Comparing Renin-Angiotensin-Aldosterone Blockade Regimens for Long-Term Chemotherapy-Related Cardiac Dysfunction: A Network Meta-Analysis.

PURPOSE: Cancer therapies including trastuzumab and anthracyclines are cardiotoxic and cause cardiac dysfunction. To prevent cardiotoxicity, pharmacological agents used in heart failure have been administered concomitantly with cardiotoxic cancer therapy, but few studies to date have performed a head-to-head comparison of these different agents. This systematic review and network meta-analysis of randomized-controlled trials aims to evaluate the efficacy of renin-angiotensin-aldosterone system (RAAS) blockers, namely angiotensin-converting enzyme inhibitors (ACE-Is), aldosterone receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), in primary prevention against chemotherapy-related cardiac dysfunction in patients receiving anthracyclines and/or trastuzumab. METHODS: A systematic search was performed in major web databases for studies from inception to 15 September 2022. A Bayesian network meta-analysis model was used to assess the relative effects of competing treatments on the primary outcomes of risk of significant decline in left ventricular ejection fraction (LVEF) and mean LVEF decline. Secondary outcomes included left ventricular diastolic function, global longitudinal strain, and cardiac biomarkers. This study is registered with PROSPERO, CRD42022357980. RESULTS AND CONCLUSION: Nineteen studies reported the effects of 13 interventions (N = 1905 patients). Only enalapril (RR 0.05, 95% CI 0.00-0.20) was associated with reduced risk of patients developing significant decline in LVEF relative to placebo. Subgroup analysis showed that the beneficial effect of enalapril was driven by protection against anthracycline-associated toxicity. In addition, no RAAS-inhibiting agents showed efficacy in protection against treatment with both anthracycline and trastuzumab. The use of RAAS inhibition therapy did not conclusively impact on other markers of cardiac function, including left ventricular diastolic function and cardiac biomarkers.

Rationale and Design of the Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT): A Pilot Study.

BACKGROUND: Cancer therapeutics-related cardiac dysfunction (CTRCD) is a well-recognised complication of cancer treatment. Treatment of CTRCD involves cardioprotective therapy (CPT) which can lead to a recovery of CTRCD with normalisation of the left ventricular ejection fraction (LVEF). As a result, there are potentially millions of cancer survivors with recovered CTRCD on CPT. Cardioprotective therapy can be associated with an undesirable long-term pill burden, financial costs, and side effects. Cancer survivorship is anticipated to increase significantly by the end of this decade. To date, there is no evidence of the safety of stopping CPT in this setting. This study seeks to evaluate the hypothesis that ceasing cardioprotective medication is a feasible and safe option without significant impact on LVEF in low-risk patients who have recovered from CTRCD. METHODS AND ANALYSIS: We will perform a multicentre prospective open-label randomised controlled trial with blinded endpoint (PROBE) of supervised CPT cessation compared to continuing CPT (control). The primary study end point is the change in LVEF by cardiac magnetic resonance imaging at 6 months of enrolment between the two groups. Secondary end points include changes in quality-of-life questionnaires, other cardiac imaging parameters, and recurrence of heart failure. CONCLUSION: Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT) is one of the first studies currently underway to evaluate the safety of ceasing CPT in recovered CTRCD. The results will inform clinical practice in this evidence-free zone.

Obstructive sleep apnea during rapid eye movement sleep in patients after percutaneous coronary intervention: a multicenter study.

PURPOSE: Obstructive sleep apnea (OSA) during the rapid eye movement (REM) stage of the sleep cycle is associated with intense hypoxemia and cardiovascular instability. We characterized OSA during REM sleep in patients after percutaneous coronary intervention. METHODS: In this multicenter study, 204 patients who had undergone percutaneous coronary intervention in the prior 6 to 36 months were recruited for in-laboratory polysomnography. The primary measure was respiratory events during REM sleep. The patients were divided into 2 groups: (1) OSA during REM sleep (≥ 15 events/h) and (2) absence of OSA during REM sleep (< 15 events/h). RESULTS: Based on the overall apnea-hypopnea index ≥ 15, 148 patients (74.0%) had OSA. After excluding patients with failed polysomnography or REM sleep < 30 min, 163 patients formed the cohort for this analysis. OSA during REM sleep was diagnosed in 132 patients (81%). Compared with the patients without OSA during REM sleep, those with OSA during REM sleep had a higher body mass index (p = 0.003) and systolic blood pressure (p = 0.041), and a higher prevalence of diabetes mellitus (p = 0.029). Logistic regression analysis, including age, sex, diabetes mellitus, indication for percutaneous coronary intervention, and indication for multi-vessel percutaneous coronary intervention, showed that diabetes mellitus was the only independent predictor of OSA during REM sleep (odds ratio 2.83; 95% CI, 1.17 to 6.83; p = 0.021). CONCLUSION: In patients treated with percutaneous coronary intervention, there was a high prevalence of OSA during REM sleep. Diabetes mellitus was an independent predictor of OSA during REM sleep.

