Prevalence and outcomes of heart failure phenotypes in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF). Real-world data about long-term outcomes and rhythm control interventions use in AF patients with and without HF remain scarce. METHODS: AF patients from two prospective, multicentre studies were classified based on the HF status at baseline into: HF with preserved ejection fraction (HFpEF), HF with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF), and no HF. The prespecified primary outcome was risk of HF hospitalisation. Other outcomes of interest included mortality, cardiovascular events, AF progression, and quality of life. RESULTS: A total of 1265 patients with AF were analysed (mean age 69.6 years, women 27.4%) with a median follow-up of 5.98 years. Patients with HFpEF (n = 126) had a 2.69-fold and patients with HFrEF/HFmrEF (n = 308) had a 2.12-fold increased risk of HF hospitalisation compared to patients without HF (n = 831, p < 0.001). Similar results applied for all-cause and cardiovascular mortality. The risk for AF progression was higher for patients with HFpEF and HFrEF/HFmrEF (6.30 and 6.79 per 100 patient-years, respectively) compared to patients without HF (4.20). The use of rhythm control strategies during follow-up was least in the HFpEF population (4.56 per 100 patient-years) compared to 7.74 in HFrEF/HFmrEF and 8.03 in patients with no HF. With regards to quality of life over time, this was worst among HFpEF patients. CONCLUSIONS: The presence of HFpEF among patients with AF carried a high risk of HF hospitalisations and AF progression, and worse quality of life. Rhythm control interventions were rarely offered to HFpEF patients. These results uncover an unmet need for enhanced therapeutic interventions in patients with AF and HFpEF.

Association between severity of pulmonary embolism and health-related quality of life.

Background: Health-related quality of life (QoL) impairment is common after pulmonary embolism (PE). Whether the severity of the initial PE has an impact on QoL is unknown. Objectives: To evaluate the association between severity of PE and QoL over time. Methods: We prospectively assessed PE-specific QoL using the Pulmonary Embolism Quality of Life (lower scores indicate better QoL) questionnaire and generic QoL using the Short Form 36 (higher scores indicate better QoL) questionnaire at baseline and 3 and 12 months in older patients with acute PE. We examined whether QoL differed by PE severity based on hemodynamic status, simplified Pulmonary Embolism Severity Index (sPESI), right ventricular function, and high-sensitivity troponin T in mixed-effects models, adjusting for known QoL predictors after PE. Results: Among 546 patients with PE (median age, 74 years), severe vs nonsevere PE based on the sPESI was associated with a worse PE-specific (adjusted mean Pulmonary Embolism Quality of Life score difference of 6.1 [95% CI, 2.4-9.8] at baseline, 7.6 [95% CI, 4.0-11.3] at 3 months, and 6.7 [95% CI, 2.9-10.4] at 12 months) and physical generic QoL (adjusted mean Short Form 36 Physical Component Summary score difference of -3.8 [95% CI, -5.5 to -2.1] at baseline, -4.8 [95% CI, -6.4 to -3.1] at 3 months, and -4.1 [95% CI, -5.8 to -2.3] at 12 months). Elevated troponin levels were also associated with lower PE-specific QoL at 3 months and lower physical generic QoL at 3 and 12 months. QoL did not differ by hemodynamic status or right ventricular function. Conclusion: Severe PE based on the sPESI was consistently associated with worse PE-specific and physical generic QoL over time as compared to nonsevere PE.

Risk factors for falls among hospitalized medical patients - A systematic review and meta-analysis.

