clotting mechanism.
— Oestrogen hormone therapy, including
oral contraceptives.
— Former or current cancer.
— Types of cardiovascular disease or
insufficiency (heart failure and respiratory disease).
— Depletion of body fluids causing
increased blood viscosity.
— Personal or family history of DVT.
— Increasing age above 40 years.
5. PREVENTING
VENOUS THROMBOEMBOLISM—GUIDELINES
ARE AVAILABLE
5.1 In many instances venous thromboembolism
is a preventable disorder. There are clinical guidelines that
offer recommendations for therapies that can prevent VTE occurrence.
5.2 A number of learned, professional bodies
have undertaken to assimilate and analyse results from the clinical
trials and produce guideline recommendations for the prevention
of VTE.
5.3 The guidelines provide specific recommendations
as to which groups of hospital patients should receive prophylaxis,
how it should be provided and the type of drug or other agent
that should be used. Each recommendation is based on an assessment
of the level of risk for that patient group and is provided with
a grading based on the strength of the clinical evidence that
supports it.
6. PREVENTING
VENOUS THROMBOEMBOLISM—RECOMMENDED
ACTIONS
6.1 Frequently, a lack of awareness of the
condition within the medical profession, means that those patients
who are at risk of VTE because of clearly defined risk factors
fail to receive appropriate treatment. This is particularly the
case in those patients at the highest risk of developing VTE:
patients in hospital.
6.2 Despite the high risk of VTE in patients
undergoing major surgery some 40% or more of patients undergoing
major surgery still do not receive an effective form of thromboprophylaxis9.
Standards of care and risk assessment for VTE prevention need
to be set and followed in all forms of major surgery.
6.3 Standards of care also need to be imporved
in immobilised patients on medical wards. Only 40% of medical
at risk patients eligible for preventive treatment (approx 25%
of all those in hospital for an acute medical condition) receive
an effective thromboprophylactic agent9. Standards of care and
risk assessment for VTE prevention need to be set and followed
in all patients hospitalised for an acute medical illness.
6.4 Effective measures are needed to increase
awareness of the risk of VTE and to require action to assess the
risk of thrombosis in all hospitalised patients. Hospitals should
measure and be assessed on how effectively they prevent VTE occuring
in patients under their care.
6.5 The development of a "National
Thrombosis Standard" that would require the assessment of
all hospital patients for their thrombosis risk would significantly
improve patient care; reducing the morbidity, mortality and cost
of this disease.
REFERENCES1 Oger
E. Incidence of venous thromboembolism: a community-based study
in Western France. EPI-GETBP Study Group. Groupe d'Etude de la
Thrombose de Bretagne Occidentale. Thromb Haemost 2000; 83(5):657-660.
2 Nordstrom M, Lindblad B, Bergqvist D, Kjellstrom
T. A prospective study of the incidence of deep-vein thrombosis
within a defined urban population. J Intern Med 1992; 232(2):155-160.
3 Heit J. Seminars in Thrombosis and Haemostasis.
Vol 28, Supplement 2. 2002.
4 Lindblad B, Sternby NH and Bergqvist D: Incidence
of venous thromboembolism verified by necropsy over 30 years.
BMJ, 1991; 302: 709-711.
5 Pengo V, Lensing AW, Prins MH et al. for the
Thromboembolic Pulmonary Hypertension Study Group. Incidence of
Chronic Thromboembolic Pulmonary Hypertension after Pulmonary
Embolism. N Engl J Med 2004;350:2257-2264.
6 White RH. The epidemiology of venous thromboembolism.
Circulation 2003;107(23) S:14-18.
7 Heit J. Venous thromboembolism epidemiology:
implications for prevention and management. Semin Thromb Hemost
2002;28(2):3-13.
8 Samama MM et al. N Eng J Med 1999;341:793-800.
9 O'Shuaghnessy D. VERITY Venous Thromboembolism
Registry Second Annual Report 2004. ISBN 1-903968-08-9.
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