Ventralink Medication Education Series

ACE Inhibitors & ARBs • Article 3 of 6

Protecting a Wounded Heart

Why Starting ACE Inhibitors or ARBs After a Heart Attack Can Save Your Life

When to Start Lisinopril or Ramipril After a Heart Attack and How It Prevents Heart Failure

Key Takeaways

A heart attack damages your heart, but the damage continues for months afterward through a process called remodeling
ACE inhibitors and ARBs interrupt this harmful remodeling, preventing a damaged heart from becoming a failing heart
Starting these medications within days of a heart attack reduces the risk of dying by 19-27% over the following years
The benefit is greatest for patients whose hearts were weakened by the heart attack (low ejection fraction)

What Happens to Your Heart After a Heart Attack

During a heart attack, part of your heart muscle is starved of oxygen and dies. The immediate crisis—the chest pain, the trip to the hospital—is just the beginning of a longer story. What happens in the weeks and months after a heart attack often determines whether you recover well or develop heart failure.

This process is called ventricular remodeling, and understanding it helps explain why medications that seem unrelated to a heart attack can be lifesaving.

Days 1-7

Damaged tissue begins to heal. The dead heart muscle is replaced by scar tissue. This scar can't contract like healthy muscle, so the heart's pumping power is reduced.

Weeks 2-4

The heart tries to compensate. The remaining healthy muscle works harder. Your body's stress hormones—including the renin-angiotensin system—kick into overdrive trying to maintain blood pressure.

Months 1-6

Harmful remodeling begins. Under constant stress, the heart muscle starts to stretch and thin. The heart chamber enlarges—at first this seems helpful, but it actually makes the heart less efficient.

Months to Years

Heart failure develops. Without intervention, this progressive weakening can lead to heart failure—the condition we discussed in Article 2.

This is why what you do after a heart attack matters so much. The goal isn't just to survive the initial event—it's to prevent the cascade of changes that can turn a damaged heart into a failing heart.

How ACE Inhibitors and ARBs Protect a Wounded Heart

Remember the blood pressure control system we discussed in Article 1? After a heart attack, this system goes into overdrive. Your body senses that the heart is weaker and tries to compensate by raising blood pressure and retaining fluid.

The problem is that this "help" is actually harmful. The extra strain accelerates the remodeling process. ACE inhibitors and ARBs block this harmful response:

With Treatment

Less strain on the damaged heart. By relaxing blood vessels, these medications reduce how hard the heart has to work.

With Treatment

Less harmful remodeling. By blocking stress hormones, they slow or prevent the stretching and thinning of heart muscle.

With Treatment

Better long-term function. Hearts treated with these medications maintain their pumping ability better over time.

The Evidence: Three Trials That Changed Practice

In the early 1990s, three major trials asked the same question: if we give ACE inhibitors to patients shortly after a heart attack, can we prevent death and heart failure? The answer was a resounding yes.

1992: SAVE — Survival and Ventricular Enlargement Trial

The Question: If we start captopril (an ACE inhibitor) within 3-16 days after a heart attack in patients with weakened hearts but no obvious heart failure, will it save lives?

The SAVE trial enrolled 2,231 patients whose hearts had been weakened by a heart attack (ejection fraction ≤40%) but who didn't yet have symptoms of heart failure. Half received captopril; half received a placebo. They were followed for an average of 3.5 years.

SAVE Results: ~3.5 Years Follow-up

Without captopril

25%

died

With captopril

20%

died

19% reduction in the risk of death. Additionally, 25% fewer recurrent heart attacks.

💡 Key Insight from SAVE: This was the first proof that you don't have to wait for heart failure symptoms to start treatment. Early intervention—while the heart is still relatively stable—prevents problems from developing in the first place.

1993: AIRE — Acute Infarction Ramipril Efficacy Study

The Question: What about patients who already show signs of heart failure after their heart attack? Can ramipril (another ACE inhibitor) help them?

AIRE enrolled 2,006 patients who had clinical signs of heart failure (shortness of breath, fluid in the lungs, swelling) at some point during their heart attack hospitalization. Treatment was started between day 3 and day 10 after the heart attack.

AIRE Results: Average 15 Months Follow-up

Without ramipril

23%

died

With ramipril

17%

died

27% reduction in the risk of death—benefit visible within 30 days.

1995: TRACE — Trandolapril Cardiac Evaluation Study

The Question: SAVE and AIRE were selective about which patients they enrolled. Would ACE inhibitors still work in a broader, more "real-world" group of heart attack patients?

TRACE screened over 6,600 consecutive heart attack patients in Denmark and enrolled 1,749 whose hearts showed significant weakness on echocardiogram (ejection fraction ≤35%). Importantly, TRACE didn't exclude patients who had ongoing chest pain or obvious heart failure—making it more representative of typical heart attack survivors.

TRACE Results: 2-4 Years Follow-up

Without trandolapril

42%

died

With trandolapril

35%

died

22% reduction in the risk of death. Also 29% reduction in progression to severe heart failure.