OBJECTIVE: To identify and quantify risk factors for in-hospital falls in medical patients. DATA SOURCES: Six databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, and Google Scholar) were systematically screened until April 11, 2023, to identify relevant articles. STUDY SELECTION: All titles and abstracts of the retrieved articles were independently screened by two researchers who also read the full texts of the remaining articles. Quantitative studies that assessed risk factors for falls among adult patients acutely hospitalized were included in the review. Publications that did not capture internal medicine patients or focused on other specific populations were excluded. DATA EXTRACTION: Information on study characteristics and potential risk factors were systematically extracted. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. PRISMA and MOOSE guidelines were followed for reporting. DATA SYNTHESIS: The main outcome was any in-hospital falls. Using a random-effects meta-analysis model, association measures for each risk factor reported in five or more studies were pooled. Separate analyses according to effect measure and studies adjusted for sex and age at least were performed. Of 5,067 records retrieved, 119 original publications from 25 countries were included. In conclusion, 23 potential risk factors were meta-analyzed. Strong evidence with large effect sizes was found for a history of falls (OR 2.54; 95% CI 1.63- 3.96; I2 91%), antidepressants (pooled OR 2.25; 95% confidence interval [95% CI] 1.92-2.65; I2 0%), benzodiazepines (OR 1.97; 95% CI 1.68-2.31; I2 0%), hypnotics-sedatives (OR 1.90; 95% CI 1.53-2.36; I2 46%), and antipsychotics (OR 1.61; 95% CI 1.33-1.95; I2 0%). Furthermore, evidence of associations with male sex (OR 1.22, 95% CI 0.99-1.50, I2 65%) and age (OR 1.17, 95% CI 1.02-1.35, I2 72%) were found, but effect sizes were small. CONCLUSIONS: The comprehensive list of risk factors, which specifies the strength of evidence and effect sizes, could assist in the prioritization of preventive measures and interventions.

Association Between Patient Sex and Familial Hypercholesterolemia and Long-Term Cardiovascular Risk Factor Management 5 Years After Acute Coronary Syndrome.

BACKGROUND: Long-term control of cardiovascular risk factors after acute coronary syndrome (ACS) is the cornerstone for preventing recurrence. We investigated the extent of cardiovascular risk factor management in males and females with and without familial hypercholesterolemia (FH) 5 years after ACS. METHODS: We studied patients hospitalized for ACS between 2009 and 2017 in a Swiss multicenter prospective cohort study. FH was defined based on clinical criteria from the Dutch Lipid Clinic Network and Simon Broome definitions. Five years post-ACS, we assessed low-density lipoprotein-cholesterol (LDL-c) levels, lipid-lowering therapy (LLT), and other cardiovascular risk factors, comparing males to females with and without FH using generalized estimating equations. RESULTS: A total of 3139 patients were included; mean age was 61.4 years (SD, 12.1), 620 (19.8%) were female, and 747 (23.5%) had possible FH. Compared with males at 5-years post-ACS, females were more likely to not use statins (odds ratio, 1.61 [95% CI, 1.28-2.03]) and less likely to have combination LLT (odds ratio, 0.72 [95% CI, 0.55-0.93]), without difference between patients with FH and without FH. Females in both FH and non-FH groups less frequently reached LDL-c values ≤1.8 mmol/L (odds ratio, 0.78 [95% CI, 0.78-0.93]). Overall, patients with FH were more frequently on high-dose statins compared with patients without FH (51.0% versus 42.9%; P=0.001) and presented more frequently with a combination of 2 or more LLT compared with patients without FH (33.8% versus 17.7%; P<0.001), but less frequently reached LDL-c targets of ≤1.8 mmol/L (33.5% versus 44.3%; P<0.001) or ≤2.6 mmol/L (70.2% versus 78.1%; P=0.001). CONCLUSIONS: Five years after ACS, females had less intensive LLT and were less likely to reach target LDL-c levels than males, regardless of FH status. Males and females with FH had less optimal control of LDL-c despite more frequently taking high-dose statins or combination LLT compared with patients without FH. Long-term management of patients with ACS and FH, especially females, warrants optimization.

Heart rate variability and stroke or systemic embolism in patients with atrial fibrillation.

