elderly patients

Importance: The optimal duration of dual antiplatelet therapy (DAPT) for older adults after percutaneous coronary intervention (PCI) is uncertain because they are simultaneously at higher risk for both ischemic and bleeding events.

Objective: To investigate the association of abbreviated DAPT with adverse clinical events among older adults after PCI.

Data sources: The Cochrane Library, Google Scholar, Embase, MEDLINE, PubMed, Scopus, and Web of Science were searched from inception to August 9, 2023.

Study selection: Randomized clinical trials comparing any 2 of 1, 3, 6, and 12 months of DAPT were included if they reported results for adults aged 65 years or older or 75 years or older.

Data extraction and synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was used to abstract data and assess data quality. Risk ratios for each duration of DAPT were calculated with alternation of the reference group.

Main outcomes and measures: The primary outcome of interest was net adverse clinical events (NACE). Secondary outcomes were major adverse cardiovascular events (MACE) and bleeding.

Results: In 14 randomized clinical trials comprising 19 102 older adults, no differences were observed in the risks of NACE or MACE for 1, 3, 6, and 12 months of DAPT. However, 3 months of DAPT was associated with a lower risk of bleeding compared with 6 months of DAPT (relative risk [RR], 0.50 [95% CI, 0.29-0.84]) and 12 months of DAPT (RR, 0.57 [95% CI, 0.45-0.71]) among older adults. One month of DAPT was also associated with a lower risk of bleeding compared with 6 months of DAPT (RR, 0.68 [95% CI, 0.54-0.86]).

Conclusions and relevance: In this systematic review and meta-analysis of different durations of DAPT for older adults after PCI, an abbreviated DAPT duration was associated with a lower risk of bleeding without any concomitant increase in the risk of MACE or NACE despite the concern for higher-risk coronary anatomy and comorbidities among older adults. This study, which represents the first network meta-analysis of this shortened treatment for older adults, suggests that clinicians may consider abbreviating DAPT for older adults.

A 64-year-old man presented with concern about an abnormal genetic test result for apolipoprotein E (APOE) obtained through his primary care physician. He reported forgetfulness and word-finding difficulties for 3 years but performed all activities of daily living independently and was generally healthy. His father and maternal great aunt developed dementia in their 70s. Physical (including neurologic) examination, basic laboratory studies, and brain magnetic resonance imaging results were normal. The Short Test of Mental Status (STMS) score was 33 (maximal attainable score of 38 indicates best performance). Neuropsychological assessment showed average to above-average performance in all cognitive domains, accounting for age and education. Results of his genetic testing for APOE were reported as follows: “This individual possesses an apolipoprotein E genotype (3 and 4) that indicates, with high specificity, that Alzheimer’s disease is the cause of or a contributor to the observed dementia.”

Structured Abstract

Background. Opioid-related harms are increasing among older adults. Until we better understand the factors contributing to this trend, we will be unable to design and implement effective interventions to optimally manage opioid use and its potential harms among older adults. Although considerable research has been done in younger or mixed-age populations, the degree to which it is directly applicable to older adults is uncertain.

Objectives. To provide a framework for understanding how to reduce adverse outcomes of opioid use among older adults, and to describe the evidence available for different factors associated with and interventions to reduce adverse outcomes related to opioid use in this population.

Approach. With input from a diverse panel of content experts and other stakeholders, we developed a conceptual framework and evidence map to characterize empirical studies of factors associated with opioid-related outcomes and interventions to reduce opioid-related harms in older adults. We identified relevant literature among older adults (age ≥60 years) for an evidence map by systematically searching PubMed, PsycINFO, and CINAHL for studies published in English between 2000 and May 6, 2020.

Findings. We identified 5,933 citations, from which we identified 41 studies with multivariable models of factors associated with opioid-related outcomes and 16 studies of interventions in older adults. More than half (22/41) of the multivariable analysis studies evaluated factors associated with long-term opioid use (which, though not a harm per se, may increase the risk of harms if not appropriately managed). Prior or early postoperative opioid use, or greater amounts of prescribed opioids (high number of opioid prescriptions or higher opioid dose), were consistently (100% agreement) and strongly (measure of association ≥2.0) associated with long-term opioid use. Back pain, depression, concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), and fibromyalgia also had consistent, but weaker, associations with long-term opioid use. Several factors were mostly associated (>75% agreement) with long-term opioid use, including benzodiazepine use, comorbidity scores, (generally undefined) substance misuse, tobacco use, and low income. However, studies were mostly consistent that alcohol abuse and healthcare utilization were not associated with long-term opioid use. Gender, age among older adults, Black race, dementia, rural/nonurban residence, prescription of long-acting opioids, unmarried status, and use of muscle relaxants were variably associated (<75% agreement) with long-term opioid use.

