VentralinkVentralink Medication Education Series
ACE Inhibitors & ARBs • Article 4 of 6
Beyond Blood Pressure
How ACE Inhibitors Protect Your Blood Vessels Even Without Heart Failure
Evidence from HOPE, EUROPA, and ONTARGET: Why Your Doctor Prescribes Lisinopril, Losartan, or Valsartan for Diabetes and Coronary Artery Disease
Key Takeaways
- ACE inhibitors and ARBs protect against heart attacks and strokes even in people without heart failure—reducing risk by about 20%
- The benefits go beyond blood pressure lowering; these medications also reduce inflammation and stabilize dangerous plaques in arteries
- If you have diabetes, coronary artery disease, or peripheral artery disease, these medications are protecting your blood vessels from the inside out
- ARBs (like losartan) work just as well as ACE inhibitors (like lisinopril) for this protection
The Question That Changed Everything
By the late 1990s, cardiologists knew ACE inhibitors (like lisinopril, ramipril, and perindopril) and ARBs (like losartan, valsartan, and telmisartan) could save lives in specific situations. Heart failure patients lived longer on these medications. Heart attack survivors with weakened hearts had fewer complications. The evidence was clear—if your heart was already damaged, these drugs could protect what remained.
But a nagging question remained: what about the millions of people whose hearts hadn't failed yet? What about patients with diabetes, or those with narrowed arteries who were at high risk for a heart attack or stroke but hadn't yet experienced one?
The prevailing wisdom was simple: ACE inhibitors work by lowering blood pressure and reducing strain on the heart. If your blood pressure is already controlled and your heart is pumping normally, why would you need these medications?
Then came a study that would fundamentally change how we think about cardiovascular prevention.
The HOPE Trial: A Paradigm Shift
Heart Outcomes Prevention Evaluation
This landmark trial asked a bold question: can ACE inhibitors prevent heart attacks and strokes in high-risk patients who don't have heart failure?
Who was in this trial? Patients who were at high risk for cardiovascular events but did not have heart failure or known weak hearts. This included people with existing vascular disease (previous heart attack, stroke, or peripheral artery disease) or diabetes plus at least one other risk factor.
The intervention: Ramipril 10 mg daily versus placebo, added on top of whatever other medications patients were already taking.
The Results That Stopped the Trial Early
The findings were so striking that the independent safety monitoring committee stopped the study early—it would have been unethical to continue giving placebo when ramipril was clearly saving lives.
But it wasn't just the combined outcome. Every individual component improved:
Why This Changed Everything
Here's what made HOPE so remarkable: the blood pressure reduction with ramipril was modest—only about 3-4 mmHg systolic. Yet the cardiovascular benefits were enormous. This suggested that ACE inhibitors were doing something beyond just lowering blood pressure. They appeared to be directly protecting blood vessels from the damage that leads to heart attacks and strokes.
What's Actually Happening Inside Your Arteries?
Scientists have since identified several mechanisms that explain why these medications protect blood vessels independent of their blood pressure effects:
Quieting Inflammation
Angiotensin II isn't just a blood pressure hormone—it's also a powerful driver of inflammation inside artery walls. It activates inflammatory genes, attracts white blood cells into vessel walls, and promotes the oxidative stress that damages the delicate lining of arteries (the endothelium). By blocking angiotensin II production, ACE inhibitors reduce this chronic, low-grade inflammation that drives atherosclerosis.
Stabilizing Plaques
Heart attacks and strokes usually happen when a cholesterol plaque in an artery ruptures. ACE inhibitors make plaques more stable and less likely to rupture by reducing inflammation and strengthening the fibrous cap that covers vulnerable plaques.
Improving Endothelial Function
The endothelium (inner lining of blood vessels) produces nitric oxide, which keeps vessels relaxed and healthy. ACE inhibitors boost nitric oxide availability, helping vessels dilate properly and resist the formation of blood clots.
Who Should Consider These Medications for Vascular Protection?
Patient Profiles That Benefit
- 🫀Known coronary artery disease: Previous heart attack, angina, or coronary stents/bypass surgery
- 🧠Previous stroke or TIA: Cerebrovascular disease indicates high risk for future events
- 🦵Peripheral artery disease: Narrowed arteries in the legs often indicate widespread vascular disease
- 💉Diabetes with other risk factors: High blood pressure, smoking, abnormal cholesterol, or family history of early heart disease