BACKGROUND: Stroke remains one of the most serious complications in atrial fibrillation (AF) patients and has been linked to disturbances of the autonomic nervous system. OBJECTIVE: The purpose of this study was to test the hypothesis that impaired cardiac autonomic function might be associated with an enhanced stroke risk in AF patients. METHODS: A total of 1922 AF patients who were in either sinus rhythm (SR group; n = 1121) or AF (AF group; n = 801) on a 5-minute resting electrocardiographic (ECG) recording were enrolled in the study. Heart rate variability triangular index (HRVI), standard deviation of normal-to-normal intervals, root mean square root of successive differences of normal-to-normal intervals, mean heart rate, 5-minute total power, and power in the high-frequency, low-frequency, and very-low-frequency ranges were calculated. Cox regression models were constructed to examine the association of heart rate variability (HRV) parameters with the composite endpoint of stroke or systemic embolism. RESULTS: Mean age was 71 ± 8 years in the SR group and 75 ± 8 years in the AF group. Thirty-seven patients in the SR group (3.4%) and 60 patients in the AF group (8.0%) experienced a stroke or systemic embolism during follow-up of 5 years. In patients with SR, HRVI <15 was the strongest HRV parameter to be associated with stroke or systemic embolism (hazard ratio 3.04; 95% confidence interval 1.3-7.0; P = .009) after adjustment for multiple confounders. In the AF group, no HRV parameter was found to be associated with the composite endpoint. CONCLUSION: HRVI measured during SR on a single 5-minute ECG recording is independently associated with stroke or systemic embolism in AF patients. HRV analysis in SR may help to improve risk stratification in AF patients.

Barriers, facilitators and needs to deprescribe benzodiazepines and other sedatives in older adults: a mixed methods study of primary care provider perspectives.

BACKGROUND: Benzodiazepines and other sedative hypnotic drugs (BSHs) are frequently prescribed for sleep problems, but cause substantial adverse effects, particularly in older adults. Improving knowledge on barriers, facilitators and needs of primary care providers (PCPs) to BSH deprescribing could help reduce BSH use and thus negative effects. METHODS: We conducted a mixed methods study (February-May 2023) including a survey, semi-structured interviews and focus groups with PCPs in Switzerland. We assessed barriers, facilitators and needs of PCPs to BSH deprescribing. Quantitative data were analyzed descriptively, qualitative data deductively and inductively using the Theoretical Domain Framework (TDF). Quantitative and qualitative data were integrated using meta-interferences. RESULTS: The survey was completed by 126 PCPs (53% female) and 16 PCPs participated to a focus group or individual interview. The main barriers to BSH deprescribing included patient and PCP lack of knowledge on BSH effects and side effects, lack of PCP education on treatment of sleep problems and BSH deprescribing, patient lack of motivation, PCP lack of time, limited access to cognitive behavioral therapy for insomnia and absence of public dialogue on BSHs. Facilitators included informing on side effects to motivate patients to discontinue BSHs and start of deprescribing during a hospitalization. Main PCP needs were practical recommendations for pharmacological and non-pharmacological treatment of sleep problems and deprescribing schemes. Patient brochures were wished by 69% of PCPs. PCPs suggested the brochures to contain explanations about risks and benefits of BSHs, sleep hygiene and sleep physiology, alternative treatments, discontinuation process and tapering schemes. CONCLUSION: The barriers and facilitators as well as PCP needs and opinions on patient material we identified can be used to develop PCP training and material on BSH deprescribing, which could help reduce the inappropriate use of BSHs for sleep problems.

Patient-Reported Satisfaction with Thyroid Hormone Replacement Therapy for Subclinical Hypothyroidism in Older Adults: A Pooled Analysis of Individual Participant Data from Two Randomized Controlled Trials.

Background: The benefit of levothyroxine treatment of subclinical hypothyroidism (SCH) is subject to debate. This study compared treatment satisfaction between older adults with SCH using levothyroxine or placebo. Methods: We analyzed pooled individual participant data from two randomized, double-blind, placebo-controlled trials investigating the effects of levothyroxine treatment in older adults with SCH. Community-dwelling participants aged ≥65 years, with SCH (persistent thyrotropin levels 4.60-19.99 mIU/L for >3 months and normal free T4 level), were included. Intervention dose titration until thyrotropin levels normalized, with a mock dose adjustment of placebo. Treatment satisfaction was determined during the final study visit using the Treatment Satisfaction Questionnaire for Medication (TSQM), encompassing perceived effectiveness, side effects, convenience, and global satisfaction, along with the participants' desire to continue study medication after the trial. Results: We included 536 participants. At baseline, the median (interquartile range [IQR]) age was 74.9 (69.7-81.4) years, and 292 (55%) were women. The median (IQR) thyrotropin levels were 5.80 (5.10-7.00) mIU/L at baseline in both groups; at final visit, 4.97 (3.90-6.35) mIU/L in the placebo and 3.24 (2.49-4.41) mIU/L in the levothyroxine group. After treatment, the groups did not differ significantly in global satisfaction (mean difference [CI] -1.1 [-4.5 to 2.1], p = 0.48), nor in any other domain of treatment satisfaction. These results held true regardless of baseline thyrotropin levels or symptom burden. No major differences were found in the numbers of participants who wished to continue medication after the trial (levothyroxine 35% vs. placebo 27%), did not wish to continue (levothyroxine 27% vs. placebo 30%), or did not know (levothyroxine 37% vs. placebo 42%) (p = 0.14). In a subpopulation with high symptom burden from hypothyroid symptoms at baseline, those using levothyroxine more often desired to continue the medication after the trial than those using placebo (mean difference [CI]: -21.1% [-35.6% to -6.5%]). Conclusion: These pooled data from two RCTs showed no major differences in treatment satisfaction between older adults receiving levothyroxine or placebo. This finding has important implications for decision-making regarding initiating levothyroxine treatment for SCH. Our findings generally support refraining from routinely prescribing levothyroxine in older adults with SCH.

