Ranolazine Improves Angina in Women With Evidence of Myocardial Ischemia But No Obstructive Coronary Artery Disease

Mehta, Puja K.; Goykhman, Pavel; Thomson, Louise; Shufelt, Chrisandra; Wei, Janet; Yang, Yuching; Gill, Edward; Minissian, Margo; Shaw, Leslee J.; Slomka, Piotr J.; Slivka, Melissa; Berman, Daniel S.; Merz, C. Noel Bairey

doi:10.1016/j.jcmg.2011.03.007

Cited by 187 publications

(112 citation statements)

References 34 publications

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“…One pilot study showed improved symptoms in women with angina, evidence of ischemia but no obstructive CAD, and patients with low CFR demonstrated improved CFR with treatment. 106 A similar-sized study showed some improvement in symptoms but no effect on coronary microvascular function. 107 A recent large randomized trial of a 2-week course of ranolazine vs. placebo found no difference in symptoms or myocardial perfusion reserve.…”

Section: Invasive Testingmentioning

confidence: 92%

Coronary Microvascular Dysfunction　― Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy ―

Chen

Wei

AlBadri

et al. 2017

Circ J

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Angina has traditionally been thought to be caused by obstructive coronary artery disease (CAD). However, a substantial number of patients with angina are found to not have obstructive CAD when undergoing coronary angiography. A significant proportion of these patients have coronary microvascular dysfunction (CMD), characterized by heightened sensitivity to vasoconstrictor stimuli and limited microvascular vasodilator capacity. With the advent of non-invasive and invasive techniques, the coronary microvasculature has been more extensively studied in the past 2 decades. CMD has been identified as a cause of cardiac ischemia, in addition to traditional atherosclerotic disease and vasospastic disease. CMD can occur alone or in the presence obstructive CAD. CMD shares many similar risk factors with macrovascular CAD. Diagnosis is achieved through detection of an attenuated response of coronary blood flow in response to vasodilatory agents. Imaging modalities such as cardiovascular magnetic resonance, positron emission tomography, and transthoracic Doppler echocardiography have become more widely used, but have not yet completely replaced the traditional intracoronary vasoreactivity testing. Treatment of CMD starts with lifestyle modification and risk factor control. The use of traditional antianginal, antiatherosclerotic medications and some novel agents may be beneficial; however, clinical trials are needed to assess the efficacy of the pharmacologic and non-pharmacologic therapeutic modalities. In addition, studies with longer-term follow-up are needed to determine the prognostic benefits of these agents. We review the epidemiology, prognosis, pathogenesis, diagnosis, risk factors and current therapies for CMD.

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Section: Invasive Testingmentioning

confidence: 92%

Coronary Microvascular Dysfunction　― Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy ―

Chen

Wei

AlBadri

et al. 2017

Circ J

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“…In addition, ranolazine might also improve coronary self-regulation 96 . A small trial with ranolazine suggested improvement of anginal symptoms in women with microvascular angina 97 . Subsequently, in a double-blind, placebo-controlled, crossover study conducted in women with effort angina but no obstructive coronary artery disease, ranolazine produced no significant benefits except in some patients with impaired coronary flow reserve 65 .…”

Section: Microvascular Anginamentioning

confidence: 99%

A 'diamond' approach to personalized treatment of angina

et al. 2017

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Chronic stable angina pectoris is the most prevalent symptomatic manifestation of ischaemic heart disease, and its management is a priority (BOX 1). Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revasculariza tion [1][2][3][4] . However, revascularization by either percutaneous coronary angioplasty or CABG surgery is indicated in patients who have significant artery steno sis (50% left main narrowing or proximal three-vessel disease) to reduce myocardial ischaemia and its adverse clinical manifestation. Antianginal agents are approved by documenting that they improve total exercise duration, together with a reduction in daily frequency of chronic stable angina compared with placebo and/or equivalence to an active comparator. Cardiovascular outcomes, although highly advocated, are not a pre requisite for regulatory approval. None of the antianginal drugs has been proved to reduce cardiovascular mortality or the rate of myocardial infarction. When patients are optimally treated, mortality for chronic stable angina is low, which might explain why all trials designed to improve prognosis have been negative. Guidelines recom mend a first-choice and a second-choice approach, based more on tradition and expert opinion, rather than evidence. This categorical approach has been questioned in the past couple of years 5-8 . Newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than is available for the traditional first-choice drugs. Equally, the often-needed combin ation of double or triple therapy is based on expert opinion and not related to the underlying pathophysio logy. What constitutes optimal antianginal treatment, therefore, varies considerably between countries, and the majority of doctors treat their patients according to their own preconceptions.A group of experts with experience and interest in chronic stable angina met at the University of Ferrara, Italy, to discuss an individualized approach to medical treatment of chronic stable angina, on the basis E X P E RT C O N S E N S U S D O C U M E N TA 'diamond' approach to personalized treatment of angina Abstract | In clinical guidelines, drugs for symptomatic angina are classified as being first choice (β-blockers, calcium-channel blockers, short-acting nitrates) or second choice (ivabradine, nicorandil, ranolazine, trimetazidine), with the recommendation to reserve second-choice medications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. No direct comparisons between first-choice and second-choice treatments have demonstrated the superiority of one group of drugs over the other. Meta-analyses show that all antianginal drugs have similar efficacy in reducing symptoms, but provide no evidence for improvement in survival. The newer, second-choice drugs have more evidence-based clinical data that are more contemporary than is available for tr...

