Prologue: the misplaced alternative
Everybody is aware of Viagra because the “little blue tablet” that revolutionized the bed room. However what if its biggest potential was by no means about intercourse, however about saving lives?
A long-term research from Manchester adopted males with each diabetes and a previous coronary heart assault, about as high-risk a gaggle as you may think about. The outcomes had been astonishing: those that used sildenafil (Viagra) had a thirty-eight p.c decrease threat of one other coronary heart assault and a 15 p.c discount in general mortality.
Against this, the landmark Coronary heart Safety Research (the most important “high-risk” statin trial) discovered a discount in general mortality of simply 1.8 p.c over 5 years. When annualized, sildenafil’s absolute mortality discount was roughly 5 to 6 occasions better than that achieved with statins.
And but, Viagra was by no means studied as a coronary heart drug. Why? As a result of it didn’t decrease ldl cholesterol.
Act one: How sildenafil was born and rebranded
Sarcastically, sildenafil began life as a coronary heart drug. Within the early Nineteen Nineties, Pfizer developed it for angina, hoping to take advantage of its vasodilatory results. It failed to indicate convincing outcomes on train tolerance, the endpoint of alternative on the time.
What did emerge, famously, was a placing impact on erectile perform. Pfizer pivoted, and in 1998 Viagra turned one of the vital profitable way of life medication in historical past.
However buried inside that “aspect impact” was one thing way more profound. Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor, which boosts cyclic GMP ranges and enhances nitric oxide signaling. That is the very pathway that protects the endothelium, improves vascular reactivity, reduces platelet activation, and mitigates post-MI transforming. In different phrases, it focused the true drivers of atherosclerosis: endothelial dysfunction and thrombosis.
Act two: the statin shadow
By the mid-Nineteen Nineties, the ldl cholesterol speculation had achieved near-total dominance. Cardiovascular prevention was synonymous with LDL decreasing. Endpoints like endothelial well being, thrombosis, or nitric oxide had been handled as curiosities, not the “actual” markers of prevention.
Pfizer, in the meantime, had simply launched atorvastatin (Lipitor), which might turn into essentially the most worthwhile drug in historical past. Why would they make investments billions in consequence trials for sildenafil, when their ldl cholesterol drug was already a blockbuster? Worse, if sildenafil proved superior, it would undermine their crown jewel.
And so, a molecule that will have outperformed statins at saving lives was rebranded as a intercourse tablet, sidelined as a cardiovascular remedy, and largely forgotten outdoors of its area of interest in pulmonary hypertension.
Act three: the proof we ignored
The Manchester research was not a fluke. PDE5 inhibitors have constantly demonstrated vascular advantages:
The biology matches the outcomes. The endothelium is a dynamic organ that governs vascular tone, nitric oxide launch, platelet activation, and the fragile stability between therapeutic and clotting. When it fails, atherosclerosis begins.
Act 4: the blindness of lipid dogma
Why did medication miss this? The reply lies within the lipid-centric obsession that dominated cardiology.
Within the Nineteen Nineties, we already knew endothelial dysfunction and nitric oxide had been elementary to vascular well being. We already knew thrombosis was the ultimate frequent pathway of coronary heart assaults. And Pfizer had the brightest scientists on the earth; they might not have been unaware of this.
However ldl cholesterol was the one foreign money of credibility. To get into pointers, a drug needed to decrease LDL and show outcomes by means of that lens. Sildenafil didn’t; so it was invisible, at the same time as real-world proof piled up.
This isn’t merely a narrative a few missed alternative. It’s a parable of how medication’s fixation on one biomarker (ldl cholesterol) created blind spots that price lives.
Act 5: the tragedy of what might need been
If sildenafil had been studied within the Nineteen Nineties the way in which statins had been, it may have turn into a every day endothelial protector, saving thousands and thousands of lives, with the added bonus of a really fascinating aspect impact. Protected, oral, generic immediately, with twin advantages males (and ladies) would possibly really wish to take.
As an alternative, we obtained twenty years of statin hegemony, modest mortality advantages, disagreeable uncomfortable side effects, and untold billions in earnings; whereas a greater remedy sat on the shelf.
Now, with the patent lengthy gone, there is no such thing as a monetary incentive to fund the mega-trials that would have confirmed it. The second has handed.
Closing: a severe drug, diminished to a joke
Viagra as a coronary heart drug just isn’t a joke, and never a fantasy. It’s an emblem of how medication, blinded by lipid dogma and pushed by revenue incentives, squandered a profound alternative. If sildenafil had been found immediately, in a world much less obsessive about LDL, it could be hailed as the best cardiovascular drug of our period. As an alternative, it turned the butt of jokes, diminished to late-night comedy sketches about erections, reasonably than acknowledged as a remedy that would have saved thousands and thousands of hearts. A drug that would have added not solely years to life, however life to years, turned one more casualty of the lipid-centric mannequin.
Bharat Desai is an inside medication and pulmonary doctor.