Chemotherapy and adverse cardiovascular events in colorectal cancer patients undergoing surgical resection.

BACKGROUND: Colorectal cancer patients undergoing surgical resection are at increased short-term risk of post-operative adverse events. However, specific predictors for long-term major adverse cardiac and cerebrovascular events (MACCE) are unclear. We hypothesised that patients who receive chemotherapy are at higher risk of MACCE than those who did not. METHODS: In this retrospective study, 412 patients who underwent surgical resection for newly diagnosed colorectal cancer from January 2013 to April 2015 were grouped according to chemotherapy status. MACCE was defined as a composite of cardiovascular death, myocardial infarction, stroke, unplanned revascularisation, hospitalisation for heart failure or angina. Predictors of MACCE were identified using competing risks regression, with non-cardiovascular death a competing risk. RESULTS: There were 200 patients in the chemotherapy group and 212 patients in the non-chemotherapy group. The overall prevalence of prior cardiovascular disease was 20.9%. Over a median follow-up duration of 5.1 years from diagnosis, the incidence of MACCE was 13.3%. Diabetes mellitus and prior cardiovascular disease were associated with an increased risk of MACCE (subdistribution hazard ratio, 2.56; 95% CI, 1.48-4.42) and 2.38 (95% CI, 1.36-4.18) respectively. The chemotherapy group was associated with a lower risk of MACCE (subdistribution hazard ratio, 0.37; 95% CI, 0.19-0.75) compared to the non-chemotherapy group. CONCLUSIONS: Amongst colorectal cancer patients undergoing surgical resection, there was a high incidence of MACCE. Diabetes mellitus and prior cardiovascular disease were associated with an increased risk of MACCE. Chemotherapy was associated with a lower risk of MACCE, but further research is required to clarify this association.

Obstructive Sleep Apnea and Cardiovascular Events After Percutaneous Coronary Intervention.

BACKGROUND: There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention. METHODS AND RESULTS: The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p=0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10-2.24; P=0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension. CONCLUSIONS: OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01306526.

Effects of Ethnicity on the Prevalence of Obstructive Sleep Apnoea in Patients with Acute Coronary Syndrome: A Pooled Analysis of the ISAACC Trial and Sleep and Stent Study.

BACKGROUND: Obstructive sleep apnoea (OSA) is an emerging risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study. METHODS: A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. Using the same portable diagnostic device, OSA was defined as an apnoea-hypopnoea index of ≥15 events per hour. RESULTS: A total of 1961 patients were analysed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3kg/m2 for Indians and 25.4kg/m2 for Chinese to 28.6kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian (36.1%) patients. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve (AUC) for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161). CONCLUSION: There was significant ethnic variation in the prevalence of OSA in patients with ACS. The magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients.

Optimal Body Mass Index Cut-offs for Identification of Patients with Coronary Artery Disease at High Risk of Obstructive Sleep Apnoea.

