ACE or ARB: the blood pressure medication question Black patients should ask their doctor

In the AASK trial of 1,094 Black adults with hypertensive kidney disease, ramipril (an ACE inhibitor) produced a 22 percent risk reduction in the clinical composite of kidney failure or death versus metoprolol (P = 0.04) and a 38 percent reduction versus amlodipine (P = 0.004; Wright et al., JAMA 2002, PMID 12435255). In the earlier ALLHAT trial of 33,357 high-risk hypertensive adults, approximately 35 percent of whom were Black, secondary analyses showed worse stroke and cardiovascular outcomes for Black participants assigned to the ACE inhibitor lisinopril compared with those assigned to the thiazide-type diuretic chlorthalidone (ALLHAT Officers and Coordinators, JAMA 2002, PMID 12479763). The two JAMA 2002 randomized trials point in different directions. The factor that reconciles them is chronic kidney disease.

For a Black adult with hypertension, the first-line medication question has a specific answer the peer-reviewed evidence supports, and the answer changes when a patient is reclassified as having CKD. Here is what the trials found, what the JNC 8 guideline codified, and the questions to ask your clinician on your next visit.

Hypertension in Black adults is more often low-renin: the renin-angiotensin system is less activated than in many non-Black hypertensive populations, and drugs that block that system (ACE inhibitors, ARBs) produce smaller blood-pressure reductions on average. Diuretics, which act primarily on sodium and volume rather than on the renin-angiotensin axis, produce larger reductions in the same population. Calcium channel blockers act on vascular smooth muscle independent of renin; they also perform well.

The physiology is the backdrop. The ALLHAT and AASK trials are the randomized evidence that turned the physiology into clinical policy.

ALLHAT enrolled 33,357 adults across 623 North American centers for a head-to-head randomized comparison of first-line antihypertensive drug classes. Between 1994 and 2002, adults age 55 and older with hypertension and at least one additional coronary risk factor were randomized to chlorthalidone (a thiazide-type diuretic), amlodipine (a calcium channel blocker), or lisinopril (an ACE inhibitor), with mean follow-up of 4.9 years. Approximately 35 percent of participants were Black, giving the prespecified Black-subgroup analysis a randomized base of roughly 11,700 Black hypertensive patients for between-drug-class comparisons.

On the primary endpoint of fatal coronary heart disease plus nonfatal myocardial infarction, the three drug classes did not differ significantly. On secondary endpoints that included stroke and combined cardiovascular disease, Black participants assigned to lisinopril had worse outcomes than Black participants assigned to chlorthalidone. The specific hazard ratios appear in the full paper's subgroup tables; the widely referenced summary is that the diuretic outperformed the ACE inhibitor in Black participants on stroke prevention. That Black-subgroup finding is the basis for every US guideline recommendation that distinguishes Black-adult first-line antihypertensive treatment from the general population.

AASK is the counterpoint. The African American Study of Kidney Disease and Hypertension enrolled 1,094 Black adults aged 18 to 70 with hypertensive kidney disease (GFR 20 to 65 mL/min/1.73 m²) and no other identified cause of kidney disease. Between 1995 and 1998 they were randomized to one of three first-line medications: ramipril (an ACE inhibitor), metoprolol (a beta-blocker), or amlodipine (a calcium channel blocker). The amlodipine arm was stopped early because Black CKD patients on the calcium channel blocker had worse kidney-progression outcomes than those on the ACE inhibitor.

The published ramipril results are directly comparable to ALLHAT's drug-class framework but produce the opposite recommendation. Ramipril produced a 22 percent reduction in the composite of GFR decline, end-stage renal disease, or death versus metoprolol, and a 38 percent reduction versus amlodipine. Angiotensin-receptor blockers (ARBs) share the renin-angiotensin-blocking mechanism with ACE inhibitors and are treated as an equivalent first-line option for Black CKD patients in subsequent guidelines, with the practical advantage that they do not carry the ACE-specific bradykinin-mediated angioedema risk.

Black Americans on ACE inhibitors carry a well-documented higher angioedema risk than white Americans. In a retrospective cohort study of Tennessee Medicaid enrollees, Brown and colleagues identified 82 cases of angioedema across 51,752 person-years of ACE inhibitor use and reported an adjusted relative risk of 4.5 (95 percent CI 2.9 to 6.8) for Black versus white patients (Brown et al., Clinical Pharmacology and Therapeutics 1996, PMID 8689816). The effect was not explained by dose, specific ACE inhibitor, or concurrent medications. A 2020 review in International Immunopharmacology confirmed the racial predisposition with a mechanistic explanation (bradykinin catabolism differences in polymorphisms linked to African ancestry) and added a second finding relevant to care: icatibant, the standard rescue therapy for ACE-induced angioedema, has demonstrated efficacy in Caucasian but not Black patients in the limited available trial data (Montinaro and Cicardi, PMID 31835086).