Six studies examined factors associated with opioid-related disorders, although only one study evaluated factors associated with opioid use disorder. Alcohol misuse and gender were variably associated with opioid misuse (examined by three studies each).

All other evaluations of specific pairs of associated factors and outcomes of interest were evaluated by only one or two studies each. These included analyses of factors associated with multiple opioid prescribers, mental health outcomes, physical health outcomes, all-cause hospitalization, opioid-related hospitalization, nonopioid-specific hospitalization, emergency department visits, opioid overdose, all-cause death, opioid-related death, and nonopioid-related death.

The evidence on interventions directed at older adults is sparse. Of the 16 studies of opioid-related interventions in older adults, six examined screening tools to predict opioid-related harms, but none of these tools was tested in clinical practice to assess real-world results. Two studies found that prescription drug monitoring programs are associated with less opioid use in communities. Other studied interventions include multidisciplinary pain education for patients, an educational pamphlet for patients, implementation of an opioid safety initiative, provision of patient information and pain management training for clinicians, a bundle of educational modalities for clinicians, free prescription acetaminophen, a nationally mandated tamper-resistant opioid formulation, and motivational interview training for nursing students. Few intervention studies evaluated pain or other patient-centered outcomes such as disability and functioning.

Conclusions. The evidence base that is directly applicable to older adults who are prescribed opioids or have opioid-related disorders is limited. Fundamental research is necessary to determine which factors may predict clinically important, patient-centered, opioid-related outcomes. Studies to date have identified numerous possible factors associated with long-term opioid use (whether appropriate or not), but analyses of other opioid-related outcomes in older adults are relatively sparse. Research is also needed to identify interventions to reduce opioid prescribing where harms outweigh benefits (including screening tools), reduce opioid-related harms and disorders, and treat existing misuse or opioid use disorder among older adults.

Importance  Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain.

Objective  To compare opioid vs nonopioid medications over 12 months on pain-related function, pain intensity, and adverse effects.

Design, Setting, and Participants  Pragmatic, 12-month, randomized trial with masked outcome assessment. Patients were recruited from Veterans Affairs primary care clinics from June 2013 through December 2015; follow-up was completed December 2016. Eligible patients had moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use. Of 265 patients enrolled, 25 withdrew prior to randomization and 240 were randomized.

Interventions  Both interventions (opioid and nonopioid medication therapy) followed a treat-to-target strategy aiming for improved pain and function. Each intervention had its own prescribing strategy that included multiple medication options in 3 steps. In the opioid group, the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen. For the nonopioid group, the first step was acetaminophen (paracetamol) or a nonsteroidal anti-inflammatory drug. Medications were changed, added, or adjusted within the assigned treatment group according to individual patient response.

Main Outcomes and Measures  The primary outcome was pain-related function (Brief Pain Inventory [BPI] interference scale) over 12 months and the main secondary outcome was pain intensity (BPI severity scale). For both BPI scales (range, 0-10; higher scores = worse function or pain intensity), a 1-point improvement was clinically important. The primary adverse outcome was medication-related symptoms (patient-reported checklist; range, 0-19).

Results  Among 240 randomized patients (mean age, 58.3 years; women, 32 [13.0%]), 234 (97.5%) completed the trial. Groups did not significantly differ on pain-related function over 12 months (overall P = .58); mean 12-month BPI interference was 3.4 for the opioid group and 3.3 for the nonopioid group (difference, 0.1 [95% CI, −0.5 to 0.7]). Pain intensity was significantly better in the nonopioid group over 12 months (overall P = .03); mean 12-month BPI severity was 4.0 for the opioid group and 3.5 for the nonopioid group (difference, 0.5 [95% CI, 0.0 to 1.0]). Adverse medication-related symptoms were significantly more common in the opioid group over 12 months (overall P = .03); mean medication-related symptoms at 12 months were 1.8 in the opioid group and 0.9 in the nonopioid group (difference, 0.9 [95% CI, 0.3 to 1.5]).

Conclusions and Relevance  Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months. Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain.

Trial Registration  clinicaltrials.gov Identifier: NCT01583985