Short-Term Dual Antiplatelet Therapy After Drug-Eluting Stenting in Patients With Acute Coronary Syndromes: A Systematic Review and Network Meta-Analysis.

Importance: The optimal duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) remains under debate. Objectives: To analyze the efficacy and safety of DAPT strategies in patients with ACS using a bayesian network meta-analysis. Data Sources: MEDLINE, Embase, Cochrane, and LILACS databases were searched from inception to April 8, 2024. Study Selection: Randomized clinical trials (RCTs) comparing DAPT duration strategies in patients with ACS undergoing PCI were selected. Short-term strategies (1 month of DAPT followed by P2Y12 inhibitors, 3 months of DAPT followed by P2Y12 inhibitors, 3 months of DAPT followed by aspirin, and 6 months of DAPT followed by aspirin) were compared with conventional 12 months of DAPT. Data Extraction and Synthesis: This systematic review and network meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The risk ratio (RR) with a 95% credible interval (CrI) was calculated within a bayesian random-effects network meta-analysis. Treatments were ranked using surface under the cumulative ranking (SUCRA). Main Outcomes and Measures: The primary efficacy end point was major adverse cardiac and cerebrovascular events (MACCE); the primary safety end point was major bleeding. Results: A total of 15 RCTs randomizing 35 326 patients (mean [SD] age, 63.1 [11.1] years; 26 954 male [76.3%]; 11 339 STEMI [32.1%]) with ACS were included. A total of 24 797 patients (70.2%) received potent P2Y12 inhibitors (ticagrelor or prasugrel). Compared with 12 months of DAPT, 1 month of DAPT followed by P2Y12 inhibitors reduced major bleeding (RR, 0.47; 95% CrI, 0.26-0.74) with no difference in MACCE (RR, 1.00; 95% CrI, 0.70-1.41). No significant differences were observed in MACCE incidence between strategies, although CrIs were wide. SUCRA ranked 1 month of DAPT followed by P2Y12 inhibitors as the best for reducing major bleeding and 3 months of DAPT followed by P2Y12 inhibitors as optimal for reducing MACCE (RR, 0.85; 95% CrI, 0.56-1.21). Conclusion and Relevance: Results of this systematic review and network meta-analysis reveal that, in patients with ACS undergoing PCI with DES, 1 month of DAPT followed by potent P2Y12 inhibitor monotherapy was associated with a reduction in major bleeding without increasing MACCE when compared with 12 months of DAPT. However, an increased risk of MACCE cannot be excluded, and 3 months of DAPT followed by potent P2Y12 inhibitor monotherapy was ranked as the best option to reduce MACCE. Because most patients receiving P2Y12 inhibitor monotherapy were taking ticagrelor, the safety of stopping aspirin in those taking clopidogrel remains unclear.

Effects of Catheter-Based Renal Denervation in Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension. METHODS: We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data. RESULTS: Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; P<0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; P<0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; P<0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; P=0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication (P for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; P=0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; P=0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; P=0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; P=0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups (P for interaction, 0.84). There was significant heterogeneity between trials. CONCLUSIONS: RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medication.

Smoking Habits Following Cancer Diagnosis and Heart Failure.

This cohort study examines the risk of heart failure in patients by smoking status after diagnosis of cancer.

Competing Risks in Clinical Trials: Do They Matter and How Should We Account for Them?

During patient follow-up in a randomized trial, some deaths may occur. Where death (or noncardiovascular death) is not part of an outcome of interest it is termed a competing risk. Conventional analyses (eg, Cox proportional hazards model) handle death similarly to other censored follow-up. Patients still alive are unrealistically assumed to be representative of those who died. The Fine and Gray model has been used to handle competing risks, but is often used inappropriately and can be misleading. We propose an alternative multiple imputation approach that plausibly accounts for the fact that patients who die tend also to be at high risk for the (unobserved) outcome of interest. This provides a logical framework for exploring the impact of a competing risk, recognizing that there is no unique solution. We illustrate these issues in 3 cardiovascular trials and in simulation studies. We conclude with practical recommendations for handling competing risks in future trials.

