Background/Purpose: Chronic inflammation is associated with a greater risk of hypertension (HTN) while inflammatory cytokines such as TNF-α have been shown to have vasodilator effects. It thus remains unclear how treatment of rheumatoid arthritis (RA) might affect blood pressure (BP). Our goal was to quantify changes in systolic and diastolic blood pressure (SBP, DBP) in the 6 months after initiating new DMARDs in a large administrative database.

Methods: We used 3 VA database sources: the Corporate Data Warehouse (CDW), the Decision Support System (DSS) National Pharmacy Extract, and the Pharmacy Benefits Management (PBM) database. Among patients with at least one diagnosis code for RA, algorithms integrated sources to define unique dispensing episodes of methotrexate, prednisone, leflunomide, and TNF inhibitors (TNFi). The closest values for BP, CRP, CCP, and BMI within 30 days of the treatment start date were used as baseline values. Values -180, 90, and 180 days from the treatment start date (+/- 30 days) were also recorded. A significant increase in BP was defined as an increase in SBP >20 mm or DBP >10 mm. Incident HTN was defined as a new diagnosis code for HTN after the course start. Multiple imputation was utilized to account for missing laboratory values. Propensity analyses using matched-weighting techniques were used to address confounding by indication.

Results: There were 25,811 unique treatment courses in 18,119 patients identified. Overall, there were no changes in BP in the 6-months prior to drug initiation (all p>0.62). In contrast, there was a small but significant overall decline in SBP [β: -1.08 mmHg (-1.32, -0.85) p<0.0001] and DBP [β: -0.48 (-0.62, -0.33) p<0.0001] over the 6 months after initiating drug. The greatest decline was observed among those treated with methotrexate or prednisone (Figure). Patients treated with leflunomide had less decline in SBP and DBP and a greater odds of a significant increase in BP at 6-months compared to methotrexate (Figure, Table). Users of TNFi had less reduction in BP compared to methotrexate, however this difference was attenuated and not significant in sensitivity analyses (Table). The risk of an incident diagnosis of HTN over 3 years was greater for leflunomide [HR 1.42 (1.05, 1.93) p=0.02] and similar for prednisone and TNFi (all p>0.14) compared to methotrexate (not shown).

Conclusion: Patients initiating treatment for RA, particularly methotrexate, generally demonstrate reductions in BP over 6 months. Leflunomide use is associated with less improvement in BP and a modestly increased risk of incident HTN compared to the use of other DMARDS in a large population study.

\