Older Adult Attitudes toward Deprescribing Statins in Primary Cardiovascular Prevention Versus General Medications.

Background: There is little evidence for statins for primary cardiovascular prevention in older adults. Consequently, it is important to assess patient attitudes toward the use of statins, which might differ from attitudes toward other medications. We aimed to describe older patient attitudes toward deprescribing statins versus general medications. Methods: We conducted a survey using the revised Patients' Attitudes Toward Deprescribing questionnaire in its original version and adapted to statin use in adults ≥65 years taking a statin for primary prevention. Results: Among the 47 participants (mean age 74.6 years), 42 (89%) were satisfied with their current therapy, but still willing to stop ≥1 of their medications upon their doctor's advice. About 68% (N = 32) were satisfied with their statin therapy, while 83% (N = 39) would accept to consider deprescribing. Twenty-six (55%) participants were concerned about missing future benefits when stopping their general medications and 17 (36%) when stopping their statin. Eight (17%) participants believed they were experiencing side effects of statins and twice as many for general medication (38%, N = 18). Conclusion: Our study provides insight about differences and similarities in patient attitudes toward deprescribing general medications and statins in primary prevention. This information could support patient-centered conversations and shared-decision making about deprescribing.

[Deprescribing statinsand other cardiovascular medications Barriers and facilitators]. / Déprescription des statines et autres médicaments cardiovasculaires. Obstacles et facilitateurs.

Considering the growing problematic of polypharmacy, this article summarizes barriers and facilitators to deprescribing cardiovascular medications, from the point of view of physicians and patients. Patients seem to be more open to discontinue cardiovascular medications when their physician suggests to do so, or if they dislike the medication. Physicians tend to consider deprescribing more if they had positive experiences with deprescribing in the past, or if their patients ask them to. The most common barrier for patients is the fear of health deterioration. Patient desire to continue with their usual medication or past negative experiences with depresecribing are frequently reported as barriers by physicians.

Vu le problème croissant de la polypharmacie, cet article résume les différents obstacles et facilitateurs à la déprescription des médicaments cardiovasculaires, du point de vue des médecins et des patients. Ces derniers sont plus enclins à stopper des médicaments cardiovasculaires lorsque cela leur est proposé par leur médecin traitant ou s'ils n'aiment pas le médicament. Les médecins arrêtent plus facilement les traitements s'ils ont déjà eu des expériences positives de déprescription et si leurs patients le leur demandent. L'obstacle le plus fréquent pour les patients est la peur d'une détérioration de leur état de santé. Pour les médecins, la volonté du patient de poursuivre le traitement, ou une expérience passée négative avec la déprescription, sont des obstacles fréquents.

Older Adult Perspectives on Statin Continuation and Discontinuation in Primary Cardiovascular Disease Prevention: A Mixed-Methods Study.

Background and Purpose: Evidence for statin use for primary cardiovascular disease prevention in older adults is limited. When evidence on risk-benefit profile of a medication is uncertain, using it or not becomes a preference-sensitive decision. We aimed to assess and explore patient perspectives on continuation and discontinuation of statins used for primary cardiovascular prevention in older adults. Patients and Methods: We used a convergent mixed-methods design, conducting in parallel a survey among 47 patients and three focus groups (FGs) with 14 patients total. We recruited patients aged ≥65 years and taking a statin for primary cardiovascular prevention. The survey and FGs aimed to assess and explore patient experiences of statin use, and views on statin continuation and discontinuation, including patient decision-making. Quantitative and qualitative data were first analyzed separately - descriptive statistics for quantitative data and thematic analysis for qualitative data - and then integrated to create metainferences, using joint displays. Results: Forty-one percent of patients (N=19) were reluctant to discontinue the statin, whereas 22% (N=10) were willing to try discontinuing it. A reason to continue the statin was its perceived necessity, while self-estimated low cardiovascular risk and wish to reduce medication burden were given as reasons to discontinue it. Lack of expertise assumed by the patients to decide about statin continuation or discontinuation, uncertainty about statin indication, and fear of having a cardiovascular event after discontinuation made many patients uncertain about deciding to continue or discontinue the statin. In this context, 70% (N=33) would rather have their physician choose for them, and 94% (N=44) would continue taking the statin for as long as their physician told them to do so. Conclusion: This study highlights factors that influence patient willingness to continue or discontinue statins, patient uncertainty about statin continuation or discontinuation, and the important role physicians play in the decision-making process.