Triglyceride Levels, Alirocumab Treatment, and Cardiovascular Outcomes After an Acute Coronary Syndrome.

BACKGROUND: It is unknown whether clinical benefit of proprotein convertase subtilisin/kexin type 9 inhibitors is associated with baseline or on-treatment triglyceride concentrations. OBJECTIVES: This study sought to examine relations between triglyceride levels and the effect of alirocumab vs placebo on cardiovascular outcomes using prespecified and post hoc analyses of the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial. METHODS: Patients with recent acute coronary syndrome (ACS) (n = 18,924) and elevated atherogenic lipoproteins despite optimized statin therapy were randomized to alirocumab 75 to 150 mg or matching placebo every 2 weeks subcutaneously. Major adverse cardiovascular events (MACE) were examined in relation to continuous or dichotomous triglyceride concentrations. RESULTS: Median baseline triglyceride concentration was 129 mg/dL. In both treatment groups, a 10-mg/dL higher baseline concentration was associated with an adjusted MACE HR of 1.008 (95% CI: 1.003-1.013; P < 0.005). Baseline triglycerides ≥150 vs <150 mg/dL were associated with a HR of 1.184 (95% CI: 1.080-1.297; P < 0.005). Versus placebo, alirocumab reduced low-density lipoprotein cholesterol from baseline (average, 54.7%) and reduced MACE (HR: 0.85; 95% CI: 0.78-0.93). At month 4, triglyceride levels were reduced from baseline by median 17.7 mg/dL (P < 0.001) and 0.9 mg/dL (P = NS) with alirocumab and placebo, respectively. A 10-mg/dL decline from baseline in triglycerides was associated with lower subsequent risk of MACE with placebo (HR: 0.988; 95% CI: 0.982-0.995; P < 0.005) but not with alirocumab (HR: 0.999; 95% CI: 0.987-1.010; P = 0.82). CONCLUSIONS: Among patients with recent ACS on optimized statin therapy, baseline triglycerides was associated with cardiovascular risk. However, the reduction in triglycerides with alirocumab did not contribute to its clinical benefit. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).

Prediction of Severe Baseline Asymptomatic Carotid Stenosis and Subsequent Risk of Stroke and Cardiovascular Disease.

BACKGROUND: Risk models to identify patients at high risk of asymptomatic carotid artery stenosis (ACAS) can help in selecting patients for screening, but long-term outcomes in these patients are unknown. We assessed the diagnostic and prognostic value of the previously published Prevalence of ACAS (PACAS) risk model to detect ACAS at baseline and to predict subsequent risk of stroke and cardiovascular disease (CVD) during follow-up. METHODS: We validated the discrimination and calibration of the PACAS risk model to detect severe (≥70% narrowing) ACAS with patients from the Reduction of Atherothrombosis for Continued Health registry. We subsequently calculated the incidence rates of stroke and CVD (fatal and nonfatal stroke or myocardial infarction or vascular death) during follow-up in 4 risk groups (low, medium, high, and very high, corresponding to sum scores of ≤9, 10-13, 14-17, and ≥18, respectively). RESULTS: Among 26 384 patients, aged between 45 and 80 years, without prior carotid procedures, 1662 (6.3%) had severe baseline ACAS. During ≈70 000 patient-years of follow-up, 1124 strokes and 2484 CVD events occurred. Discrimination of the PACAS model was 0.67 (95% CI, 0.65-0.68), and calibration showed adequate concordance between predicted and observed risks of severe baseline ACAS after recalibration. Significantly higher incidence rates of stroke (Ptrend<0.011) and CVD (Ptrend<0.0001) during follow-up were found with increasing PACAS risk groups. Among patients with high PACAS sum score of ≥14 (corresponding to 27.7% of all patients), severe baseline ACAS prevalence was 11.4%. In addition, 56.6% of incident strokes and 64.9% of incident CVD events occurred in this group. CONCLUSIONS: The PACAS risk model can reliably identify patients at high risk of severe baseline ACAS. Incidence rates of stroke and CVD during follow-up were significantly higher in patients with high PACAS sum scores. Selective screening of patients with high PACAS sum scores may help to prevent future stroke or CVD.

