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

Disclosures

Eur Heart J. 2015;35(48):3426-3433. 

In This Article

Results

There were 1240 patients (25.4%) in Group A (no history of angina and no chest pain at baseline), 1353 (27.7%) in Group B (history of angina but no chest pain), and 2285 (46.8%) in Group C (history of angina and chest pain at baseline). In Group C, 27% of patients described chest pain on heavy exertion, 49% on moderate exertion, 20% on slight exertion, and 4% at rest.

Baseline Characteristics

Baseline characteristics stratified by groups are presented in Table 1.

Comparison of Groups A and B. When patients with no history of angina or chest pain were compared with those with a history of angina and no chest pain, the main differences were in previous MI (Group A 49% vs. Group B 70%, respectively), CABG (8 vs. 32%) and PCI (9 vs. 17%). Other characteristics including age, sex, and LVEF were similar although more patients in Group A had a history of atrial fibrillation/flutter (28 vs. 22%).

Comparison of Groups A and C. More differences were noted when patients with no history of angina or chest pain were compared with those with a history of angina and chest pain. These included differences in proportion of women (Group A 20% vs. Group C 27%), proportion in NYHA class III/IV (54 vs. 71%), current smoking (10 vs. 7%); history of MI/CABG/PCI (49/8/9 vs. 60/17/10%), hypertension (57 vs. 71%), and baseline atrial fibrillation/flutter (28 vs. 22%). Patients in Group A also had a slightly but significantly lower LVEF (30 vs. 32%) and BMI (27 vs. 28 kg/m[2]) than those in Group C, as well as a higher serum creatinine (117 vs. 113 μmol/L) and baseline NT-proBNP (193 vs. 151 pmol/L).

Comparison of Groups B and C. The most notable differences between patients with a history of angina and no chest pain and those with a history of angina and chest pain were in proportion of women (20 vs. 27%), proportion in NYHA functional class III/IV (58 vs. 71%), LVEF (30 vs. 32%), history of MI/CABG/PCI (70/32/17 vs. 60/17/10%), hypertension (57 vs. 71%), serum creatinine (118 vs. 113 μmol/L), and NT-proBNP (187 vs. 151 pmol/L).

In addition to the above findings, patients in Group C had the lowest use of anti-arrhythmic and anti-coagulant drugs and the lowest rate of smoking; they had the highest prevalence of diabetes, the highest use of nitrates and highest systolic BP and LVEF.

Patients in Group A had the lowest use of beta-blockers and antiplatelet agents, highest prevalence of atrial fibrillation/flutter, highest use of digitalis glycosides, anti-arrhythmic drugs, and anti-coagulants, and highest NT-proBNP.

Clinical outcomes

Coronary Outcomes. The rate of all three coronary composite outcomes was higher in patients with a history of angina and chest pain at baseline (Group C), compared with patients with neither a history of angina nor chest pain (Group A), as shown in Table 2 and Figure 1. However, only the risk of the composites of MI or UA and MI, UA or coronary revascularization were increased significantly, with an approximate doubling of each in the unadjusted analyses for patients in Group C vs. A. This increase in risk persisted after adjustment for other prognostic variables. Patients in Group B had rates of these two outcomes intermediate between those in Group A and C, with a 50–90% increase in risk compared with Group A.

Figure 1.

Relationship between history of angina, current chest pain and coronary outcomes. (A) Composite coronary outcome of sudden death, fatal or non-fatal myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, ventricular defibrillation by implantable cardioverter defibrillator, resuscitation after cardiac arrest or hospitalization for unstable angina (Kaplan–Meier). (B) Composite of non-fatal myocardial infarction, unstable angina, percutaneous coronary intervention, or coronary artery bypass graft surgery (cumulative incidence function). (C) Composite of non-fatal myocardial infarction and unstable angina (cumulative incidence function). CR, competing risk.

Heart Failure Outcomes. The risk of the composite of CV death or HF hospitalization was increased in Group C, but not in Group B, when compared with Group A (Table 2 and Figure 2). Examination of the components of this composite also showed no increase in risk of CV death in Groups B and C. However, patients with a history of angina and chest pain at baseline (Group C), had a modestly increased risk of HF hospitalization in the adjusted analyses [HR 1.35 (1.13–1.63); P = 0.001)], compared with patients with neither a history of angina or chest pain (Group A). A similar trend was seen when Group B was compared with Group A but the increase in risk was not statistically significant (Table 2 and Figure 2).

Figure 2.

Relationship between history of angina, current chest pain and heart failure outcomes, as well as all-cause death. (A) Composite of cardiovascular death or hospitalization for heart failure (Kaplan–Meier). (B) Cardiovascular death (C) Hospitalization for heart failure (cumulative incidence function) (D) All-cause death (Kaplan–Meier). CR, competing risk.

All-cause Mortality

There was no difference in the risk of death between the three groups of patients (Table 2 and Figure 2).

Similar findings were also obtained when the relationship between current chest pain, irrespective of history of angina, and outcomes was analysed (Supplementary material online, appendix http://eurheartj.oxfordjournals.org/content/suppl/2014/09/28/ehu342.DC1). Finally, analysis of the association between chest pain and outcomes with chest pain entered as a time-updated covariate in a Cox model also gave similar outcomes (Supplementary material online, appendix http://eurheartj.oxfordjournals.org/content/suppl/2014/09/28/ehu342.DC1).

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