In the Frank Schofield Plenary Lecture on Monday morning, Eugene Braunwald, Brigham and Women’s Hospital, Harvard Medical School, Boston, first thanked the members of ISTH for what they have achieved so far in controlling thrombosis and then asked for more.

“We want you to give us greater improvement in the efficacy-bleeding relationship,” Braunwald said at the ISTH 2015 Congress. In a lecture that identified pivotal advances in the treatment of thrombosis that have led to major reductions in cardiovascular mortality and morbidity, Braunwald said, “Enormous credit goes to members of this society for this success.” But, he acknowledged, “You always want more.”

Braunwald identified the two clinical situations of greatest unmet need. The first was more effective and safer anticoagulants that can be used in primary prevention. In the acute management of advanced cardiovascular disease, a lengthy list of powerful anticoagulants can be used alone or in combination to inhibit clot formation, but the benefit-to-risk ratio in chronic treatment of patients with moderate risk is delicate. He suggested more must be done to identify agents with a greater dissociation between antithrombotic effect and bleeding.

The second unmet need is in aging patients with multiple diseases and a high risk of both thrombus formation and bleeding.

“As the population ages with more co-morbidities, we need safer antithrombotic therapies in sicker patients. An example would be a patient with atrial fibrillation and an acute coronary syndrome,” Braunwald said. “The elderly have a high bleeding risk, and this is a growing population.”

Braunwald took the audience on a journey through the highlights of scientific advances that led to an understanding of how clots form, how clot formation can be prevented, and what this has meant for the management of cardiovascular disease. He noted that several key advances, including the development of a purified form of heparin, took place in Canada.

“To me, the most important impact that heparin has had is not only in the prevention of thromboembolism, but heparin was the drug that made open heart surgery possible. Without heparin, we would not have been able to put patients on a heart-lung machine,” Braunwald noted.

The clinical evidence of benefit with vitamin K antagonists can be traced to 1948 when one of the first multicenter clinical trials of any kind was conducted, according to Braunwald. More than 65 years later, however, approximately half of patients on the vitamin K antagonist warfarin are receiving suboptimal doses, said Braunwald, citing a published study (Diott JL et al. Circulation 2014;129:1407-14).

Relative to warfarin, the more recently introduced oral factor Xa anticoagulants reduce risk of stroke and systemic embolic events with a trend toward less bleeding (Ruff CT et al. Lancet 2014;383:955-62), but Braunwald noted that warfarin remains the most widely used anticoagulant worldwide. According to recent work at his own institution (Mega JL et al. Lancet 2015;385:2280-7), Braunwald indicated that genetic subtyping of patients might be a tool for personalizing therapy. In the study he cited, genetics were useful for predicting patients at a high relative risk for bleeding on warfarin relative to the factor Xa inhibitor edoxaban.

In his plenary address, Braunwald also reviewed the implications for the clinical use of factor Xa inhibitors now that agents are being developed to reverse their effects. Some of this work, as Braunwald acknowledged, was presented at the ISTH 2015 Congress just before the Schofield address. Not least of his remarks, Braunwald also reviewed the path to the current options for use of antiplatelets in preventing clot formation.

All of these advances, he suggested, can be traced back to the work of scientists in disciplines now being promoted through the ISTH. Many of the advances have led to large reductions in risk of cardiovascular events, including fatal events.

“I am here to express my admiration and thank the community of preclinical scientists and clinical investigators in the field of thrombosis and coagulation who have contributed so much to my specialty of cardiology,” Dr. Braunwald said. “Thank you for improving the lives of patients with cardiovascular disease.”

By Ted Bosworth |June 22, 2015