Warfarin therapy and systolic hypertension in men with atrial fibrillation

Warfarin decreases the activity of matrix Gla-protein and causes extensive arterial calcification leading to increased systolic blood pressure (SBP) and pulse pressure (PP) in rats. We performed post hoc analyses of the Stroke Prevention in Non-Rheumatic Atrial Fibrillation (SPINAF) trial, aiming to analyze the effects of warfarin on SBP and PP.

The SPINAF trial was a randomized, double-blind, placebo-controlled trial comparing warfarin and placebo in 525 subjects with nonrheumatic atrial fibrillation. After exclusions for inadequate follow-up, 284 subjects with average treatment lasting 23.7 months were available for analysis (144 given placebo and 140 warfarin).

Baseline SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), and PP were 132 +/- 18, 81 +/- 9, 98 +/- 11, and 50 +/- 16 mm Hg in the warfarin group, and 133 +/- 21, 80 +/- 13, 97 +/- 14, and 54 +/- 15 mm Hg in the placebo groups (all P values, NS). There was no statistically significant difference between the placebo and warfarin groups in any of the BP parameters at any time point. However, stratified analyses showed a significant increase in PP in warfarin-treated subjects with a history of hypertension (4.9 +/- 13.1 mm Hg v 0.2 +/- 11.9 mm Hg in the placebo group, P = 0.022), and those with baseline SBP > or =140 mm Hg (4.8 +/- 18.9 mm Hg v -3.4 +/- 11.2 mm Hg in the placebo group, P = .038). A similar trend was noted in diabetic subjects but it was not statistically significant.

Based on the study results, treatment with warfarin does not result in increased BP in men with atrial fibrillation. However, it is possible that subjects at higher baseline cardiovascular risk may be more susceptible to the chronic effects of warfarin on arterial hemodynamics.