Expert Review: Coronary Artery Disease

Ranolazine reduces patient-reported angina severity and frequency and improves quality of life in selected patients with chronic angina

Background and objectives:

Coronary heart disease (CHD) is the most common cause of death (and premature death) in the United Kingdom (UK) with 94,000 deaths from CHD in the UK each year (1 in 5 men and 1 in 7 women die from CHD). There are about 52,000 new cases of angina per year in men and about 43,000 new cases in women1,2. Of note, although mortality from CHD is falling, morbidity appears to be rising. Chronic stable angina is a negative predictor of quality of life (QoL) in many patients with CHD3-5, with a high burden on the healthcare system. Mortality reduction is fastest in those aged 55 years and over. This is largely due to a reduction in major risk factors (mostly smoking) and improvement in treatment and secondary prevention. Therefore, management of angina aims to improve prognosis and reduce symptoms.
The antianginal drugs recommended for initial treatment are β blockers and calcium channel blockers, which reduce myocardial ischaemia by heart rate reduction and vasodilatory mechanisms, respectively. Either or both of these drug classes should be prescribed, together with a short acting nitrate for prompt alleviation of angina attacks. The 2013 European guidelines on stable coronary artery disease recommend adding long-acting nitrates, ivabradine, nicorandil, ranolazine (class IIa), or trimetazidine (class IIb) for second-line treatment. Although these new anti-anginal agents have been proved useful to better control the symptoms, little is known regarding their impact of QoL over long treatment durations.
The aim of the study was to evaluate the effect of long-term (up to >4 years) impact in terms of self-perception of QoL, severity and frequency of angina episodes in individuals with chronic stable angina treated with ranolazine.

Methods
Prospective observational study from a large UK centre patient survey of individuals with chronic stable angina who had not undergone revascularization and who were prescribed and remained on ranolazine. Assessment was based on their perceptions of angina prior to ranolazine initiation (based on recall of previous experience) and during ranolazine treatment. These perceptions included self-reported angina severity, frequency, impact on daily activities and QoL. Angina severity was rated using a 7-point Likert scale (where 1 = extremely mild and 7 = extremely severe). Change in QoL was assessed using the Patient Global Impression of Change scale.

Results
A total of 399 patients completed the survey (respondents); 92 (23%) had not undergone revascularization and constituted the study population. Most of them were female (64 %), were already on antianginal treatment (76%) and had taken ranolazine for ≥6 months (89 %); mean age was 64 years and the most frequent comorbidity was high blood pressure (71%). Before ranolazine treatment, the majority of respondents reported higher scores for angina severity (54%) and frequency of angina episodes (82% ≥1 angina attack/week). On the contrary, while on ranolazine, most respondents selected lower scores of severity (68%) and fewer angina episodes (73% <1 attack/). The effect of angina on daily activities was less while taking ranolazine than before ranolazine treatment; 52 and 8 % of respondents, respectively, reported significant impact, and 12 and 67 %, respectively, reported little/no impact. Noticeably improvement in angina-related QoL was experienced by most respondents (79 %) while taking ranolazine.

Conclusion
Substantial self-reported improvements in angina severity, frequency, and QoL are seen in patients with chronic stable angina who maintain ranolazine treatment for durations ranging from <6 months to >4 years.

Clinical Impact:
The self-reported improvement in QoL, angina frequency, and angina severity of respondents with chronic angina who did not have a history of revascularization and initiated therapy with ranolazine raises two important messages:
1.-Ranolazine can be used as initial anti-anginal therapy (particularly in situations where there is a contraindication to traditional anti-angina medications, or a concern about decreases in blood pressure or heart rate), or as add-on therapy to nitrates, b-blockers and calcium channel blockers.
2.-The improvements in QoL and severity of angina attacks reported by respondents on ranolazine in the present survey reflect the efficacy of outcomes tools such as the angina questionnaire used to assess QoL in patients with chronic stable angina.

Corresponding author from original paper
Joseph B. Muhlestein. Intermountain Medical Center, 5121 S. Cottonwood Street, Murray, UT 84107 USA. Gilead Sciences, Inc, Foster City, CA USA
Phone: +1-801-5074760, Fax: +1-801-5074792,
Email:brent.muhlestein@imail.org

References
1.- Coronary Heart Disease Statistics 2010, British Heart Foundation
2.-Mikhail GW; Coronary heart disease in women. BMJ. 2005;331(7515):467-8.
3.-Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6–245.

Citation: Muhlestein JB, Grehan S. Ranolazine reduces patient-reported angina severity and frequency and improves quality of life in selected patients with chronic angina. Drugs R D. 2013;13(3):207-13.

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