Current and Future Treatment Strategies for Refractory Angina

doi:10.4065/79.10.1284

Mayo Clinic Proceedings

Volume 79, Issue 10, October 2004, Pages 1284-1292

https://doi.org/10.4065/79.10.1284 Get rights and content

Patients with refractory angina are not candidates for revascularization and have both class III or IV angina and objective evidence of ischemia despite optimal medical therapy. An estimated 300,000 to 900,000 patients in the United States have refractory angina, and 25,000 to 75,000 new cases are diagnosed each year. This review focuses on treatment strategies for refractory angina and includes the mechanism of action and clinical trial data for each strategy. The pharmacological agents that have been used are ranolazine, ivabradine, nicorandil, L-arginine, testosterone, and estrogen; currently, only L-arginine, testosterone, and estrogen are approved by the Food and Drug Administration. Results with the noninvasive treatments of enhanced external counterpulsation and transcutaneous electrical nerve stimulation are provided. Invasive treatment strategies including spinal cord stimulation, transmyocardial revascularization, percutaneous myocardial revascularization, and gene therapy are also reviewed.

Section snippets

Optimal Standard Therapy

Angina is the result of myocardial ischemia that occurs when the supply of oxygen is unable to meet the demand. Treatment strategies focus on decreasing oxygen demand and/or increasing the supply. The standard treatment for symptomatic relief in patients with chronic stable angina should include β-blockers and/or non–dihydropyridine calcium channel blockers titrated to the lowest heart rate and blood pressure level tolerated. In addition, a long-acting nitrate should be given with use of an

Enhanced External Counterpulsation

Enhanced external counterpulsation (EECP) is based on the concept of counterpulsation and consists of 3 pairs of pneumatic cuffs placed around the lower extremities at the calves, lower thighs, and upper thighs (Figure 1). An electrocardiographic trigger is used to sequentially inflate the cuffs, starting at the calves, during onset of diastole and simultaneously deflate all cuffs before onset of systole. A standard course of EECP therapy consists of 35 one-hour sessions during a 7-week period.

Spinal Cord Stimulation

Spinal cord stimulation (SCS) is similar to TENS in concept and consists of 3 components: an epidural lead, an extension wire, and a pulse generator (Figure 2). The epidural lead is placed in the epidural space at the level of C7 through T1, and the pacemaker-sized generator is surgically implanted in the left lower abdominal area. Patients receive 3 one-hour stimulations a day and can activate the device with a handheld magnet to treat episodes of breakthrough pain. It is believed that SCS

CONCLUSION

Refractory angina is a difficult clinical condition that is growing in prevalence. Current treatment options for refractory angina can be classified into 3 groups: pharmacological, nonpharmacological noninvasive, and invasive. Although none of these therapies have been shown to improve mortality, some improve symptoms and quality of life. At this time, L-arginine, testosterone, estrogen, EECP, TENS, SCS, and TMR are the only treatments that are FDA approved. Currently, EECP is the most widely

