A recent article by Bharat Desai, an American physician specializing in internal medicine and pulmonary disease, argues that sildenafil could have revolutionized cardiovascular prevention, but was relegated to being an erectile dysfunction drug due to the at-the-time medical environment’s obsession with cholesterol.
The Forgotten Origins
Sildenafil was originally developed in the early 1990s as a heart drug for angina. While it failed to show convincing results on exercise tolerance (the endpoint used at the time), it was actually providing significant cardiovascular benefits through other mechanisms. However, its effect on erectile function emerged as the more notable finding, and Pfizer rebranded it as Viagra in 1998.
The Biological Mechanism As a PDE5 inhibitor, sildenafil:
- Targets the true drivers of atherosclerosis: endothelial dysfunction and thrombosis
- Protects the vascular endothelium
- Improves vascular reactivity
- Reduces platelet activation
- Enhances nitric oxide signaling
Why It Was Abandoned
- Total dominance of the cholesterol hypothesis in the 1990s
- Pfizer had just launched Lipitor (atorvastatin), destined to become the most profitable drug in history
- Sildenafil didn’t lower cholesterol, so it didn’t fit the era’s credibility criteria
The Ignored Evidence
Subsequent studies showed that PDE5 inhibitors:
- Improve survival in pulmonary arterial hypertension
- Reduce cardiovascular events in diabetic and post-myocardial infarction patients
- Improve endothelial function and quality of life
Conclusion If sildenafil had been studied in the 1990s like statins were, it could have:
- Saved millions of lives as a daily endothelial protector
- Offered mortality benefits with desirable side effects
- Been safe, oral, and now generic
Author’s Conclusion
Sildenafil represents how medicine, blinded by lipid dogma and driven by profit incentives, squandered a profound opportunity. A drug that could have added not only years to life, but life to years, became the butt of jokes instead of being recognized as a life-saving therapy.
Our comment
The author of the article does not mention this but studies were indeed conducted in the early years 2000, with the 6-minute walk test as primary endpoint (exercise capacity), and in June 2005, the Food and Drug Administration approved sildenafil under the brand name Revatio for the treatment of pulmonary arterial hypertension.
Read more at this link on MedPage Today