I've shared many examples of how N-of-8 can shift opinion to practice.
Another case was when I moderated a group of leading cardiologists to discuss eplerenone, the first agent designed to selectively block aldosterone for the treatment of high blood pressure.
The eight participants in this group included the chair of a major medical society, the client’s chief medical director, and six of world’s top hypertension specialists. We were to discuss how aldosterone blockade reduces mortality and morbidity among patients with severe heart failure. Simply put, eplerenone is used to treat high blood pressure by blocking aldosterone, which in turn lowers the amount of sodium and water the body retains. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems. Eplerenone is also used to treat congestive heart failure following a heart attack.
To say I felt intimidated would be an understatement. As their facilitator, however, my job was not to go toe-to-toe on the science. Instead, I was to help determine how emerging science could apply to practice.
The conversation turned to the difference between diastolic and systolic blood pressure. And after several minutes, I asked the most innocent and naive question:
“When you say systolic BP,
what would that mean to
the average family physician?”
Well, the question was apparently so elementary that my client almost had a cardiovascular event right there. But then, one doctor responded, “You know, that’s a very provocative question and one that has created some controversy.” This led to a lively, engaging, and fruitful debate – with more implications for practice than we expected.
Approximately 50 million, or one in four, adult Americans, have high blood pressure. Of those, 73 percent are not adequately controlled, and are at increased risk of heart attack, stroke, kidney failure, damage to the eyes, heart failure and atherosclerosis. Control of hypertension has remained inadequate despite the availability of several key classes of compounds.
"Hypertension is a complex disease with many factors contributing to the problem," said the advisors during our N-of-8. "For patients and their health care providers who face unique challenges in achieving and maintaining control of their high blood pressure, eplerenone could represent an important new treatment option that goes beyond standard therapies in targeting the aldosterone pathway."
Preclinical and clinical studies had suggested that eplerenone works with relative selectivity to block aldosterone receptors, a key component within the RAAS (renin angiotensin aldosterone system). This fact, the advisors said, plays a significant role in the body's regulation of the cardiovascular system.
In the discussion, they concluded that data showed the addition of eplerenone to optimize medical therapy could reduce morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.
This all ultimately contributed to the company’s marketing strategy. FDA initially approved eplerenone for the treatment of hypertension, but the brand team decided to wait another year for a second indication – the treatment of congestive heart failure (CHF) secondary to an acute myocardial infarction – a first for any drug in the class.
Eplerenone was launched, and marketed by Pfizer, under the brand name Inspra.