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Real-time flashes from the 21st Congress

CONGRESS DAILY Thrombosis 2010

Milan, July 6th

The 21t h Congress: a new milestone against Thrombosis

Primary prevention is the best ally of drugs

PIER MANNUCCIO MANNUCCI*

Three new molecules in oral treatments future The availabilty of oral anticoagulants that do not require routine coagulation monitoring for extended prophylaxis in patients undergoing major surgery and for long-term treatment of deep vein thrombosis is a urgent need for specialists. But, most of all, they need safer drugs that are easier to administer for stroke prevention in patients with atrial fibrillation. This is what specialists ask at the congress in Milan. Drug research is actually moving in that direction. Over the past few years there have been numerous clinical trials on novel compounds which could improve the efficacy of anticoagulation treatment and the quality of life of patients. Amongst the most promising candidates that could meet the needs of patients and physicians there are three molecules: the reversible direct thrombin inhibitor, dabigatran exetilate, and two selective direct Xa factor inhibitors: rivaroxaban and apixaban. Many others are in the pipeline. As to antiplatelet treatments, more frequently used in arterial thrombosis, great

And many others are in the pipeline, for patients and physicians compliance interest is aroused by ticagrelor, the first reversibly binding P2Y12 adenosine diphosphate (ADP) receptor antagonist. “Dabigatran - explained Professor Mannucci - is a reversible oral direct thrombin inhibitor. Dabigatran acts selectively by specifically blocking the activity of thrombin (both free and clotbound), the key enzyme in the process responsible for clot formation. Dabigatran provides effective, predictable and consistent anticoagulation without requiring routine coagulation monitoring or dose adjustment. Dabigatran has already been approved and used in over 50 countries for the primary prevention of deep vein thrombosis due to vascular damage and prolonged immobility after surgery in adult patients after elective total hip or total knee replacement surgery. Then, there are rivaroxaban and

apixaban, novel anticoagulant molecules that act directly on (and inhibit) factor Xa. Rivaroxaban - continued Professor Mannucci is the first direct reversible inhibitor of factor Xa (free or in the fibrin clot), and of prothrombinase activity; thus it also indirectly inhibits the formation of thrombin. The third molecule, apixaban, is an investigational compound for the prevention and treatment of thrombosis. As to artery thrombosis, in spite of the recent progress made with the two antiplatelet agents, acetylsalicylic acid and clopidogrel, in the management of the acute phase and secondary prevention of acute coronary syndromes (ACS), ACS remains one of the leading causes of morbidity and mortality in western countries (about 40%). To overcome the limitations of current antiplatelet treatments, research has focused on the development of novel antiplatelet agents. At present, one of the most promising is ticagrelor, the first direct-acting P2Y12 inhibitor that - unlike thienopyridines such as clopidogrel or prasugrel - does not require metabolic activation by the liver. In addition, unlike clopidogrel and prasugrel that covalently bind to and permanently inactivate P2Y12, ticagrelor reversibly binds to the P2Y12 receptor with rapid onset/offset.

CONGRESS DAILY is a special edition of NTR - Notiziario in Tempo Reale by e.press® srl - registration Trib. NA no. 4560 Editor and Director Enrico Sbandi Professional journalist Claudio Ravel - Translation Giovanna Basilio - direct printing at Marriot Hotel, Milan Exclusive distributor for medical and health sector: VALUE RELATIONS INTERNATIONAL srl, via G. B. Morgagni, 30 - 20129 Milan, Italy

Together with the members of the various Committees that have tremendously helped me (Executive Committee, International Committee, Advisory Committee and the Mediterranean League Council), I welcome you in Milan at the 21st International Thrombosis Congress, which I am organizing on behalf of the Mediterranean League against Thromboembolic Diseases. The year of the Congress (2010) marks the end of the first decade of the third Millennium: the right time to make a balance on the most important steps forward in the field of thrombosis. In 2010 new anticoagulants will provide long-term treatment of arterial and venous thrombosis without the need of regular laboratory monitoring. Progress is also likely to take place in antiplatelet agents, and advances in pharmacogenomics should help to better personalize the drug treatment of thromboembolism. The 1990s has been the decade of thrombophilia and of our understanding of the major mechanistic role played by gain-of-function mutations of coagulation factors in venous thromboembolism. The first decade of the third Millennium is likely to witness progress on the genetic basis of complex diseases, such as coronary artery disease and stroke, through whole genome search of associated gene varicontinues in page 2 ants.

