Ranolazine Did Not Improve Angina, Myocardial Perfusion Index in Certain Patients with Microvascular Dysfunction

In the RWISE study, ranolazine did not improve SAQ angina or myocardial perfusion index in patients with microvascular dysfunction.

ORLANDO, Fla. — Short-term use of ranolazine had no significant effect on Seattle Angina Questionnaire (SAQ) measured angina or coronary microvascular dysfunction in patients with no obstructive coronary artery disease (CAD) but evidence of coronary microvascular dysfunction, according to new research.

C. Noel Bairey Merz, MD, of Cedars-Sinai Medical Center, Los Angeles, presented the RWISE (Ranolazine Women’s Ischemia Syndrome Evaluation) study findings at the American Heart Association Scientific Sessions.

The primary goal of the study, Dr Bairey Merz said at a press conference, was to mechanistically test short-term late sodium current inhibition with ranolazine (Gilead Sciences, Foster City, CA) in symptomatic patients with no obstructive CAD but evidence of coronary microvascular dysfunction, and to determine its effects on SAQ angina, myocardial perfusion reserve and diastolic filling.  

The cross-over study included 128 patients (mean age, 55.2 years; 96% women) who received ranolazine and placebo for a short, 2-week exposure.

Co-primary outcomes were SAQ measured angina stability, angina frequency, and the SAQ-7 summary score. The secondary outcome was diary-measured angina.

Overall pill count compliance was 97%.

Primary end point results indicated that SAQ angina stability (P=.24), angina frequency (P=.97) and SAQ-7 score (P=.87) were comparable between ranolazine and placebo groups. Diary-measured angina episodes (P=.81) and Duke Activity Status Inventory (P=.49), a surrogate for functional capacity, were also similar, whereas the Health Insurance Study-General Well-Being depressed score was significantly improved in the ranolazine arm (P=.009).

In addition, compared with placebo, ranolazine reduced the stress heart rate (treatment change, -3.55; P<.0001) and stress rate pressure product (treatment change, -523; P=.01). Dr Bairey Merz said that these 2 findings were clinically meaningful and have not previously been described in humans.

However, there were no significant between-group differences in stress myocardial perfusion reserve index (P=.88), peak filling rate (PFR; P=.52) and time to PFR (P=.09)

“Short-term late sodium current blockade with ranolazine—known to be effective for effort angina in patients with obstructive CAD—did not significantly improve SAQ angina or myocardial perfusion index in subjects with no obstructive coronary disease but evidence of coronary microvascular dysfunction,” Dr Bairey Merz concluded.  “Changes in the SAQ and myocardial perfusion index were directly related, indicating that symptoms are related to myocardial perfusion index in these patients.”

Dr Bairey Merz added that angina and perfusion index improved in ranolazine-treated patients with lower baseline coronary flow reserve. “This is the population we would propose future clinical trials with novel and traditional anti-ischemic agents be tested,” she said.

Disclosures: Dr Bairey Merz has received research grant support from Gilead RWISE, and serves as a consultant/on the advisory board for Amgen, Gilead Sciences and Pfizer. The study was funded in part by Gilead Sciences.


  1. Bairey Merz CN. LBCT 04. Novel Therapies for Common Problems. RWISE A Randomized, Placebo Controlled Trial of Late Na Current Inhibition (ranolazine) in Coronary Microvascular Dysfunction: Impact on Angina and Myocardial Perfusion Reserve. Presented at: American Heart Association Scientific Sessions; November 7-11, 2015; Orlando, FL.