ACE Inhibitors for Blood Pressure Control and Organ Protection

1) RAAS pathway and where ACE inhibitors act

RAAS in plain language (the “pressure and salt-saving” system)

The renin–angiotensin–aldosterone system (RAAS) is a hormone cascade that raises blood pressure and helps the body retain sodium and water when it senses low kidney perfusion, low sodium delivery, or sympathetic activation.

• Trigger: The kidney’s juxtaglomerular cells release renin when renal perfusion is low (e.g., dehydration, heart failure), when sodium delivery to the macula densa is low, or when beta-1 sympathetic tone is high.
• Step 1: Renin converts angiotensinogen (from the liver) into angiotensin I.
• Step 2: ACE (angiotensin-converting enzyme)—found largely on vascular endothelium, especially in the lungs—converts angiotensin I into angiotensin II.
• Step 3: Angiotensin II causes vasoconstriction (raises BP), stimulates aldosterone release (sodium/water retention and potassium loss), increases sympathetic tone, and promotes cardiac/vascular remodeling.
• Step 4: Aldosterone acts in the distal nephron to retain sodium and water and excrete potassium and hydrogen ions.

Where ACE inhibitors act

ACE inhibitors (ACEi) block ACE, which leads to:

• ↓ Angiotensin II → less vasoconstriction, less aldosterone stimulation, less remodeling.
• ↓ Aldosterone effects (indirectly) → less sodium/water retention and tendency toward higher potassium.
• ↑ Bradykinin (ACE also breaks down bradykinin) → contributes to vasodilation but also explains dry cough and some risk of angioedema.

Kidney hemodynamics: why creatinine can rise

Angiotensin II preferentially constricts the efferent arteriole of the glomerulus, helping maintain intraglomerular pressure when renal perfusion is low. ACE inhibitors reduce angiotensin II, causing efferent dilation and a drop in intraglomerular pressure. This can:

• Lower protein leakage (helpful in albuminuria).
• Cause a small, expected rise in serum creatinine after starting or increasing the dose.

2) Indications (when ACE inhibitors are used)

Hypertension

ACE inhibitors are common first-line options for blood pressure control, especially when there are compelling comorbidities such as diabetes with albuminuria, chronic kidney disease with albuminuria, heart failure, or post–myocardial infarction.

Heart failure (especially HFrEF)

ACE inhibitors reduce afterload and neurohormonal activation, improving symptoms and reducing hospitalizations and mortality in heart failure with reduced ejection fraction (HFrEF). They are foundational therapy unless contraindicated or not tolerated.

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Post–myocardial infarction (post-MI)

After MI, ACE inhibitors help limit adverse ventricular remodeling and reduce recurrent events and mortality, particularly in patients with reduced ejection fraction, anterior MI, diabetes, or clinical heart failure.

Diabetic kidney disease and albuminuria (and other albuminuric CKD)

ACE inhibitors reduce intraglomerular pressure and protein filtration, which can slow progression of kidney disease in patients with albuminuria (e.g., diabetes with elevated urine albumin-to-creatinine ratio). The key benefit is strongest when albuminuria is present.

3) Expected clinical effects (what you should see)

Lower blood pressure

• Mechanism: less angiotensin II–mediated vasoconstriction and less aldosterone-driven volume expansion.
• What to expect: BP reduction over days to weeks; full effect may take a few weeks, especially as doses are titrated.

Reduced remodeling (heart and vessels)

• Mechanism: reduced angiotensin II signaling decreases hypertrophy and fibrosis.
• Clinical translation: improved outcomes in HFrEF and post-MI patients (less progressive dilation and dysfunction).

Kidney protection in albuminuria

• Mechanism: efferent arteriole dilation lowers intraglomerular pressure → less protein leak.
• Clinical translation: reduced urine albumin excretion and slower CKD progression in albuminuric disease.

Safety and counseling (what to warn about and what to do)

Dry cough

• Why it happens: increased bradykinin.
• How it presents: persistent, dry, tickling cough that can start days to months after initiation.
• What to do: rule out other causes; if bothersome and persistent, switching to an ARB is a common strategy (ARB discussion may be elsewhere, but the practical concept is “same pathway, less bradykinin cough”).

Hyperkalemia

• Why it happens: reduced aldosterone effect → less potassium excretion.
• Higher risk in: CKD, diabetes, older age, baseline high potassium, and when combined with potassium-raising drugs.
• What to do: check potassium at baseline and after starting/titration; counsel on avoiding unnecessary potassium supplements and salt substitutes containing potassium.

Rise in creatinine: expected vs concerning

A mild creatinine increase is common because of the hemodynamic change at the glomerulus.

Key counseling point: “A small bump in creatinine can be normal; we monitor to ensure it stays within a safe range.”

