Issue: October 2020
Perspective from Carl J. Pepine, MD, MACC
Source: Sheppard JP, et al. JAMA. 2020;doi:10.1001/jama.2020.4871.
Disclosures: Beavers, Kirkpatrick and Wenger report no relevant financial disclosures. Goyal reports he received funding from the AHA and the National Institute on Aging. Messerli reports he has financial relationships with the ACC, Berlin Chemie, Medtronic, Menarini, Novartis, Sandoz, The Lancet and WebMD. Vouri reports he receives grant funding from the Claude D. Pepper Society within the National Institute on Aging.
October 20, 2020
12 min read

Deprescribing CV medications may benefit elderly patients with evolving treatment goals

Issue: October 2020
Perspective from Carl J. Pepine, MD, MACC
Source: Sheppard JP, et al. JAMA. 2020;doi:10.1001/jama.2020.4871.
Disclosures: Beavers, Kirkpatrick and Wenger report no relevant financial disclosures. Goyal reports he received funding from the AHA and the National Institute on Aging. Messerli reports he has financial relationships with the ACC, Berlin Chemie, Medtronic, Menarini, Novartis, Sandoz, The Lancet and WebMD. Vouri reports he receives grant funding from the Claude D. Pepper Society within the National Institute on Aging.
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In recent years, there has been increased emphasis on deprescribing strategies for patients near the end of their lives who are taking a large number of medications, which can be difficult to manage on a day-to-day basis.

In addition, the patient’s goals of care may switch from prolonging life to improving quality of life, which can lead a cardiologist to reassess a patient’s medications. As patients age, metabolism and other physiological processes may change, highlighting another important reason to consider a medication review and, if needed, a deprescribing strategy.

“All patients would benefit from a more comprehensive approach to medication optimization where we’re thinking about prescribing the right medications and deprescribing the wrong medications,” Parag Goyal, MD, MSc, FACC, assistant professor of medicine in the division of cardiology and director of the HFpEF Program at Weill Cornell Medicine, told Cardiology Today.

The recent OPTIMISE trial, published in JAMA in May, provided further insight into the potential benefits of a deprescribing approach in older patients (mean age, 85 years). At 12 weeks, 86.4% of patients assigned an antihypertensive medication reduction strategy had systolic BP less than 150 mm Hg compared with 87.7% of those assigned usual care (adjusted RR = 0.98; 97.5% 1-sided CI, 0.92-).

Further research is needed in this area, although studying an elderly population is a difficult task.

“Even with the OPTIMISE trial, we’ll get a sense of what has been done before, but it’ll require larger sample sizes to compare which drugs were stopped and what kind of impact did it have down the road. That’s still unknown even in the clinical trial,” Scott M. Vouri, PhD, PharmD, clinical assistant professor in the department of pharmaceutical outcomes and policy at the University of Florida College of Pharmacy in Gainesville and assistant director of pharmacy services at University of Florida Health Physicians, said in an interview.

Parag Goyal, MD, MSc, FACC, from Weill Cornell Medicine, is one of several cardiologists working on a more comprehensive CV medication approach for older patients.
Parag Goyal, MD, MSc, FACC, from Weill Cornell Medicine, is one of several cardiologists working on a more comprehensive CV medication approach for older patients.

Source: Rene Perez. Reprinted with permission.

Further complicating matters, several misconceptions remain with regard to deprescribing medications.

“It does not mean that we stop all of the medicines or certain medicines that might be improving patient’s quality of life,” James N. Kirkpatrick, MD, FACC, professor of medicine, director of the echocardiography laboratory and attending physician at University of Washington Medical Center in Seattle and chair of the ACC Geriatric Cardiology Section Leadership Council, told Cardiology Today. “It does not necessarily mean that for all patients who are over a certain age that we stop life-prolonging medicines.”

Benefit-risk balance

As patients age, several factors can influence how they tolerate a medication, including the presence of multiple disease states and changes in metabolism and body weight. Older patients often have reduced kidney function, which can lead to medications staying in the body for longer than before. The liver also becomes less efficient as patients age.

Nanette K. Wenger, MD, MACC, MACP, FAHA, FASPC
Nanette K. Wenger

“If you use guideline-based therapy for every disease, then you have medications interfering with each other,” Cardiology Today Editorial Board Member Nanette K. Wenger, MD, MACC, MACP, FAHA, FASPC, emeritus professor of medicine (cardiology) at Emory University School of Medicine, consultant at Emory Heart and Vascular Center and founding consultant at Emory Women’s Heart Center, said in an interview. “When you prescribe for an elderly patient, you’re treating the patient, not just the disease. Because if you treat all the diseases, you may have the medications fighting each other. Most important are the patient’s goals of care.”

Patients near the end of their lives can have increased risk for several types of interactions, including drug-drug interactions, drug-disease interactions and drug-person interactions, which highlights the importance of determining the benefit-risk balance of their medications, especially as that balance diminishes.

