Effect of phosphodiesterase type 5 inhibition on microvascular coronary dysfunction in women: a Women's Ischemia Syndrome Evaluation (WISE) ancillary study.
BACKGROUND:Microvascular coronary dysfunction (MCD) is associated with symptoms and signs of ischemia, and also adverse outcomes in women without macrovascular obstructive coronary artery disease (M-CAD). Although MCD can be quantified using coronary flow reserve (CFR), treatment is poorly defined. HYPOTHESIS:Phosphodiesterase type 5 (PDE-5) inhibition acutely improves MCD in these women. METHODS:The subjects were 23 symptomatic women (age 54 ± 11 y) participating in an ancillary study of the Women's Ischemia Syndrome Evaluation with baseline CFR ≤3.0 (Doppler flow wire and intracoronary adenosine) and without M-CAD. Coronary flow reserve was remeasured 45 minutes after PDE-5 inhibition (100 mg oral sildenafil). The primary measure of interest was change in CFR adjusted for baseline variables. RESULTS:The relationship between log(2)-transformed CFR post-PDE-5 inhibition (adjusted) and baseline was different from the line of identity (slope: 0.55 vs 1.0, P = 0.008; intercept: 0.73 vs 0.0, P = 0.01), indicating that PDE-5 inhibition improves CFR and the lower the baseline CFR, the greater the response. Among women with baseline CFR ≤2.5 (n = 11), CFR increased from 2.1 ± 0.2 to 2.7 ± 0.6 (P = 0.006). For women with baseline CFR >2.5 (n = 12), CFR did not change (3.1 ± 0.3 to 3.0 ± 0.6; P = 0.70). CONCLUSIONS:For women with symptoms and signs of ischemia and no M-CAD, PDE-5 inhibition is associated with acute improvement in CFR, and the effect concentrates among those with CFR ≤2.5. If these acute effects are sustained, then PDE-5 inhibition would provide a rational strategy for management of MCD in symptomatic women without M-CAD. The longer-term effects warrant study in a randomized trial using a sustained-acting PDE-5 inhibitor.
Denardo, SJ; Wen, X; Handberg, EM; Bairey Merz, CN; Sopko, GS; Cooper-Dehoff, RM; Pepine, CJ
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