Prologue: the lost opportunity

Everyone knows Viagra as the “little blue pill” that revolutionized the bedroom. But what if its greatest potential was never about sex, but about saving lives?

A long-term study from Manchester followed men with both diabetes and a prior heart attack, about as high-risk a group as you can imagine. The results were astonishing: those who used sildenafil (Viagra) had a thirty-eight percent lower risk of another heart attack and a fifteen percent reduction in overall mortality.

By contrast, the landmark Heart Protection Study (the largest “high-risk” statin trial) found a reduction in overall mortality of just 1.8 percent over five years. When annualized, sildenafil’s absolute mortality reduction was roughly five to six times greater than that achieved with statins.

And yet, Viagra was never studied as a heart drug. Why? Because it did not lower cholesterol.

Act one: How sildenafil was born and rebranded

Ironically, sildenafil started life as a heart drug. In the early 1990s, Pfizer developed it for angina, hoping to exploit its vasodilatory effects. It failed to show convincing results on exercise tolerance, the endpoint of choice at the time.

What did emerge, famously, was a striking effect on erectile function. Pfizer pivoted, and in 1998 Viagra became one of the most successful lifestyle drugs in history.

But buried inside that “side effect” was something far more profound. Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor, which boosts cyclic GMP levels and enhances nitric oxide signaling. This is the very pathway that protects the endothelium, improves vascular reactivity, reduces platelet activation, and mitigates post-MI remodeling. In other words, it targeted the true drivers of atherosclerosis: endothelial dysfunction and thrombosis.

Act two: the statin shadow

By the mid-1990s, the cholesterol hypothesis had achieved near-total dominance. Cardiovascular prevention was synonymous with LDL lowering. Endpoints like endothelial health, thrombosis, or nitric oxide were treated as curiosities, not the “real” markers of prevention.

Pfizer, meanwhile, had just launched atorvastatin (Lipitor), which would become the most profitable drug in history. Why would they invest billions in outcome trials for sildenafil, when their cholesterol drug was already a blockbuster? Worse, if sildenafil proved superior, it might undermine their crown jewel.

And so, a molecule that may have outperformed statins at saving lives was rebranded as a sex pill, sidelined as a cardiovascular therapy, and largely forgotten outside of its niche in pulmonary hypertension.

Act three: the evidence we ignored

The Manchester study was not a fluke. PDE5 inhibitors have consistently demonstrated vascular benefits:

• Pulmonary hypertension trials: sildenafil improves survival, exercise tolerance, and endothelial function.
• Heart failure with reduced EF: small RCTs show improved pulmonary pressures and quality of life.
• Observational cohorts: diabetic and post-MI men taking PDE5 inhibitors live longer and have fewer cardiovascular events than those who do not; precisely because PDE5 inhibition stabilizes the endothelium and promotes nitric oxide–induced vasodilation, key pathways in preventing atherosclerosis.

The biology matches the outcomes. The endothelium is a dynamic organ that governs vascular tone, nitric oxide release, platelet activation, and the delicate balance between healing and clotting. When it fails, atherosclerosis begins.

Act four: the blindness of lipid dogma

Why did medicine miss this? The answer lies in the lipid-centric obsession that dominated cardiology.

In the 1990s, we already knew endothelial dysfunction and nitric oxide were fundamental to vascular health. We already knew thrombosis was the final common pathway of heart attacks. And Pfizer had the brightest scientists in the world; they could not have been ignorant of this.

But cholesterol was the only currency of credibility. To get into guidelines, a drug had to lower LDL and prove outcomes through that lens. Sildenafil did not; so it was invisible, even as real-world evidence piled up.

This is not simply a story about a missed opportunity. It is a parable of how medicine’s fixation on one biomarker (cholesterol) created blind spots that cost lives.

Act five: the tragedy of what might have been

If sildenafil had been studied in the 1990s the way statins were, it could have become a daily endothelial protector, saving millions of lives, with the added bonus of a very desirable side effect. Safe, oral, generic today, with dual benefits men (and women) might actually want to take.

Instead, we got two decades of statin hegemony, modest mortality benefits, unpleasant side effects, and untold billions in profits; while a better therapy sat on the shelf.

Now, with the patent long gone, there is no financial incentive to fund the mega-trials that could have proven it. The moment has passed.

Closing: a serious drug, reduced to a joke

Viagra as a heart drug is not a joke, and not a fantasy. It is an emblem of how medicine, blinded by lipid dogma and driven by profit incentives, squandered a profound opportunity. If sildenafil were discovered today, in a world less obsessed with LDL, it might be hailed as the greatest cardiovascular drug of our era. Instead, it became the butt of jokes, reduced to late-night comedy sketches about erections, rather than recognized as a therapy that could have saved millions of hearts. A drug that could have added not only years to life, but life to years, became yet another casualty of the lipid-centric model.

Bharat Desai is an internal medicine and pulmonary physician.