Effects of Sotagliflozin on Health Status in Patients With Worsening Heart Failure: Results From SOLOIST-WHF.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve health status in heart failure (HF) across the left ejection fraction ejection spectrum. However, the effects of SGLT1 and SGLT2 inhibition on health status are unknown. OBJECTIVES: These prespecified analyses of the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trial examined the effects of sotagliflozin vs placebo on HF-related health status. METHODS: SOLOIST-WHF randomized patients hospitalized or recently discharged after a worsening HF episode to receive sotagliflozin or placebo. The primary endpoint was total number of HF hospitalizations, urgent HF visits, and cardiovascular death. Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) score was a prespecified secondary endpoint. This analysis evaluated change in the KCCQ-12 score from baseline to month 4. RESULTS: Of 1,222 patients randomized, 1,113 (91%) had complete KCCQ-12 data at baseline and 4 months. The baseline KCCQ-12 score was low overall (median: 41.7; Q1-Q3: 27.1-58.3) and improved by 4 months in both groups. Sotagliflozin vs placebo reduced the risk of the primary endpoint consistently across KCCQ-12 tertiles (Ptrend = 0.54). Sotagliflozin-treated patients vs those receiving placebo experienced modest improvement in KCCQ-12 at 4 months (adjusted mean change: 4.1 points; 95% CI: 1.3-7.0 points; P = 0.005). KCCQ-12 improvements were consistent across prespecified subgroups, including left ventricular ejection fraction <50% or ≥50%. More patients receiving sotagliflozin vs those receiving placebo had at least small (≥5 points) improvements in KCCQ-12 at 4 months (OR: 1.38; 95% CI: 1.06-1.80; P = 0.017). CONCLUSIONS: Sotagliflozin improved symptoms, physical limitations, and quality of life within 4 months after worsening HF, with consistent benefits across baseline demographic and clinical characteristics. (Effect of Sotagliflozin on Cardiovascular Events in Participants With Type 2 Diabetes Post Worsening Heart Failure [SOLOIST-WHF]; NCT03521934).

Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y12 Inhibitor Therapy: The CAMEO Registry.

Background: Little is known about the bleeding risk associated with cangrelor use in patients with myocardial infarction (MI) who are exposed to an oral P2Y12 inhibitor before coronary angiography. Methods: Cangrelor in Acute MI: Effectiveness and Outcomes (CAMEO) is an observational registry studying platelet inhibition for patients with MI. Upstream oral P2Y12 inhibition was defined as receipt of an oral P2Y12 inhibitor within 24 hours before hospitalization or in-hospital before angiography. Among cangrelor-treated patients, we compared bleeding after cangrelor use through 7 days postdischarge between patients with and without upstream oral P2Y12 inhibitor exposure. Results: Among 1802 cangrelor-treated patients with MI, 385 (21.4%) received upstream oral P2Y12 inhibitor treatment. Of these, 101 patients (33.8%) started cangrelor within 1 hour, 103 (34.4%) between 1 and 3 hours, and 95 (31.8%), >3 hours after in-hospital oral P2Y12 inhibitor administration; the remaining received an oral P2Y12 inhibitor before hospitalization. There was no statistically significant difference in rates of bleeding among cangrelor-treated patients with and without upstream oral P2Y12 inhibitor exposure (6.5% vs 8.8%; adjusted odds ratio [OR], 0.62; 95% CI, 0.38-1.01). Bleeding was observed in 5.0%, 10.7%, and 3.2% of patients treated with cangrelor <1, 1 to 3, and >3 hours after the last oral PY12 inhibitor dose, respectively; bleeding rates were not statistically different between groups (1-3 hours vs <1 hour: adjusted OR, 2.70; 95% CI, 0.87-8.32; >3 hours vs <1 hour: adjusted OR, 0.65; 95% CI, 0.15-2.85). Conclusions: Bleeding risk was not observed to be significantly higher after cangrelor treatment in patients with and without upstream oral P2Y12 inhibitor exposure.

Trends and Outcomes of Acute Myocardial Infarction During the Early COVID-19 Pandemic in the United States: A National Inpatient Sample Study.

