Clinical concerns surrounding polypharmacy in the elderly and patients with terminal illness are stimulating new research aimed at determining when and how drugs can be safely discontinued.
Very often, elderly patients are prescribed a large and diverse set of medications to address multiple different health issues. There is growing recognition that although each drug has been prescribed for a different justified reason, the combination may do more harm than good. Sometimes, elderly patients continue to take take medications for problems they no longer have. It is often difficult for physicians to reduce the medication prescribed by a different doctor.
This article from the Journal of the American Medical Association addresses the issue of end of life medications. The issue is broader and affects many elderly people and younger people with multiple health issues or a disease in younger people with complex manifestations. Integrated care and integrated health records can assist both patients and doctors in prescribing the minimum necessary drugs.
It wasn’t a popular idea at the outset. Amy Abernethy, MD, PhD, and her colleagues suggested a decade ago that patients nearing the end of life could stop at least some of their medications. But their attempts to publish material on the subject initially met with resistance. “There was great angst among reviewers about medication discontinuation of any kind,” she said of a commentary they eventually published in BMJ (Stevenson J et al. BMJ. 2004;329[7471]:909-912). “They felt it would be equivalent to saying to a patient, ‘You’re not worthy to be on this medication.'”
Today, however, the resistance is easing. Concern about the effects of polypharmacy among patients with terminal illnesses, including the potential for adverse drug events and drug-drug interactions, is fueling a new wave of research. Studies that explore end of life prescribing patterns are attempting to document the extent of potentially inappropriate medication use and suggest conditions under which drugs might be discontinued.
Drugs being questioned in this population include statins, prescribed to prevent future heart attacks and strokes; cholinesterase inhibitors, to ameliorate symptoms associated with Alzheimer disease; bisphosphonates, to prevent the loss of bone mass; and others (Holmes H et al. J Am Geriatr Soc. 2008;56[7]:1306-1311; van Nordennen RT et al. Drugs Aging. 2014;31[4]:501-12). Tight treatment targets for hypertension and diabetes among patients with limited life expectancies also are coming under scrutiny (Garfinkel D and Mangin D. Arch Intern Med. 2010;170[18]:1648-1654).
Because they’re widely used and well studied, statins top the list of drugs whose efficacy is being reexamined. Although it takes at least two years for statins to be effective as primary prevention for cardiovascular disease, fifty seven percent of palliative care physicians who prescribe the drugs for this purpose usually don’t stop them even when patients have life threatening illnesses, according to a new survey. That report, by members of the Palliative Care Research Cooperative Group, has not yet been published.
Questionable Benefit
Elizabeth Bayliss, MD, MSPH, director of scientific development at Kaiser Permanente Colorado’s Institute for Health Research, called the phenomenon “clinical momentum,” which she defined in a recent study as the failure to “deintensify treatment in the face of a changing clinical context” (Bayliss EA et al. J Palliat Med. 2013;16[4]:412-418). Among 539 patients with advanced cancer who were taking statins, Bayliss and her colleagues showed thirty six percent did so for the purpose of primary prevention despite questionable benefit.
Meanwhile, another recent report found that nearly seventeen percent of bedbound patients with end stage dementia in nursing homes were still being prescribed statins (Tjia J et al. J Am Geriatr Soc. 2014;62[11]:2095-2101). Although these patients could barely move and had great difficulty eating, only thirty seven percent eventually stopped taking the drugs. Of 924 patients who died during the study, sixty two percent took the medications until death.
Jennifer Tjia, MD, MSCE, associate professor of quantitative health sciences at the University of Massachusetts Medical School and lead author of the report, worked as a nursing home physician for ten years. She knows how difficult it is to administer medications to people with end stage dementia, who typically have difficulty swallowing.
Citing the ethical principle of beneficence, she said, “I think that doing what’s right for these patients means keeping them free of drugs they don’t need.” Statins fall into that category, she added, because they can cause muscle pain and do not contribute to comfort care, the top priority for more than ninety percent of patients’ surrogate decision makers.
Are You Crazy?
Tjia’s assessment may not be controversial, but a broader reexamination of statin use among patients with other life threatening illnesses such as advanced cancer, end stage organ failure, or irreversible lung disease has generated its share of push-back.
“Some physicians are very wedded to their therapies,” said Jean Kutner, MD, MSPH, Gordon Meiklejohn Endowed professor of medicine at the University of Colorado. She and Abernethy, director of Duke University’s Cancer Care Research Program, are coauthors of a new paper on discontinuing statins in people with less than a year to live, currently under review for publication. Results disclosed earlier this year at the American Society of Clinical Oncology annual meeting showed that terminating statin use was not harmful and actually improved some dimensions of quality of life in this population.
