Design and validation of a new questionnaire with a gender perspective to measure medication adherence for secondary prevention of ischaemic heart disease: study protocol.

INTRODUCTION AND OBJECTIVES: Only about 50% of chronic patients in high-income countries adhere to their treatment. There are methods to measure medication adherence but none of them can be considered optimal. This study will aim to design and validate a questionnaire to measure medication adherence in patients with ischaemic heart disease using a direct method as a gold-standard adherence measure and taking into account the gender perspective. Moreover, the profile of low adherence in these patients will be determined. METHODS AND ANALYSIS: First study phase consists on the questionnaire design following the next steps: identification of the dimensions, definition of the target population, questionnaire items and order, response coding, questionnaire instructions, content validity by experts and understandability. In the second phase, a cross-sectional study will be performed to end the questionnaire development and validate it. Four hundred and forty patients (50% female) with acute coronary syndrome receiving treatment within the previous 12 months will be included. Patient will answer the initial questionnaire and adherence to aspirin and statin will be measured using a direct method (drug concentration analysis in blood) and other questionnaires. From the set of preselected questionnaire items, those most closely associated with the gold standard measure will be selected using multivariate statistics. ETHICS AND DISSEMINATION: All participants gave their written informed consent before participating in the study. The study protocol follows the recommendations of the Declaration of Helsinki and was approved by the ethics committees of the three participating centres. The results of this study will be displayed at national and international conferences and in peer-reviewed scientific journals.

Mobile phone text messaging for medication adherence in secondary prevention of cardiovascular disease.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death globally, accounting for almost 18 million deaths annually. People with CVDs have a five times greater chance of suffering a recurrent cardiovascular event than people without known CVDs. Although drug interventions have been shown to be cost-effective in reducing the risk of recurrent cardiovascular events, adherence to medication remains suboptimal. As a scalable and cost-effective approach, mobile phone text messaging presents an opportunity to convey health information, deliver electronic reminders, and encourage behaviour change. However, it is uncertain whether text messaging can improve medication adherence and clinical outcomes. This is an update of a Cochrane review published in 2017. OBJECTIVES: To evaluate the benefits and harms of mobile phone text messaging for improving medication adherence in people with CVDs compared to usual care. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, four other databases, and two trial registers. We also checked the reference lists of all primary included studies and relevant systematic reviews and meta-analyses. The date of the latest search was 30 August 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with participants with established arterial occlusive events. We included trials investigating interventions using short message service (SMS) or multimedia messaging service (MMS) with the aim of improving adherence to medication for the secondary prevention of cardiovascular events. The comparator was usual care. We excluded cluster-RCTs and quasi-RCTs. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were medication adherence, fatal cardiovascular events, non-fatal cardiovascular events, and combined CVD event. Secondary outcomes were low-density lipoprotein cholesterol for the effect of statins, blood pressure for antihypertensive drugs, heart rate for the effect of beta-blockers, urinary 11-dehydrothromboxane B2 for the antiplatelet effects of aspirin, adverse effects, and patient-reported experience. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 18 RCTs involving a total of 8136 participants with CVDs. We identified 11 new studies in the review update and seven studies in the previous version of the review. Participants had various CVDs including acute coronary syndrome, coronary heart disease, stroke, myocardial infarction, and angina. All studies were conducted in middle- and high-income countries, with no studies conducted in low-income countries. The mean age of participants was 53 to 64 years. Participants were recruited from hospitals or cardiac rehabilitation facilities. Follow-up ranged from one to 12 months. There was variation in the characteristics of text messages amongst studies (e.g. delivery method, frequency, theoretical grounding, content used, personalisation, and directionality). The content of text messages varied across studies, but generally included medication reminders and healthy lifestyle information such as diet, physical activity, and weight loss. Text messages offered advice, motivation, social support, and health education to promote behaviour changes and regular medication-taking. We assessed risk of bias for all studies as high, as all studies had at least one domain at unclear or high risk of bias. Medication adherence Due to different evaluation score systems and inconsistent definitions applied for the measurement of medication adherence, we did not conduct meta-analysis for medication adherence. Ten out of 18 studies showed a beneficial effect of mobile phone text messaging for medication adherence compared to usual care, whereas the other eight studies showed either a reduction or no difference in medication adherence with text messaging compared to usual care. Overall, the evidence is very uncertain about the effects of mobile phone text messaging for medication adherence when compared to usual care. Fatal cardiovascular events Text messaging may have little to no effect on fatal cardiovascular events compared to usual care (odds ratio 0.83, 95% confidence interval (CI) 0.47 to 1.45; 4 studies, 1654 participants; low-certainty evidence). Non-fatal cardiovascular events We found very low-certainty evidence that text messaging may have little to no effect on non-fatal cardiovascular events. Two studies reported non-fatal cardiovascular events, neither of which found evidence of a difference between groups. Combined CVD events We found very low-certainty evidence that text messaging may have little to no effect on combined CVD events. Only one study reported combined CVD events, and did not find evidence of a difference between groups. Low-density lipoprotein cholesterol Text messaging may have little to no effect on low-density lipoprotein cholesterol compared to usual care (mean difference (MD) -1.79 mg/dL, 95% CI -4.71 to 1.12; 8 studies, 4983 participants; very low-certainty evidence). Blood pressure Text messaging may have little to no effect on systolic blood pressure (MD -0.93 mmHg, 95% CI -3.55 to 1.69; 8 studies, 5173 participants; very low-certainty evidence) and diastolic blood pressure (MD -1.00 mmHg, 95% CI -2.49 to 0.50; 5 studies, 3137 participants; very low-certainty evidence) when compared to usual care. Heart rate Text messaging may have little to no effect on heart rate compared to usual care (MD -0.46 beats per minute, 95% CI -1.74 to 0.82; 4 studies, 2946 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: Due to limited evidence, we are uncertain if text messaging reduces medication adherence, fatal and non-fatal cardiovascular events, and combined cardiovascular events in people with cardiovascular diseases when compared to usual care. Furthermore, text messaging may result in little or no effect on low-density lipoprotein cholesterol, blood pressure, and heart rate compared to usual care. The included studies were of low methodological quality, and no studies assessed the effects of text messaging in low-income countries or beyond the 12-month follow-up. Long-term and high-quality randomised trials are needed, particularly in low-income countries.