The 21st Congress has started Worldwide experts together against thromboembolic diseases Every year in Italy thromboembolic diseases cause about 400,000 deaths and severe disabilities, of which 200,000 attributable to infarction, 150,000 to stroke and 50,000 to deep vein thrombosis. It is the most frequent cause of death and invalidity in the Western world. Drug research provided important outcomes: “But drugs alone are not enough, primary prevention is the urgent need now”, states Pier Mannuccio Mannucci, MD, Milan University Internal Medicine Professor and Head of IRRCS Foundation's Ospedale Maggiore Medical Clinic, Milan. The congress opened today and organized by MLTD, The Mediterranean League Against Thromboembolic Diseases, faces problems related to this disease from different points of view: the most recent research outcomes,

realized with the contribution of

diet, new drugs, problems coming from enviromental pollution and the most patient-complying treatments. The trend leads to the more frequent drugs' oral administration so as to conjuigate effectiveness, convenience, and tolerabilty, to improve the patient’s compliance. “Thus, we need novel effective, well tolerated drugs that improve treatment compliance, do not require regular coagulation monitoring and are not administered via subcutaneous injections like heparins”, Mannucci explains. In the fight against thromboembolic diseases, prevention plays a crucial role. Changes in lifestyle can eliminate risk factors such as smoking, wrong diet, lack of exercise, while drug prophylaxis is recommended when there are risk factors such as prolonged immobility, major surgery (especially orthopaedic surgery), cardiovascular disease, such as atrial fibrillation. continues in page 2 In the photo: h. 7 p.m.: Christos Liapis (on the podium) and Pier Mannuccio Mannucci at the opening ceremony


2

3

“Identify specific disease mechanism”

Research reveals pollution increases the risk of thrombosis

Genetic base for TTP: an Italian study

In the lecture of Maseri the new targets in cardiovascular prevention In his plenary lecture “New targets in cardiovascular prevention: the identification of specific disease mechanism”, Attilio Maseri, President of the Heart Care Foundation, Florence, Italy, has stressed primary prevention worldwide as being the most ambitious challenge nowadays in this field. Actually the urgency points at an immediate implementation of the strategies of risk reduction proven successful and cost effective. Yet the preventive approach presents limitations namely embodied in two questions: why the large majority, in spite of the same burden of global predisposing factors does not develop events and why a substantial percentage develops events in spite of correction of risk or in the absence of any known risk factor? Actually an innovative approach should start from the reconsideration of the universal validity of the traditionally established - and reductionistic - paradigm that risk factors, acting over a period of years cause the progressive accumulation of coronary atherosclerosis, which in turn, when it reaches a critical threshold causes ischaemic cardiac events. As far as environmental and genetic risk factors for acute myocardial infarction are concerned, the similarity of risk factor in very carefully selected patients with unequivocal diagnosis of acute infarction from metropolitan areas of three distinct ethnic groups (Italian, Scottish and Chinese) suggests a large prevalence of “western” life style predisposing risk factors compared to genetic mechanism which play a modulatory role in some individuals. So the immediate goal is the promotion of the preventive strategies which are already proven to be on average, costeffective.

In the photo above: the Washington Hall during the Plenary Lectures. In the pict on the left, from the top, Attilio Maseri and Meyer Michel Samama

Serendipity and the discovery of drugs A new philosophy in medical progress It is well known that several important drug discoveries have been made by chance, yet, as mentioned by Pasteur, the most famous French scientist, “in the fields of observation, chance favors only the prepared minds.” This is the theme of M.M. Samama’s plenary lecture “Discovery of drugs in haemostasis and thrombosis by serendipity” The discovery of drugs such as penicillin (1928), insulin (1923), cyclosporine (1973), and Viagra (1995), or the unexpected drug activity could be said to have been uncovered by serendipity. The best example of genuine serendipity is the discovery of America (1942) by Christopher Colombo when he was looking for a new way to go to India and landed to America: native Americans were therefore called Indians. Among the drugs in thrombosis and haemostasis, we believe that heparin, the antiplatelet activity of aspirin and, more recently, previously unknown thalidomide antineoplastic activity were discovered by serendipity. These examples illustrate the role of serendipity in medical progress in drug therapy saving a multitude of lives worldwide.

