Lack of Prognostic Value of T-Wave Alternans for Implantable Cardioverter-Defibrillator Benefit in Primary Prevention.

BACKGROUND: New methods to identify patients who benefit from a primary prophylactic implantable cardioverter-defibrillator (ICD) are needed. T-wave alternans (TWA) has been shown to associate with arrhythmogenesis of the heart and sudden cardiac death. We hypothesized that TWA might be associated with benefit from ICD implantation in primary prevention. METHODS AND RESULTS: In the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter-Defibrillators) study, we prospectively enrolled 2327 candidates for primary prophylactic ICD. A 24-hour Holter monitor reading was taken from all recruited patients at enrollment. TWA was assessed from Holter monitoring using the modified moving average method. Study outcomes were all-cause death, appropriate shock, and survival benefit. TWA was assessed both as a contiguous variable and as a dichotomized variable with cutoff points <47 µV and <60 µV. The final cohort included 1734 valid T-wave alternans samples, 1211 patients with ICD, and 523 control patients with conservative treatment, with a mean follow-up time of 2.3 years. TWA ≥60 µV was a predicter for a higher all-cause death in patients with an ICD on the basis of a univariate Cox regression model (hazard ratio, 1.484 [95% CI, 1.024-2.151]; P=0.0374; concordance statistic, 0.51). In multivariable models, TWA was not prognostic of death or appropriate shocks in patients with an ICD. In addition, TWA was not prognostic of death in control patients. In a propensity score-adjusted Cox regression model, TWA was not a predictor of ICD benefit. CONCLUSIONS: T-wave alternans is poorly prognostic in patients with a primary prophylactic ICD. Although it may be prognostic of life-threatening arrhythmias and sudden cardiac death in several patient populations, it does not seem to be useful in assessing benefit from ICD therapy in primary prevention among patients with an ejection fraction of ≤35%.

Implementation of a Pharmacist-Driven Aspirin Deprescribing Protocol Among Older Veterans in a Primary Care Setting.

Background Recent cardiovascular guideline updates recommend against the use of aspirin for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in older people. However, aspirin use remains common in this population. Objective To implement and evaluate the benefit of a pharmacist-driven aspirin deprescribing protocol compared with primary care provider (PCP) education-only in a primary care setting. Methods This prospective, cohort project targeted deprescribing for patients prescribed aspirin for primary prevention of ASCVD. Patients were included if they received primary care services at the Milwaukee Veterans Health Administration Medical Center (VHA) and were 70 years of age or older. Criteria for exclusion were aspirin obtained outside the VHA system, aspirin prescribed for a non-ASCVD-related condition, and/or a history of ASCVD. Active deprescribing by pharmacists and PCP education took place in the intervention group with PCP education only in the standard-of-care group. The primary outcome was the proportion of patients who had aspirin deprescribed in each group. Secondary outcomes included patient acceptability of the intervention and barriers to implementation. Results A total of 520 patients were prescribed aspirin in the intervention group versus 417 in the education-only group. Sixty-five patients met intervention criteria and were contacted for aspirin deprescribing. The pharmacist-led active deprescribing group led to a higher rate of aspirin deprescriptions versus the education-only group (54% vs 18%; P = 0.0001) for patients who met criteria. Conclusion A pharmacist-led aspirin deprescribing protocol within a primary care setting significantly decreased the number of aspirin prescriptions compared with PCP education only.

Pharmacist-Led Deprescribing of Aspirin in Older People in an Outpatient Setting.