[Prescription of osteoporosis drugs and secondary fracture prevention still at low levels and with large regional variation]. / Låg förskrivning av läkemedel för osteoporos inom Sverige.

In Sweden, secondary prevention of fragility fractures through osteoporosis medication is directed by national guidelines. According to these, postmenopausal women and men who have suffered a fragility fracture should be assessed and pharmaceutical treatment of osteoporosis should always be considered. For the most serious fractures (hip and vertebral fractures), treatment can be initiated immediately. Despite this, previous studies have shown that the level of pharmaceutical treatment is low. In Sweden, osteoporosis drugs are predominantly administered by prescription, but about one-third of drugs are nowadays administered on-site in the health care system, which is not recorded in national registers. We have estimated the total amount of osteoporosis drugs through aggregated sales statistics. Our results show that medical treatment with osteoporosis drugs is still at low levels, covering approximately 5 percent of the population aged 70 or older, with clear differences between regions.

Management of patent foramen ovale; findings from a nationwide survey.

OBJECTIVES: Several clinical trials have provided evidence supporting the transcatheter closure of patent foramen ovale (PFO) in selected patients following a cryptogenic stroke. However, it remains unknown to what extent these guidelines have been implemented in everyday clinical practice and the familiarity of physicians from different specialties with PFO closure. The aim of our nationwide survey is to explore the implementation of transcatheter PFO occlusion in Greek clinical practice. MATERIALS AND METHODS: Attending level cardiologists, internal medicine physicians and neurologists involved in the management of PFO-related strokes working in Greece were invited to complete an online questionnaire. The questionnaire consisted of 19 questions and was designed to obtain comprehensive data on provider demographics, PFO characteristics, and specific clinical scenarios. RESULTS: A total of 51 physicians (56.9 % cardiologists, 25.5 % neurologists and 17.6 % internal medicine physicians) completed the survey, resulting in a response rate of 53 %. Cardiologists, internal medicine physicians and neurologists agree on several issues regarding PFO closure, such as PFO closure as first line treatment, management of patients with DVT or prior decompression sickness, and post-closure antithrombotic treatment, but different approaches were reported regarding closure in patients with thrombophilia treated with oral anticoagulation (p=0.012) and implantable loop recorder placement for atrial fibrillation exclusion (p=0.029 and p=0.020). CONCLUSIONS: Our findings show that cardiologists, internal medicine physicians and neurologists agree in numerous issues, but share different views in the management of patients with thrombophilia and rhythm monitoring duration. These results highlight the significance of collaboration among physicians from different medical specialties for achieving optimal results.

