Amlodipine vs Lisinopril

Both amlodipine and lisinopril effectively lower blood pressure as monotherapy. Amlodipine 5–10 mg typically reduces systolic blood pressure by 10–15 mmHg, comparable to lisinopril 10–40 mg ^[1][2]. The ALLHAT trial (>33,000 patients), the largest hypertension outcomes trial ever conducted, compared amlodipine, lisinopril, and chlorthalidone and found no difference in the primary endpoint of fatal coronary heart disease or non-fatal MI ^[3]. However, amlodipine was superior to lisinopril in preventing stroke (RR 0.77) and combined cardiovascular disease. Lisinopril was superior for preventing heart failure. For patients with diabetes, lisinopril (and ACE inhibitors generally) provide additional renal protection by reducing intraglomerular pressure and proteinuria ^[2]. Amlodipine has demonstrated superior efficacy in Black patients, who tend to have lower-renin hypertension that responds better to CCBs than to ACE inhibitors ^[3]. Both drugs are effective for stable angina, though amlodipine has a specific FDA indication for this use ^[1].

Amlodipine's most common side effect is peripheral edema (ankle swelling), occurring in 5–15% of patients at therapeutic doses and up to 30% at the maximum 10 mg dose ^[1]. Other CCB-class effects include flushing (2–4%), headache (7%), dizziness (3%), and palpitations. Notably, amlodipine does not cause cough, hyperkalemia, or angioedema. Lisinopril's hallmark side effect is dry cough, occurring in 5–20% of patients due to bradykinin accumulation ^[2]. Angioedema is rare (0.1–0.7%) but can be life-threatening, with higher incidence in Black patients. Hyperkalemia (1–3%) is a concern, especially in patients with CKD or those taking potassium supplements. Lisinopril can cause first-dose hypotension and dizziness ^[3]. Neither drug significantly affects lipid profiles or glucose metabolism. Lisinopril is contraindicated in pregnancy (fetal toxicity), while amlodipine has limited pregnancy data and is also generally avoided ^[4]. Amlodipine does not require monitoring beyond blood pressure, while lisinopril requires periodic potassium and creatinine checks.

Both medications are among the most affordable prescription drugs available. Generic amlodipine 5 mg (30 tablets) costs $3–8 ^[1]. Generic lisinopril 10 mg (30 tablets) costs $3–8. Both are on most pharmacy $4 generic lists. Brand-name Norvasc and Zestril cost $100–200/month but are rarely prescribed. The fixed-dose combination of amlodipine/benazepril (Lotrel generic) is also affordable at $10–25/month. Insurance coverage is universal for both medications at the lowest copay tier.

Both medications are taken once daily, which maximizes adherence. Amlodipine can be taken at any time, with or without food ^[1]. Lisinopril can similarly be taken at any time, with or without food ^[2]. Amlodipine is available in 2.5, 5, and 10 mg tablets. Lisinopril comes in 2.5, 5, 10, 20, 30, and 40 mg tablets, offering more granular dose titration. Amlodipine has a very long half-life (30–50 hours), meaning missed doses have less impact on blood pressure control compared to lisinopril (half-life 12 hours) ^[1]. Neither drug requires laboratory monitoring beyond standard blood pressure checks, though lisinopril warrants periodic potassium and renal function testing. Both have excellent shelf stability and no special storage requirements.

For most patients with uncomplicated hypertension, either amlodipine or lisinopril is an appropriate first choice ^[3]. Amlodipine may be preferred for Black patients (better response to CCBs), elderly patients with isolated systolic hypertension, patients who cannot tolerate ACE inhibitor cough, patients with Raynaud phenomenon (vasodilatory benefit), or patients with stable angina ^[1][3]. Lisinopril may be preferred for patients with diabetes and proteinuria (renal protection), heart failure with reduced ejection fraction (mortality benefit), post-myocardial infarction patients, or young white patients with higher-renin hypertension ^[2][3]. When blood pressure is not adequately controlled with monotherapy, combining amlodipine and an ACE inhibitor is a well-studied and effective strategy recommended by guidelines ^[4]. Consult your healthcare provider to determine which first-line antihypertensive best fits your risk profile.