Benzodiazepine Receptor Agonists Use and Cessation Among Multimorbid Older Adults with Polypharmacy: Secondary Analysis from the OPERAM Trial.

BACKGROUND: Benzodiazepine receptor agonists (BZRAs) are commonly prescribed in older adults despite an unfavorable risk-benefit ratio. Hospitalizations may provide a unique opportunity to initiate BZRA cessation, yet little is known about cessation during and after hospitalization. We aimed to measure the prevalence of BZRA use before hospitalization and the rate of cessation 6 months later, and to identify factors associated with these outcomes. METHODS: We conducted a secondary analysis of a cluster randomized controlled trial (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly [OPERAM]), comparing usual care and in-hospital pharmacotherapy optimization in adults aged 70 years or over with multimorbidity and polypharmacy in four European countries. BZRA cessation was defined as taking one or more BZRA before hospitalization and not taking any BZRA at the 6-month follow-up. Multivariable logistic regression was performed to identify factors associated with BZRA use before hospitalization and with cessation at 6 months. RESULTS: Among 1601 participants with complete 6-month follow-up data, 378 (23.6%) were BZRA users before hospitalization. Female sex (odds ratio [OR] 1.52 [95% confidence interval 1.18-1.96]), a higher reported level of depression/anxiety (OR up to 2.45 [1.54-3.89]), a higher number of daily drugs (OR 1.08 [1.05-1.12]), use of an antidepressant (OR 1.74 [1.31-2.31]) or an antiepileptic (OR 1.46 [1.02-2.07]), and trial site were associated with BZRA use. Diabetes mellitus (OR 0.60 [0.44-0.80]) was associated with a lower probability of BZRA use. BZRA cessation occurred in 86 BZRA users (22.8%). Antidepressant use (OR 1.74 [1.06-2.86]) and a history of falling in the previous 12 months (OR 1.75 [1.10-2.78]) were associated with higher BZRA cessation, and chronic obstructive pulmonary disease (COPD) (OR 0.45 [0.20-0.91]) with lower BZRA cessation. CONCLUSION: BZRA prevalence was high among included multimorbid older adults, and BZRA cessation occurred in almost a quarter of them within 6 months after hospitalization. Targeted BZRA deprescribing programs could further enhance cessation. Specific attention is needed for females, central nervous system-acting co-medication, and COPD co-morbidity. REGISTRATION: ClinicalTrials.gov identifier: NCT02986425. December 8, 2016.

Barriers and facilitators to deprescribing of cardiovascular medications: a systematic review.

OBJECTIVE: To synthesise the current knowledge on barriers and facilitators to deprescribing cardiovascular medications (CVMs) at the levels of patients, informal caregivers and healthcare providers (HCPs). DESIGN/SETTING: We conducted a systematic review of studies exploring/assessing patient, informal caregiver and/or HCP barriers and/or facilitators to deprescribing CVMs. DATA SOURCES: Ovid/MEDLINE and Embase from January 2003 to November 2021. DATA EXTRACTION AND SYNTHESIS: We performed a deductive thematic analysis based on the framework of specific barriers and facilitators to deprescribing CVMs created by Goyal et al. We added a quantification of the occurrence of categories and themes in the selected articles to identify the resounding themes that indicate the greater impetus to address in future research. RESULTS: Most frequent deprescribing barriers for patients, informal caregivers and HCPs included uncertainty due to lack of evidence regarding CVM deprescribing (in n=10 studies), fear of negative consequences following deprescribing (n=13) and social influences (n=14). A frequently reported facilitator to deprescribing, especially for patients and informal caregivers, was the occurrence of adverse drug events (n=7). Another frequently reported facilitator for patients were dislike of CVMs (n=9). Necessity and benefit of CVMs were seen as barriers or facilitators similarly by patients and HCPs. CONCLUSION: The differences in patient, informal caregiver and HCP regarding barriers and facilitators to deprescribing CVMs stress the need for ground discussions about beliefs and preferences of each stakeholder implicated in deprescribing decisions. Furthermore, HCP uncertainty regarding CVM deprescribing highlights the need to provide HCPs with tools that enable sharing the risks and benefits of deprescribing with patients and ensure a safe deprescribing process. PROSPERO REGISTRATION NUMBER: CRD42020221973.

Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study.