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.

A mixed methods analysis of the medication review intervention centered around the use of the 'Systematic Tool to Reduce Inappropriate Prescribing' Assistant (STRIPA) in Swiss primary care practices.

BACKGROUND: Electronic clinical decision support systems (eCDSS), such as the 'Systematic Tool to Reduce Inappropriate Prescribing' Assistant (STRIPA), have become promising tools for assisting general practitioners (GPs) with conducting medication reviews in older adults. Little is known about how GPs perceive eCDSS-assisted recommendations for pharmacotherapy optimization. The aim of this study was to explore the implementation of a medication review intervention centered around STRIPA in the 'Optimising PharmacoTherapy In the multimorbid elderly in primary CAre' (OPTICA) trial. METHODS: We used an explanatory mixed methods design combining quantitative and qualitative data. First, quantitative data about the acceptance and implementation of eCDSS-generated recommendations from GPs (n = 21) and their patients (n = 160) in the OPTICA intervention group were collected. Then, semi-structured qualitative interviews were conducted with GPs from the OPTICA intervention group (n = 8), and interview data were analyzed through thematic analysis. RESULTS: In quantitative findings, GPs reported averages of 13 min spent per patient preparing the eCDSS, 10 min performing medication reviews, and 5 min discussing prescribing recommendations with patients. On average, out of the mean generated 3.7 recommendations (SD=1.8). One recommendation to stop or start a medication was reported to be implemented per patient in the intervention group (SD=1.2). Overall, GPs found the STRIPA useful and acceptable. They particularly appreciated its ability to generate recommendations based on large amounts of patient information. During qualitative interviews, GPs reported the main reasons for limited implementation of STRIPA were related to problems with data sourcing (e.g., incomplete data imports), preparation of the eCDSS (e.g., time expenditure for updating and adapting information), its functionality (e.g., technical problems downloading PDF recommendation reports), and appropriateness of recommendations. CONCLUSIONS: Qualitative findings help explain the relatively low implementation of recommendations demonstrated by quantitative findings, but also show GPs' overall acceptance of STRIPA. Our results provide crucial insights for adapting STRIPA to make it more suitable for regular use in future primary care settings (e.g., necessity to improve data imports). TRIAL REGISTRATION: Clinicaltrials.gov NCT03724539, date of first registration: 29/10/2018.

[For which patients do the latest lipid lowering treatments reduce cardiovascular events?] / Pour quels patients les nouveaux traitements hypolipémiants réduisent-ils les événements cardiovasculaires ?

Dyslipidemia is a modifiable risk factor for cardiovascular diseases. Recommendations are based on achieving LDL-C target levels, but it is essential to assess the benefits of intensifying lipid-lowering therapy in terms of absolute risk reduction of cardiovascular events across different risk groups. Current data on the absolute benefits of the latest lipid-lowering treatments are more limited in comparison with statins. A recent analysis showed that adding a second lipid-lowering treatment only reduces the absolute cardiovascular risk in patients at very high and high cardiovascular risk, without a substantial benefit in patients at moderate or low cardiovascular risk, as mentioned in the recent recommendations free of conflict of interest and published in the British Medical Journal.