Osteoporosis.

Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. Evidence-based screening strategies improve identification of patients who are most likely to benefit from drug treatment to prevent fracture. In addition, careful consideration of when pharmacotherapy should be started, choice of medication, and duration of treatment maximizes the benefits of fracture prevention while minimizing potential harms of long-term drug exposure.

Approval, Evidence, and "Off-Label" Device Utilization: The Patent Foramen Ovale Closure Story.

BACKGROUND: Following regulatory approval, medical devices may be used "off-label." Patent foramen ovale (PFO) closure is indicated to reduce recurrent stroke but has been proposed for other indications, including migraine, transient ischemic attack, and diving decompression illness. We sought to evaluate PFO closure rates and indications relative to the timing of regulatory approval and publication of key randomized trials. METHODS: We performed a retrospective cohort study using the OptumLabs Data Warehouse of US commercial insurance enrollees from 2006 to 2019. We quantified PFO closure among individuals with ≥2 years of preprocedure coverage to establish indications, classified hierarchically as stroke/systemic embolism, migraine, transient ischemia attack, or other. RESULTS: We identified 5315 patients undergoing PFO closure (51.8% female, 29.2%≥60 years old), which increased from 4.75 per 100 000 person-years in 2006 to 6.60 per 100 000 person-years in 2019. Patients aged ≥60 years accounted for 29.2% of closures. Procedure volumes corresponded weakly with supportive clinical publications and device approval. Among patients with PFO closure, 58.6% underwent closure for stroke/systemic embolism, 10.2% for transient ischemia attack, 8.8% for migraine, and 22.4% for other indications; 17.6% of patients had atrial fibrillation at baseline; and 11.9% developed atrial fibrillation postprocedure. Those aged ≥60 years and male were less likely to undergo closure for migraine than stroke/systemic embolism. CONCLUSIONS: From 2006 to 2019, PFO closure use was consistently low and corresponded weakly with clinical trial publications and regulatory status. Nearly half of patients underwent PFO closure for indications unapproved by the Food and Drug Administration. Regulators and payers should coordinate mechanisms to promote utilization for approved indications to ensure patient safety and should facilitate clinical trials for other possible indications.

Long-term risk-factor control and secondary prevention are insufficient after first TIA: Results from QregPV.

INTRODUCTION: Long-term risk-factor control and secondary prevention are not well characterized in patients with a first transient ischemic attack (TIA). With baseline levels as reference, we compared primary-care data on blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), smoking, and use of antihypertensives, statins and antiplatelet treatment/oral anticoagulation (APT/OAC) during 5 years after a first TIA. PATIENTS AND METHODS: Patients in QregPV, a Swedish primary-care register for the Region of Västra Götaland, with a first TIA discharge diagnosis from wards proficient in stroke care 2010 to 2012 were identified and followed up to 5 years. BP, LDL-C, smoking, use of antihypertensives, statins, APT/OAC, and achievement of target levels were calculated. We used logistic mixed-effect models to analyze the effect of follow-up over time on risk-factor control and secondary prevention treatment. RESULTS: We identified 942 patients without prior cerebrovascular disease who had a first TIA. Compared to baseline, the first year of follow-up was associated with improvements in concomitant attainment of BP <140/90 mmHg, LDL-C < 2.6 mmol/L and non-smoking, which rose from 20% to 33% (OR 2.08, 95% CI 1.38-3.13), but then stagnated in years 2-5. In the first year of follow-up, 47% of patients had complete secondary prevention treatment (antihypertensives, APT/OAC and statin), but continued follow-up was associated with a yearly decrease in secondary prevention treatment (OR 0.94, 95% CI 0.94-0.98). CONCLUSION: Risk-factor control was inadequate, leaving considerable potential for improved secondary prevention treatment after a first TIA in Swedish patients followed up to 5 years.