BACKGROUND: Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. METHODS: Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model. RESULTS: At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (ß coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00-1.04, p < 0.001), triglycerides (0.11, 0.03-0.20, p = 0.007), log(RANKL) (0.07, 0.02-0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15-0.57, p = 0.001), statin use (0.39, 0.06-0.72, p = 0.023) and duration of follow up (0.04, 0.01-0.06, p = 0.004). CONCLUSION: In patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy. Trial registration NCT02431234.

Correction: Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes.

[This corrects the article DOI: 10.1371/journal.pone.0229145.].

Patterns of multimorbidity in medical inpatients: a multinational retrospective cohort study.

Multimorbidity is frequent and represents a significant burden for patients and healthcare systems. However, there are limited data on the most common combinations of comorbidities in multimorbid patients. We aimed to describe and quantify the most common combinations of comorbidities in multimorbid medical inpatients. We used a large retrospective cohort of adults discharged from the medical department of 11 hospitals across 3 countries (USA, Switzerland, and Israel) between 2010 and 2011. Diseases were classified into acute versus chronic. Chronic diseases were grouped into clinically meaningful categories of comorbidities. We identified the most prevalent combinations of comorbidities and compared the observed and expected prevalence of the combinations. We assessed the distribution of acute and chronic diseases and the median number of body systems in relationship to the total number of diseases. Eighty-six percent (n = 126,828/147,806) of the patients were multimorbid (≥ 2 chronic diseases), with a median of five chronic diseases; 13% of the patients had ≥ 10 chronic diseases. Among the most frequent combinations of comorbidities, the most prevalent comorbidity was chronic heart disease. Other high prevalent comorbidities included mood disorders, arthropathy and arthritis, and esophageal disorders. The ratio of chronic versus acute diseases was approximately 2:1. Multimorbidity affected almost 90% of patients, with a median of five chronic diseases. Over 10% had ≥ 10 chronic diseases. This identification and quantification of frequent combinations of comorbidities among multimorbid medical inpatients may increase awareness of what should be taken into account when treating such patients, a growth in the need for special care considerations.

Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes.

AIMS/HYPOTHESIS: Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP. METHODS: 198 patients with Type 2 Diabetes were included. Presence of sensitive diabetic neuropathy was defined by a neuropathy disability score (NDS) ≥6. Plasma levels of dp-ucMGP were measured by ELISA. RESULTS: In this cohort, the mean age was 64+/-8.4 years old, and 80% of patients were men. Peripheral neuropathy was present in 15.7% of the patients and was significantly associated (r = 0.51, p<0.0001) with dp-ucMGP levels (ß = -0.26, p = 0.045) after integrating effects of height (ß = -0.38, p = 0.01), insulin treatment (ß = 0.42, p = 0.002), retinopathy treated by laser (ß = 0.26, p = 0.02), and total cholesterol levels (ß = 0.3, p = 0.03) by multivariable analysis. CONCLUSIONS: The association between diabetic neuropathy and the inactive form of MGP suggests the existence of new pathophysiological pathways to explore. Further studies are needed to determine if dp-ucMGP may be used as a biomarker of sensitive neuropathy. Since dp-ucMGP is a marker of poor vitamin K status, clinical studies are warranted to explore the potential protective effect of high vitamin K intake on diabetic peripheral neuropathy.

Prevalence of potentially inappropriate prescribing in a subpopulation of older European clinical trial participants: a cross-sectional study.