Background In 2019, the American College of Cardiology and American Heart Association updated their joint guidelines stating low-dose aspirin should not be used on a routine basis for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among people older than 70 years of age because of increased bleeding risk.1 In addition to these updated guidelines, a statement released by the US Preventive Services Task Force in April 2022 recommends against the initiation of low-dose aspirin for primary prevention of cardiovascular disease in people 60 years of age or older.² Despite these updated recommendations, aspirin continues to be a common medication older patients take, providing an opportunity for a clinical pharmacist deprescribing intervention. Objective To identify the role of a pharmacist-led aspirin deprescribing intervention within a safety-net health system in the outpatient setting. Methods This project included patients 70 years of age and older who had aspirin listed as an active medication without documented ASCVD. This project assessed aspirin deprescribing rates, time spent on pharmacist outreach, and reasons for patient and/or provider refusal to discontinue aspirin. Results One hundred thirty-one eligible patients were contacted. Of those, 78 (60%) patients discontinued aspirin after speaking with the pharmacist, and 8 patients discontinued aspirin after a clinical pharmacist recommendation to the patient's primary care provider (PCP). The median time spent on outreach was approximately eight minutes. Of the 6 patients who consented to the project but declined to discontinue aspirin therapy based on pharmacist intervention, 5 preferred to discuss the issue with their PCP, while 1 patient was told by an outside provider to take aspirin. Conclusion Results indicate the successful impact a clinical pharmacist may have in deprescribing aspirin in a high-risk population. These data may also suggest that an active and intentional approach to deprescribing is likely to be more effective than a written recommendation to providers.

Interactions between antiepileptic drugs and direct oral anticoagulants for primary and secondary stroke prevention.

INTRODUCTION: Direct oral anticoagulants (DOAC) are the guideline-recommended therapy for prevention of stroke in atrial fibrillation (AF) and venous thromboembolism. Since approximately 10% of patients using antiepileptic drugs (AED) also receive DOAC, aim of this review is to summarize data about drug-drug interactions (DDI) of DOAC with AED by using data from PubMed until December 2023. AREAS COVERED: Of 49 AED, only 16 have been investigated regarding DDI with DOAC by case reports or observational studies. No increased risk for stroke was reported only for topiramate, zonisamide, pregabalin, and gabapentin, whereas for the remaining 12 AED conflicting results regarding the risk for stroke and bleeding were found. Further 16 AED have the potential for pharmacodynamic or pharmacokinetic DDI, but no data regarding DOAC are available. For the remaining 17 AED it is unknown if they have DDI with DOAC. EXPERT OPINION: Knowledge about pharmacokinetic and pharmacodynamic DDI of AED and DOAC is limited and frequently restricted to in vitro and in vivo findings. Since no data about DDI with DOAC are available for 67% of AED and an increasing number of patients have a combined medication of DOAC and AED, there is an urgent need for research on this topic.

Reducing the risks when using benzodiazepines to treat insomnia: A public health approach.

Benzodiazepines are widely used but can cause considerable harm, including sedation, addiction, falls, fractures, and cognitive impairment, especially with long-term use and in elderly patients. The authors propose a public health approach to reduce the potential for harm when using benzodiazepines to treat insomnia. Primary prevention involves judicious patient selection and patient education. Secondary prevention requires keeping the duration of use as short as possible according to guidelines. Tertiary prevention, for patients who have been taking a benzodiazepine for a long time, uses shared decision-making to introduce a gradual and carefully monitored taper.

Effects of primary or secondary prevention with vitamin A supplementation on clinically important outcomes: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis.