Quality control in treating patients with patent foramen ovale: 7-year-experience of the Heart and Brain team of the Careggi University Hospital.

BACKGROUND: The right comprehension of ischemic stroke pathogenesis guarantees the best prevention therapy. The term "patent foramen ovale (PFO) related stroke" has been proposed for those events where PFO is supposed to be pathogenetic, but their definition is challenging. A multidisciplinary evaluation in a "Heart & Brain" team (HBteam) including stroke neurologists and interventional cardiologists was therefore highly recommended in the recent guidelines of secondary stroke prevention. OBJECTIVE: We aimed at describing the organization of the HBteam of Careggi-University-Hospital of Florence (Italy), and the results of the first seven years of activity. METHODS: In 2016 Interventional Cardiologists and Stroke Neurologists set up an outpatient clinic for the joined evaluation of patients with PFO and other cardio/neurological conditions. A specific diagnostic-therapeutic hospital plan was produced for PFO patients. Patient empowerment was guaranteed by a hospital explicative webpage, a booklet regarding risks/benefits of PFO closure and a 3D heartmodel to simulate the intervention. Data were collected in a dedicated registry. RESULTS: We evaluated 594 patients for PFO, 40 for left atrial appendage closure and 38 for other conditions. In 20% of PFO-patients, HBteam diagnosis was discordant from that of referring physicians, 14% were stroke misdiagnoses. We advised against closure in 53% of patients. At follow-up 94% of closed patients had no/minimum residual shunt; 3 patients had a cerebral ischemic event. CONCLUSIONS: A dedicated HBteam represents a unique opportunity to share decisions with patients after a thorough empowerment process. The joining of cardioneurological skills allows a better classification of PFO-patients, reducing futile interventions.

Medical Therapy After CABG: the Known Knowns, the Known Unknowns, and the Unknown Unknowns.

PURPOSE: Medical therapies play a central role in secondary prevention after surgical revascularization. While coronary artery bypass grafting is the most definitive treatment for ischemic heart disease, progression of atherosclerotic disease in native coronary arteries and bypass grafts result in recurrent adverse ischemic events. The aim of this review is to summarize the recent evidence regarding current therapies in secondary prevention of adverse cardiovascular outcomes after CABG and review the existing recommendations as they pertain to the CABG subpopulations. RECENT FINDINGS: There are many pharmacologic interventions recommended for secondary prevention in patients after coronary artery bypass grafting. Most of these recommendations are based on secondary outcomes from trials which include but did not focus on surgical patients as a cohort. Even those designed with CABG in mind lack the technical and demographic scope to provide universal recommendations for all CABG patients. CONCLUSION: Recommendations for medical therapy after surgical revascularization are chiefly based on large-scale randomized controlled trials and meta-analyses. Much of what is known about medical management after surgical revascularization results from trials comparing surgical to non-surgical approaches and important characteristics of the operative patients are omitted. These omissions create a group of patients who are relatively heterogenous making solid recommendations elusive. While advances in pharmacologic therapies are clearly adding to the armamentarium of options for secondary prevention, knowing what patients benefit most from each therapeutic option remains challenging and a personalized approach is still required.

Patent Foramen Ovale Management for Secondary Stroke Prevention: State-of-the-Art Appraisal of Current Evidence.

Patent foramen ovale (PFO) is frequently identified in young patients with ischemic stroke. Randomized controlled trials provide robust evidence supporting PFO closure in selected patients with cryptogenic ischemic stroke; however, several questions remain unanswered. This report summarizes current knowledge on the epidemiology of PFO-associated stroke, the role of PFO as a cause of stroke, and anatomic high-risk features. We also comment on breakthrough developments in patient selection algorithms for PFO closure in relation to the PFO-associated stroke causal likelihood risk stratification system. We further highlight areas for future research in PFO-associated stroke including the efficacy and safety of PFO closure in the elderly population, incidence, and long-term consequences of atrial fibrillation post-PFO closure, generalizability of the results of clinical trials in the real world, and the need for assessing the effect of neurocardiology teams on adherence to international recommendations. Other important knowledge gaps such as sex, race/ethnicity, and regional disparities in access to diagnostic technologies, PFO closure devices, and clinical outcomes in the real world are also discussed as priority research topics.

