Which has the greatest mortality benefit between beta blockers (Beta Adrenergic Blockers), ACE inhibitors (Angiotensin-Converting Enzyme inhibitors), and aldosterone antagonists?

From the Guidelines

Among beta blockers, ACE inhibitors (ACEIs), and aldosterone antagonists, ACE inhibitors generally provide the greatest mortality benefit for patients with heart failure and reduced ejection fraction. This is based on the most recent and highest quality study, which demonstrated a reduction in all-cause death and MACE with the addition of an oral ACEi in patients with AMI with LVEF ≤40% 1. Medications like enalapril, lisinopril, and ramipril have demonstrated significant reductions in mortality in large clinical trials, with typical dosing ranges of enalapril 10-20 mg twice daily, lisinopril 20-40 mg daily, or ramipril 5-10 mg daily.

The optimal approach for most patients involves using all three medication classes together as part of guideline-directed medical therapy, as they work through complementary mechanisms. ACEIs block the renin-angiotensin-aldosterone system, reducing vasoconstriction and preventing cardiac remodeling. Beta blockers like carvedilol, metoprolol succinate, and bisoprolol block harmful sympathetic nervous system effects on the heart. Aldosterone antagonists such as spironolactone (25-50 mg daily) or eplerenone (25-50 mg daily) provide additional benefit by preventing the harmful effects of aldosterone.

When initiating these medications, start at low doses and titrate upward while monitoring blood pressure, heart rate, potassium levels, and renal function to achieve target doses that provide maximum mortality benefit. It is also important to note that concomitant initiation of both an ACEi and ARB in patients with AMI should be avoided due to an increase in adverse events without added benefit compared with either drug alone 1.

Key points to consider when using ACEIs include:

• They should be administered to patients who have experienced heart failure in the acute phase, even if no features of this persist, who have an EF of 40%, or a wall motion index of 1.2, provided there are no contraindications 1.
• They can be used in all patients with STEMI from admission, provided there are no contraindications 1.
• They have been shown to reduce mortality and stroke in patients with stable cardiovascular disease but without LV dysfunction 1.

Overall, the use of ACEIs, beta blockers, and aldosterone antagonists as part of guideline-directed medical therapy can provide significant mortality benefits for patients with heart failure and reduced ejection fraction.

From the FDA Drug Label

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits Lisinopril tablets USP are indicated to reduce signs and symptoms of systolic heart failure [see Clinical Studies (14.2)]. Lisinopril tablets USP are indicated for the reduction of mortality in treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction. Spironolactone tablets are indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure.

The ACE inhibitors (e.g., lisinopril) and aldosterone antagonists (e.g., spironolactone) have been shown to have a mortality benefit in specific patient populations, such as those with heart failure or after acute myocardial infarction.

• ACE inhibitors have been indicated for the reduction of mortality in treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction.
• Aldosterone antagonists have been indicated for the treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival. However, the provided drug labels do not directly compare the mortality benefits of beta blockers, ACE inhibitors, and aldosterone antagonists. Therefore, based on the provided information, it is not possible to determine which of these classes has the greatest mortality benefit 2, 3.

From the Research

Mortality Benefit Comparison

The comparison of mortality benefits among beta blockers, ACE inhibitors, and aldosterone antagonists is a complex topic. Based on the available evidence, the following points can be made:

• ACE inhibitors have been shown to reduce mortality in patients with heart failure and left ventricular systolic dysfunction 4, 5, 6, 7.
• The use of ACE inhibitors has been associated with a significant reduction in all-cause mortality and cardiovascular mortality in patients with heart failure 6.
• Beta blockers have also been shown to reduce mortality in patients with heart failure, but the evidence is not as strong as that for ACE inhibitors 7.
• Aldosterone antagonists have been shown to reduce mortality in patients with severe heart failure, but their use is generally reserved for patients who remain symptomatic despite treatment with ACE inhibitors and beta blockers 5.

Key Findings

Some key findings from the available evidence include:

• ACE inhibitors reduce all-cause mortality by 11% and cardiovascular mortality by 14% in patients with heart failure 6.
• The use of ACE inhibitors is associated with a significant reduction in the risk of myocardial infarction, regardless of systolic ventricular function 7.
• The combination of ACE inhibitors and angiotensin receptor blockers may provide additional benefits in terms of reducing cardiovascular mortality, but this approach requires close monitoring of renal function and serum potassium levels 5.

Treatment Considerations

When considering treatment options for patients with heart failure, the following points should be taken into account:

• ACE inhibitors should be considered as first-line therapy for patients with heart failure, due to their proven mortality benefits 6.
• Beta blockers should also be considered as part of the treatment regimen for patients with heart failure, due to their ability to reduce mortality and improve symptoms 7.
• Aldosterone antagonists may be considered for patients who remain symptomatic despite treatment with ACE inhibitors and beta blockers, due to their ability to reduce mortality in severe heart failure 5.