On the perspective of an aging population and its potential impact on drug attrition and pre-clinical cardiovascular safety assessment

There is no refuting that America's population is growing older: for the first time in US history, by 2034 older adults (defined as >65 years of age) are projected to outnumber children under the age of 18, representing approximately 70 million people or almost 25% of the population (Lloyd-Jones et al., 2010). Described as the "silver tsunami", this flood of older adults is driven by the baby boomers (people born after World War II, from 1946 to 1964): they are now reaching old age, living longer due to significant advances in healthcare coupled with a record low birth rate, resulting in a skewed elderly population demographic. Unfortunately, older adults are also becoming increasingly unhealthy. Many often suffer from several chronic disorders requiring the use of multiple medications at a level higher than any other age group, resulting in an increased risk of drug-drug interactions (DDIs) and adverse drug reactions (ADRs). Indeed, because of age-related changes in pharmacokinetics (PK) and pharmacodynamics (PD), older adults are also more vulnerable to drug toxicity. Prescribed drugs certainly improve a range of health outcomes, but also often cause considerable ADRs, leading to devastating consequences for patients, clinicians, and manufacturers. Therefore, safe and effective pharmacotherapy remains one of the greatest growing challenges in geriatric medicine. In this review we examine the effects of aging and its impact on the increased risk of experiencing ADRs, resulting in devastating consequences for patients and manufacturers. We assess the current regulatory considerations related to the development of drugs for this population and highlight issues, concerns, and propose alternatives to the standard battery of tests focused on assessing cardiovascular (CV) safety in an attempt to develop safer and efficient new drugs for the growing elderly demographic.