BACKGROUND: We sought to evaluate the relationship between Body Mass Index (BMI) and obstructive sleep apnoea (OSA) in Chinese patients hospitalised with coronary artery disease, and to determine the optimal BMI cut-off for prediction of OSA. METHODS: Consecutive Chinese patients who were hospitalised with symptomatic coronary artery disease were recruited to undergo an in-hospital sleep study. RESULTS: A total of 587 patients were recruited. Using cut-off for Asians, 81.2% of the cohort was overweight (BMI ≥23kg/m(2)) and 31.6% was obese (≥27kg/m(2)). A total of 59.5% was diagnosed with OSA, defined as apnoea-hypopnoea index ≥15. Body mass index, hypertension and smoking were predictors of OSA. Multiple logistic regression analysis showed that BMI remains an independent predictor of OSA (odds ratio: 1.11 [95% confidence interval: 1.06 to 1.17], p<0.001) after adjusting for smoking and hypertension. Further analysis using BMI and Apnoea-Hypopnoea Index (AHI) as continuous variables showed significant correlation between BMI and AHI (Pearson's r =0.25, P<0.001). In adjusted models, optimal BMI cut-offs to screen for OSA were 27.3kg/m(2), 23.0-23.9kg/m(2), and 20kg/m(2) for patients with neither, either, or both predictors (smoking and hypertension) respectively. The area under the curve for the adjusted and unadjusted models were similar (0.6013 vs 0.6262, p=0.118). CONCLUSIONS: Body mass index represents a convenient and readily available tool for bedside identification of patients at high risk of OSA. Body mass index cut-offs to predict risks of OSA in Chinese patients with symptomatic coronary artery disease are defined in this study.

A meta-analysis of the predictive accuracy of postoperative mortality using the American Society of Anesthesiologists' physical status classification system.

BACKGROUND: The American Society of Anesthesiologists' physical status (ASA) tool has been applied to determine compensation, risk adjustment and risk prediction, but little is known about the accuracy and generalizability of this tool for prediction of postoperative mortality. METHODS: We systematically investigated prior published reports of associations between ASA physical status and mortality to test the hypothesis that ASA physical status will have varying accuracy in prediction of postoperative mortality across surgical populations with varying surgical risk of mortality. We used random effects models and metaregression to account for heterogeneity. RESULTS: Combining 77 studies with 165,705 patients, the ASA physical status tool demonstrated the following pooled performance (95 % confidence intervals)--sensitivity 0.74 (0.73, 0.74), specificity 0.67 (0.67, 0.67), and area under summary receiver operating curve 0.736 (0.725, 0.747). Metaregression revealed that study death rates and surgical specialty were significant factors. CONCLUSION: ASA physical status is a better predictor of postoperative mortality in settings with lower rather than higher death rates.

Obstructive sleep apnea and temporal changes in cardiac repolarization in patients undergoing coronary artery bypass grafting.

STUDY OBJECTIVES: In coronary artery bypass grafting (CABG), abnormal cardiac repolarization is associated with adverse cardiovascular events that can be measured via the QTc interval. We investigated the impact of obstructive sleep apnea on the change in repolarization after CABG and the association of change in repolarization with the occurrence of major adverse cardiac and cerebrovascular events. METHODS: A total of 1,007 patients from 4 hospitals underwent an overnight sleep study prior to a nonemergent CABG. Electrocardiograms of 954 patients (median age: 62 years; male: 86%; mean follow-up: 2.1 years) were acquired prospectively within 48 hours before CABG (T1) and within 24 hours after CABG (T2). QTc intervals were measured using the BRAVO algorithm by Analyzing Medical Parameters for Solutions LLC. The change in T2 from T1 for QTc (ΔQTc) was derived, and Cox regression was performed. RESULTS: Compared with those without, patients who developed major adverse cardiac and cerebrovascular events (n = 115) were older and had (1) a higher prevalence of smoking, hypertension, diabetes mellitus, and chronic kidney disease; (2) a higher apnea-hypopnea index and oxygen desaturation index; and (3) a smaller ΔQTc. Cox regression analysis demonstrated a smaller ΔQTc to be an independent risk factor for major adverse cardiac and cerebrovascular events (hazard ratio: 0.997; P = .032). In the multivariable regression model, a higher oxygen desaturation index was independently associated with a smaller ΔQTc (correlation coefficient: -0.58; P < .001). CONCLUSIONS: A higher preoperative oxygen desaturation index was an independent predictor of a smaller ΔQTc. ΔQTc within 24 hours after CABG could be a novel predictor of occurrence of major adverse cardiac and cerebrovascular events at medium-term follow-up. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Undiagnosed Sleep Apnea and Bypass OperaTion (SABOT); URL: https://classic.clinicaltrials.gov/ct2/show/NCT02701504; Identifier: NCT02701504. CITATION: Teo YH, Yong CL, Ou YH, et al. Obstructive sleep apnea and temporal changes in cardiac repolarization in patients undergoing coronary artery bypass grafting. J Clin Sleep Med. 2024;20(1):49-55.