f rom page 1

The 21th Congress: a new milestone against Thrombosis This may in turn help to unravel new mechanisms of disease and open the path to new treatments. In particular, it is hoped that much progress will take place in the treatment of both ischemic and hemorrhagic stroke, dramatic scourges that have not witnessed the dramatic advances that took place recently in the field of acute coronary syndromes. Needless to say, progress in basic science is essential to foster advances in clinical medicine, and I am sure that the Milan Thrombosis Congress will feature new basic mechanisms of atherogenesis and thrombogenesis. * 21th Congress President

Primary prevention is the best ally of drugs Atrial fibrillation is one of the most common abnormalities of the rhythm of the heart beat, it affects about 1% of the population (10% of people over 80) and increases the risk of blood clot formation that, in turn, exponentially multiplies the risk of stroke (it is estimated that 15-20% of people hit by stroke suffer from atrial fibrillation). Mannucci emphasised that thrombosis specialists need oral anticoagulants that do not require routine coagulation monitoring for extended prophylaxis in patients undergoing major surgery and for long-term treatment of deep vein thrombosis. But, most of all, they need safer drugs

that are easier to administer for stroke prevention in patients with atrial fibrillation. As far as diet is concerned, over the years numerous studies have shown that the Mediterranean diet reduces cardiovascular risk. As it is well known, the Mediterranean diet entails eating fresh food such as vegetables and fruits in season, grains, fish, especially oily fish, olive oil, especially extra virgin olive oil, drinking wine in moderation, and reining in meat and animal fats. The topic will be studied thoroughly on Friday during the congress conclusive day.

Italian epigenetics studies show how exposure to particular matter induces changes in blood coagulation The opening session of the 21st International Thrombosis Congress, focused on “Air Pollutions and Thrombosis” and was chaired by J.Vermylen and P.A. Bertazzi. A.Peters, Germany, discussed “Air pollution and cardiovascular disease: evidence from epidemiological studies and impact on the population”, Andrea Baccarelli illustrated his “Beyond the DNA sequence: epigenetic mechanism of prothromotic air pollution effects”, and N.L Mills, UK, discussed “Inhaled particles and thrombosis: a clinical toxicology perspective. Andrea Baccarelli, Head of the Genetics and Molecular Epidemiology Centre, Milan Polytechnic Institute, Milan, Italy and Adjunct Professor, Harvard School of Public Health, Boston, USA, took centre stage, elucidated the cellular and molecular effects of exposure to particulate matter (PM) and new possible strategies for protection. After confirming that air pollution increases the risk of thrombosis, Italian investigators are now shedding light on how exposure to particulate matter induces changes in blood coagulation with their studies in one of the most innovative disciplines: epigenetics. “It is by now widely proven that air pollution has harmful effects not only on the respiratory system but also on many other systems including the cardiovascular system - said Baccarelli - A study I conducted in collaboration with Ospedale Maggiore Thrombosis Unit, published in Archives of Internal Medicine in 2008, showed that exposure to particulate matter air pollution considerably increases the risk of deep vein thrombosis. The study was conducted in Lombardy, Italy, involved over 2,000 people and showed that

a PM10 increase of 10 micrograms per cubic metre increases the risk of thrombosis by 70%”. Latest research studies have been shifting their focus to DNA epigenetic control mechanisms, i.e. those mechanisms that modulate gene expression without affecting the DNA sequence. “One of the best understood epigenetic mechanisms is DNA methylation, a modification of DNA in which methyl groups are added to certain bases that make up the DNA code- said Baccarelli. Our research team discovered that air pollution changes the level of DNA methylation in the cells of people who are exposed to it. Our findings prove that breathing polluted air can induce DNA alterations with subsequent reprogramming of our gene functions after just seven days of exposure to high PM levels ”. “The study was carried out in Boston yet its findings are being confirmed by other similar investigations we are conducting on Italian population groups - added Baccarelli - interestingly, in the same population in which we observed a substantial decrease in methylation in specific genome regions at pollution peaks we also observed increased rates of infarction and stroke. We suspect there is a correlation. These changes in methylation also occur naturally in aging. “It seems that exposure to smog and traffic pollution accelerates aging - commented Baccarelli - These are major findings not only to get a better understanding of the link between pollution and thrombotic diseases but also to find solutions to the problem. Luckily, epigenetic changes are reversible, so, if we find a way to reverse them we may be able to reduce the harmful effects of air pollution even when we cannot reduce pollution itself”. In the photo: Andrea Baccarelli speech during the Opening Symposium

