Sequencing of medical therapy in heart failure with a reduced ejection fraction

The management of heart failure with a reduced ejection fraction is a true success story of modern medicine. Evidence from randomised clinical trials provides the basis for an extensive catalogue of disease-modifying drug treatments that improve both symptoms and survival. These treatments have undergone rigorous scrutiny by licensing and guideline development bodies to make them eligible for clinical use. With an increasing number of drug therapies however, it has become a complex management challenge to ensure patients receive these treatments in a timely fashion and at recommended doses. The tragedy is that, for a condition with many life-prolonging drug therapies, there remains a potentially avoidable mortality risk associated with delayed treatment. Heart failure therapeutic agents have conventionally been administered to patients in the chronological order they were tested in clinical trials, in line with the aggregate benefit observed when added to existing background treatment. We review the evidence for simultaneous expedited initiation of these disease-modifying drug therapies and how these strategies may focus the heart failure clinician on a time-defined smart goal of drug titration, while catering for patient individuality. We highlight the need for adequate staffing levels, especially heart failure nurse specialists and pharmacists, in a structure to provide the capacity to deliver this care. Finally, we propose a heart failure clinic titration schedule and novel practical treatment score which, if applied at each heart failure patient contact, could tackle treatment inertia by a constant assessment of attainment of optimal medical therapy.</p

A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina

Background: Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown. Methods: We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina. Results: A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group. Conclusions: Among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others.</p