The intersection of heart failure and cancer in women: a review.

Cancer and cardiovascular disease represent the two leading causes of morbidity and mortality worldwide. Women continue to enjoy a greater life expectancy than men. However, this comes at a cost with more women developing diabetes, hypertension and coronary artery disease as they age. These traditional cardiovascular risk factors not only increase their lifetime risk of heart failure but also their overall risk of cancer. In addition to this, many of the cancers with female preponderance are treated with potentially cardiotoxic therapies, adding to their increased risk of developing heart failure. As a result, we are faced with a higher risk population, potentially suffering from both cancer and heart failure simultaneously. This is of particular concern given the coexistence of heart failure and cancer can confer a worse prognosis than either a single diagnosis of heart failure or cancer alone. This review article explores the intersection of heart failure and cancer in women at multiple levels, including traditional cardiovascular risk factors, cardiovascular toxicity derived from antineoplastic and radiation therapy, shared pathophysiology and HF as an oncogenic process. This article further identifies opportunities and strategies for intervention and optimisation, whilst highlighting the need for contemporary guidelines to better inform clinical practice.

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

The Belun sleep platform to diagnose obstructive sleep apnea in patients with hypertension and high cardiovascular risk.

STUDY OBJECTIVE: Current hypertension guidelines recommend that at-risk individuals be screened for obstructive sleep apnea (OSA). The Belun Ring is a wearable OSA diagnostic device worn on the palmar side of the proximal phalanx of the index finger. METHODS: We recruited 129 participants (age: 60 ±â€Š8 years, male sex: 88%, BMI: 27 ±â€Š4 kg/m 2 ) with hypertension and high cardiovascular risk for a simultaneous polysomnography and Belun Ring monitoring for one night. Epworth Sleepiness Scale score more than 10 was detected in 27 (21.0%) participants. RESULTS: In the 127 participants who completed the study, the apnea-hypopnea index (AHI) derived from polysomnography was 18.1 (interquartile range: 33.0) events/h and that derived from the Belun Ring was 19.5 (interquartile range: 23.3) events/h [intraclass correlation coefficient: 0.882, 95% confidence interval (95% CI): 0.837-0.916]. A Bland-Altman plot showed the difference between the Belun Ring and polysomnography AHIs to be -1.3 ±â€Š10.4 events/h. Area under the receiver operating characteristic for the Belun Ring AHI was 0.961 (95% CI: 0.932-0.990, P  < 0.001). When the Belun Ring AHI of at least 15 events/h was used to diagnose OSA, the sensitivity, specificity, positive predictive value, and negative predictive value were 95.7, 77.6, 85.3, and 93.8%, respectively. The overall accuracy was 87.4%. The Cohen's kappa agreement was 0.74 ±â€Š0.09 ( P  < 0.001). Similar results were obtained when the oxygen desaturation index was used to diagnose OSA. CONCLUSION: A high prevalence of OSA was detected in patients with hypertension and high cardiovascular risk. The Belun Ring is a reliable device for OSA diagnosis similar to polysomnography.

Hour-to-hour variability of respiratory sleep indices and ambulatory blood pressure.

STUDY OBJECTIVES: Respiratory sleep indices are traditionally reported on the basis of the average total sleep time. The relationship between the hour-to-hour variability of these parameters and blood pressure (BP) has not been reported. METHODS: We evaluated the associations of the hour-to-hour variability of the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and lowest oxygen saturation with the 24-h ambulatory BP in patients with hypertension and newly diagnosed obstructive sleep apnea. A total of 147 patients underwent polysomnography, based on which obstructive sleep apnea was diagnosed in 106 patients; these patients underwent 24-h ambulatory BP monitoring within the next 30 days. Each polysomnogram was divided into hourly reports to calculate the variability of the respiratory sleep indices. Variability independent of the mean was considered the primary measure of variability. RESULTS: The median number of hourly polysomnogram reports was 7 (range, 4-8). The hour-to-hour variability of both AHI and ODI, but not of the lowest oxygen saturation, was correlated with the 24-h pulse pressure, 24-h systolic BP, and awake systolic BP (p < 0.05 for all). The fully adjusted linear regression analysis indicated that the hour-to-hour variability of AHI and ODI remained associated with the 24-h pulse pressure (AHI: ß coefficient, 0.264 [95% CI = 0.033-0.495], p = 0.026; ODI: ß coefficient, 0.450 [95% CI = 0.174-0.726], p = 0.002). CONCLUSIONS: The hour-to-hour variability of AHI and ODI is independently associated with the 24-h pulse pressure. Further investigations are warranted to evaluate the clinical relevance of this new-found association.