The first two sessions of Symposia Satellite are on stage simultaneously “Thrombotic microangiopathies” is the topic of the meeting chaired by B. Lämmle (Switzerland) and F. Scheiflinger (Austria). “TTP is a rare life-threatening disease characterized by thrombocytopenia and microangiopathic hemolytic anemia associated with the deficiency of the Von Willebrand factor-cleaving protease (ADAMTS13) due to mutations in the corresponding gene”, specified Flora Peyvandi, in her speech on The genetic basis of congenital thrombotic thrombocytopenic purpura (TTP). The other contributions in the meeting concerned New therapies in acquired TTP, by M. Scully (UK), New diagnostic and prognostic aspects of acquired TTP, by J.A. Kremer-Hovinga (Switzerland) and Rethinking thrombotic microangiopathies, by G. Remuzzi (Italy). “New perspectives in thrombosis research” is the topic of the other meeting chaired by M.B. Donati (Italy) and H. Deckmyn (Belgium): Complete deficiency of ADAMTS13 is sufficient to cause TTP in non-human primates, by H.B. Feys, N. Vandeputte, J. Roodt, S. Lamprecht, W.J. van Rensburg, V.J. Louw, P.N. Badenhorst, H. Deckmyn, K. Vanhoorelbeke (Belgium & South Africa); Aspirin resistance: myth or reality?, by L. Muszbek, Z. Bereczky, E. Kovács, É. Katona, L. Balogh, N. Homoródi, I. Édes (Hungary); Environment and lifestyle: can they affect the response to antiplatelet agents?, by G. de Gaetano, C. Cerletti (Italy); Arterial thrombosis in antiphospholipid syndrome, by J. Musial, J. Swadzba, A. MatyjaBednarczyk, T. Iwaniec (Poland).


2

3

“Identify specific disease mechanism”

Research reveals pollution increases the risk of thrombosis

Genetic base for TTP: an Italian study

In the lecture of Maseri the new targets in cardiovascular prevention In his plenary lecture “New targets in cardiovascular prevention: the identification of specific disease mechanism”, Attilio Maseri, President of the Heart Care Foundation, Florence, Italy, has stressed primary prevention worldwide as being the most ambitious challenge nowadays in this field. Actually the urgency points at an immediate implementation of the strategies of risk reduction proven successful and cost effective. Yet the preventive approach presents limitations namely embodied in two questions: why the large majority, in spite of the same burden of global predisposing factors does not develop events and why a substantial percentage develops events in spite of correction of risk or in the absence of any known risk factor? Actually an innovative approach should start from the reconsideration of the universal validity of the traditionally established - and reductionistic - paradigm that risk factors, acting over a period of years cause the progressive accumulation of coronary atherosclerosis, which in turn, when it reaches a critical threshold causes ischaemic cardiac events. As far as environmental and genetic risk factors for acute myocardial infarction are concerned, the similarity of risk factor in very carefully selected patients with unequivocal diagnosis of acute infarction from metropolitan areas of three distinct ethnic groups (Italian, Scottish and Chinese) suggests a large prevalence of “western” life style predisposing risk factors compared to genetic mechanism which play a modulatory role in some individuals. So the immediate goal is the promotion of the preventive strategies which are already proven to be on average, costeffective.

In the photo above: the Washington Hall during the Plenary Lectures. In the pict on the left, from the top, Attilio Maseri and Meyer Michel Samama

Serendipity and the discovery of drugs A new philosophy in medical progress It is well known that several important drug discoveries have been made by chance, yet, as mentioned by Pasteur, the most famous French scientist, “in the fields of observation, chance favors only the prepared minds.” This is the theme of M.M. Samama’s plenary lecture “Discovery of drugs in haemostasis and thrombosis by serendipity” The discovery of drugs such as penicillin (1928), insulin (1923), cyclosporine (1973), and Viagra (1995), or the unexpected drug activity could be said to have been uncovered by serendipity. The best example of genuine serendipity is the discovery of America (1942) by Christopher Colombo when he was looking for a new way to go to India and landed to America: native Americans were therefore called Indians. Among the drugs in thrombosis and haemostasis, we believe that heparin, the antiplatelet activity of aspirin and, more recently, previously unknown thalidomide antineoplastic activity were discovered by serendipity. These examples illustrate the role of serendipity in medical progress in drug therapy saving a multitude of lives worldwide.

