What is the first line treatment for patients with conditions influenced by the Renin-Angiotensin-Aldosterone System (RAAS), such as hypertension or heart failure?

From the Guidelines

The first-line treatment for patients with conditions influenced by the Renin-Angiotensin-Aldosterone System (RAAS), such as hypertension or heart failure, is inhibition of the renin-angiotensin system using ARNi, ACEi, or ARB, with ARNi being recommended as first-line therapy for patients with HFrEF, as stated in the 2022 AHA/ACC/HFSA guideline 1.

Key Considerations

• The choice between ACEi, ARB, and ARNi depends on the patient's specific condition, with ARNi being preferred for patients with HFrEF due to its improvement in morbidity and mortality.
• For patients with chronic symptomatic HFrEF, switching from ACEi or ARB to ARNi is recommended if tolerated, as it provides additional benefits in reducing morbidity and mortality.
• ARB can be used as an alternative to ACEi in patients with intolerable cough or as an alternative to ACEi and ARNi in patients with a history of angioedema.

Monitoring and Dose Adjustments

• Patients should be monitored for potential side effects, including cough, angioedema, hyperkalemia, and worsening renal function, particularly during initiation and dose adjustments.
• Renal function and potassium levels should be checked within 1-2 weeks of starting therapy and after dose increases.

Benefits and Indications

• These medications are particularly beneficial in patients with diabetes, proteinuria, or left ventricular dysfunction due to their organ-protective effects beyond blood pressure control, as supported by guidelines from 2007 1 and 2012 1.
• The use of ACE inhibitors or ARBs is recommended in patients with stable ischemic heart disease who also have hypertension, diabetes mellitus, LV ejection fraction 40% or less, or chronic kidney disease, unless contraindicated.

From the FDA Drug Label

The primary endpoint was the first occurrence of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Patients with nonfatal events remained in the trial, so that there was also an examination of the first event of each type even if it was not the first event (e.g., a stroke following an initial myocardial infarction would be counted in the analysis of stroke). Treatment with losartan resulted in a 13% reduction (p=0. 021) in risk of the primary endpoint compared to the atenolol group Analysis of age, gender, and race subgroups of patients showed that men and women, and patients over and under 65, had generally similar responses. Losartan was effective in reducing blood pressure regardless of race, although the effect was somewhat less in Black patients (usually a low-renin population)

The first line treatment for patients with conditions influenced by the Renin-Angiotensin-Aldosterone System (RAAS), such as hypertension or heart failure, may include angiotensin II receptor blockers (ARBs) like losartan or angiotensin-converting enzyme (ACE) inhibitors like lisinopril.

• Losartan has been shown to be effective in reducing blood pressure in various patient populations, including those with left ventricular hypertrophy.
• Lisinopril is also used to treat hypertension and heart failure, and its use has been established in pediatric patients aged 6 to 16 years. However, the choice of first-line treatment should be individualized based on patient-specific factors, such as age, gender, race, and comorbidities. It is essential to consider the potential benefits and risks of each treatment option and to monitor patients closely for adverse effects. 2 3

From the Research

First Line Treatment for RAAS-Related Conditions

The first line treatment for patients with conditions influenced by the Renin-Angiotensin-Aldosterone System (RAAS), such as hypertension or heart failure, typically involves the use of certain medications that target this system.

• Angiotensin-converting enzyme inhibitors (ACEIs) are often used as a first line treatment for hypertension and heart failure, as they have been shown to be effective in reducing blood pressure and improving outcomes in these patients 4.
• Angiotensin II receptor blockers (ARBs) are also commonly used, particularly in patients who cannot tolerate ACEIs, and have been shown to be beneficial in reducing blood pressure and improving cardiovascular outcomes 5, 4.
• Aldosterone receptor antagonists (ARAs) are used in certain cases, such as in patients with heart failure and reduced ejection fraction, and have been shown to reduce mortality and hospitalization risk in these patients 6, 7.
• Direct renin inhibitors (DRIs) are another option, although they have been shown to have similar blood pressure reduction to ACEIs and ARBs, but with more side effects 4.

Specific Treatment Options

The choice of treatment depends on the specific condition and patient population. For example:

• In patients with heart failure and reduced ejection fraction, an angiotensin receptor-neprilysin inhibitor (ARNI) may be the most efficacious therapy for reducing mortality and hospitalization risk 7.
• In patients with hypertension, ACEIs or ARBs may be used as first line treatment, with the choice depending on patient characteristics and comorbidities 4.
• In patients with heart failure and preserved ejection fraction, the use of ARAs or other RAAS blockers may be beneficial, although more research is needed to determine the best treatment approach 8, 7.

Combination Therapy

Combination therapy with multiple RAAS blockers may be used in certain cases, although this approach has been shown to increase the risk of side effects such as hypotension, hyperkalemia, and renal impairment 5. The use of combination therapy should be carefully considered and individualized to each patient's needs and response to treatment.