Relationship Between Angina Pectoris and Outcomes in Patients With Heart Failure and Reduced Ejection Fraction

An Analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)

Athar A. Badar; Ana Cristina Perez-Moreno; Pardeep S. Jhund; Chih M. Wong; Nathaniel M. Hawkins; John G.F. Cleland; Dirk J. van Veldhuisen; John Wikstrand; John Kjekshus; Hans Wedel; Stuart Watkins; Roy S. Gardner; Mark C. Petrie; John J.V. McMurray


Eur Heart J. 2015;35(48):3426-3433. 

In This Article

Abstract and Introduction


Aim Angina pectoris is common in patients with heart failure and reduced ejection fraction (HF-REF) but its relationship with outcomes has not been well defined. This relationship was investigated further in a retrospective analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA).

Methods and results Four thousand, eight hundred and seventy-eight patients were divided into three categories: no history of angina and no chest pain at baseline (Group A; n = 1240), past history of angina but no chest pain at baseline (Group B; n = 1353) and both a history of angina and chest pain at baseline (Group C; n = 2285). Outcomes were examined using Kaplan–Meier and Cox regression survival analysis. Compared with Group A, Group C had a higher risk of non-fatal myocardial infarction or unstable angina (HR: 2.36, 1.54–3.61; P < 0.001), this composite plus coronary revascularization (HR: 2.54, 1.76–3.68; P < 0.001), as well as HF hospitalization (HR: 1.35, 1.13–1.63; P = 0.001), over a median follow-up period of 33 months. There was no difference in cardiovascular or all-cause mortality. Group B had a smaller increase in risk of coronary events but not of heart failure hospitalization.

Conclusion Patients with HF-REF and ongoing angina are at an increased risk of acute coronary syndrome and HF hospitalization. Whether these patients would benefit from more aggressive medical therapy or percutaneous revascularization is not known and merits further investigation.


Although the cause of chronic heart failure (HF) with reduced ejection fraction (HF-REF) is attributed to coronary artery disease (CAD) in approximately two-thirds of patients in the developed world, little is known about symptomatic myocardial ischaemia in these individuals.[1,2] While many trials have reported past history of myocardial infarction (MI), revascularization, and angina pectoris at baseline, few described whether patients had current angina symptoms at the time of randomization. One exception was CHARM where 65% of patients with HF-REF had an investigator-reported ischaemic aetiology, 49% a past history of angina but only 21% current angina. In COMET, the overall prevalence of ischaemic heart disease was 53% and current angina was reported in 22% of patients.[3,4]

Similarly, previous reports on the relationship between CAD and prognosis in HF-REF have focused on ischaemic aetiology or history of ischaemic heart disease without distinguishing between patients with current symptoms and those without, with one exception.[5] The presence of angina pectoris may indicate an area of viable myocardium susceptible to infarction thereby placing a patient with an already low left ventricular ejection fraction (LVEF) at risk of further reduction in systolic function, worsening HF and death from pump failure. Myocardial ischaemia without infarction might have similar adverse consequences. Likewise, infarction (and ischaemia) may lead to ventricular arrhythmias and the risk of sudden death in such vulnerable patients. Accordingly, in this post hoc analysis we have examined the relationship between current angina symptoms and outcomes in patients enrolled in CORONA, all of which had an ischaemic aetiology.[6]