f rom page 1

The 21th Congress: a new milestone against Thrombosis This may in turn help to unravel new mechanisms of disease and open the path to new treatments. In particular, it is hoped that much progress will take place in the treatment of both ischemic and hemorrhagic stroke, dramatic scourges that have not witnessed the dramatic advances that took place recently in the field of acute coronary syndromes. Needless to say, progress in basic science is essential to foster advances in clinical medicine, and I am sure that the Milan Thrombosis Congress will feature new basic mechanisms of atherogenesis and thrombogenesis. * 21th Congress President

Primary prevention is the best ally of drugs Atrial fibrillation is one of the most common abnormalities of the rhythm of the heart beat, it affects about 1% of the population (10% of people over 80) and increases the risk of blood clot formation that, in turn, exponentially multiplies the risk of stroke (it is estimated that 15-20% of people hit by stroke suffer from atrial fibrillation). Mannucci emphasised that thrombosis specialists need oral anticoagulants that do not require routine coagulation monitoring for extended prophylaxis in patients undergoing major surgery and for long-term treatment of deep vein thrombosis. But, most of all, they need safer drugs

that are easier to administer for stroke prevention in patients with atrial fibrillation. As far as diet is concerned, over the years numerous studies have shown that the Mediterranean diet reduces cardiovascular risk. As it is well known, the Mediterranean diet entails eating fresh food such as vegetables and fruits in season, grains, fish, especially oily fish, olive oil, especially extra virgin olive oil, drinking wine in moderation, and reining in meat and animal fats. The topic will be studied thoroughly on Friday during the congress conclusive day.

Italian epigenetics studies show how exposure to particular matter induces changes in blood coagulation The opening session of the 21st International Thrombosis Congress, focused on “Air Pollutions and Thrombosis” and was chaired by J.Vermylen and P.A. Bertazzi. A.Peters, Germany, discussed “Air pollution and cardiovascular disease: evidence from epidemiological studies and impact on the population”, Andrea Baccarelli illustrated his “Beyond the DNA sequence: epigenetic mechanism of prothromotic air pollution effects”, and N.L Mills, UK, discussed “Inhaled particles and thrombosis: a clinical toxicology perspective. Andrea Baccarelli, Head of the Genetics and Molecular Epidemiology Centre, Milan Polytechnic Institute, Milan, Italy and Adjunct Professor, Harvard School of Public Health, Boston, USA, took centre stage, elucidated the cellular and molecular effects of exposure to particulate matter (PM) and new possible strategies for protection. After confirming that air pollution increases the risk of thrombosis, Italian investigators are now shedding light on how exposure to particulate matter induces changes in blood coagulation with their studies in one of the most innovative disciplines: epigenetics. “It is by now widely proven that air pollution has harmful effects not only on the respiratory system but also on many other systems including the cardiovascular system - said Baccarelli - A study I conducted in collaboration with Ospedale Maggiore Thrombosis Unit, published in Archives of Internal Medicine in 2008, showed that exposure to particulate matter air pollution considerably increases the risk of deep vein thrombosis. The study was conducted in Lombardy, Italy, involved over 2,000 people and showed that

a PM10 increase of 10 micrograms per cubic metre increases the risk of thrombosis by 70%”. Latest research studies have been shifting their focus to DNA epigenetic control mechanisms, i.e. those mechanisms that modulate gene expression without affecting the DNA sequence. “One of the best understood epigenetic mechanisms is DNA methylation, a modification of DNA in which methyl groups are added to certain bases that make up the DNA code- said Baccarelli. Our research team discovered that air pollution changes the level of DNA methylation in the cells of people who are exposed to it. Our findings prove that breathing polluted air can induce DNA alterations with subsequent reprogramming of our gene functions after just seven days of exposure to high PM levels ”. “The study was carried out in Boston yet its findings are being confirmed by other similar investigations we are conducting on Italian population groups - added Baccarelli - interestingly, in the same population in which we observed a substantial decrease in methylation in specific genome regions at pollution peaks we also observed increased rates of infarction and stroke. We suspect there is a correlation. These changes in methylation also occur naturally in aging. “It seems that exposure to smog and traffic pollution accelerates aging - commented Baccarelli - These are major findings not only to get a better understanding of the link between pollution and thrombotic diseases but also to find solutions to the problem. Luckily, epigenetic changes are reversible, so, if we find a way to reverse them we may be able to reduce the harmful effects of air pollution even when we cannot reduce pollution itself”. In the photo: Andrea Baccarelli speech during the Opening Symposium