The effect of mindfulness on decision-making, inhibitory control, and impulsivity of substance use disorder in-treatment patients: A randomized clinical trial.

This study aimed to investigate the effects of Mindfulness-Based Relapse Prevention (MBRP) in decision-making, inhibitory control and impulsivity compared to Treatment as Usual (TAU) for individuals with Substance Use Disorders (SUD's) in Brazil. A randomized clinical trial was conducted with participants from a therapeutic community (n = 122). Decision-making (Iowa Gambling Task), impulsivity dimensions (UPPS-P Scale), and inhibitory control (Stroop Color-Word Test) were assessed before and after the MBRP 8-week intervention. GLM Multivariate analysis was used to evaluate the effects of MBRP on different impulsivity measures. The results showed that MBRP+TAU improved the general decision-making score (p = 0,008) compared to TAU. However, no significant effects were found in impulsivity dimensions and inhibitory control in individuals with SUDs in the therapeutic community. This study found improvement in decision-making in the total IGT score; however, no effect for self-reported impulsivity and inhibitory control among middle-aged patients after an 8-weeks intervention of MBRP protocol in an inpatient setting. It adds information to the subject, with implications and possible directions to be followed by the next clinical trials with patients with SUDs in treatment. Trial registration: EnsaiosClinicos.gov.br: RBR-6c9njc.

Adherence to CPAP Treatment and the Risk of Recurrent Cardiovascular Events: A Meta-Analysis.

Importance: The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated. Objective: To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials. Data Sources: PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023. Study Selection: For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included. Data Extraction and Synthesis: Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597]). Main Outcomes and Measures: One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day). Results: A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92]). Conclusions and Relevance: Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.

Aspirin for Secondary Prevention of Cardiovascular Disease in 51 Low-, Middle-, and High-Income Countries.

Importance: Aspirin is an effective and low-cost option for reducing atherosclerotic cardiovascular disease (CVD) events and improving mortality rates among individuals with established CVD. To guide efforts to mitigate the global CVD burden, there is a need to understand current levels of aspirin use for secondary prevention of CVD. Objective: To report and evaluate aspirin use for secondary prevention of CVD across low-, middle-, and high-income countries. Design, Setting, and Participants: Cross-sectional analysis using pooled, individual participant data from nationally representative health surveys conducted between 2013 and 2020 in 51 low-, middle-, and high-income countries. Included surveys contained data on self-reported history of CVD and aspirin use. The sample of participants included nonpregnant adults aged 40 to 69 years. Exposures: Countries' per capita income levels and world region; individuals' socioeconomic demographics. Main Outcomes and Measures: Self-reported use of aspirin for secondary prevention of CVD. Results: The overall pooled sample included 124 505 individuals. The median age was 52 (IQR, 45-59) years, and 50.5% (95% CI, 49.9%-51.1%) were women. A total of 10 589 individuals had a self-reported history of CVD (8.1% [95% CI, 7.6%-8.6%]). Among individuals with a history of CVD, aspirin use for secondary prevention in the overall pooled sample was 40.3% (95% CI, 37.6%-43.0%). By income group, estimates were 16.6% (95% CI, 12.4%-21.9%) in low-income countries, 24.5% (95% CI, 20.8%-28.6%) in lower-middle-income countries, 51.1% (95% CI, 48.2%-54.0%) in upper-middle-income countries, and 65.0% (95% CI, 59.1%-70.4%) in high-income countries. Conclusion and Relevance: Worldwide, aspirin is underused in secondary prevention, particularly in low-income countries. National health policies and health systems must develop, implement, and evaluate strategies to promote aspirin therapy.

Seeing Colchicine in a New Light: Repurposing Low-dose Colchicine for Secondary Prevention of Cardiovascular Disease.

