Introduction: The increased thrombotic cardiovascular (CV) risk in trials of cyclooxygenase-
2 (COX-2) inhibitors versus placebo, and the apparent similar risk with nonsteroidal
antiinflammatory drugs (NSAIDs), may be related to their potential to elevate blood
pressure (BP). Aims: We evaluated the relationship between baseline BP and change in
BP on CV events (CVEs) in patients receiving NSAIDs or COX-2 inhibitors in the prospective
randomized, double-blind, Multinational Etoricoxib and Diclofenac Arthritis Long-term
Program (N = 34,701) comparing etoricoxib 60 or 90 mg or diclofenac 150 mg daily for a
mean duration of 18 months. The main outcome measure was confirmed thrombotic CVEs.
The Antiplatelet Trialistsa?? Collaboration endpoint, all-cause mortality, CV/congestive heart
failure (CHF) mortality, and CHF incidence were similarly evaluated. Results: We found
that baseline systolic BP (SBP) was associated with significantly higher risk of all events
(P <0.001). Baseline diastolic BP (DBP) was inversely and significantly associated with risk
of all events (P <0.001 to P = 0.016) except CV/CHF mortality (P = 0.054). There was no
significant differential effect between etoricoxib and diclofenac in relation to CVEs, except
for confirmed CHF, for which the risk was significantly higher with etoricoxib (P = 0.019).
Only CHF risk (P = 0.020 for both SBP and DBP change), but not thrombotic endpoints,
was significantly associated with change in BP from months 0 to 4. These findings were not
meaningfully altered after covariate adjustment for baseline CV risk. Conclusions: Baseline
BP, but not change in BP, was significantly associated with risk of thrombotic CVEs through
18 months. The CV risk of COX-2s and NSAIDs did not appear to be related to the BPelevating
effects of these agents, although such analyses, i.e., from randomized controlled
trials, are unable to definitively exclude such a relationship.