The first two sessions of Symposia Satellite are on stage simultaneously “Thrombotic microangiopathies” is the topic of the meeting chaired by B. Lämmle (Switzerland) and F. Scheiflinger (Austria). “TTP is a rare life-threatening disease characterized by thrombocytopenia and microangiopathic hemolytic anemia associated with the deficiency of the Von Willebrand factor-cleaving protease (ADAMTS13) due to mutations in the corresponding gene”, specified Flora Peyvandi, in her speech on The genetic basis of congenital thrombotic thrombocytopenic purpura (TTP). The other contributions in the meeting concerned New therapies in acquired TTP, by M. Scully (UK), New diagnostic and prognostic aspects of acquired TTP, by J.A. Kremer-Hovinga (Switzerland) and Rethinking thrombotic microangiopathies, by G. Remuzzi (Italy). “New perspectives in thrombosis research” is the topic of the other meeting chaired by M.B. Donati (Italy) and H. Deckmyn (Belgium): Complete deficiency of ADAMTS13 is sufficient to cause TTP in non-human primates, by H.B. Feys, N. Vandeputte, J. Roodt, S. Lamprecht, W.J. van Rensburg, V.J. Louw, P.N. Badenhorst, H. Deckmyn, K. Vanhoorelbeke (Belgium & South Africa); Aspirin resistance: myth or reality?, by L. Muszbek, Z. Bereczky, E. Kovács, É. Katona, L. Balogh, N. Homoródi, I. Édes (Hungary); Environment and lifestyle: can they affect the response to antiplatelet agents?, by G. de Gaetano, C. Cerletti (Italy); Arterial thrombosis in antiphospholipid syndrome, by J. Musial, J. Swadzba, A. MatyjaBednarczyk, T. Iwaniec (Poland).


8.30 p.m. - real time edit

ion

4

Real-time flashes from the 21st Congress

CONGRESS DAILY Thrombosis 2010

Milan, July 6th

The 21t h Congress: a new milestone against Thrombosis

Primary prevention is the best ally of drugs

PIER MANNUCCIO MANNUCCI*

Three new molecules in oral treatments future The availabilty of oral anticoagulants that do not require routine coagulation monitoring for extended prophylaxis in patients undergoing major surgery and for long-term treatment of deep vein thrombosis is a urgent need for specialists. But, most of all, they need safer drugs that are easier to administer for stroke prevention in patients with atrial fibrillation. This is what specialists ask at the congress in Milan. Drug research is actually moving in that direction. Over the past few years there have been numerous clinical trials on novel compounds which could improve the efficacy of anticoagulation treatment and the quality of life of patients. Amongst the most promising candidates that could meet the needs of patients and physicians there are three molecules: the reversible direct thrombin inhibitor, dabigatran exetilate, and two selective direct Xa factor inhibitors: rivaroxaban and apixaban. Many others are in the pipeline. As to antiplatelet treatments, more frequently used in arterial thrombosis, great

And many others are in the pipeline, for patients and physicians compliance interest is aroused by ticagrelor, the first reversibly binding P2Y12 adenosine diphosphate (ADP) receptor antagonist. “Dabigatran - explained Professor Mannucci - is a reversible oral direct thrombin inhibitor. Dabigatran acts selectively by specifically blocking the activity of thrombin (both free and clotbound), the key enzyme in the process responsible for clot formation. Dabigatran provides effective, predictable and consistent anticoagulation without requiring routine coagulation monitoring or dose adjustment. Dabigatran has already been approved and used in over 50 countries for the primary prevention of deep vein thrombosis due to vascular damage and prolonged immobility after surgery in adult patients after elective total hip or total knee replacement surgery. Then, there are rivaroxaban and

