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RWISE: By most metrics, ranolazine fails to benefit patients with microvascular dysfunction
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ORLANDO, Fla. — Ranolazine did not affect angina or myocardial perfusion in patients with coronary microvascular dysfunction, according to data presented at the American Heart Association Scientific Sessions.
Researchers conducted the RWISE study to test the effects of short-term late sodium current inhibition via ranolazine (Ranexa, Gilead Sciences), a drug known to improve angina in patients with obstructive CAD, in 142 patients (mean age, 55 years; 96% women) with symptoms and evidence of coronary microvascular dysfunction and no evidence of obstructive CAD.
C. Noel Bairey Merz
All patients had symptoms thought to be related to ischemia, less than 50% epicardial coronary stenosis, and abnormal coronary flow reserve (< 2.5) or no dilation with acetylcholine or abnormal stress myocardial perfusion index (< 2), C. Noel Bairey Merz, MD, FACC, FAHA, the Women’s Guild Endowed Chair in Women’s Health; director of the Barbra Streisand Women’s Heart Center; director of the Linda Joy Pollin Women’s Heart Health Program; director of the Preventive Cardiac Center; and professor of medicine at Cedars-Sinai Medical Center, said during a press conference.
“The mechanistic pathways for [coronary microvascular dysfunction] with no obstructive CAD are not well-defined,” said Bairey Merz, a member of the Cardiology Today Editorial Board. “Large outcome trials are lacking and treatment guidelines absent.”
Patients were randomly assigned ranolazine or placebo for 2 weeks, and then after a washout period, patients were crossed over to the other therapy for 2 weeks, Bairey Merz said.
The primary outcomes were angina stability and frequency as measured by the Seattle Angina Questionnaire (SAQ) and SAQ-7 questionnaire score.
Compared with placebo, there was no significant difference associated with ranolazine in SAQ angina stability (treatment change, 5.12; P = .24), SAQ angina frequency (treatment change, 0.08; P = .97) or SAQ-7 score (treatment change, 1.31; P = .87), Bairey Merz said.
There also was no significant difference in angina episodes as documented by diary entry (treatment change, –0.1; P = .81) or in Duke Activity Status Inventory (treatment change, 0.31; P = .49), but ranolazine assignment was associated with improvement in depressive symptoms as measured by the Health Insurance Study–General Well-Being score (treatment change, 0.2; P = .009), according to results reported.
Ranolazine was associated with decreases in stress heart rate (treatment change, –3.55; P < .0001) and stress rate pressure product (treatment change, –523; P = .01) but did not affect stress myocardial perfusion reserve index, stress myocardial perfusion reserve index–mid subendocardial, peak filling rate or time to peak filling rate, she said.
“Notably, we observed for the first time in humans an apparent ranolazine effect on pharmacologic stress heart rate and weighted rate pressure product,” Bairey Merz said.
She added that researchers detected a “mild but quite robust” relationship between angina and myocardial perfusion reserve.
In a prespecified subgroup analysis, patients with low coronary flow reserve had greater change in mid-ventricular myocardial perfusion reserve index on ranolazine vs. on placebo, according to Bairey Merz. “Those with more severe flow abnormalities at entry were more statistically significantly improved,” she said. – by Erik Swain
Reference:
Bairey Merz CN, et al. Late-Breaking Clinical Trials 4. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.
Disclosure: The study was an investigator-initiated ancillary trial to the NHLBI-sponsored WISE study and was funded in part by Gilead Sciences. Bairey Merz reports consulting or serving on an advisory board for Amgen, Gilead Sciences, Medscape, Pfizer and Scripps, receiving a research grant from Gilead Sciences, and speaking for Practice Point Communications, Pri-Med and Vox Media.
Perspective
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Sidney C. Smith Jr., MD, FACC, FAHA, FESC
This was an important study because we learned from WISE that coronary microvascular dysfunction is a prevalent problem in women. But I was a little surprised and somewhat disappointed that we did not see a greater amount of symptomatic relief. I did not see any significant benefits associated with ranolazine in these patients. We need to look at some other agents. Coronary microvascular dysfunction clearly is a problem in women and carries with it a prognosis that is not as good as one would hope.
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