Angiotensin receptor blockade is associated with increased risk of giant cell arteritis

Background. Angiotensin II is implicated in giant cell arteritis (GCA) pathology. We examined whether the use of angiotensin receptor blockers (ARB) is associated with GCA risk, compared with ACE inhibitors (ACEi) or other antihypertensives.
Methods. We performed a matched cohort study including adults who were initiators of antihypertensives in UK primary care data between 1995 and 2019. Treatment naïve individuals without prior GCA or polymyalgia rheumatica (PMR) were categorised into three groups – ARB initiators, ACEi initiators, or other antihypertensive initiators (beta-blockers, calcium channel blockers, diuretics or alpha-adrenoceptor blockers) – and followed for up to 5 years. Incident GCA was defined using validated Read codes, with age of onset ≥50 years and ≥2 glucocorticoid prescriptions. Inverse-probability-weighted Cox models were used to model outcome risk, adjusting for lifestyle parameters, comorbidities, and comedications.
Results. Among over a million new starters of antihypertensives (81,780 ARB, 422,940 ACEi, and 873,066 other antihypertensives), the incidence rate of GCA per 10,000 patient-years was 2.73 (95%CI 2.12-3.50) in the ARB group, 1.76 (95%CI 1.25-2.39) in the ACEi group, and 1.90 (95%CI 1.37-2.56) in other antihypertensive group. The hazard of GCA was higher in ARB initiators (HR 1.55; 95%CI 1.16-2.06) than initiators of ACEi, but similar between initiators of other antihypertensives and ACEi (HR 1.08; 95%CI 0.87-1.35).
Conclusions. Initiation of ARB is associated with higher risk of GCA compared to ACEi or other antihypertensives. Mechanistic studies of angiotensin receptor biology will provide further clarity for our findings.