The Complete Picture: Putting the Evidence Together

Trial	Patients	Follow-up	Lives Saved per 100
SAVE (1992) Weak heart, no symptoms	2,231	3.5 years	~5 fewer deaths (25%→20%)
AIRE (1993) HF symptoms present	2,006	15 months	~6 fewer deaths (23%→17%)
TRACE (1995) Broad population, EF ≤35%	1,749	2-4 years	~7 fewer deaths (42%→35%)

Across three different ACE inhibitors (captopril, ramipril, trandolapril), three different countries, and over 6,000 patients, the message was consistent: starting ACE inhibitor therapy within days of a heart attack saves lives.

What About ARBs?

The question of whether ARBs work equally well after a heart attack was answered definitively by the VALIANT trial in 2003.

2003: VALIANT — Valsartan in Acute Myocardial Infarction Trial

VALIANT was the largest post-heart attack trial ever conducted, enrolling over 14,700 patients with either heart weakness or heart failure symptoms. Patients were randomly assigned to receive captopril alone, valsartan alone, or both medications together.

VALIANT's Key Finding

Valsartan was just as effective as captopril. Over a median follow-up of 2 years, death rates were virtually identical between the two medications (19.9% with valsartan vs. 19.5% with captopril).

Interestingly, combining both medications didn't improve outcomes—it just increased side effects. So for most patients, one medication is enough.

This means that if you can't tolerate an ACE inhibitor (usually because of cough), an ARB provides the same protection. You have options.

Timing Matters: When Should Treatment Start?

One of the most important findings from these trials is that earlier is better:

The Window of Opportunity

SAVE: Started treatment 3-16 days after heart attack (average 11 days)
AIRE: Started treatment 2-9 days after heart attack (typically day 3-5)
TRACE: Started treatment 3-7 days after heart attack

Most cardiologists now aim to start ACE inhibitors or ARBs within the first few days after a heart attack—often before the patient leaves the hospital.

Why does timing matter? Because the harmful remodeling process begins immediately. The earlier you interrupt it, the more damage you prevent.

Who Benefits Most?

While nearly all heart attack patients may benefit from ACE inhibitors or ARBs, the evidence is strongest for:

Patients Who Benefit Most

Reduced ejection fraction: If your heart's pumping power is below 40% (especially below 35%), the benefit is substantial
Signs of heart failure: Shortness of breath, fluid retention, or lung congestion during hospitalization
Anterior (front wall) heart attack: These tend to cause more heart damage
Large heart attacks: More damage means more potential for harmful remodeling
Diabetes: Subgroup analyses consistently show strong benefit in diabetic patients

Even patients with milder heart attacks may benefit, though the absolute number of lives saved will be smaller (because fewer would have died anyway).

Questions to Ask Your Doctor

If you've had a heart attack, these questions can help you understand your treatment:

"What is my ejection fraction, and how does it affect my treatment plan?"
"Am I on an ACE inhibitor or ARB? Why was that one chosen for me?"
"Am I on the target dose, or will my dose be increased over time?"
"How long will I need to take this medication?"
"What other medications should I be taking alongside this one?"
"What symptoms should prompt me to call you—especially related to blood pressure or kidney function?"

📊 YOUR TAKE-HOME NUMBERS

For patients with heart weakness or heart failure after a heart attack:

If 100 patients like you take an ACE inhibitor or ARB starting within days of a heart attack:

5-7 fewer will die over the next 2-4 years
Fewer will develop heart failure (up to 37% reduction in SAVE)
Fewer will have another heart attack (25% reduction in SAVE)
Protection continues for years as long as you keep taking the medication

The key message: A heart attack is a critical moment, but what happens next isn't set in stone. ACE inhibitors and ARBs give your heart the best chance to heal well and avoid the downward spiral toward heart failure.

Ventralink Medication Education Series

ACE Inhibitors & ARBs • Article 3 of 6

Protecting a Wounded Heart

Why Starting ACE Inhibitors or ARBs After a Heart Attack Can Save Your Life

When to Start Lisinopril or Ramipril After a Heart Attack and How It Prevents Heart Failure

Key Takeaways

A heart attack damages your heart, but the damage continues for months afterward through a process called remodeling
ACE inhibitors and ARBs interrupt this harmful remodeling, preventing a damaged heart from becoming a failing heart
Starting these medications within days of a heart attack reduces the risk of dying by 19-27% over the following years
The benefit is greatest for patients whose hearts were weakened by the heart attack (low ejection fraction)

What Happens to Your Heart After a Heart Attack

This process is called ventricular remodeling, and understanding it helps explain why medications that seem unrelated to a heart attack can be lifesaving.

Days 1-7

Damaged tissue begins to heal. The dead heart muscle is replaced by scar tissue. This scar can't contract like healthy muscle, so the heart's pumping power is reduced.

Weeks 2-4

Months 1-6

Months to Years

Heart failure develops. Without intervention, this progressive weakening can lead to heart failure—the condition we discussed in Article 2.