That study randomly assigned 192 patients to a “stay on statins” group and 189 patients to a “stop the drug” group and depended on cooperation from the patients’ physicians. Some physicians had no problem with the notion of letting their patients discontinue the medications. But others were taken aback, Kutner said, and responded, “Are you crazy?”
“The mindset of most cardiologists is ‘We can help everyone,'” said Mariell Jessup, MD, immediate past president of the American Heart Association and medical director of the heart and vascular center at the University of Pennsylvania. “But we’ve all begun to recognize that aggressive medical and surgical treatment may not be appropriate at every stage of every patient’s life.”
Although research is scant, at least one recent published study produced findings similar to those of Kutner and colleagues. Investigators showed that among sixty four of seventy older adults who stopped many of their medications, no significant adverse events or deaths were linked with discontinuation. In fact, eighty eight percent of the patients said their health improved (Garfinkel D and Mangin D. Arch Intern Med. 2010;170[18]:1648-1654).
Clinical Dilemmas
Questioning whether or how to adjust patients’ medication regimens is common in clinical practice. Kutner recalled an eighty five year old woman with progressive dementia, high cholesterol, and hypertension who had survived a stroke, was falling frequently, and was taking twenty different drugs, including a statin.
Kutner estimated that the patient had more than a year to live so she recommended continuing to take the statin to reduce the risk of another stroke. If the woman’s life expectancy had been less than a year, she said, “I would have discussed stopping it with her daughter.” Meanwhile, to minimize the risk of another fall-an immediate threat-she lowered doses for the woman’s hypertension medications.
Because the evidence base for these kinds of decisions isn’t well established and care goals change with the onset of advanced illness, “this has to be a shared decision making process” with patients and their families, Kutner said. But how best to conduct these discussions is a thorny issue. No patient wants to think a physician is giving up hope, and many are attached to drugs they’ve been taking for years.
“You don’t want to say, ‘We’ve figured out you have about 1.5 years to live and this medication takes two years to accrue benefits and so we’re going to stop,'” said Greg Sachs, MD, a professor of medicine at Indiana University School of Medicine. “Instead, we would frame this as, ‘Let’s think about establishing priorities and using our time and resources to focus on the things that really matter to you.'”
A short term drug discontinuation trial may be helpful. “Sometimes I’ll suggest that older people who are worried about stopping medications try not taking them for a month or two and see if they feel better,” said Paul Thompson, MD, chief of cardiology at Hartford Hospital in Connecticut.
He recalled the case of an eighty year old woman whose family thought she was very depressed. Thompson suggested that she stop taking her statin medication, and two weeks later the woman’s family called to report that she was feeling much better. “I think, in retrospect, she felt lousy because her muscles ached,” a common statin adverse effect, he said.
In the absence of guidelines, Sachs and colleagues have proposed a framework for evaluating whether medications might be discontinued (Holmes H et al. Arch Intern Med. 2006;166[6]:605-609). It includes assessing the patient’s likely remaining life expectancy, the goals of care (such as relieving symptoms, treating acute illness, prolonging life, or maintaining current functioning), the treatment target, and the time it takes a medication to achieve its intended benefit.
William Dale, MD, PhD, chief of geriatrics and palliative care medicine at University of Chicago Medicine, adds “time to harm” to this framework, although it’s difficult to find good information about it in the research literature. He often sees frail older patients with advanced cancer and diabetes that has been managed aggressively. In considering whether a less aggressive control regimen might be warranted, he considers multiple outcomes-vascular disease, kidney disease, eye disease, and mortality-all of which have different time horizons and involve a different set of calculations.
Other Medications
Another recent study by Tjia and colleagues raises questions about the use of cholinesterase inhibitors and memantine hydrochloride for people with advanced dementia who reside in nursing homes (Tjia et al.JAMA Intern Med. 2014;174[11]:1763-1771). Although research hasn’t demonstrated a meaningful benefit in this population, more than thirty six percent of the 5,406 patients examined in this study were taking cholinesterase inhibitors and twenty two percent took memantine.
Without strong empirical data, clinical judgment must rule. David Knopman, MD, a professor of neurology at the Mayo Clinic in Rochester, Minnesota, usually opts to continue cholinesterase inhibitors for patients with dementia who live at home because he doesn’t want to run the risk of precipitating decline. But if a patient enters a skilled nursing facility, he is likely to stop the medications. “If upon stopping them, the patient worsened, more resources would be at hand,” he said.
Topping the list of medications that Sachs considers stopping in patients with advanced illness are drugs to prevent osteoporosis. “They’re difficult to take and several studies have shown that if you’ve been on these medications for five years, their benefits carry on for some time beyond,” he said.
Stephen Kates, MD, Hansjorg Wyss professor of orthopedics at the University of Rochester School of Medicine and Dentistry in New York, agreed. For patients with life threatening cancer, advanced dementia, or end stage pulmonary disease, his recommendation is decisive: “Stop the medicine altogether.”