OBJECTIVES: This systematic review with meta-analyses of randomised trials evaluated the preventive effects of vitamin A supplements versus placebo or no intervention on clinically important outcomes, in people of any age. METHODS: We searched different electronic databases and other resources for randomised clinical trials that had compared vitamin A supplements versus placebo or no intervention (last search 16 April 2024). We used Cochrane methodology. We used the random-effects model to calculate risk ratios (RRs), with 95% CIs. We analysed individually and cluster randomised trials separately. Our primary outcomes were mortality, adverse events and quality of life. We assessed risks of bias in the trials and used Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to assess the certainty of the evidence. RESULTS: We included 120 randomised trials (1 671 672 participants); 105 trials allocated individuals and 15 allocated clusters. 92 trials included children (78 individually; 14 cluster randomised) and 28 adults (27 individually; 1 cluster randomised). 14/105 individually randomised trials (13%) and none of the cluster randomised trials were at overall low risk of bias. Vitamin A did not reduce mortality in individually randomised trials (RR 0.99, 95% CI 0.93 to 1.05; I²=32%; p=0.19; 105 trials; moderate certainty), and this effect was not affected by the risk of bias. In individually randomised trials, vitamin A had no effect on mortality in children (RR 0.96, 95% CI 0.88 to 1.04; I²=24%; p=0.28; 78 trials, 178 094 participants) nor in adults (RR 1.04, 95% CI 0.97 to 1.13; I²=24%; p=0.27; 27 trials, 61 880 participants). Vitamin A reduced mortality in the cluster randomised trials (0.84, 95% CI 0.76 to 0.93; I²=66%; p=0.0008; 15 trials, 14 in children and 1 in adults; 364 343 participants; very low certainty). No trial reported serious adverse events or quality of life. Vitamin A slightly increased bulging fontanelle of neonates and infants. We are uncertain whether vitamin A influences blindness under the conditions examined. CONCLUSIONS: Based on moderate certainty of evidence, vitamin A had no effect on mortality in the individually randomised trials. Very low certainty evidence obtained from cluster randomised trials suggested a beneficial effect of vitamin A on mortality. If preventive vitamin A programmes are to be continued, supporting evidence should come from randomised trials allocating individuals and assessing patient-meaningful outcomes. PROSPERO REGISTRATION NUMBER: CRD42018104347.

Primary Prevention of Cardiovascular Disease for People Living with Human Immunodeficiency Virus.

People living with HIV (PLWH) have a risk of cardiovascular disease (CVD) that is 1.5 to 2 times higher than the general population owing to traditional risk factors, HIV-mediated factors like chronic inflammation and immune dysfunction, and exposure to antiretroviral therapy. Currently available CVD risk estimation calculators tend to underestimate risk in PLWH but can be useful when an individual's HIV history is considered. Improving modifiable risks is the primary intervention for reducing CVD risk in PLWH. Statin therapy is important for specific individuals, but attention should be given to drug interactions with antiretroviral agents used to treat HIV.

Effect of bempedoic acid on mortality and cardiovascular events in primary and secondary prevention: A post-hoc analysis of the CLEAR-outcomes trial.

BACKGROUND: The effects of bempedoic acid on mortality in the secondary prevention setting have not been examined. METHODS: We used data from the overall and primary prevention reports of CLEAR - Outcomes to reconstruct data for the secondary prevention population. A Bayesian analyses was employed to calculate the posterior probability of benefit or harm for the outcomes of all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Relative effect sizes are presented as risk ratios (RR) with 95% credible intervals (CrI), which represent the intervals that true effect sizes are expected to fall in with 95% probability, given the priors and model. RESULTS: In primary prevention, the posterior probability of bempedoic acid decreasing all-cause and cardiovascular mortality was 99.4% (RR: 0.70; 95% CrI: 0.51 to 0.92) and 99.7% (RR: 0.58; 95% CrI: 0.38 to 0.86) respectively. In secondary prevention, the posterior probability of bempedoic acid increasing all-cause and cardiovascular mortality was 96.6% (RR: 1.15; 95% CrI: 0.99 to 1.33) and 97.2% (RR: 1.21; 95% CrI: 1.00 to 1.45) respectively. The probability of bemepdoic acid reducing MACE in the primary and secondary prevention settings was 99.9% (RR: 0.70; 95% CrI: 0.54 to 0.88) and 95.8% (RR: 0.92; 95% CrI: 0.84 to 1.01) respectively. CONCLUSION: In contrast to its effect in the primary prevention subgroup of CLEAR - Outcomes, bempedoic acid resulted in a more modest MACE reduction and a potential increase in mortality in the secondary prevention subgroup. Whether these findings represent true treatment effect heterogeneity or the play of chance requires further evidence.

Achievement of Primary Prevention Cardiometabolic Targets in Women with HIV: An Urgent Call to Action to Pursue Cardiovascular Health.