La dyslipidémie est un facteur de risque modifiable des maladies cardiovasculaires. Les recommandations sont basées sur l'atteinte de valeurs cibles du LDL-C mais il est essentiel d'évaluer les avantages de l'intensification du traitement hypolipémiant en termes de réduction du risque absolu d'événements cardiovasculaires dans les différents groupes à risque. Les données actuelles sur le bénéfice des nouveaux traitements hypolipémiants sont plus limitées comparées aux statines. Une analyse récente a montré que l'addition d'un second traitement hypolipémiant réduit le risque cardiovasculaire (CV) absolu uniquement chez les patients avec un risque CV très élevé ou élevé, sans bénéfice absolu substantiel chez les patients à risque CV modéré ou faible, ce qui a été repris des recommandations internationales sans conflit d'intérêts dans le British Medical Journal.

[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.

Patients on vitamin K treatment: is switching to direct-acting oral anticoagulation cost-effective? A target trial on a prospective cohort.

AIMS: Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment. METHODS: The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment. RESULTS: 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained. CONCLUSIONS: Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial.

Effect of dairy consumption on cognition in older adults: A population-based cohort study.

OBJECTIVE: We aimed to assess the effect on cognitive function of adding dairy (total, fermented, non-fermented, full fat, low fat, and sugary) to the diet and of substituting some food groups for dairy. DESIGN: Secondary analysis of a prospective population-based cohort study. PARTICIPANTS: We analyzed data from 1334 cognitively healthy participants (median age 67 years at baseline) with a mean follow-up of 5.6 years from the CoLaus|PsyColaus cohort in Lausanne, Switzerland. MEASUREMENTS: The participants completed a food frequency questionnaire at baseline and cognitive tests at baseline and at follow-up. Clinical dementia rating was the primary outcome. Subjective cognitive decline, memory, verbal fluency, executive and motor functions were secondary outcomes. METHODS: Our exposure was the consumption of total and 5 sub-types of dairy products (g/d). We used marginal structural models to compute average causal effects of 1) increasing dairy consumption by 100 g/d and 2) substituting 100 g/d of meat, fish, eggs, fruits and vegetables with dairy on the outcomes. We used inverse probability of the treatment and lost to follow-up weighting to account for measured confounding and non-random loss to follow-up. RESULTS: Overall, the effects of adding dairy products to the diet on cognition were negligible and imprecise. No substitution had a substantial and consistent effect on clinical dementia rating. The substitution of fish [11.7% (-3% to 26.5%)] and eggs [18% (2.3%-33.7%)] for dairy products could negatively impact verbal memory and neurolinguistic processes. CONCLUSION: We found no effect of adding dairy to the diet or substituting meat, vegetables or fruit for dairy on cognitive function in this cohort of older adults. The substitution of fish and eggs for dairy could have a negative effect on some secondary outcomes, but more studies modeling food substitutions are needed to confirm these results.

Lipid-Lowering Therapy and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin low-density lipoprotein-cholesterol (LDL-C)- and triglyceride-lowering therapies. METHODS AND RESULTS: We performed a systematic review of large randomized clinical trials (≥1000 patients with ≥2 years follow-up) of LDL-C-lowering therapy (statin, ezetimibe, and PCSK-9 [proprotein convertase subtilisin/kexin type 9] inhibitor) and triglyceride-lowering therapy (omega-3 supplements and fibrate) that reported hemorrhagic stroke as an outcome. We searched MEDLINE, Embase, and Cochrane Library up to July 2, 2021 and updated a meta-analysis of cardiovascular statin trials published in 2012. Among our several subgroup analyses, we looked at difference depending on stroke status and also depending on age. We identified 37 trials for LDL-C lowering (284 301 participants) and 11 for triglyceride lowering (120 984 participants). Overall, we found a higher risk of hemorrhagic stroke for LDL-C lowering, risk ratio (RR) 1.16 (95% CI, 1.01-1.32, P=0.03). For statins (33 trials, 216 258 participants), RR=1.17 (95% CI, 1.01-1.36); for PCSK-9 inhibitors (2 trials, 46 488 participants), RR=0.86 (95% CI, 0.43-1.74); and for ezetimibe (2 trials, 21 555 participants), RR=1.14 (95% CI, 0.64-2.03). In statin trials of patients with previous stroke/transient ischemic attack, RR was 1.46 (95% CI, 1.05-2.04), and in trials with mean age ≥65 years old, RR=1.34 (95% CI, 1.04-1.73) (Pint=0.14 and Pint=0.23 respectively); for triglyceride lowering (11 trials, 120 984 participants), RR=1.05 (95% CI, 0.86-1.30). CONCLUSIONS: We found evidence for a small increased risk of hemorrhagic stroke events with LDL-C-lowering therapies but no clear evidence for triglyceride-lowering therapies. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42021275363.