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“…Additional benefit may be seen from agents with alpha-blockade, such as carvedilol, in patients with coronary spasm [24]. Recently, a pilot study of Ranolazine, an anti-anginal agent that reduces calcium flow in myocytes through inhibition of the late sodium current, has been shown to improve angina in women with evidence of ischemia but no obstructive CAD [25]. While there are no clinical trials regarding the role of nitrates in patients with MCD, at least observationally, their effects on angina frequency and duration can be unpredictable in these patients.…”

Section: Discussionmentioning

confidence: 99%

Microvascular Coronary Dysfunction in a Woman With Signs and Symptoms of Myocardial Ischemia but No Obstructive Coronary Artery Disease

Kahlon

2013

J Med Cases

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Women with signs and symptoms of myocardial ischemia often have no obstructive coronary artery disease by invasive coronary angiography when compared to men. Microvascular coronary dysfunction (MCD) is thought to be a key contributory mechanism for myocardial ischemia in women with chest pain and no obstructive CAD. We report a case of a 53-year-old post-menopausal female with hyperlipidemia evaluated for persistent chest pain following a non-ST elevation myocardial infarction (NSTEMI) and no obstructive CAD by coronary angiography. Vital signs and physical examination were within normal limits. Prior EKG showed diffuse abnormal T wave inversion and flattening in anterior and inferior leads. Echocardiography demonstrated an ejection fraction of 72% with no regional wall motion abnormalities. Laboratory values revealed a positive heterozygote factor V Leiden mutation. Given the constellation of persistent chest pain, no obstructive CAD, and prior NSTEMI, a diagnosis of MCD was suspected and she underwent coronary reactivity testing (CRT) with intracoronary infusions of adenosine, acetylcholine, and nitroglycerin to test non-endothelial and endothelial dependent, micro-and macrovascular coronary function. CRT results were consistent with a diagnosis of MCD. A statin and angiotensin converting enzyme inhibitor was added to her existing treatment of beta-blocker and nitrates. Additionally, she was started on warfarin therapy due to a positive factor V Leiden in the setting of prior NSTEMI. Her symptoms improved at one-month follow-up and she is currently asymptomatic by selfreport. In women with signs and symptoms of myocardial ischemia and no obstructive CAD, it is important to identify and diagnose MCD, as inadequate diagnosis is associated with an increased risk of adverse cardiovascular events including myocardial infarction, congestive heart failure, and sudden cardiac death. Identification of MCD and clinical awareness are vital for optimal medical therapy and reduced CVD risk. Clinical trials testing efficacy of traditional and novel interventions are needed in MCD populations.

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Ranolazine Improves Angina in Women With Evidence of Myocardial Ischemia But No Obstructive Coronary Artery Disease

Cited by 187 publications

References 34 publications

Coronary Microvascular Dysfunction　― Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy ―

Coronary Microvascular Dysfunction　― Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy ―

A 'diamond' approach to personalized treatment of angina

Microvascular Coronary Dysfunction in a Woman With Signs and Symptoms of Myocardial Ischemia but No Obstructive Coronary Artery Disease

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Ranolazine Improves Angina in Women With Evidence of Myocardial Ischemia But No Obstructive Coronary Artery Disease

Cited by 187 publications

References 34 publications

Coronary Microvascular Dysfunction ― Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy ―

Coronary Microvascular Dysfunction ― Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy ―

A 'diamond' approach to personalized treatment of angina

Microvascular Coronary Dysfunction in a Woman With Signs and Symptoms of Myocardial Ischemia but No Obstructive Coronary Artery Disease

Contact Info

Product

Resources

About

Coronary Microvascular Dysfunction　― Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy ―

Coronary Microvascular Dysfunction　― Epidemiology, Pathogenesis, Prognosis, Diagnosis, Risk Factors and Therapy ―