TY - JOUR
T1 - A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD)
T2 - Impact on angina and myocardial perfusion reserve
AU - Merz, C. Noel Bairey
AU - Handberg, Eileen M.
AU - Shufelt, Chrisandra L.
AU - Mehta, Puja K.
AU - Minissian, Margo B.
AU - Wei, Janet
AU - Thomson, Louise E.J.
AU - Berman, Daniel S.
AU - Shaw, Leslee J.
AU - Petersen, John W.
AU - Brown, Garrett H.
AU - Anderson, R. David
AU - Shuster, Jonathan J.
AU - Cook-Wiens, Galen
AU - Rogatko, Andre
AU - Pepine, Carl J.
N1 - Publisher Copyright:
© 2015 The Author 2015.
PY - 2016/5/14
Y1 - 2016/5/14
N2 - Aims The mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling. Materials and results Randomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041). Conclusions In this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects. Trial registration clinicaltrials.gov Identifier: NCT01342029.
AB - Aims The mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling. Materials and results Randomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041). Conclusions In this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects. Trial registration clinicaltrials.gov Identifier: NCT01342029.
KW - Eosinophils
KW - Histopathology
KW - Neutrophil extracellular traps
KW - Neutrophils
KW - Platelets
KW - Stent thrombosis
KW - Thrombus aspiration
UR - http://www.scopus.com/inward/record.url?scp=84975727145&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehv647
DO - 10.1093/eurheartj/ehv647
M3 - Article
C2 - 26614823
AN - SCOPUS:84975727145
SN - 0195-668X
VL - 37
SP - 1504
EP - 1513
JO - European Heart Journal
JF - European Heart Journal
IS - 19
ER -