BACKGROUND: Cardiometabolic health has become crucial, especially for women with HIV (WWH). We assessed the achievement of targets for hypertension, dyslipidemia, and diabetes (H/Dy/DT) in primary prevention in a WWH cohort. METHODS: Cross-sectional analysis including all WWH in our clinic, excluding those who had a myocardial infarction. H/Dy/DT achievement was assessed by both EACS guidelines and individual cardiovascular risk, CVR (measured by ESC calculator), using logistic regression to evaluate differences in H/Dy/DT achievement between migrant and Italian women. RESULTS: We included 292 WWH, 55.5% Italian and 44.5% migrant women; the median age was 50 (IQR:42-58) years, 94.5% had undetectable HIV-RNA, 55.1% had a high level of education, 27.1% were smokers, and 19.2% did regularly physical exercise. Overall, 76%, 19%, and 5% of women presented a low, a high, and a very high CVR, respectively. Among Italians, 28.4% and 6.2% women presented a high and a very high CVR, respectively. Considering migrants, 7.7% and 3.8% women presented a high and a very high CVR, respectively. Overall, among migrant women, those with a high CVR were more likely to be not at target than those with a low risk (especially for LDL-c and blood pressure among people on treatment), despite the fact that we did not detect a statistically significant difference. By contrast, migrants were more likely to achieve glycemic targets than Italians (p = 0.032). CONCLUSIONS: H/Dy/DT target achievement is suboptimal, especially in migrants. A more aggressive pharmacological treatment, also assessing adherence to medical prescriptions, and promotion of healthy lifestyle should be urgently implemented, possibly redrawing the current model of care.

European and US Guideline-Based Statin Eligibility, Genetically Predicted Coronary Artery Disease, and the Risk of Major Coronary Events.

BACKGROUND: A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD-PRS) may guide lipid-lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores. METHODS AND RESULTS: Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals. CONCLUSIONS: CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.

De-imFAR phase II project: a study protocol for a cluster randomised implementation trial to evaluate the effectiveness of de-implementation strategies to reduce low-value statin prescribing in the primary prevention of cardiovascular disease.

INTRODUCTION: This study aims to reduce potentially inappropriate prescribing (PIP) of statins and foster healthy lifestyle promotion in cardiovascular disease (CVD) primary prevention in low-risk patients. To this end, we will compare the effectiveness and feasibility of several de-implementation strategies developed following the structured design process of the Behaviour Change Wheel targeting key determinants of the clinical decision-making process in CVD prevention. METHODS AND ANALYSIS: A cluster randomised implementation trial, with an additional control group, will be launched, involving family physicians (FPs) from 13 Integrated Healthcare Organisations (IHOs) of Osakidetza-Basque Health Service with non-zero incidence rates of PIP of statins in 2021. All FPs will be exposed to a non-reflective decision assistance strategy based on reminders and decision support tools. Additionally, FPs from two of the IHOs will be randomly assigned to one of two increasingly intensive de-implementation strategies: adding a decision information strategy based on knowledge dissemination and a reflective decision structure strategy through audit/feedback. The target population comprises women aged 45-74 years and men aged 40-74 years with moderately elevated cholesterol levels but no diagnosed CVD and low cardiovascular risk (REGICOR<7.5%), who attend at least one appointment with any of the participating FPs (May 2022-May 2023), and will be followed until May 2024. We use the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate outcomes. The main outcome will be the change in the incidence rate of PIP of statins and healthy lifestyle counselling in the study population 12 and 24 months after FPs' exposure to the strategies. Moreover, FPs' perception of their feasibility and acceptability, and patient experience regarding the quality of care received will be evaluated. ETHICS AND DISSEMINATION: The study was approved by the Basque Country Clinical Research Ethics Committee and was registered in ClinicalTrials.gov (NCT04022850). Results will be disseminated in scientific peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04022850.

Primary surgical prevention of lymphedema.