BACKGROUND AND OBJECTIVES: There are limited national data on the trends and outcomes of patients hospitalized with acute myocardial infarction (AMI) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the impact of early COVID-19 pandemic on the trends and outcomes of AMI using the National Inpatient Sample (NIS) database. METHODS: The NIS database was queried from January 2019 to December 2020 to identify adult (age ≥18 years) AMI hospitalizations and were categorized into ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) based on International Classification of Diseases, Tenth Revision, Clinical Modification codes. In addition, the in-hospital mortality, revascularization, and resource utilization of AMI hospitalizations early in the COVID-19 pandemic (2020) were compared to those in the pre-pandemic period (2019) using multivariate logistic and linear regression analysis. RESULTS: Amongst 1,709,480 AMI hospitalizations, 209,450 STEMI and 677,355 NSTEMI occurred in 2019 while 196,230 STEMI and 626,445 NSTEMI hospitalizations occurred in 2020. Compared with those in 2019, the AMI hospitalizations in 2020 had higher odds of in-hospital mortality (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], [1.23-1.32]; p<0.01) and lower odds of percutaneous coronary intervention (aOR, 0.95 [0.92-0.99]; p=0.02), and coronary artery bypass graft (aOR, 0.90 [0.85-0.97]; p<0.01). CONCLUSIONS: We found a significant decline in AMI hospitalizations and use of revascularization, with higher in-hospital mortality, during the early COVID-19 pandemic period (2020) compared with the pre-pandemic period (2019). Further research into the factors associated with increased mortality could help with preparedness in future pandemics.

Myocardial Ischemic Syndromes: A New Nomenclature to Harmonize Evolving International Clinical Practice Guidelines.

Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischemia, various classifications have emerged over time, often with conflicting terminology-eg, "stable coronary artery disease" (CAD), "stable ischemic heart disease," and "chronic coronary syndromes" (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with "acute coronary syndromes" (ACS), the 2023 American guidelines endorsed the alternative term "chronic coronary disease." An unintended consequence of these competing classifications is perpetuation of the restrictive terms "coronary" and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of "acute myocardial ischemic syndromes" and "non-acute myocardial ischemic syndromes," which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischemia, and infarction.

Role of anticoagulation therapy in modifying stroke risk associated with new-onset atrial fibrillation after non-cardiac surgery.

The role of antithrombotic therapy in the prevention of ischemic stroke after non-cardiac surgery is unclear. In this study, we tested the hypothesis that the association of new-onset postoperative atrial fibrillation (POAF) on ischemic stroke can be mitigated by postoperative oral anticoagulation therapy. Of 251,837 adult patients (155,111 female (61.6%) and 96,726 male (38.4%)) who underwent non-cardiac surgical procedures at two sites, POAF was detected in 4,538 (1.8%) patients. The occurrence of POAF was associated with increased 1-year ischemic stroke risk (3.6% versus 2.3%; adjusted risk ratio (RRadj) = 1.60 (95% confidence interval (CI): 1.37-1.87), P < 0.001). In patients with POAF, the risk of developing stroke attributable to POAF was 1.81 (95% CI: 1.44-2.28; P < 0.001) without oral anticoagulation, whereas, in patients treated with anticoagulation, no significant association was observed between POAF and stroke (RRadj = 1.04 (95% CI: 0.71-1.51), P = 0.847, P for interaction = 0.013). Furthermore, we derived and validated a computational model for the prediction of POAF after non-cardiac surgery based on demographics, comorbidities and procedural risk. These findings suggest that POAF is predictable and associated with an increased risk of postoperative ischemic stroke in patients who do not receive postoperative anticoagulation.

Clonal hematopoiesis, cardiovascular events and treatment benefit in 63,700 individuals from five TIMI randomized trials.

Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with an increased risk of cardiovascular (CV) disease in the general population. Currently, it is unclear whether this association is observed in large clinical trial cohorts with a high burden of existing CV disease or whether CV therapies can mitigate CHIP-associated CV risk. To address these questions, we studied 63,700 patients from five randomized trials that tested established therapies for CV disease, including treatments targeting the proteins PCSK9, SGLT2, P2Y12 and FXa. During a median follow-up of 2.5 years, 7,453 patients had at least one CV event (CV death, myocardial infarction (MI), ischemic stroke or coronary revascularization). The adjusted hazard ratio (aHR) for CV events for CHIP+ patients was 1.07 (95% CI: 0.99-1.16, P = 0.08), with consistent risk estimates across each component of CV risk. Significant heterogeneity in the risk of MI was observed, such that CHIP+ patients had a 30% increased risk of first MI (aHR = 1.31 (1.05-1.64), P = 0.02) but no increased risk of recurrent MI (aHR = 0.94 (0.79-1.13), Pint = 0.008), as compared to CHIP- patients. Moreover, no significant heterogeneity in treatment effect between individuals with and without CHIP was observed for any of the therapies studied in the five trials. These results indicate that in clinical trial populations, CHIP is associated with incident but not recurrent coronary events and that the presence of CHIP does not appear to identify patients who will derive greater benefit from commonly used CV therapies.

Myocardial ischaemic syndromes: a new nomenclature to harmonize evolving international clinical practice guidelines.

Since the 1960s, cardiologists have adopted several binary classification systems for acute myocardial infarction (MI) that facilitated improved patient management. Conversely, for chronic stable manifestations of myocardial ischaemia, various classifications have emerged over time, often with conflicting terminology-e.g. 'stable coronary artery disease' (CAD), 'stable ischaemic heart disease', and 'chronic coronary syndromes' (CCS). While the 2019 European guidelines introduced CCS to impart symmetry with 'acute coronary syndromes' (ACS), the 2023 American guidelines endorsed the alternative term 'chronic coronary disease'. An unintended consequence of these competing classifications is perpetuation of the restrictive terms 'coronary' and 'disease', often connoting only a singular obstructive CAD mechanism. It is now important to advance a more broadly inclusive terminology for both obstructive and non-obstructive causes of angina and myocardial ischaemia that fosters conceptual clarity and unifies dyssynchronous nomenclatures across guidelines. We, therefore, propose a new binary classification of 'acute myocardial ischaemic syndromes' and 'non-acute myocardial ischaemic syndromes', which comprises both obstructive epicardial and non-obstructive pathogenetic mechanisms, including microvascular dysfunction, vasospastic disorders, and non-coronary causes. We herein retain accepted categories of ACS, ST-segment elevation MI, and non-ST-segment elevation MI, as important subsets for which revascularization is of proven clinical benefit, as well as new terms like ischaemia and MI with non-obstructive coronary arteries. Overall, such a more encompassing nomenclature better aligns, unifies, and harmonizes different pathophysiologic causes of myocardial ischaemia and should result in more refined diagnostic and therapeutic approaches targeted to the multiple pathobiological precipitants of angina pectoris, ischaemia and infarction.

GLP-1 Receptor Agonists Among Patients With Overweight or Obesity, Diabetes, and HFpEF on SGLT2 Inhibitors.

BACKGROUND: Although the use of glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with obesity and heart failure with preserved ejection fraction (HFpEF) has demonstrated improvement in cardiovascular outcomes, the incremental benefits of GLP-1 RA for patients already on sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored. OBJECTIVES: This study aimed to assess the incremental benefits of GLP-1 RA in patients with type 2 diabetes mellitus, overweight/obesity, and HFpEF receiving SGLT2i therapy. METHODS: The authors conducted a retrospective cohort study using the TriNetX research database including patients ≥18 years with type 2 diabetes mellitus, body mass index ≥27 kg/m2, and HFpEF on SGLT2i. Two cohorts were created based on GLP-1 RA prescription. The outcomes were heart failure exacerbation, all-cause emergency department visits/hospitalizations among others over a 12-month period. RESULTS: A total of 7,044 patients remained in each cohort after propensity score matching. There was a significantly lower risk of heart failure exacerbations, all-cause emergency department visits/hospitalizations, new-onset atrial arrhythmias, new-onset acute kidney injury, and pulmonary hypertension in the GLP-1 RA plus SGLT2i cohort compared with the SGLT2i-only cohort. The associated benefits persisted across different body mass indexes and ejection fractions as well as in patients with elevated natriuretic peptide. The risk of diabetic retinopathy was higher in the combination therapy group than with SGLT2i-only use. CONCLUSIONS: GLP-1 RA, in addition to SGLT2i, was associated with a significantly lower risk of heart failure hospitalizations in this patient population, suggesting a potential incremental benefit. This highlights the need for prospective studies to confirm the clinical benefits.