Angioedema on ACE inhibitors is rare in absolute terms, affecting roughly 0.1 to 0.7 percent of all treated patients. The 4.5-fold relative risk operates on that small base rate. For any individual Black patient on an ACE inhibitor, the absolute risk is still low; for a patient who does develop angioedema, the presentation can include airway compromise and the standard rescue therapy performs worse.

The 2014 Eighth Joint National Committee report codified the ALLHAT and AASK evidence into two Black-specific recommendations that remain the current US guideline framework (James et al., JAMA 2014, PMID 24352797).

For Black adults with hypertension but without CKD, JNC 8 Recommendation 5 says initial treatment should include a thiazide-type diuretic or a calcium channel blocker (moderate recommendation, grade B). ACE inhibitors and ARBs are not excluded from the treatment plan; they are deprioritized as first-line because ALLHAT's Black-subgroup evidence and Brown 1996's angioedema risk together argue for starting with a different class.

For Black adults with CKD, JNC 8 Recommendation 6 says initial or add-on treatment should include an ACE inhibitor or an ARB. AASK's kidney-protective evidence applies. The recommendation covers all CKD patients with hypertension regardless of race or diabetes status; AASK is the Black-specific randomized evidence that underpins the Black-CKD extension of the general recommendation.

The eGFR calculation that determines whether a Black patient is classified as having CKD was itself updated in 2021. The National Kidney Foundation and the American Society of Nephrology jointly recommended removing the race variable from the CKD-EPI equation, which for Black patients can shift a previously "normal" eGFR into the CKD range (Delgado et al., JASN 2021, PMID 34556489). A Black patient whose eGFR report was race-adjusted before 2022 may now be reclassified under the newer equation, which moves them from Recommendation 5 (thiazide or CCB first-line) to Recommendation 6 (ACE or ARB first-line).

The AASK trial compared ramipril to two other drug classes, not to an ARB. The direct randomized head-to-head of ACE inhibitor versus ARB in Black CKD patients is thinner than the ACE-versus-non-ACE evidence. ARBs and ACE inhibitors share the renin-angiotensin-blocking mechanism that produces AASK's kidney-protection effect. The practical clinical difference is the side-effect profile: ACE inhibitors carry the bradykinin-mediated angioedema risk; ARBs do not. For a Black CKD patient who develops ACE-associated angioedema or a persistent dry cough, switching to an ARB is the standard clinical move.

For a Black CKD patient who has not yet started a first-line medication, the choice between ACE inhibitor and ARB is less settled by randomized head-to-head data than by side-effect considerations and by whether the patient has another indication (for example, a post-myocardial-infarction ACE-specific recommendation) that tips the choice.

"Do I have chronic kidney disease? What is my eGFR, and is the calculation being done without a race adjustment?" The NKF-ASN 2021 recommendation is the reason to ask. A recent eGFR under the race-free CKD-EPI equation may reclassify a Black patient who was previously told they did not have CKD.

"If I don't have CKD, is my first-line medication a thiazide-type diuretic or a calcium channel blocker?" JNC 8 Recommendation 5 is the reason to ask. A Black adult without CKD who is being started on an ACE inhibitor or ARB as first-line may want to ask why their clinician is not starting with a diuretic or CCB.

"If I am on an ACE inhibitor, what are the warning signs of angioedema, and is an ARB an appropriate alternative?" Brown 1996 is the reason to ask. The 4.5-fold relative risk and the limited rescue-therapy options make this a specific first-visit question with practical stakes.

If you have hypertension and are unsure whether any of the above applies to you, the first concrete step is a conversation with your primary care clinician about your most recent eGFR calculation, whether it was done with or without a race adjustment, and what class of medication you are currently on. Our reporting on finding a Black primary care physician, with whom these evidence-based conversations sometimes go easier, is at /articles/find-a-black-doctor-near-you-why-it-matters/. Our earlier reporting on the Greenwood 2020 and Borjas 2024 PNAS replication on racial concordance and newborn mortality is at /articles/racial-concordance-replication-greenwood-borjas/.