PURPOSE: This review presents a modern perspective on the cardiovascular re-purposing of colchicine, the oldest drug in the pharmacopeia other than aspirin that is still in regular use. METHODS: This article presents a brief overview of colchicine's long history as a medicine, as well as a critical review of safety and efficacy from the results of recent cardiovascular clinical trials. FINDINGS: Long-term continuous colchicine use at doses between 0.6 and 2.4 mg has been used to prevent inflammatory flares in patients with gout and familial Mediterranean fever and less commonly employed in a range of other inflammatory conditions. In these settings, lifelong therapy has been found to be safe and well tolerated. Understanding the central role of inflammation in atherosclerosis has led to the search for effective anti-inflammatory agents that can be used continuously in combination with a range of other medications, including lipid-lowering therapies, antiplatelet therapy, and anticoagulants. The results of recent robust randomized clinical trials of low-dose colchicine (0.5 mg daily) in patients with coronary disease recently led the US Food and Drug Administration to approve its use as a new cornerstone therapy for secondary prevention in patients with coronary disease. Several misconceptions regarding the safety and tolerability of low dose colchicine are addressed. IMPLICATIONS: Colchicine has emerged from its traditional role in medicine as the prevention of gout flare as the first anti-inflammatory agent to be approved by the US Food and Drug Administration for the secondary prevention of atherosclerosis.

New-onset atrial fibrillation after percutaneous patent foramen ovale closure: a meta-analysis.

BACKGROUND: The exact incidence and predictors of new-onset atrial fibrillation (AF) after percutaneous closure of patent foramen ovale (PFO) are unknown. OBJECTIVE: We sought to find post-procedural AF incidence rates and differences due to different screening strategies and devices. METHODS: A systematic search was conducted in Cochrane, MEDLINE and EMBASE. Controlled trials fulfilling the inclusion criteria were included into this meta-analysis. The incidence of new-onset AF was the primary outcome. Further parameters were surveillance strategy, device type, AF treatment and neurological events. New AF was determined as early onset within one month after implantation and late thereafter. RESULTS: 8 controlled trials and 16 cohort studies were eligible for quantitative analysis. 7643 patients received percutaneous PFO closure after cryptogenic stroke or transient ischaemic attack, 117 with other indications, whereas 1792 patients formed the control group. Meta-analysis of controlled trials showed an AF incidence of 5.1% in the interventional and 1.6% in the conservative arm, respectively (OR 3.17, 95% CI 1.46-6.86, P = 0.03, I2 = 55%). 4.7% received high-quality surveillance strategy with Holter-ECG or Loop recorder whereby AF incidence was overall higher compared to the low-quality group with 12-lead ECG only (3.3-15% vs. 0.2-4.3%). Heterogeneous results on time of AF onset were found, limited by different follow-up strategies. CardioSEAL and Starflex seemed to have higher AF incidences in early and late onset with 4.5% and 4.2%, respectively. CONCLUSION: Percutaneous PFO closure led to higher AF post-procedural incidence compared to the conservative strategy. Heterogeneity in surveillance and follow-up strategy limited the generalizability. TRIAL REGISTRATION: Registered on PROSPERO (CRD42022359945).

Effectiveness of Transcatheter Closure of Patent Foramen Ovale in Clinical Practice.

Background Transcatheter closure of patent foramen ovale (PFO) has reduced the risk of recurrent stroke in patients with cryptogenic strokes in randomized clinical trials. Whether PFO closure in clinical practice is associated with similar benefit remains unknown. Methods and Results We identified patients with PFO and a history of ischemic stroke or transient ischemic attack who were treated with PFO closure or medical therapy in the OptumLabs database. The primary end point was recurrent ischemic stroke or systemic embolization. Secondary outcomes included mortality, all stroke, transient ischemic attack, and major bleeding. A total of 6668 propensity-matched patients were included (PFO closure n=4111; medical therapy n=2557). The incidence of stroke or systemic embolization per 100 person-years was 2.38 after PFO cohort and 2.99 with medical therapy (hazard ratio [HR], 0.85 [95% CI, 0.68-1.05], P=0.13). Mortality was lower in the PFO closure cohort (1.78 versus 2.59 per 100 person-years: HR, 0.69 [95% CI, 0.55-0.87], P=0.002). Falsification end points showed that this difference is unlikely to be completely explained by residual confounders. There were no significant differences between the groups in secondary end points including intracranial hemorrhage and major bleeding except for an increase in nonintracranial hemorrhage bleeding among patients treated with oral anticoagulation (1.42 versus 2.16 per 100 person-years: HR, 0.69 [95% CI, 0.48-0.99], P=0.043). The main end point was consistent in subanalyses including patients <60 years of age, patients with prior stroke, and those treated after the publication of the positive PFO trials in 2017. Conclusions In contemporary US practice, PFO closure is not associated with lower rates of recurrent ischemic stroke or systemic embolization compared with medical therapy. Potential reasons for this discrepancy warrant further investigation.