“For a skillful clinician, it is very important to look at this progressive change carefully and to catch the moment when a very specific medication is no longer efficacious [and] actually can do more harm than good,” Cardiology Today Editorial Board Member Franz H. Messerli, MD, HonD, FACC, FESC, professor of medicine at the Swiss Cardiovascular Center at University of Bern in Switzerland, at Icahn School of Medicine at Mount Sinai and at Jagiellonian University in Krakow, Poland, said in an interview.

Adding multiple medications to an older patient’s regimen can increase the risk for drug interactions.

“It’s an evolving paradigm; it really depends on the disease state and where they’re at in their age,” Craig Beavers, PharmD, cardiovascular clinical pharmacy coordinator at University of Kentucky Healthcare in Lexington, assistant adjunct professor at the University of Kentucky College of Pharmacy and director of cardiovascular services at Baptist Health System in Paducah, Kentucky, told Cardiology Today.

Craig Beavers, PharmD
Craig Beavers

Goals of care, including life expectancy and quality of life, are factors to contemplate when determining the benefit-risk balance of a CV medication.

“A lot of very elderly patients are more interested in their quality of life than necessarily prolonging life, especially if their quality of life is not quite that good,” Kirkpatrick said. “That needs to be taken into consideration when considering the benefit-risk balance of all of the medicines they’re taking — cardiovascular and otherwise.”

Challenges of polypharmacy

The logistics of taking many medications can also determine whether an older patient is a candidate for deprescribing. Medications need to be taken multiple times a day, some with food, some without food, and juggling the correct timing can be a struggle for patients.

“It can be overwhelming to try to keep up with it and not just for the patient. They [may] have a caregiver helping them to do that and to remember to not take a certain therapy with this drug, and you have to take this one with food,” Beavers said.

Polypharmacy can also pose a financial burden.

Scott M. Vouri, PhD, PharmD
Scott M. Vouri

“Many elderly patients are on fixed incomes, and each additional medication is associated with a copay,” Vouri said. “That cuts into the bottom line for each additional medication they’re on.”

The difficulty of taking medications can be further affected by common issues related to aging such as impaired vision and cognitive impairment.

Accidentally taking more of a medication than instructed can lead to certain adverse events. For example, if a patient takes an extra pill of an antihypertensive medication, it can cause the patient to become hypotensive, which can increase risk for falling.

Drug-drug interactions can also lead to adverse effects. For example, adding an anticoagulant therapy for atrial fibrillation to a patient who is already taking aspirin can increase risk for bleeding. Another example is a patient who presents with joint pain or arthritis for whom the clinician prescribes an NSAID without realizing that the patient also has HF and hypertension.

Certain medications have their own specific adverse events, such as ACE inhibitors, which may raise risk for acute kidney injury. Diuretics can also become more or less effective depending on the specific medication a patient is taking. For example, if accumulated, loop diuretics can lead to hypokalemia and thiazide diuretics can result in hyponatremia.

Other drug-drug interactions can occur beyond the range of CV medications.

Franz H. Messerli, MD, HonD, FACC, FESC
Franz H. Messerli

“Despite the fact that you are very careful in looking at this, there are some drug-drug interactions that are awfully hard to catch,” Messerli said.

Cardiologists should also be cognizant of the prescribing cascade, which occurs when adverse effects of a drug are misinterpreted as symptoms of another condition, resulting in additional prescriptions. An example of this is when a patient with hypertension is prescribed a calcium channel blocker, which may cause ankle swelling. Instead of stopping the calcium channel blocker, a clinician may prescribe a diuretic, then a potassium supplement to address potential potassium loss. Not uncommonly, such a prescribing cascade may occur as an after-effect in a patient treated by multiple subspecialists who are not communicating with each other.

“I look for this prescribing cascade because that’s the easiest part to change, but check first for medications for inactive problems and then medications that are part of a prescribing cascade makes it easier,” Wenger said.

Implementing a deprescribing strategy

The Geriatric Cardiology Section Leadership Council of the American College of Cardiology published a perspective in the Journal of the American College of Cardiology in 2019 that defined a proper deprescribing strategy, outlined the steps for deprescribing (Graphic) and listed four common triggers to deploy such a strategy: adverse drug reactions, polypharmacy with long-term use of five or more medications, prescribing cascades and palliative care.

Once a patient is identified as a candidate for a deprescribing strategy, the process for deployment should be individualized, based on comorbid conditions, current medications and the benefit-risk balance, among other factors.

“My big push is always a shared decision between the provider and the patient, laying out the risk and benefit of these medications and being specific to that patient where the risk is associated with a potential for an adverse event,” Vouri said.

The ACC review paper also details steps to deprescribing. This starts with a mediation review and reconciliation to identify drugs that may post a risk for drug interactions and duplicate medications.