Lymphedema in the upper and lower extremities can lead to significant morbidity in patients, resulting in restricted joint movements, pain, discomfort, and reduced quality of life. While physiological lymphatic reconstructions such as lymphovenous anastomosis (LVA), lymphovenous implantation (LVI), and vascularized lymph node transfer (VLNT) have shown promise in improving patients' conditions, they only provide limited disease progression control or modest reversal. As lymphedema remains an incurable condition, the focus has shifted toward preventive measures in developed countries where most cases are iatrogenic due to cancer treatments. Breast cancer-related lymphedema (BCRL) has been a particular concern, prompting the implementation of preventive measures like axillary reverse mapping. Similarly, techniques with lymph node-preserving concepts have been used to treat lower extremity lymphedema caused by gynecological cancers. Preventive lymphedema measures can be classified into primary, secondary, and tertiary prevention. In this comprehensive review, we will explore the principles and methodologies encompassing lymphatic microsurgical preventive healing approach (LYMPHA), LVA, lymphaticolymphatic anastomosis (LLA), VLNT, and lymph-interpositional-flap transfer (LIFT). By evaluating the advantages and limitations of these techniques, we aim to equip surgeons with the necessary knowledge to effectively address patients at high risk of developing lymphedema.

Intensity of statin therapy and primary prevention of cardiovascular in Korean patients with dyslipidemia.

This study aimed to investigate the association between the intensity of statin therapy and the development of cardiovascular disease (CVD) and diabetes in individuals without prior diabetes who were being treated for dyslipidemia with statins for the primary prevention of CVD, using the National Health Insurance Service-Health Screening database. The database is a longitudinal cohort study of Korean men and women 40 years of age or older who underwent comprehensive biannual screening health examinations by Korean National Health Insurance Service from January 1, 2002, to December 31, 2015. We included patients in the health screening checkup cohort who underwent health checkups in 2009 and 2010.The primary outcome was the occurrence of a first major cardiovascular or cerebrovascular event, new-onset diabetes. A total of 20,322 participants without prior diabetes at baseline from 2009 to 2015 were followed up for a mean duration of 81.2 ±â€…6.6 months. The mean age of all participants at baseline was 59.2 ±â€…8.4 years and 43.0% of them were male. Their index low lipoprotein cholesterol level was 130.4 ±â€…mg/dL, the mean duration of taking statins was 337.4 ±â€…52.3 days, and 93.9% of them had been taking moderate-intensity statins. At that time, a total of 641 diabetes cases occurred, 41 from using low-intensity statins, 588 from moderate-intensity statins, and 11 from high-intensity statins. The results indicated no significant differences in the incidence of death, CVD death, or CVD among those in the strong statin group compared with the reference groups. While statin treatment for the primary prevention of CVD in patients with dyslipidemia showed a subtle difference in the incidence of diabetes, there was no difference in the occurrence of CVD or CVD death according to statin intensity.

Peer-led lifestyle interventions for the primary prevention of cardiovascular disease in community: a systematic review of randomised controlled trials.

BACKGROUND: Peer-led lifestyle interventions have gained recognition as effective approaches for managing and preventing chronic diseases. However, there remains a critical knowledge gap regarding the impact and effectiveness of peer-led interventions specifically in the primary prevention of cardiovascular disease (CVD). Our systematic review aims to synthesise the available evidence and evaluate the impact of peer-led lifestyle interventions, providing invaluable insights that can guide the development of peer-led strategies for preventing CVD. METHODS: Systematic database searches were conducted on Ovid Medline, Embase, Cochrane Centre for Controlled Trials, PubMed and Scopus to source peer-reviewed articles published between 2013 and 2023. Reference lists of the included publications were also manually searched. RESULTS: Fourteen unique randomised controlled trials were identified, of which three were pilot studies. Most of the interventions were conducted among individuals at moderate to high risk of CVD and lasted for a year. There is a variety of components in intervention delivery, including group discussions and individual counselling. Peer leader training mostly covered intervention delivery, communication, and research-specific skills. Systolic blood pressure showed the most promising CVD-related improvement, while mixed results were found for several other dietary and lifestyle behavioural outcomes. CONCLUSION: Peer-led lifestyle interventions have shown varying effectiveness in cardiovascular health outcomes. The competencies and roles of peer leaders were identified to guide future intervention development with a more comprehensive approach to the primary prevention of CVD.