Effect of Phosphodiesterase Type 5 Inhibition on Microvascular Coronary Dysfunction in Women: A Women's Ischemia Syndrome Evaluation (WISE) Ancillary Study
Authors: Denardo Scott J. , Wen Xuerong , Handberg Eileen M. , Bairey Merz C. Noel , Sopko George S. , Cooper‐DeHoff Rhonda M. , Pepine Carl J. 
Published: July 2011

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 log2‐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. © 2011 Wiley Periodicals, Inc.

This work was supported by contracts from the National Institutes of Health/National Heart, Lung and Blood Institute (NIH/NHLBI) nos. N01‐HV‐68161, N01‐HV‐68162, N01‐HV‐68163, and N01‐HV‐68164, and grants U0164829, U01 HL649141, U01 HL649241, and T32HL69751; General Clinical Research Center (GCRC) grant MO1‐RR00425 from the National Center for Research Resources (NCRR); and grants from Pfizer, Inc., New York, NY; the Gustavus and Louis Pfeiffer Research Foundation, Danville, NJ; the Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh; and the Edythe L. Broad Women's Heart Research Fellowship, The Women's Guild, and the Barbra Streisand Women's Cardiovascular Research and Education Program, Cedars‐Sinai Medical Center, Los Angeles, CA. Dr. Pepine was funded, in part, from the Eminent Scholar Research Chair, American Heart Association Suncoast Chapter; by NIH/NHLBI grants 5 U01 HL087366‐04, 5‐UL1 RR025208‐02, 5 R01 HL091005‐03, 5 R01 HL090957‐03, and 2 U01 GM074492‐06, NIH/AG grant 3 U01 AG022376‐05A2S1, and NIH/NCRR grant 5 UL1 RR029890‐02. All authors had access to the data and a role in writing the manuscript.

Drs. Pepine and Handberg have a research grant and educational grants from Pfizer. The authors have no other funding, financial relationships, or conflicts of interest to disclose.