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Baseline Left Ventricle Longitudinal Strain as a Predictor for Clinical Improvement Following Coronary Sinus Reducer Implantation
2023, American Journal of Cardiology
Coronary sinus narrowing device (reducer) implantation has emerged as an effective treatment to improve the quality of life and functional capacity in patients suffering from disabling refractory angina. Left ventricle global longitudinal strain (LV-GLS) is a useful tool for early diagnosis of subclinical cardiac injury and an independent predictor for coronary artery disease. We aimed to investigate whether LV-GLS could help predict clinical improvement after coronary sinus reducer implantation. LV-GLS assessments were performed at baseline and 6 months after reducer implantation in consecutive patients treated for refractory angina. Patients were divided into 2 groups based on reduced (<17% absolute value) or preserved baseline LV-GLS. Clinical improvement was defined as an increase of ≥25 m in the 6-minute walk test (6MWT) at follow-up. Overall, 41 patients were included, 31 in the reduced LV-GLS group and 10 in the preserved LV-GLS group. The mean age was 68 ± 8 years, with only 2 female patients (5%). Baseline characteristics did not differ significantly between the 2 groups. Univariable analysis revealed that LV-GLS was the only significant predictor for 6MWT improvement. Baseline preserved LV-GLS reduced the likelihood of 6MWT improvement by 82% (odds ratio 0.18 [0.04 to 0.83], p = 0.029). A significant increase in 6MWT (307 ± 97 m to 343 ± 92 m, p = 0.017) was observed in the reduced LV-GLS group, compared with a decrease in the preserved LV-GLS group (378 ± 86 m to 361 ± 123 m, p = 0.651). In conclusion, reduced LV-GLS may serve as a marker for potential clinical improvement in patients with refractory angina treated with reducer. Larger clinical trials are needed to establish its role.
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Effect of long-term thoracic epidural analgesia on refractory angina pectoris: A 10-year experience
2012, Journal of Cardiothoracic and Vascular Anesthesia
In patients with refractory angina, the adjuvant effects of long-term home self-treatment with thoracic epidural analgesia on angina, quality of life, and safety were evaluated.
A prospective, consecutive study.
A university hospital.
Between January 1998 and August 2007, 152 consecutive patients with refractory angina began treatment with thoracic epidural analgesia by intermittent injections of bupivacaine (139 home treatment and 13 palliative). Data were collected until August 2008; therefore, the follow-up for each patient was between 1 and 9 years.
All but 7 of the patients improved symptomatically, and the improvement was maintained throughout the period of treatment (median = 19 months; range, 1 month-8.9 years). After 1 to 2 weeks, the median (interquartile range [IQR]) Canadian Cardiovascular Society angina class decreased from 4.0 (3.0-4.0) to 2.0 (1.0-2.0), the mean ± standard deviation frequency of anginal attacks decreased from 36 ± 19 to 4.4 ± 6.8 a week, the nitroglycerin intake decreased from 27.7 ± 15.7 to 2.7 ± 4.9 a week, and the median (IQR) overall self-rated quality of life assessed by the visual analog scale increased from 25 (20-30) to 70 (50-75) (all p < 0.001). About one-third of the patients had a dislodgement of the epidural catheter. Apart from 1 epidural hematoma that appeared in 1 patient with a previously undiagnosed bleeding defect, no other serious catheter-related complications occurred.
Long-term self-administered home treatment with thoracic epidural analgesia is a safe, widely available adjuvant treatment for patients with severe refractory angina. It produces symptomatic relief of angina and improves quality of life. The technical development of the method to protect the catheter against dislodgement is needed.
Therapeutic goals in patients with refractory chronic angina
2010, Revista Espanola de Cardiologia
La angina refractaria constituye un importante reto clínico para la medicina actual. A pesar del amplio uso de las estatinas y del perfeccionamiento de las técnicas de revascularización, una parte importante de los pacientes con una función ventricular izquierda preservada y sin arritmias con peligro para la vida continúan presentando síntomas, con una angina grave debilitante. Dado que las tasas de eventos cardiacos mayores en esa población son relativamente bajas, las metas principales del tratamiento deben ser no sólo la prolongación de la supervivencia, sino también la mejora de la calidad de vida. La modificación enérgica de los factores de riesgo mediante tratamientos basados en la evidencia, con objeto de estabilizar el proceso de la enfermedad y mejorar la supervivencia, debe constituir el tratamiento de base en todos estos pacientes. No deben pasarse por alto las posibilidades de revascularización. Deben aplicarse estrategias complementarias para elevar el umbral anginoso, ya sea mediante la reducción de la demanda de oxígeno, ya mediante la mejora de la hemodinámica para aumentar el aporte de oxígeno miocárdico. En esta revisión se presenta una actualización sobre las estrategias y las metas terapéuticas y se resalta la necesidad de un enfoque multidisciplinario del tratamiento de los pacientes con angina refractaria.
Refractory angina presents a major clinical challenge for everyday medical practice. Despite the widespread use of statins and improvements in revascularization techniques, a substantial proportion of patients with preserved left ventricular function and no life-threatening arrhythmias remain symptomatic, with severe debilitating angina. Because the rate of major cardiac events in this population is relatively low, the major aim of therapy should be not only to prolong survival but also to improve quality of life. The cornerstone of therapy for all these patients should be the aggressive modification of risk factors using evidencebased treatment, with the aim of stabilizing the disease process and improving overall survival. No opportunity for revascularization should be overlooked. Complementary approaches should be implemented to raise the angina threshold by either reducing oxygen demand or improving hemodynamics to increase myocardial oxygen supply. This review provides an update on therapeutic techniques and goals, and reinforces the need for a multidisciplinary approach to the management of patients with refractory angina.
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ReviewCurrent and Future Treatment Strategies for Refractory Angina

Section snippets

Optimal Standard Therapy

Enhanced External Counterpulsation

Spinal Cord Stimulation

CONCLUSION

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Pain

Am J Cardiol

Am Heart J

J Am Coll Cardiol

Am Heart J

Am J Cardiol

J Thorac Surg

Lancet

Lancet

J Am Coll Cardiol

Ann Thorac Surg

J Am Coll Cardiol

J Thorac Cardiovasc Surg

Lancet

J Am Coll Cardiol

Am J Cardiol

Lancet

Am J Cardiol

J Am Coll Cardiol

The problem of chronic refractory angina: report from the ESC Joint Study Group on the Treatment of Refractory Angina

Eur Heart J

Plan and operation of the Third National Health and Nutrition Examination Survey, 1988-94. Series 1: programs and collection procedures

Vital Health Stat 1

Ranolazine: a potential new treatment for chronic stable angina

Heart Dis

Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial

JAMA

Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells

Br J Pharmacol

Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial

Circulation

Nicorandil: an updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects

Drugs

A comparison of nicorandil with isosorbide mononitrate in elderly patients with stable coronary heart disease: the SNAPE study

Am Heart J

A double-blind comparison of nicorandil and metoprolol in stable effort angina pectoris

Cardiovasc Drugs Ther

Efficacy of nicorandil versus propranolol in mild stable angina pectoris of effort: a long-term, double-blind, randomized study

J Cardiovasc Pharmacol

A double-blind comparison of a beta-blocker and a potassium channel opener in exercise induced angina

Eur Heart J

Evaluation of the efficacy of nicorandil in patients with ischemic heart disease by exercise Tl-201 myocardial SPECT

Int J Clin Pharmacol Ther

Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial [published correction appears in Lancet. 2002;360:806]

Lancet

Effects of L-arginine supplementation on endothelium-dependent coronary vasodilation in patients with angina pectoris and normal coronary arteriograms

Circulation

Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo

Circulation

Review
Current and Future Treatment Strategies for Refractory Angina