Natural Progression of Left Ventricular Function following Anthracyclines without Cardioprotective Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Anthracyclines form the backbone of many systemic chemotherapy regimens but are accompanied by dose-limiting cardiotoxicity. We elucidate the progression and severity of cardiac function over time, in the absence of cardioprotection, which less is known about. METHODS: This PRISMA-guideline-adherent review was registered on PROSPERO (CRD42022373496). RESULTS: 26 studies met the eligibility criteria including a total of 910 patients. The overall reduction in post-anthracycline pooled mean left ventricular ejection fraction (LVEF) in placebo arms of the included randomised-controlled trials was 4.5% (95% CI, 2.6 to 6.4). The trend in LVEF showed a progressive decline until approximately 180 days, after which there was no significant change. Those receiving a cumulative anthracycline dose of 300 mg/m2 experienced a more profound reduction. The overall pooled risk of a 10% absolute decline in LVEF from baseline, or a decline to an LVEF below 50%, was 17% (95% CI: 11 to 24; I2 = 71%). Sensitivity analyses of baseline LVEF and trastuzumab treatment status did not yield significant differences. CONCLUSION: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines is required.

Global Registry of Acute Coronary Events Score Underestimates Post-Acute Coronary Syndrome Mortality among Cancer Patients.

Background Patients with prior cancer are at increased risk of acute coronary syndrome (ACS) with poorer post-ACS outcomes. We aimed to ascertain if the Global Registry of Acute Coronary Events (GRACE) score accurately predicts mortality risk among patients with ACS and prior cancer. Methods We linked nationwide ACS and cancer registries from 2007 to 2018 in Singapore. A total of 24,529 eligible patients had in-hospital and 1-year all-cause mortality risk calculated using the GRACE score (2471 prior cancer; 22,058 no cancer). Results Patients with prior cancer had two-fold higher all-cause mortality compared to patients without cancer (in-hospital: 22.8% versus 10.3%, p < 0.001; 1-year: 49.0% vs. 18.7%, p < 0.001). Cardiovascular mortality did not differ between groups (in-hospital: 5.2% vs. 4.8%, p = 0.346; 1-year: 6.9% vs. 6.1%, p = 0.12). The area under the receiver operating characteristic curve of the GRACE score for prediction of all-cause mortality was less for prior cancer (in-hospital: 0.64 vs. 0.80, p < 0.001; 1-year: 0.66 vs. 0.83, p < 0.001). Among patients with prior cancer and a high-risk GRACE score > 140, in-hospital revascularization was not associated with lower cardiovascular mortality than without in-hospital revascularization (6.7% vs. 7.6%, p = 0.50). Conclusions The GRACE score performs poorly in risk stratification of patients with prior cancer and ACS.

Non-Vitamin K Antagonist Oral Anticoagulants versus Low Molecular Weight Heparin for Cancer-Related Venous Thromboembolic Events: Individual Patient Data Meta-Analysis.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. Low molecular weight heparin (LMWH) has been the standard of care but new guidelines have approved the use of non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Three databases were searched from inception until 19 October 2022. IPD was reconstructed from Kaplan-Meier curves. Shared frailty, stratified Cox and Royston-Parmar models were fit to compare the outcomes of venous thromboembolism recurrence and major bleeding. For studies without Kaplan-Meier curves, aggregate data meta-analysis was conducted using random-effects models. Eleven RCTs involving 4844 patients were included. Aggregate data meta-analysis showed that administering NOACs led to a significantly lower risk of recurrent VTE (RR = 0.65; 95%CI: 0.50-0.84) and deep vein thrombosis (DVT) (RR = 0.60; 95%CI: 0.40-0.90). In the IPD meta-analysis, NOAC when compared with LMWH has an HR of 0.65 (95%CI: 0.49-0.86) for VTE recurrence. Stratified Cox and Royston-Parmar models demonstrated similar results. In reducing risks of recurrent VTE and DVT among cancer patients, NOACs are superior to LMWHs without increased major bleeding.

