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.