Author: Dr Tim Glenie
Therapy treatments for cardiovascular conditions have varied in significance over the past 100 years. Post mid-1950s, experimentation in the field has seen both age-old and progressive therapy treatments come to the fore. Here Dr Tim Glenie reveals trials and tribulations behind two cardiovascular treatments that have created decades of waves across the medical world.
Harking back to 400BC, aspirin to treat inflammation was nothing new to the ancient world.
“Hippocrates used it to reduce fever, but it wasn’t until the 18th century that willow bark extract – which aspirin derives from – was first recognised for its effect on pain, fever and inflammation,” explains Dr Glenie. “And it wasn’t until the 1960s and 70s that physicians finally realised what the action mechanism of aspirin was.”
Subsequently, numerous aspirin trials were carried out on myocardial infarction impact in the late 1970s. The world’s first largest, randomised aspirin therapy trial – conducted entirely by mail – was carried out in 1980 by a team of investigators from Harvard Medical School, Bringham and Women’s Hospital – titled the Physicians’ Health Study. It undertook a major analysis into the significant benefits of aspirin therapy and the prevention of myocardial infarction and other cardiovascular events.
How did the study play out?
- A total of 11,037 physicians were randomised to aspirin and 11,034 to aspirin placebo.
- The trial’s Data and Safety Monitoring Board shortened the study several years ahead because it was clear that aspirin had a significant effect on the risk of a first myocardial infarction.
- It was later reported, by The New England Journal of Medicine, that aspirin reduced the risk of first myocardial infarction by 44% – P less than 0.00001.
Aspirin as a therapy for infarct got physicians thinking about consequences across other life threatening conditions – namely strokes. The aspirin-stroke-prevention findings uncovered by Houston physician, William Field and neurologist William Hass in the late 70s and 80s, were detrimental in swaying the minds of big players in the drug division – Sterling and, eventually, the Food and Drug Administration of America.
“In 1980, the FDA approved aspirin after a stroke,” explains Dr Glenie. “In 1985, it was finally approved after an infarct and in early 1996 for a suspected infarct. So very recent therapy that for something that has been around since 400BC.”
However, dealing with an actual blood clot itself, was something aspirin couldn’t remedy. Thrombolysis treatment – thrombolytic therapy – dissolving the dangerous clots in blood vessels that are causing a myocardial infarction, was a hotly debated treatment due to pyrogenic reactions.
“In 1933, it was Tillet who first discovered that streptococci could synthese a fibrinolytic agent,” explains Dr Glenie. “Initially it was used in pleural effusion and it was not really until 1959 that it was used for intracoronary thrombus. However, in effect, the initial investigators threw away the substance because the pyrogenic reactions were so severe.”
What followed over the next 20-years was much to-ing and fro-ing over the use of streptokinase.
“There was the fact that the time periods between onset of the infarct and the administration of the streptokinase were variable and often long, and a European cooperative study in 1979 argued whether it should be intracoronary or intravenous,” says Dr Glenie. “So, we had multiple small trials playing out, however, eventually, it did become apparent – largely due to the GISSI trial – that the time factor indeed was a critical factor.”
A working protocol for IV streptokinase was set up and subsequent trials proved that fibrinolysis was a beneficial treatment strategy. So now armed with a medical therapy to dissolve a blood clot, physicians turned their focus towards mechanical solutions.
“There were concerns around the bleeding risks with fibrinolysis, so angioplasty was then considered,” explains Dr Glenie.
“In 2003, we saw the first publication of primary angioplasty versus thrombolysis and it demonstrated a reduction in death through infarction and intracranial bleeding. The field of primary intervention in the setting of myocardial infarction was born.”