Is there a shift from cardiovascular to cancer death in lipid-lowering trials? A systematic review and meta-analysis.

BACKGROUND: Lipid-lowering therapy (LLT) reduces cardiovascular (CV) events, but data are conflicting on all-cause mortality, especially among older adults. Though LLT does not induce cancer, some randomized clinical trials (RCTs) found a pattern of increased cancer death under LLT. Our objective was to assess a possible shift from CV to cancer death in LLT trials (i.e. an increase in cancer and decrease in CV death) and to investigate potential subgroups at risk. METHODS: We performed a systematic review and meta-analysis. We retrieved RCTs from MEDLINE, Embase, and Cochrane Central until 08/2023. We extracted the number of CV and cancer deaths in the treatment vs. in the control arm, calculated the relative risk (RR) by dividing the risk of death in the treatment over the risk of death in the control group and then pooled them using random-effect meta-analysis. We performed subgroup analyses on primary and secondary prevention, and according to different age cut-offs. RESULTS: We included 27 trials with 188'259 participants (23 statin; 4 ezetimibe trials). The trials reported 4056 cancer deaths, 2061 under LLT and 1995 in control groups. Overall, there was no increased risk of cancer mortality (RR 1.03, 95% confidence interval 0.97-1.10), with no difference between primary and secondary prevention. In the subgroup analyses for RCTs with ≥15% of participants aged ≥75 years, the RR of cancer death was 1.11 (1.00-1.23), while the RR for CV death was 0.96 (0.91-1.01). For RCTs with a mean age ≥ 70 years, the RR for cancer death was 1.21 (0.99-1.47). CONCLUSION: LLT does not lead to a shift from CV to cancer death. However, there might be a possible shift with a pattern of increased cancer deaths in trials with more older adults, particularly ≥75 years. Individual participant data from LLT trials should be made public to allow further investigations. PROSPERO REGISTRATION: CRD42021271658.

Electronic Nicotine-Delivery Systems for Smoking Cessation.

BACKGROUND: Electronic nicotine-delivery systems - also called e-cigarettes - are used by some tobacco smokers to assist with quitting. Evidence regarding the efficacy and safety of these systems is needed. METHODS: In this open-label, controlled trial, we randomly assigned adults who were smoking at least five tobacco cigarettes per day and who wanted to set a quit date to an intervention group, which received free e-cigarettes and e-liquids, standard-of-care smoking-cessation counseling, and optional (not free) nicotine-replacement therapy, or to a control group, which received standard counseling and a voucher, which they could use for any purpose, including nicotine-replacement therapy. The primary outcome was biochemically validated, continuous abstinence from smoking at 6 months. Secondary outcomes included participant-reported abstinence from tobacco and from any nicotine (including smoking, e-cigarettes, and nicotine-replacement therapy) at 6 months, respiratory symptoms, and serious adverse events. RESULTS: A total of 1246 participants underwent randomization; 622 participants were assigned to the intervention group, and 624 to the control group. The percentage of participants with validated continuous abstinence from tobacco smoking was 28.9% in the intervention group and 16.3% in the control group (relative risk, 1.77; 95% confidence interval, 1.43 to 2.20). The percentage of participants who abstained from smoking in the 7 days before the 6-month visit was 59.6% in the intervention group and 38.5% in the control group, but the percentage who abstained from any nicotine use was 20.1% in the intervention group and 33.7% in the control group. Serious adverse events occurred in 25 participants (4.0%) in the intervention group and in 31 (5.0%) in the control group; adverse events occurred in 272 participants (43.7%) and 229 participants (36.7%), respectively. CONCLUSIONS: The addition of e-cigarettes to standard smoking-cessation counseling resulted in greater abstinence from tobacco use among smokers than smoking-cessation counseling alone. (Funded by the Swiss National Science Foundation and others; ESTxENDS ClinicalTrials.gov number, NCT03589989.).

