Lead Investigator: Stuart Pocock, London School of Hygiene and Tropical Medicine
Title of Proposal Research: Patterns of heart failure hospitalisations and cardiovascular death in EMPEROR studies
Vivli Data Request: 8946
Funding Source: None
Potential Conflicts of Interest: Stuart Pocock has served on the trial management committee for the EMPEROR trials and received personal fees from Boehringer (and other pharmaceutical companies).
We will mitigate this by declaring all conflicts of interest for all work in any published work or conference presentations that result from this work.
John Gregson has received personal fees from Boehringer for working on the EMPEROR studies.
Various other funding from pharmaceutical industry (none relevant to proposed research here).
We will mitigate this by declaring all conflicts of interest for all work in any published work or conference presentations that result from this work.
Dr. Hazelwinkel reports: Various research funding from pharmaceutical industry-will be declared on conflict of interest forms.
Summary of the Proposed Research:
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms, caused by an impairment of the heart’s blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, and leg swelling.
The global burden of heart failure is huge. In the United States, heart failure affects 5.8 million people, and each year 550,000 new cases are diagnosed. In 2011, heart failure was the most common reason for hospitalization for adults aged 85 years and older, and the second-most common for adults aged 65–84 years. An estimated one in five adults at age 40 will develop heart failure during their remaining lifetimes and about half of people who develop heart failure die within 5 years of diagnosis.
The aim of the current project is to improve statistical methods for the analysis of heart failure trials.
Traditionally trials in heart failure have used time to an event happening as the main outcome of the trial. In trials in heart failure this will often be the time until the first heart failure hospitalisation or cardiovascular death (whichever occurs first).
But recently there has been a trend in trials to make use of a not only the first event, but also recurrent events (those after the first). For example, if a person dies sometime after a heart failure hospitalisation, this event is ignored in an analysis of time to first event, but in ‘recurrent’ events analysis it would be included and the patient is counted as having had two events.
A major reason that people wish to include these ‘recurrent’ events in trials is because by using more events there is a belief that they can more efficiently determine whether a treatment works or not (referred to as improved statistical power in medical statistics). But this belief is based partly on an assumption that recurrent events are independent of the first (e.g. following discharge from a first hospitalisation risk returns to the same level as before the hospitalisation). But few studies have explored whether this really true, if it isn’t it has consequences for trial design.
We intend to study the relationships between first and recurrent heart failure hospitalisations and cardiovascular death. The analysis will provide medical insights (as to the pattern of heart failure hospitalisations over time), and insights into how future trials should be designed.
To conduct these analyses we will use several statistical techniques. For example:
1) Compare distribution of the gap between repeat heart failure hospitalisations to that which we would expect if they were not related to one another
2) Compare risk of HFH and CV death before and after a first HFH
3) Compare risk of HFH and CV death according to the length of HFH, adjusting for baseline characteristics
Requested Studies:
A Phase III Randomised, Double-blind Trial to Evaluate Efficacy and Safety of Once Daily Empagliflozin 10 mg Compared to Placebo, in Patients With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)
Data Contributor: Boehringer Ingelheim
Study ID: NCT03057977
Sponsor ID: 1245.121
A Phase III Randomised, Double-blind Trial to Evaluate Efficacy and Safety of Once Daily Empagliflozin 10 mg Compared to Placebo, in Patients With Chronic Heart Failure With Preserved Ejection Fraction (HFpEF)
Data Contributor: Boehringer Ingelheim
Study ID: NCT03057951
Sponsor ID: 1245.110