DEVELOPMENT AND INNOVATION IN CARDIOVASCULAR MEDICINE - Innovation in the Biopharmaceutical Industry - page 38

metabolism and vascular pathology. Therefore it will remain the focus of intense
research. As the picture becomes clarified, opportunities for further innovation of
ACE inhibitors and other modulation of the RAAS and bradykinin system will
emerge.
Antithrombotic therapy
Angina pectoris was first described by Heberden in 1768. Parry attributed it to
coronary artery disease in 1799. However it was not until the early 20th century
that this was widely accepted. For example, in 1923, McKenzie published a topic
on angina pectoris in which he attributed the condition to heart failure. One of
the most important achievements of the second half of the 20th century was the
development of a more detailed understanding of the pathology of acute and chronic
coronary atheromatous disease. In particular, understanding of the importance of
coronary plaque and plaque instability, along with the importance of endothelial
integrity in maintaining blood flow and prevention of thrombosis, have been critical.
Experimental studies undoubtedly contributed to this, but the intensive study of
patients in the early stages of myocardial infarction that was made possible following
the introduction of coronary care units was extremely important (Julian, 2001).
In addition, the introduction of coronary angiography permitted the recognition
of coronary angiographic features associated with unstable coronary syndromes.
Understanding that thrombosis was a key element in precipitating heart attacks led
to the introduction of thrombolytic treatment (Rentrop et al. , 1979). Streptokinase,
which was discovered in 1933 following the observation that an infiltrate of a culture
of group C streptococci could lyse human plasma clot (Tillet and Garner, 1933), was
first successfully used to liquefy pleural clot (Tillet and Sherry, 1949). Early studies
in acute myocardial infarction gave conflicting, but overall encouraging results,
which justified large randomised clinical trials that eventually demonstrated the
ability of thrombolytic treatment to reduce mortality, and to preserve myocardial
function when given early to patients with evolving heart attacks (Italian Group for
the Study of Strptokinase in Myocardial Infarction (GISSI), 1986).
Although originally extracted from willow in 1825, the mechanisms of the anti-
platelet properties of aspirin were not discovered until 1971 (Ferreira et al. , 1971).
Platelet micro-embolisation had been demonstrated at post-mortem examination in
the coronary arteries of victims of sudden cardiac death. This led to the concept that
the anti-platelet properties of aspirin may be beneficial in preventing complications
of coronary heart disease. The ISIS-2 study (ISIS-2 Collaboration Group, 1988),
demonstrated the ability of aspirin to reduce mortality in patients suffering from
heart attacks. Both aspirin and streptokinase had been available for approximately
150 and 50 years, respectively, prior to these discoveries. Their “rediscovery” as