Regional variation and temporal trends in transcatheter and surgical aortic valve replacement in Switzerland: A population-based small area analysis.

BACKGROUND: Aortic valve stenosis (AS) is the most common valvular heart disease and if severe, is treated with either transcatheter (TAVR) or surgical aortic valve replacement (SAVR). We assessed temporal trends and regional variation of these interventions in Switzerland and examined potential determinants of geographic variation. METHODS: We conducted a population-based analysis using patient discharge data from all Swiss public and private acute care hospitals from 2013 to 2018. We generated hospital service areas (HSAs) based on patient flows for TAVR. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). Using multilevel regression, we calculated the influence of calendar year and regional demographics, socioeconomic factors (language, insurance status), burden of disease, and number of cardiologists/cardiovascular surgeons on geographic variation. RESULTS: Overall, 8074 TAVR and 11,825 SAVR procedures were performed in 8 HSAs from 2013 to 2018. Whereas the age-/sex-standardized rate of TAVR increased from 12 to 22 procedures/100,000 persons, the SAVR rate decreased from 33 to 24 procedures during this period. After full adjustment, the predicted TAVR and SAVR rates varied from 12 to 22 and 20 to 35 per 100,000 persons across HSAs, respectively. The regional procedure variation was low to moderate over time, with a low overall variation in TAVR (EQ 1.9, SCV 3.9) and SAVR (EQ 1.6, SCV 2.2). In multilevel regression, TAVR rates increased annually by 10% and SAVR rates decreased by 5%. Determinants of higher TAVR rates were older age, male sex, living in a German speaking area, and higher burden of disease. A higher proportion of (semi)private insurance was also associated with higher TAVR and lower SAVR rates. After full adjustment, 10.6% of the variance in TAVR and 18.4% of the variance in SAVR remained unexplained. Most variance in TAVR and SAVR rates was explained by language region and insurance status. CONCLUSION: The geographic variation in TAVR and SAVR rates was low to moderate across Swiss regions and largely explained by differences in regional demographics and socioeconomic factors. The use of TAVR increased at the expense of SAVR over time.

Large regional variation in cardiac closure procedures to prevent ischemic stroke in Switzerland a population-based small area analysis.

BACKGROUND: Percutaneous closure of a patent foramen ovale (PFO) or the left atrial appendage (LAA) are controversial procedures to prevent stroke but often used in clinical practice. We assessed the regional variation of these interventions and explored potential determinants of such a variation. METHODS: We conducted a population-based analysis using patient discharge data from all Swiss hospitals from 2013-2018. We derived hospital service areas (HSAs) using patient flows for PFO and LAA closure. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). SCV values >5.4 indicate a high and >10 a very high variation. Because the evidence on the efficacy of PFO closure may differ in patients aged <60 years and ≥60 years, age-stratified analyses were performed. We assessed the influence of potential determinants of variation using multilevel regression models with incremental adjustment for demographics, cultural/socioeconomic, health, and supply factors. RESULTS: Overall, 2574 PFO and 2081 LAA closures from 10 HSAs were analyzed. The fully adjusted PFO and LAA closure rates varied from 3 to 8 and from 1 to 9 procedures per 100,000 persons per year across HSAs, respectively. The regional variation was high with respect to overall PFO closures (EQ 3.0, SCV 8.3) and very high in patients aged ≥60 years (EQ 4.0, SCV 12.3). The variation in LAA closures was very high (EQ 16.2, SCV 32.1). In multivariate analysis, women had a 28% lower PFO and a 59% lower LAA closure rate than men. French/Italian language areas had a 63% lower LAA closure rate than Swiss German speaking regions and areas with a higher proportion of privately insured patients had a 86% higher LAA closure rate. After full adjustment, 44.2% of the variance in PFO closure and 30.3% in LAA closure remained unexplained. CONCLUSIONS: We found a high to very high regional variation in PFO closure and LAA closure rates within Switzerland. Several factors, including sex, language area, and insurance status, were associated with procedure rates. Overall, 30-45% of the regional procedure variation remained unexplained and most probably represents differing physician practices.