In the late 1990s, Pfizer’s revenue stream was predominantly fuelled from the sales of antihypertensive drugs. The climax, so to speak, of its rigorous anti-hypertensive research efforts was the discovery of Viagra’s unanticipated vascular system consequences. When the team at the Pfizer European Research centre, where the cardiovascular work was undertaken, proposed closing it all down, to move on to the next big thing, it was met with surprise and resistance from the commercial teams. The argument was, we’ve found the drugs to treat hypertension, our job is done. This poses the pivotal question: how has hypertension, despite decades of medical leaps, persisted as one of the world’s biggest healthcare challenges?
Indeed in 2020, the first year of the COVID-19 global pandemic and before vaccine rollout, SARS-CoV-2 was only the third biggest killer in the Western world’s leading causes of death; behind cancer and hypertension at number one. And it is not just the deaths from heart disease and strokes, for which hypertension is responsible for over half, but also the disease’s core role in accelerating dementia.1 There would be far more impact from rigorous control of blood pressure at a population level on dementia rates and outcomes than any of the anti-amyloid forerunners.
The scope of this challenge becomes apparent when considering approximately 1.28 billion adults between the ages of 30 and 79 are grappling with hypertension worldwide.2 Notably, two-thirds of these individuals reside in low- and middle-income countries, highlighting the complex interplay between health and socio-economic factors. Adding to the complexity is the fact that an estimated 46% of affected adults are unaware of their condition. Moreover, less than half (42%) of those diagnosed receive appropriate treatment, and only around 1 in 5 (21%) maintain disease control. In response, a global target has been set by the World Health Organisation to reduce the prevalence of hypertension by 33% between 2010 and 2030, calling for innovative strategies to enhance personalised treatment and comprehensive management approaches.
Decoding the Complexities of Precise Dosing
What then has gone wrong in the effective management of hypertension, globally? There are two key issues, dose and process failure. The words of Paracelsus, the father of pharmacology, resonate profoundly to this day: the only thing separating a drug from a poison is the dose. Or in modern-day parlance, the concentration of a drug at its effector site critically determines both benefits and side effects. Yet, amidst the pressures of clinical practice, this is not always at the forefront of clinicians’ minds when reviewing a disease management plan. Partly this is due to the time and resource constraints in the modern healthcare system, but most critically, because of how clinical trials have historically been conducted to determine drug doses, based on average populations, paired with the simplified marketing narratives that pharmaceutical companies would ideally promote.
