Time for Action: Including Older Adults in Clinical Trials

dodson%20headshotWe recently published an editorial in the Journal of the American Geriatrics Society entitled “Time for a New Approach to Studying Older People with Ischemic Heart Disease”. This was in response to a research article by Bourgeois et al. demonstrating that of medication trials for patients with ischemic heart disease published between 2006 and 2016, over half (53%) excluded older adults. The authors’ findings underscore the continued problem of under-representation of older adults in the most rigorously conducted research studies, which makes translating these studies’ results into practice especially challenging.

This is a longstanding problem that was highlighted by the FDA over 25 years ago. In our editorial, we highlighted several potential next steps to address this issue:

  1. Design clinical research studies with no upper age limit. Alternatively, mandate an explicit lower age limit for inclusion – for example, only enroll patients age ≥75. Since there are fundamental phenotypic differences in older patients (including aging-related impairments such as frailty, sarcopenia, visual/sensory impairments, and cognitive impairment), this approach would ensure these characteristics are adequately represented.
  2. Create an Office of Geriatric Health and Aging within FDA, which would provide expertise for review of protocols on dosing, enrollment, and data collection in older patients.
  3. Add an exclusivity rule to extend patent life in drugs with proven safety and efficacy specifically in older adults, which would incentivize drug manufacturers to focus on aging. This approach has been previously described by Skolnick and Alexander.

These are just few examples of concrete steps that can be taken to address a problem that has long been recognized. With our aging population, and in light of current clinical uncertainties in cardiovascular medicine, there is a critical need for action.

 

By: John Dodson, MD

Frailty and Advanced Heart Failure

dodson%20headshotThis week we published a review in the Journal Current Cardiovascular Risk Reports  on the concept of frailty and advanced heart failure in older adults. As geriatricians have long known, frailty–defined as an increased vulnerability to physiologic stressors–is an incredibly common and often unrecognized syndrome in older patients. Cardiologists are increasingly recognizing that frailty predicts a broad range of outcomes, including mortality, in conditions such as heart failure, but also other situations such as acute myocardial infarction and transcatheter aortic valve replacement.

A few highlights from our paper:

– 80% of patients with heart failure are over age 65.

– As the heart failure population continues to age, the burden of frailty has increased.

– The estimated prevalence of frailty in advanced heart failure varies widely, with some estimates ranging up to 3 out of every 4 patients.

– It is challenging to determine causality between heart failure and frailty; they share common inflammatory pathways and one syndrome may mimic the other.

With our current technologies, one of the most pressing clinical questions is whether placement of a left ventricular assist device (LVAD) in advanced systolic heart failure can reverse the frailty phenotype, by correcting underlying physiologic derangements. Flint et al. have put forward the concept of “LVAD-responsive frailty” and “LVAD-independent frailty” – with an illustrative figure cited in our paper. Their concept emphasizes the considerable heterogeneity that exists within heart failure populations. We will need further studies to be able to predict where frailty may improve, in order to better counsel patients about their expected outcomes.

 

By: John Dodson