Incidence and Predictors of Angioedema in Elderly Hypertensive Patients at High Risk for Cardiovascular Disease: A Report From the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Angioedema is a rare, potentially life‐threatening condition that has been associated with angiotensin‐converting enzyme inhibitors since their introduction in the 1980s. The Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the largest antihypertensive study conducted to date, randomized 42,418 participants to a diuretic (chlorthalidone), a calcium channel blocker (amlodipine), an angiotensin‐converting enzyme inhibitor (lisinopril), or an α‐blocker (doxazosin). Patients who developed angioedema were compared for baseline characteristics and changes in antihypertensive drug administration. Fifty‐three participants developed angioedema during active follow‐up: 55% were black, 60% men, and 70% were assigned to lisinopril (including 62% of black participants with angioedema), 15% to chlorthalidone, 9% to doxazosin, and 6% to amlodipine. Six percent occurred within a day of randomization and 23% within the first week. Over half did not have an increase in their assigned (blinded) antihypertensive drug before angioedema onset; 3 (6%) had a dose increase within a week before onset. One patient died following an angioedema episode. The occurrence of angioedema in the angiotensin‐converting enzyme inhibitor arm corresponds with previously reported angioedema–angiotensin‐converting enzyme inhibitor associations.