Prior Cancer Is Associated with Lower Atherosclerotic Cardiovascular Disease Risk at First Acute Myocardial Infarction.

Background: Patients with cancer are at increased risk of acute myocardial infarction (AMI). It is unclear if the Atherosclerotic Cardiovascular Disease (ASCVD) risk score at incident AMI is reflective of this higher risk in patients with prior cancer than those without. Methods: We linked nationwide AMI and cancer registries from 2008 to 2019. A total of 18,200 eligible patients with ASCVD risk score calculated at incident AMI were identified (1086 prior cancer; 17,114 no cancer). Results: At incident AMI, age-standardized mean ASCVD risk was lower in the prior cancer group (18.6%) than no cancer group (20.9%) (p < 0.001). Prior to incident AMI, smoking, hypertension, hyperlipidemia and diabetes mellitus were better controlled in the prior cancer group. However post-AMI, prior cancer was associated with lower guideline-directed medical therapy usage and higher all-cause mortality (adjusted hazard ratio 1.85, 95% confidence interval 1.66−2.07). Conclusions: AMI occurred despite better control of cardiovascular risk factors and lower age-standardized estimated mean 10-year ASCVD risk among patients with prior cancer than no cancer. Prior cancer was associated with lower guideline-directed medical therapy post-AMI and higher mortality.

Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. Can inflammatory markers distinguish streptococcal from viral tonsillitis?

A short-cut review was performed to evaluate whether inflammatory markers such as C reactive protein (CRP), erythrocyte sedimentation rate (ESR), white cell count (WCC) and procalcitonin (PCT) are able to discriminate between streptococcal and viral tonsillitis, enabling a reduction in the overuse of antibiotics. Eight studies with a total of 1031 participants were found. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that WCC, CRP and PCT levels are higher in patients with streptococcal tonsillitis compared to patients with tonsillitis or pharyngitis without group A streptococcus isolated from a throat swab. Which of these markers has the best test performance characteristics requires further study.

Recurrent Stent Thrombosis Secondary to Immunoglobulin G4-Related Disease.

Immunoglobulin G4-related disease (IgG4-RD) is an insidiously progressive multiorgan disease. However, lack of familiarity with IgG4-RD results in patients often being undiagnosed and undertreated. IgG4-RD can affect any organ, and manifests as aortitis within the cardiovascular system. Cardiac involvement is less common, and myocardial infarction is rarely reported. We report the first case of a patient with multiple myocardial infarctions caused by recurrent stent thrombosis associated with IgG4-RD, which resolved upon treatment of IgG4-RD. This case highlights the importance for cardiologists to consider IgG4-RD as a rare but possible association with stent thrombosis.

Lipid profiles and outcomes of patients with prior cancer and subsequent myocardial infarction or stroke.

Patients with cancer are at increased risk of myocardial infarction (MI) and stroke. Guidelines do not address lipid profile targets for these patients. Within the lipid profiles, we hypothesized that patients with cancer develop MI or stroke at lower low density lipoprotein cholesterol (LDL-C) concentrations than patients without cancer and suffer worse outcomes. We linked nationwide longitudinal MI, stroke and cancer registries from years 2007-2017. We identified 42,148 eligible patients with MI (2421 prior cancer; 39,727 no cancer) and 43,888 eligible patients with stroke (3152 prior cancer; 40,738 no cancer). Median LDL-C concentration was lower in the prior cancer group than the no cancer group at incident MI [2.43 versus 3.10 mmol/L, adjusted ratio 0.87 (95% CI 0.85-0.89)] and stroke [2.81 versus 3.22 mmol/L, adjusted ratio 0.93, 95% CI 0.91-0.95)]. Similarly, median triglyceride and total cholesterol concentrations were lower in the prior cancer group, with no difference in high density lipoprotein cholesterol. Prior cancer was associated with higher post-MI mortality [adjusted hazard ratio (HR) 1.48, 95% CI 1.37-1.59] and post-stroke mortality (adjusted HR 1.95, 95% CI 1.52-2.52). Despite lower LDL-C concentrations, patients with prior cancer had worse post-MI and stroke mortality than patients without cancer.