The medication review and reconciliation should also include supplements and nonprescription drugs, which older patients often take but may not be in their medical record, Wenger said.

Cardiologists should consider other diseases when considering deprescribing medications.

“There may be little reason for [a patient with cancer] to continue antihypertensive medicines because blood pressure will fall usually because of cancer and its therapy, and the patient may simply be more vulnerable to cancer therapy because of cardiovascular medicine,” Messerli said.

Several assessments should be performed during this process, including risk assessment of adverse effects of individual medications and a drug’s eligibility for discontinuation.

“Have we taken the initiative to look and say, ‘Why are we treating this patient with this therapy and is it even still working for them?” Beavers said. “A particular therapy may have been effective for the patient at the time, but may not be effective now.”

Deprescribing should be done one medication at a time, rather than all at once, and cardiologists should monitor the patient for any adverse effects or withdrawal symptoms.

James N. Kirkpatrick, MD, FACC
James N. Kirkpatrick

“It is vitally important to be able to see if deprescribing worked,” Kirkpatrick said. “Part of it that may be defined as success is nothing bad happened. The fact that we have one less medicine may actually be a future good, but what we need to make sure is that there’s no worsening of symptom status.”

Need for more research, better communication

When considering a deprescribing strategy, it is important to involve all other clinicians who are caring for the patient, including the primary care provider.

“We need to look at this as a team endeavor in which we are all trying to make the patient feel better and live longer when it’s within the goals of care,” Kirkpatrick said.

In some cases, the this may also include the patient’s pharmacy.

“Communicating this plan with the pharmacy that we’re doing this to formally stop that medication can be important,” Vouri said. “What happens is 30 days later, a medication is ready that the physician or cardiologist wanted to stop, the older adult might be confused ... and might restart that without any providers being aware of that.”

Such messaging ideally can be done directly through electronic medical records, but sometimes platforms cannot communicate with each other.

“We don’t have a good system for communication right now, and we need to figure out ways to improve this,” Goyal said. “I don’t know yet what is the best way to optimize communication. It certainly needs to happen, and it certainly needs to be across multiple disciplines.”

More research is needed to determine the proper order in which to deprescribe and which drugs may still be beneficial in patients as they age. It can be challenging to conduct randomized controlled trials in older adults to obtain the data needed.

“You’re not sure whether they can be consented or whether they take the medication as they should,” Messerli said. “I’m not sure whether this problem actually ever will be analyzed as it should be. It comes back to a good clinician that needs to look at the patient and make the decision from day to day about these issues.”

One trial currently underway is expected to provide further insight. The randomized PREVENTABLE trial will compare 40 mg atorvastatin vs. placebo in older adults with CVD or dementia. The primary outcome is a composite of dementia, death and persistent disability, and the secondary outcome includes composites of mild cognitive impairment and CV events. All outcomes will be assessed at 4 years.

“[The PREVENTABLE] trial is going to have a very big impact on primary prevention with statins in the elderly,” Kirkpatrick said.

More guidelines and recommendations are also needed in this area.

“I believe that guideline statements should specifically address the need to review medication lists not only to identify interactions and potential allergic reactions (which is usually accomplished quite adequately by electronic medical record system programs), but also to identify which medicines may not be aligned with patient’s goals of care and should therefore be discontinued, presuming that goals of care discussions have occurred,” Kirkpatrick said. “A guideline statement may provide examples to guide these discussions.”

The ACC, AHA and American Geriatrics Society in 2016 released a scientific statement on knowledge gaps in the CV care of older adults. The statement did not specifically address deprescribing but cited many areas in which medication-related questions in older adults require more research. Few guidelines and many knowledge gaps exist in part because older patients are not well-represented in CV clinical trials, experts said.

“What we need to do is to have principles of where, when and how this is addressed, with whom the information is shared,” Wenger said.

Increased awareness

Increased awareness of the treatment of elderly patients is evident not only in clinical practice, but also in professional societies within cardiology. The ACC instituted the Geriatric Cardiology Section Leadership Council in 2012, and the AHA has an Older Populations Committee. The council’s role within the ACC is to inform the rest of the cardiology community that older patients have unique vulnerabilities, and that the care of these patients need to be adapted to address those needs, Goyal said.

Beyond cardiology, the U.S. Deprescribing Research Network, funded by the National Institute on Aging, brings together experts to address deprescribing in older adults. The network aims to improve research focused on deprescribing in older adults, in addition to informing clinicians of evidence on this topic.

As time progresses and more is learned about deprescribing, education is needed to improve care for elderly patients.

“You’re going to hear a lot more about this going forth in the community,” Beavers said. “We need to do a good job educating not just cardiologists, but other health care providers, other specialties, and so on, regarding the need to help be the champion, carry the banner, look at what we need to do and find ways to consider [deprescribing] as a part of the treatment paradigm.”