Effect of phosphodiesterase type 5 inhibition on microvascular coronary dysfunction in women: a Women's Ischemia Syndrome Evaluation (WISE) ancillary study

Clin Cardiol. 2011 Aug;34(8):483-7. doi: 10.1002/clc.20935. Epub 2011 Jul 21.

Abstract

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine
  • Adult
  • Aged
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / enzymology
  • Coronary Artery Disease / physiopathology
  • Coronary Circulation / drug effects
  • Coronary Vessels / drug effects*
  • Coronary Vessels / enzymology
  • Coronary Vessels / physiopathology
  • Echocardiography, Doppler
  • Female
  • Humans
  • Linear Models
  • Microcirculation / drug effects
  • Microvessels / drug effects*
  • Microvessels / enzymology
  • Microvessels / physiopathology
  • Middle Aged
  • Myocardial Ischemia / diagnosis
  • Myocardial Ischemia / drug therapy*
  • Myocardial Ischemia / enzymology
  • Myocardial Ischemia / physiopathology
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Piperazines / therapeutic use*
  • Predictive Value of Tests
  • Prospective Studies
  • Purines / therapeutic use
  • Sildenafil Citrate
  • Sulfones / therapeutic use*
  • Treatment Outcome
  • United States
  • Vasodilator Agents / therapeutic use*
  • Women's Health

Substances

  • Phosphodiesterase 5 Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • Sildenafil Citrate
  • Adenosine