apixaban, novel anticoagulant molecules that act directly on (and inhibit) factor Xa. Rivaroxaban - continued Professor Mannucci is the first direct reversible inhibitor of factor Xa (free or in the fibrin clot), and of prothrombinase activity; thus it also indirectly inhibits the formation of thrombin. The third molecule, apixaban, is an investigational compound for the prevention and treatment of thrombosis. As to artery thrombosis, in spite of the recent progress made with the two antiplatelet agents, acetylsalicylic acid and clopidogrel, in the management of the acute phase and secondary prevention of acute coronary syndromes (ACS), ACS remains one of the leading causes of morbidity and mortality in western countries (about 40%). To overcome the limitations of current antiplatelet treatments, research has focused on the development of novel antiplatelet agents. At present, one of the most promising is ticagrelor, the first direct-acting P2Y12 inhibitor that - unlike thienopyridines such as clopidogrel or prasugrel - does not require metabolic activation by the liver. In addition, unlike clopidogrel and prasugrel that covalently bind to and permanently inactivate P2Y12, ticagrelor reversibly binds to the P2Y12 receptor with rapid onset/offset.

CONGRESS DAILY is a special edition of NTR - Notiziario in Tempo Reale by e.press® srl - registration Trib. NA no. 4560 Editor and Director Enrico Sbandi Professional journalist Claudio Ravel - Translation Giovanna Basilio - direct printing at Marriot Hotel, Milan Exclusive distributor for medical and health sector: VALUE RELATIONS INTERNATIONAL srl, via G. B. Morgagni, 30 - 20129 Milan, Italy

Together with the members of the various Committees that have tremendously helped me (Executive Committee, International Committee, Advisory Committee and the Mediterranean League Council), I welcome you in Milan at the 21st International Thrombosis Congress, which I am organizing on behalf of the Mediterranean League against Thromboembolic Diseases. The year of the Congress (2010) marks the end of the first decade of the third Millennium: the right time to make a balance on the most important steps forward in the field of thrombosis. In 2010 new anticoagulants will provide long-term treatment of arterial and venous thrombosis without the need of regular laboratory monitoring. Progress is also likely to take place in antiplatelet agents, and advances in pharmacogenomics should help to better personalize the drug treatment of thromboembolism. The 1990s has been the decade of thrombophilia and of our understanding of the major mechanistic role played by gain-of-function mutations of coagulation factors in venous thromboembolism. The first decade of the third Millennium is likely to witness progress on the genetic basis of complex diseases, such as coronary artery disease and stroke, through whole genome search of associated gene varicontinues in page 2 ants.

The 21st Congress has started Worldwide experts together against thromboembolic diseases Every year in Italy thromboembolic diseases cause about 400,000 deaths and severe disabilities, of which 200,000 attributable to infarction, 150,000 to stroke and 50,000 to deep vein thrombosis. It is the most frequent cause of death and invalidity in the Western world. Drug research provided important outcomes: “But drugs alone are not enough, primary prevention is the urgent need now”, states Pier Mannuccio Mannucci, MD, Milan University Internal Medicine Professor and Head of IRRCS Foundation's Ospedale Maggiore Medical Clinic, Milan. The congress opened today and organized by MLTD, The Mediterranean League Against Thromboembolic Diseases, faces problems related to this disease from different points of view: the most recent research outcomes,

realized with the contribution of

diet, new drugs, problems coming from enviromental pollution and the most patient-complying treatments. The trend leads to the more frequent drugs' oral administration so as to conjuigate effectiveness, convenience, and tolerabilty, to improve the patient’s compliance. “Thus, we need novel effective, well tolerated drugs that improve treatment compliance, do not require regular coagulation monitoring and are not administered via subcutaneous injections like heparins”, Mannucci explains. In the fight against thromboembolic diseases, prevention plays a crucial role. Changes in lifestyle can eliminate risk factors such as smoking, wrong diet, lack of exercise, while drug prophylaxis is recommended when there are risk factors such as prolonged immobility, major surgery (especially orthopaedic surgery), cardiovascular disease, such as atrial fibrillation. continues in page 2 In the photo: h. 7 p.m.: Christos Liapis (on the podium) and Pier Mannuccio Mannucci at the opening ceremony


Congress_Daily_Thrombosis 2010 n. 1