Polypill-based strategy vs. usual care for secondary prevention of cardiovascular disease: a meta-analysis of randomized controlled trials.

AIMS: We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the impact of a polypill-based strategy (PBS) on therapeutic adherence and cardiovascular outcomes compared with usual care for secondary prevention of cardiovascular diseases (CVDs). METHODS AND RESULTS: We systematically searched PubMed, Cochrane, and Scopus databases from inception to January 2023, including RCTs comparing PBS with usual care in patients with prior CVD. We assessed efficacy outcomes of therapeutic adherence, systolic blood pressure (SBP), and LDL-cholesterol (LDL-C) and safety outcomes of all-cause and cardiovascular mortality. Statistical analysis was performed with Review Manager 5.4.1 and R Version 4.2.1. A total of 8 RCTs with a population of 6541 individuals were included, of whom 3318 (50.7%) were treated with the PBS. Follow-up ranged from 6 to 60 months. The polypill-based strategy was associated with a significantly increased therapeutic adherence [risk ratio (RR) 1.22; 95% confidence interval (CI) 1.10-1.34; P < 0.001]. Cardiovascular mortality (RR 0.61; 95% CI 0.44-0.85; P = 0.004), SBP [mean difference (MD) -1.47 mmHg; 95% CI -2.86 to -0.09; P = 0.04], and LDL-C (MD -3.83 mg/dL; 95% CI -6.99 to -0.67; P = 0.02) were significantly lower in the PBS group. The incidence of all-cause mortality was similar between groups (RR 0.83; 95% CI 0.54-1.29; P = 0.41). CONCLUSION: In patients with pre-existing CVD, a PBS is associated with lower cardiovascular mortality and improved therapeutic adherence, along with a modest decrease in SBP and LDL-C compared with usual care. Thus, a PBS may be considered a preferred option for this patient population.

Adherence to medical therapy plays a critical role in the prevention of atherosclerotic events. Previous studies have shown that a polypill-based strategy (PBS) increases treatment adherence in the context of primary prevention of cardiovascular diseases. However, the effectiveness of this strategy in secondary prevention is yet to be determined. Herein, we demonstrate the following: Polypill-based strategy improved therapeutic adherence and reduced LDL-cholesterol and systolic blood pressure levels.There was a reduction in cardiovascular mortality with the use of the PBS; however, no significant difference was found in all-cause mortality between groups.

Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention.

Despite treatment with statins, patients with elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides remain at increased risk for adverse cardiovascular events. Consequently, novel pharmaceutical drugs have been developed to control and modify the composition of blood lipids to ultimately prevent fatal cardiovascular events in patients with dyslipidaemia. This article reviews established and emerging lipid-lowering drugs regarding their mechanism of action, development stage, ongoing clinical trials, side effects, effect on blood lipids and reduction in cardiovascular morbidity and mortality. We conducted a keyword search to identify studies on established and emerging lipid modifying drugs. Results were summarized in a narrative overview. Established pharmaceutical treatment options include the Niemann-Pick-C1 like-1 protein (NPC1L1) inhibitor ezetimibe, the protein convertase subtilisin-kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab, fibrates as peroxisome proliferator receptor alpha (PPAR-α) activators, and the omega-3 fatty acid icosapent ethyl. Statins are recommended as the first-line therapy for primary and secondary cardiovascular prevention in patients with hypercholesterinaemia and hypertriglyceridemia. For secondary prevention in hypercholesterinaemia, second-line options such as statin add-on or statin-intolerant treatments are ezetimibe, alirocumab and evolocumab. For secondary prevention in hypertriglyceridemia, second-line options such as statin add-on or statin-intolerant treatments are icosapent ethyl and fenofibrate. Robust data for these add-on therapeutics in primary cardiovascular prevention remains scarce. Recent biotechnological advances have led to the development of innovative small molecules (bempedoic acid, lomitapide, pemafibrate, docosapentaenoic and eicosapentaenoic acid), antibodies (evinacumab), antisense oligonucleotides (mipomersen, volanesorsen, pelcarsen, olezarsen), small interfering RNA (inclisiran, olpasiran), and gene therapies for patients with dyslipidemia. These molecules specifically target new cellular pathways, such as the adenosine triphosphate-citrate lyase (bempedoic acid), PCSK9 (inclisiran), angiopoietin-like 3 (ANGPTL3: evinacumab), microsomal triglyceride transfer protein (MTP: lomitapide), apolipoprotein B-100 (ApoB-100: mipomersen), apolipoprotein C-III (ApoC-III: volanesorsen, olezarsen), and lipoprotein (a) (Lp(a): pelcarsen, olpasiran). The authors are hopeful that the development of new treatment modalities alongside new therapeutic targets will further reduce patients' risk of adverse cardiovascular events. Apart from statins, data on new drugs' use in primary cardiovascular prevention remain scarce. For their swift adoption into clinical routine, these treatments must demonstrate safety and efficacy as well as cost-effectiveness in randomized cardiovascular outcome trials.