How ACE Inhibitors and ARBs Protect a Wounded Heart

The problem is that this "help" is actually harmful. The extra strain accelerates the remodeling process. ACE inhibitors and ARBs block this harmful response:

With Treatment

Less strain on the damaged heart. By relaxing blood vessels, these medications reduce how hard the heart has to work.

With Treatment

Less harmful remodeling. By blocking stress hormones, they slow or prevent the stretching and thinning of heart muscle.

With Treatment

Better long-term function. Hearts treated with these medications maintain their pumping ability better over time.

The Evidence: Three Trials That Changed Practice

1992: SAVE — Survival and Ventricular Enlargement Trial

The Question: If we start captopril (an ACE inhibitor) within 3-16 days after a heart attack in patients with weakened hearts but no obvious heart failure, will it save lives?

SAVE Results: ~3.5 Years Follow-up

Without captopril

25%

died

With captopril

20%

died

19% reduction in the risk of death. Additionally, 25% fewer recurrent heart attacks.

1993: AIRE — Acute Infarction Ramipril Efficacy Study

The Question: What about patients who already show signs of heart failure after their heart attack? Can ramipril (another ACE inhibitor) help them?

AIRE Results: Average 15 Months Follow-up

Without ramipril

23%

died

With ramipril

17%

died

27% reduction in the risk of death—benefit visible within 30 days.

1995: TRACE — Trandolapril Cardiac Evaluation Study

The Question: SAVE and AIRE were selective about which patients they enrolled. Would ACE inhibitors still work in a broader, more "real-world" group of heart attack patients?

TRACE Results: 2-4 Years Follow-up

Without trandolapril

42%

died

With trandolapril

35%

died

22% reduction in the risk of death. Also 29% reduction in progression to severe heart failure.

The Complete Picture: Putting the Evidence Together

Trial	Patients	Follow-up	Lives Saved per 100
SAVE (1992) Weak heart, no symptoms	2,231	3.5 years	~5 fewer deaths (25%→20%)
AIRE (1993) HF symptoms present	2,006	15 months	~6 fewer deaths (23%→17%)
TRACE (1995) Broad population, EF ≤35%	1,749	2-4 years	~7 fewer deaths (42%→35%)

What About ARBs?

The question of whether ARBs work equally well after a heart attack was answered definitively by the VALIANT trial in 2003.

2003: VALIANT — Valsartan in Acute Myocardial Infarction Trial

VALIANT's Key Finding

Valsartan was just as effective as captopril. Over a median follow-up of 2 years, death rates were virtually identical between the two medications (19.9% with valsartan vs. 19.5% with captopril).

Interestingly, combining both medications didn't improve outcomes—it just increased side effects. So for most patients, one medication is enough.

This means that if you can't tolerate an ACE inhibitor (usually because of cough), an ARB provides the same protection. You have options.

Timing Matters: When Should Treatment Start?

One of the most important findings from these trials is that earlier is better:

The Window of Opportunity

SAVE: Started treatment 3-16 days after heart attack (average 11 days)
AIRE: Started treatment 2-9 days after heart attack (typically day 3-5)
TRACE: Started treatment 3-7 days after heart attack

Most cardiologists now aim to start ACE inhibitors or ARBs within the first few days after a heart attack—often before the patient leaves the hospital.

Why does timing matter? Because the harmful remodeling process begins immediately. The earlier you interrupt it, the more damage you prevent.

Who Benefits Most?

While nearly all heart attack patients may benefit from ACE inhibitors or ARBs, the evidence is strongest for:

Patients Who Benefit Most

Reduced ejection fraction: If your heart's pumping power is below 40% (especially below 35%), the benefit is substantial
Signs of heart failure: Shortness of breath, fluid retention, or lung congestion during hospitalization
Anterior (front wall) heart attack: These tend to cause more heart damage
Large heart attacks: More damage means more potential for harmful remodeling
Diabetes: Subgroup analyses consistently show strong benefit in diabetic patients

Even patients with milder heart attacks may benefit, though the absolute number of lives saved will be smaller (because fewer would have died anyway).

Questions to Ask Your Doctor

If you've had a heart attack, these questions can help you understand your treatment:

"What is my ejection fraction, and how does it affect my treatment plan?"
"Am I on an ACE inhibitor or ARB? Why was that one chosen for me?"
"Am I on the target dose, or will my dose be increased over time?"
"How long will I need to take this medication?"
"What other medications should I be taking alongside this one?"
"What symptoms should prompt me to call you—especially related to blood pressure or kidney function?"

📊 YOUR TAKE-HOME NUMBERS

For patients with heart weakness or heart failure after a heart attack:

If 100 patients like you take an ACE inhibitor or ARB starting within days of a heart attack:

5-7 fewer will die over the next 2-4 years
Fewer will develop heart failure (up to 37% reduction in SAVE)
Fewer will have another heart attack (25% reduction in SAVE)
Protection continues for years as long as you keep taking the medication