OBJECTIVES: To estimate and compare the prevalence and type of potentially inappropriate prescribing (PIP) and potential prescribing omissions (PPOs) among community-dwelling older adults (≥65 years) enrolled to a clinical trial in three European countries. DESIGN: A secondary analysis of the Thyroid Hormone Replacement for Subclinical Hypothyroidism Trial dataset. PARTICIPANTS: A subset of 48/80 PIP and 22/34 PPOs indicators from the Screening Tool of Older Persons Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) V2 criteria were applied to prescribed medication data for 532/737 trial participants in Ireland, Switzerland and the Netherlands. RESULTS: The overall prevalence of PIP was lower in the Irish participants (8.7%) compared with the Swiss (16.7%) and Dutch (12.5%) participants (P=0.15) and was not statistically significant. The overall prevalence of PPOs was approximately one-quarter in the Swiss (25.3%) and Dutch (24%) participants and lower in the Irish (14%) participants (P=0.04) and the difference was statistically significant. The hypnotic Z-drugs were the most frequent PIP in Irish participants, (3.5%, n=4), while it was non-steroidal anti-inflammatory drug and oral anticoagulant combination, sulfonylureas with a long duration of action, and benzodiazepines (all 4.3%, n=7) in Swiss, and benzodiazepines (7.1%, n=18) in Dutch participants. The most frequent PPOs in Irish participants were vitamin D and calcium in osteoporosis (3.5%, n=4). In the Swiss and Dutch participants, they were bone antiresorptive/anabolic therapy in osteoporosis (9.9%, n=16, 8.6%, n=22) respectively. The odds of any PIP after adjusting for age, sex, multimorbidity and polypharmacy were (adjusted OR (aOR)) 3.04 (95% CI 1.33 to 6.95, P<0.01) for Swiss participants and aOR 1.74 (95% CI 0.79 to 3.85, P=0.17) for Dutch participants compared with Irish participants. The odds of any PPOs were aOR 2.48 (95% CI 1.27 to 4.85, P<0.01) for Swiss participants and aOR 2.10 (95% CI 1.11 to 3.96, P=0.02) for Dutch participants compared with Irish participants. CONCLUSIONS: This study has estimated and compared the prevalence and type of PIP and PPOs among this cohort of community-dwelling older people. It demonstrated a significant difference in the prevalence of PPOs between the three populations. Further research is urgently needed into the impact of system level factors as this has important implications for patient safety, healthcare provision and economic costs.

Association between metformin use and below-the-knee arterial calcification score in type 2 diabetic patients.

BACKGROUND: Vascular calcification (VC) is common in type 2 diabetes, and is associated with cardiovascular complications. Recent preclinical data suggest that metformin inhibits VC both in vitro and in animal models. However, metformin's effects in patients with diabetic VC have not previously been characterized. The present study investigated the association between metformin use and lower-limb arterial calcification in patients with type 2 diabetes and high cardiovascular risk. METHODS: The DIACART cross-sectional cohort study included 198 patients with type 2 diabetes but without severe chronic kidney disease. Below-the-knee calcification scores were assessed by computed tomography and supplemented by colour duplex ultrasonography. Data on anti-diabetic drugs were carefully collected from the patients' medical records and during patient interviews. Biochemical and clinical data were studied as potential confounding factors. RESULTS: Metformin-treated patients had a significantly lower calcification score than metformin-free patients (mean ± standard deviation: 2033 ± 4514 and 4684 ± 9291, respectively; p = 0.01). A univariate analysis showed that metformin was associated with a significantly lower prevalence of severe below-the-knee arterial calcification (p = 0.02). VC was not significantly associated with the use of other antidiabetic drugs, including sulfonylureas, insulin, gliptin, and glucagon like peptide-1 analogues. A multivariate logistic regression analysis indicated that the association between metformin use and calcification score (odds ratio [95% confidence interval] = 0.33 [0.11-0.98]; p = 0.045) was independent of age, gender, tobacco use, renal function, previous cardiovascular disease, diabetes duration, neuropathy, retinopathy, HbA1c levels, and inflammation. CONCLUSIONS: In patients with type 2 diabetes, metformin use was independently associated with a lower below-the-knee arterial calcification score. This association may contribute to metformin's well-known vascular protective effect. Further prospective investigations of metformin's potential ability to inhibit VC in patients with and without type 2 diabetes are now needed to confirm these results.

Prospective validation and adaptation of the HOSPITAL score to predict high risk of unplanned readmission of medical patients.

PRINCIPLES: The HOSPITAL score is a simple prediction model that accurately identifies patients at high risk of readmission and showed good performance in an international multicentre retrospective study. We aimed to demonstrate prospectively its accuracy to predict 30-day unplanned readmission and death. METHODS: We prospectively screened all consecutive patients aged ≥50 years admitted to the department of general internal medicine of a large community hospital in Switzerland. We excluded patients who refused to give consent, who died during hospitalisation, or who were transferred to another acute care, rehabilitation or palliative care facility. The primary outcome was the first unplanned readmission or death within 30 days after discharge. Some of the predictors of the original score (discharge from an oncology service and length of stay) were adapted according to the setting for practical reasons, before the start of patient inclusion. We also assessed a simplified version of the score, without the variable "any procedure performed during hospitalisation". The performance of the score was evaluated according to its overall accuracy (Brier score), its discriminatory power (C-statistic), and its calibration (Hosmer-Lemeshow goodness-of-fit test). RESULTS: Among the 346 included patients, 40 (11.6%) had a 30-day unplanned readmission or death. The HOSPITAL score showed very good accuracy (Brier score 0.10), good discriminatory power (C-statistic 0.70, 95% confidence interval [CI] 0.62-0.79), and an excellent calibration (p = 0.77). Patients were classified into three risk categories for the primary outcome: low (59%), intermediate (20.8%) and high risk (20.2%). The estimated risks of unplanned readmission/death for each category were 8.2%, 11.3% and 21.6%, respectively. The simplified score showed the same performance, with a Brier score of 0.10, a C-statistic of 0.70 (95% CI 0.61-0.79), and a goodness-of-fit statistic of 0.40. CONCLUSIONS: The HOSPITAL score prospectively identified patients at high risk of 30-day unplanned readmission or death with good performance in medical patients in Switzerland. Its simplicity and good performance make it an easy-to-use tool to target patients who might most benefit from intensive transitional care interventions.