Relapse Prevention and Prediction Strategies in Substance Use Disorder: A Scoping Review.

BACKGROUND: Relapse prevention for those with substance use disorder (SUD) is an evolving practice. Initiatives focused on relapse prevention from other populations may provide the foundation for future considerations and recommendations for recovering anesthesia providers in the workplace. The purpose of this scoping review was to examine what is known about return-to-use prediction and prevention strategies in various populations struggling with SUDs to inform future considerations and implications for recovering anesthesia providers with a history of SUD. METHODS: The Arksey and O'Malley framework was used to conduct a scoping review of the literature. A systematic search was conducted across three databases (PubMed, CINAHL, and PsycInfo) for relevant literature. Search terms used were "measures predicting relapse in substance use disorder" and "relapse prevention in substance use disorder AND anesthesia." Data from articles that met the eligibility criteria were extracted and summarized by the primary author. RESULTS: The search identified 46 articles highlighting various relapse prediction and prevention strategies related to craving and stress, underlying biological factors, neuroimaging, and mindfulness. Relapse prediction and prevention strategies ranged from cell phone applications, monitoring biological markers, and functional neuroimaging of the brain. CONCLUSIONS: Relapse is a concern for individuals with a history of SUD. For anesthesia providers, immediate access to powerful anesthesia medications requires return-to-use prediction and prevention strategies when anesthesia providers return to work after SUD treatment. Although some identified strategies are practical, more research is needed to predict and prevent return to use for recovering anesthesia providers.

Management of Patients With Patent Foramen Ovale and Stroke: A National Survey of Interventional Cardiologists and Vascular Neurologists.

Background Results from multiple clinical trials support patent foramen ovale closure after cryptogenic stroke in select patients, but it remains unclear how new data and updated professional society guidelines have impacted clinical practice. Here, we aimed to compare how stroke neurologists and interventional cardiologists approach patients with cryptogenic stroke with patent foramen ovale and how critical anatomic and clinical factors influence decision making. Methods and Results An electronic survey was administered to 1556 vascular neurologists and 1057 interventional cardiologists throughout the United States. The survey addressed factors such as patient age, preclosure workup, and postclosure antithrombotics. Clinical vignettes highlighted critical variables and used a 5-point Likert scale to assess the providers' level of support for closure. There were 491 survey responses received from 301 (of 1556) vascular neurologists and 190 (of 1057) interventional cardiologists, with an overall response rate of 19%. Vascular neurologists were more likely to recommend against closure on the basis of older age (P<0.001). Interventional cardiologists are more supportive of closure across a range of clinical vignettes, including a very carefully selected patient with cryptogenic stroke (P<0.001), a patient with a high-risk alternative stroke cause (P<0.001), and a range of cases highlighting clinical variables where data are lacking. The majority of interventionalists (88%) seek neurology consultation before pursuing patent foramen ovale closure. Conclusions lnterventional cardiologists are more likely than vascular neurologists to support patent foramen ovale closure across a range of situations. This emphasizes the importance of collaboration and shared decision making, but also reveals an opportunity for professional society educational outreach.