Is losartan more effective than lisinopril for treating hypertension in an African American male?

Lisinopril is NOT Better Than Losartan for This Patient—But Neither Should Be First-Line

For an African American male with hypertension, neither lisinopril nor losartan should be the initial monotherapy; a thiazide-type diuretic (chlorthalidone 12.5-25 mg daily or hydrochlorothiazide 25-50 mg daily) or a calcium channel blocker (amlodipine) is the preferred first-line agent. 1, 2 However, if forced to choose between these two ACE inhibitor/ARB options, losartan has a marginally better safety profile than lisinopril in African Americans, though both are less effective than diuretics or calcium channel blockers for blood pressure reduction and cardiovascular outcomes in this population. 3

Why ACE Inhibitors and ARBs Are Suboptimal First-Line Choices

Blood Pressure Reduction Efficacy

• ACE inhibitors (including lisinopril) lower blood pressure to a significantly lesser degree in African Americans compared to whites due to the typically suppressed renin-angiotensin system in this population 3
• In the landmark ALLHAT trial with over 15,000 black patients, lisinopril was less effective in lowering blood pressure than either chlorthalidone or amlodipine 3
• ARBs (including losartan) also demonstrate reduced blood pressure-lowering efficacy as monotherapy in African Americans, though the effect is somewhat less pronounced than with ACE inhibitors 3, 4

Cardiovascular Outcomes: The Critical Difference

• In ALLHAT, African Americans randomized to lisinopril versus chlorthalidone experienced a 40% greater risk of stroke, 32% greater risk of heart failure, and 19% greater risk of combined cardiovascular disease 3
• These outcome differences persisted even after time-dependent blood pressure adjustment, suggesting mechanisms beyond blood pressure control 5
• No large cardiovascular outcome studies have been conducted with ARBs specifically in African American populations 3

The LIFE Study Paradox

• In the LIFE study subanalysis of 533 black patients with left ventricular hypertrophy, losartan was associated with worse cardiovascular outcomes than atenolol (hazard ratio 1.666, p=0.033), despite similar blood pressure reduction and greater LVH regression 6
• This contrasts sharply with the overall LIFE study population where losartan was superior 6
• This finding suggests that losartan should not be first-line therapy for cardiovascular risk reduction in black patients with LVH 6

Direct Comparison: Lisinopril vs. Losartan in African Americans

Safety Profile Advantage for Losartan

• African Americans have a 3- to 4-fold higher risk of angioedema with ACE inhibitors (like lisinopril) compared to whites 3, 1
• African Americans also experience more cough with ACE inhibitors than other racial groups 3
• ARBs like losartan do not carry the same angioedema risk, making them the preferred renin-angiotensin system inhibitor when one is needed 1

Efficacy Comparison

• Both agents demonstrate reduced blood pressure-lowering efficacy as monotherapy in African Americans 3, 4
• In African Americans specifically, losartan monotherapy (50-150 mg) produced a response rate of 45.8% with mean blood pressure reductions of 6.4/6.6 mmHg 7
• Direct head-to-head outcome data comparing losartan to lisinopril specifically in African Americans is lacking 3

When RAS Inhibitors Are Appropriate in African Americans

Compelling Indications

• For African Americans with chronic kidney disease and proteinuria (urinary albumin-to-creatinine ratio ≥300 mg/g), ACE inhibitors or ARBs are recommended as part of a multidrug regimen 1, 8, 9
• In the AASK trial, African Americans with hypertensive nephrosclerosis treated with an ACE inhibitor-containing regimen showed greater preservation of renal function compared to beta-blockers or calcium antagonists 3
• For heart failure with reduced ejection fraction, ACE inhibitors or ARBs are foundational therapy regardless of race 1, 2

Always Use Combination Therapy

• The blood pressure-lowering differences between ACE inhibitors/ARBs and other drug classes are abolished when combined with a diuretic 3
• Most African American patients require two or more antihypertensive medications to achieve blood pressure targets below 130/80 mmHg 1, 2
• When losartan was combined with hydrochlorothiazide 12.5 mg in African Americans, the response rate increased to 62.7% with blood pressure reductions of 16.8/10.8 mmHg 7

Recommended Treatment Algorithm for This Patient

Initial Therapy Selection

• Start with chlorthalidone 12.5-25 mg daily (preferred over hydrochlorothiazide due to longer half-life and more cardiovascular outcome data) or amlodipine 5-10 mg daily 1, 2
• If blood pressure is >15/10 mmHg above goal, initiate combination therapy with a calcium channel blocker plus thiazide diuretic, or calcium channel blocker plus ARB 1

When to Add or Switch to Losartan

• If the patient has diabetic nephropathy with proteinuria, add losartan (not lisinopril due to angioedema risk) to the thiazide or calcium channel blocker 1, 9
• If blood pressure remains uncontrolled on dual therapy, progress to triple therapy with calcium channel blocker + thiazide diuretic + ARB (losartan preferred over lisinopril) 1

Critical Monitoring Points

• Monitor for angioedema more vigilantly if an ACE inhibitor must be used, recognizing the 3-4 fold increased risk in African Americans 3
• Assess for chronic kidney disease and proteinuria, as this shifts the risk-benefit calculation toward including a RAS inhibitor 1, 9
• Evaluate for heart failure or left ventricular dysfunction, which may require different therapeutic priorities 1, 8

Bottom Line

Neither losartan nor lisinopril should be your first choice for this African American male. If you must choose between them—perhaps because the patient is already on one or has a compelling indication like diabetic nephropathy—losartan is marginally preferable to lisinopril solely due to the significantly lower risk of angioedema. 3, 1 However, the optimal approach is to use a thiazide diuretic or calcium channel blocker as the foundation, adding losartan (not lisinopril) only when there is a specific indication such as proteinuric kidney disease or when combination therapy is needed for blood pressure control. 1, 2