Below-knee arterial calcification in type 2 diabetes: association with receptor activator of nuclear factor κB ligand, osteoprotegerin, and neuropathy.

CONTEXT: Calcification of the arterial wall in diabetes contributes to the arterial occlusive process occurring below the knee. The osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) system is suspected to be involved in the calcification process. OBJECTIVE: The aim of the study was to investigate whether there is a link between arterial calcification in type 2 diabetes and 1) conventional cardiovascular risk factors, 2) serum RANKL and OPG levels, and 3) neuropathy. PATIENTS AND METHODS: We objectively scored, in a cross-sectional study, infrapopliteal vascular calcification using computed tomography scanning in 198 patients with type 2 diabetes, a high cardiovascular risk, and a glomerular filtration rate >30 mL/min. Color duplex ultrasonography was performed to assess peripheral arterial occlusive disease, and mediacalcosis. Peripheral neuropathy was defined by a neuropathy disability score >6. RANKL and OPG were measured in the serum by routine chemistry. RESULTS: Below-knee arterial calcification was associated with arterial occlusive disease. In multivariate logistic regression analysis, the variables significantly and independently associated with the calcification score were age (odds ratio [OR] = 1.08; 95% confidence interval [CI] = 1.04-1.13; P < .0001), male gender (OR = 3.53; 95% CI = 1.54-8.08; P = .003), previous cardiovascular disease (OR = 2.78; 95% CI = 1.39-5.59; P = .005), and neuropathy disability score (per 1 point, OR = 1.21; 95% CI = 1.05-1.38; P = .006). The association with ln OPG, significantly associated with calcification score in univariate analysis (OR = 3.14; 95% CI = 1.05-9.40; P = .045), was no longer significant in multivariate analysis. RANKL and OPG/RANKL were not significantly associated with the calcification score. CONCLUSIONS: Below-knee arterial calcification severity is clearly correlated with peripheral neuropathy severity and with several usual cardiovascular risk factors, but not with serum RANKL level.

Vascular calcification in patients with type 2 diabetes: the involvement of matrix Gla protein.

BACKGROUND: Matrix Gla protein (MGP) is an important inhibitor of calcification. The objective of the present study of patients with type 2 diabetes and normal or slightly altered kidney function was to evaluate levels of inactive, dephospho-uncarboxylated MGP(dp-ucMGP) and total uncarboxylated MGP(t-ucMGP) and assess their links with biological and clinical parameters (including peripheral vascular calcification). METHODS: The DIACART study is a cross-sectional cohort study of 198 patients with type 2 diabetes and normal or slightly altered kidney function. Matrix Gla protein levels were measured with an ELISA and all patients underwent multislice spiral computed tomography scans to score below-knee arterial calcification. RESULTS: In the study population as a whole, the mean dp-ucMGP and t-ucMGP levels were 627 ± 451 pM and 4868 ± 1613 nM, respectively. Glomerular filtration rate, age and current vitamin K antagonist use were independently associated with dp-ucMGP levels. When the study population was divided according to the median peripheral arterial calcification score, patients with the higher score displayed significantly lower t-ucMGP and significantly higher dp-ucMGP levels. Furthermore, plasma dp-ucMGP was positively associated with the peripheral arterial calcification score (independently of age, gender, previous cardiovascular disease and t-ucMGP levels). CONCLUSIONS: High dp-ucMGP levels were independently associated with below-knee arterial calcification score in patients with type 2 diabetes and normal or slightly altered kidney function. The reversibility of the elevation of dp-ucMGP levels and the latter's relationship with clinical events merit further investigation.