Hypotension (especially with volume depletion)

• Who is at risk: dehydrated patients (vomiting/diarrhea), low-salt intake, aggressive diuresis, older adults, and those with heart failure.
• Symptoms: dizziness, lightheadedness, near-syncope, weakness.
• What to do: start low, titrate slowly; consider taking the first dose at bedtime; correct volume depletion before initiation when possible.

Angioedema (medical emergency)

• What it is: swelling of lips, tongue, face, or throat; may occur at any time (even after long-term use).
• Action: stop ACE inhibitor immediately and seek emergency care if airway symptoms occur.
• Important note: do not “rechallenge” with an ACE inhibitor after angioedema.

Pregnancy contraindication

• Why: RAAS blockade can cause fetal kidney injury and other serious fetal harm.
• Action: avoid in pregnancy; counsel patients of childbearing potential about contraception and to contact the clinician immediately if pregnancy occurs.

Interactions (common and clinically important)

Potassium supplements and potassium-sparing drugs

• Risk: additive hyperkalemia.
• Examples: potassium supplements, potassium-based salt substitutes, and potassium-sparing agents.
• Practical approach: avoid routine potassium supplementation unless clearly indicated; monitor potassium closely if combination is necessary.

NSAIDs (kidney risk)

• Mechanism: NSAIDs constrict the afferent arteriole (via prostaglandin inhibition) while ACEi dilate the efferent arteriole → reduced glomerular filtration pressure.
• Clinical risk: acute kidney injury, especially with dehydration or other nephrotoxic stressors.
• Counseling: avoid frequent NSAID use; if needed, use the lowest dose for the shortest time and ensure hydration; consider alternatives for pain when appropriate.

Lithium

• Risk: ACE inhibitors can increase lithium levels and toxicity.
• What to do: coordinate with the prescriber managing lithium; monitor lithium levels and clinical signs of toxicity (tremor, confusion, GI symptoms).

Monitoring plan (baseline, follow-up, and symptom checklist)

Baseline before starting

• Blood pressure (home readings if available).
• Serum creatinine/eGFR and potassium.
• Volume status (recent vomiting/diarrhea, poor intake, heavy sweating, over-diuresis).
• Pregnancy status when relevant.
• Medication review for NSAIDs, potassium products, and lithium.

Follow-up after start or dose increase

• Timing: recheck potassium and creatinine typically within 1–2 weeks (earlier for high-risk patients such as CKD, older adults, or those on interacting meds).
• BP check: assess home BP log and symptoms of hypotension.
• Symptom checklist: cough, dizziness/lightheadedness, swelling of lips/tongue/face, reduced urine output, muscle weakness/palpitations (possible hyperkalemia).

Ongoing monitoring

• Periodic potassium/creatinine (frequency depends on kidney function, stability, and comedications).
• BP and adherence checks; reinforce avoidance of unnecessary NSAIDs and potassium-containing salt substitutes.

Practical beginner-friendly sequence: starting and titrating an ACE inhibitor

Step 1: Choose the right patient

• Good candidates: hypertension with albuminuria, HFrEF, post-MI with LV dysfunction, diabetic kidney disease with albuminuria.
• Pause and reassess if: pregnancy, history of ACEi angioedema, markedly elevated baseline potassium, or unstable kidney function.

Step 2: Get baseline numbers and review meds

• Document BP (including orthostatic symptoms if present).
• Order/check creatinine/eGFR and potassium.
• Identify NSAID use, potassium supplements/salt substitutes, potassium-sparing drugs, and lithium.

Step 3: Start low (especially if high-risk for hypotension)

• Use a low initial dose and consider first dose at bedtime if dizziness risk is high.
• If the patient is volume depleted (recent GI losses, poor intake), correct that first to reduce first-dose hypotension and kidney injury risk.

Step 4: Provide targeted counseling in 60 seconds

• Expected: BP improvement; possible mild creatinine rise.
• Call promptly: facial/lip/tongue swelling, severe dizziness/fainting, very low urine output.
• Common nuisance: dry cough—report if persistent.
• Avoid: frequent NSAIDs; potassium supplements or potassium salt substitutes unless instructed.

Step 5: Recheck labs and BP soon after initiation

• Recheck potassium/creatinine in ~1–2 weeks (earlier if CKD, older age, interacting meds).
• Review home BP readings and symptoms.

Step 6: Titrate toward the goal

• If BP remains above target and labs are acceptable: increase dose gradually (commonly every 2–4 weeks in stable outpatients).
• If creatinine rises within expected range and stabilizes: continue and monitor.
• If potassium rises: address reversible causes (dietary potassium, supplements, interacting meds) and consider dose adjustment if needed.

Step 7: Troubleshoot common problems

• Cough: if persistent and bothersome, discuss switching therapy.
• Symptomatic hypotension: assess dehydration, timing with other BP meds, and consider dose reduction or slower titration.
• Creatinine rise >30%: evaluate volume status, NSAID use, renal artery stenosis risk; consider holding/reducing and repeat labs.
• Angioedema: stop immediately; emergency evaluation; avoid future ACE inhibitors.