Too much, too late? Drug prescribing for older people near the end of life

Background: The burden of drugs prescribed to older persons at the end of life has recently drawn increasing scrutiny. Growing evidence suggests that patients with lifelimiting diseases and poor prognosis are prescribed drugs that may do more harm than good or treatments that have little chance of achieving their benefit during the patients’ short remaining lifespan. The overall aim of this thesis was to evaluate the quality of drug prescribing in older adults near the end of life. Except for Study III, all studies are based on routinely collected administrative and healthcare data with national coverage in Sweden.

Study I: We found that, throughout their last year of life, older adults (n=511 843) used an increasing number of prescription drugs. The proportion of older adults exposed to ≥10 drugs increased from 30.3% one year before death to 47.2% during the last month of life. Polypharmacy was fuelled not only by the initiation of symptomatic drugs to ensure comfort but also by the frequent continuation of long-term preventive treatments and medicines prescribed for the management of chronic diseases that may otherwise lead to short-term complications.

Study II: Older adults who died with solid cancer (n=151 201) often continued to receive preventive drugs until the very end of life. Over the course of the last 12 months of life, there was little change in the receipt of antihypertensive agents (absolute change -0.3%, 95% CI -0.6 to 0.0), vitamin K antagonists (+1.5%, 95% CI 1.1 to 1.9), antiplatelet agents (- 1.5%, 95% CI -1.8 to -1.2), statins (-4.7%, 95% CI -5.0 to -4.4), bisphosphonates (-0.3%, 95% CI -0.4 to -0.2), or vitamins (+1.0, 95% CI 0.8 to 1.2). During the last year before death, median drug costs amounted to $1482 (interquartile range [IQR], $700-$2896]) per person, including $213 (IQR, $77-$490) for preventive therapies. We found important differences between cancer types with regard to the use and costs of preventive drugs, which can be explained only in part by age and chronic multimorbidity.

Study III: Forty European experts in geriatrics, clinical pharmacology, and palliative medicine from 10 different countries participated in a Delphi consensus panel to identify drugs deemed “often adequate”, “questionable”, or “often inadequate” for use in older patients aged ≥75 years with an estimated life expectancy of 3 months or less. Drug classes rated as “often adequate” are predominantly indicated for symptom management and comfort care. Among the drugs and drug classes considered “questionable” for use near the end of life, a vast majority are prescribed for the longterm management of non-life-threatening chronic conditions or for the secondary prevention of chronic diseases that may otherwise quickly lead to serious clinical complications. Finally, drugs defined as “often inadequate” encompasses mostly drugs and supplements prescribed for primary prevention or as part of a long-term strategy of secondary or tertiary prevention.

Study IV: By applying the list mentioned above to a cohort of 58 415 older persons who died from conditions potentially amenable to palliative care in 2015, we found that 32% continued and 14% initiated at least one drug considered “often inadequate” during their last three months of life. Excluding older adults who died from acute and potentially unpredictable fatal events had little if any influence on the results.

Conclusion: Older people are prescribed an increasing number of drugs as they approach the end of life. A sizeable fraction of these drugs is not directed towards the relief of distressing symptoms but instead aims at prolonging survival and managing chronic comorbidities. We have developed a consensus-based set of explicit criteria for delineating drugs that are “often adequate” from those deemed “questionable” or “often inadequate” for use in older persons at the end of life. In the absence of high-quality data from randomised clinical trials and sufficiently robust observational studies, these criteria can be used not only to provide guidance at the bedside but also to generate comparable epidemiological evidence across patient groups, care settings, regions, and countries.

List of scientific papers

I. Morin L, Vetrano DL, Rizzuto D, Calderón-Larrañaga A, Fastbom J, Johnell K. Choosing Wisely? Measuring the Burden of Medications in Older Adults near the End of Life: Nationwide, Longitudinal Cohort Study. The American Journal of Medicine. 2017;130(8):927–936.e9.
https://doi.org/10.1016/j.amjmed.2017.02.028

II. Morin L, Todd A, Barclay S, Wastesson JW, Fastbom J, Johnell K. Preventive drugs in the last year of life of older adults with cancer: Is there room for deprescribing? Cancer. 2019;125(13):2309-2317.
https://doi.org/10.1002/cncr.32044

III. Morin L, Laroche ML, Vetrano DL, Fastbom J, Johnell K. Criteria for adequate and inadequate drug prescribing in older adults at the end of life: European expert consensus. European Journal of Clinical Pharmacology. 2018; 74(10):1333-42.
https://doi.org/10.1007/s00228-018-2507-4

IV. Morin L, Wastesson JW, Laroche M-L, Fastbom J, Johnell K. How many older adults receive drugs of questionable clinical benefit near the end of life? A cohort study. Palliative Medicine. 2019;33(8):1080-1090.
https://doi.org/10.1177/0269216319854013