Clinical characteristics and prognosis of patients with angina pectoris and heart failure

Although coronary artery disease (CAD) is a leading cause of both angina pectoris and Heart Failure (HF), little is known of the relationship between these two conditions. This is the focus of my thesis. Chapter one gives an overview of these two clinical conditions and presents the findings of a literature review examining the prognostic importance of angina in HF. Subsequent chapters present the results of a series of retrospective analyses, using data collected from large randomized controlled trials. In the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) 4878 patients with Heart Failure and Reduced Ejection Fraction (HF-REF) were divided into three groups according to their history of angina. Patients with past and current angina were compared with a reference group of patients with no angina. Current angina was strongly associated with greater functional limitation despite an absence of clinical features of worsening HF. Current angina was also associated with a higher risk of acute coronary syndrome (ACS) but all cause mortality was similar to patients with no angina. Patients with past angina were also at higher risk of ACS but the association was not as strong as in patients with current angina. In CHARM (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity) I sought to validate the findings of CORONA whilst also investigating the importance of angina in patients with Heart Failure and Preserved Ejection Fraction (HF-PEF). CHARM enrolled 7599 patients with HF into three discrete trials according to left ventricular ejection fraction (LVEF) and angiotensin converting enzyme inhibitor (ACEI) use: CHARM-Preserved (LVEF > 40%), CHARM-Added (LVEF ≤40% receiving ACE inhibitor treatment) and CHARM-Alternative (LVEF ≤40% not receiving an ACE inhibitor due to intolerance). As in CORONA, in CHARM patients with current angina and HF-REF were more likely to experience greater function limitation and were at higher risk of ACS than patients with no angina. In CHARM I was also able to demonstrate a similar trend in patients with HF-PEF and current angina. Investigators in the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-Preserve) study did not distinguish between past and current angina. Therefore this analysis examined the prognostic importance of a history of CAD and angina in 4128 patients with HF-PEF. The most important finding from this study was the higher risk of sudden death and all-cause mortality in patients with HF-PEF and a history of CAD. This association was present irrespective of whether or not patients had a history of angina pectoris. In the Prospective comparison of Angiotensin Receptor-Neprilysin Inhibitor with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) 8442 patients with CAD and HF-REF were categorized into four groups according to severity of angina. There was a stepwise increase in functional limitation with worsening severity of angina. When compared with patients with no angina, patients with severe angina were also at significantly higher risk of fatal and non-fatal outcomes including all-cause death. These analyses highlight the importance of angina symptoms on functional class and prognosis in patients with HF. Identification of high-risk groups could guide future treatment strategies. More specifically there may be the potential for coronary revascularization or pharmacotherapy to improve outcomes in these subgroups but such strategies need to be tested in prospective randomised controlled trials.