Multimodal fusion learning for long QT syndrome pathogenic genotypes in a racially diverse population.

Congenital long QT syndrome (LQTS) diagnosis is complicated by limited genetic testing at scale, low prevalence, and normal QT corrected interval in patients with high-risk genotypes. We developed a deep learning approach combining electrocardiogram (ECG) waveform and electronic health record data to assess whether patients had pathogenic variants causing LQTS. We defined patients with high-risk genotypes as having ≥1 pathogenic variant in one of the LQTS-susceptibility genes. We trained the model using data from United Kingdom Biobank (UKBB) and then fine-tuned in a racially/ethnically diverse cohort using Mount Sinai BioMe Biobank. Following group-stratified 5-fold splitting, the fine-tuned model achieved area under the precision-recall curve of 0.29 (95% confidence interval [CI] 0.28-0.29) and area under the receiver operating curve of 0.83 (0.82-0.83) on independent testing data from BioMe. Multimodal fusion learning has promise to identify individuals with pathogenic genetic mutations to enable patient prioritization for further work up.

Colchicine for cardiovascular and limb risk reduction in Medicare beneficiaries with peripheral artery disease: emulation of target trials.

Aims: Recent evidence from randomized trials demonstrates that colchicine can reduce the risk of major adverse cardiovascular events (MACE) in patients with coronary artery disease. Colchicine's effect on lower-extremity peripheral artery disease (PAD) is not known. Methods and results: To make inferences about the real-world effectiveness of colchicine in PAD, we emulated two target trials leveraging the variable prescribing practice of adding colchicine vs. a non-steroidal anti-inflammatory drug (NSAID) to urate-lowering therapy in patients with gout and PAD. Emulated Trial 1 compared colchicine initiators with NSAID initiators. Emulated Trial 2 compared long-term (indefinite) and short-term (3 months) treatment strategies after initiating colchicine. Eligible individuals were those continuously enrolled in Medicare receiving care at a multicentre academic health system between July 2007 and December 2019. The primary outcome for both trials was a 2 year composite of major adverse limb events (MALE), MACE, and all-cause mortality. Secondary outcomes included MALE and death, MACE and death, and individual components of the primary outcome. Inverse probability weighting was used to adjust for confounding. Percentile-based 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping. A total of 1820 eligible patients were included; the mean age was 77 years [standard deviation (SD) 7], 32% were female, and 9% were non-White. The mean (SD) duration of colchicine and NSAID therapy was 247 (345) and 137 (237) days, respectively. In the emulation of Trial 1, the risk of the primary composite outcome of MALE, MACE, and death at 2 years was 29.9% (95% CI 27.2%, 32.3%) in the colchicine group and 31.5% (28.3%, 34.6%) in the NSAID group, with a risk difference of -1.7% (95% CI -6.5%, 3.1%) and a risk ratio of 0.95 (95% CI 0.83, 1.07). Similar findings were noted in the emulation of Trial 2, with a risk of the primary composite outcome at 2 years of 30.7% (95% CI 23.7%, 38.1%) in the long-term colchicine group and 33.4% (95% CI 29.4%, 37.7%) in the short-term group, with a risk difference of -2.7% (95% CI -10.3%, 5.4%) and risk ratio of 0.92 (95% CI 0.70, 1.16). Conclusion: In a real-world sample of patients with PAD and gout, estimates of the effect of colchicine were consistent across two analyses and provided no conclusive evidence that colchicine decreased the risk of adverse cardiovascular or limb events and death. The cardiovascular and limb benefits of colchicine in older, comorbid populations with PAD and advanced systematic atherosclerosis remain uncertain.