Arrhythmic Events and Mortality in Patients With Cardiogenic Shock on Inotropic Support: Results of the DOREMI Randomized Trial.

BACKGROUND: Inotropic support is widely used in the management of cardiogenic shock (CS). Existing data on the incidence and significance of arrhythmic events in patients with CS on inotropic support is at high risk of bias. METHODS: The Dobutamine Compared to Milrinone (DOREMI) trial randomized patients to receive dobutamine or milrinone in a double-blind fashion. Patients with and without arrhythmic events (defined as arrhythmias requiring intervention or sustained ventricular arrhythmias) were compared to identify factors associated with their occurrence, and to examine their association with in-hospital mortality and secondary outcomes. RESULTS: Ninety-two patients (47.9%) had arrhythmic events, occurring equally with dobutamine and milrinone (P = 0.563). The need for vasopressor support at initiation of the inotrope and a history of atrial fibrillation were positively associated with arrhythmic events, whereas predominant right ventricular dysfunction, previous myocardial infarction, and increasing left ventricular ejection fraction were negatively associated with them. Supraventricular arrhythmic events were not associated with mortality (relative risk [RR], 0.97; 95% confidence interval [CI], 0.68-1.40; P = 0.879) but were positively associated with resuscitated cardiac arrests and hospital length of stay. Ventricular arrhythmic events were positively associated with mortality (RR, 1.66; 95% CI, 1.13-2.43; P = 0.026) and resuscitated cardiac arrests. Arrhythmic events were most often treated with amiodarone (97%) and electrical cardioversion (27%), which were not associated with mortality. CONCLUSIONS: Clinically relevant arrhythmic events occur in approximately one-half of patients with CS treated with dobutamine or milrinone and are associated with adverse clinical outcomes. Five factors may help to identify patients most at risk of arrhythmic events.

No sex-based difference in cardiogenic shock: A post-hoc analysis of the DOREMI trial.

BACKGROUND: Cardiogenic shock (CS) is associated with significant morbidity and mortality; however, there are limited randomized data evaluating the association between sex and clinical outcomes in patients with CS. Patients with CS enrolled in the DObutamine compaREd with MIlrinone (DOREMI) trial were evaluated in this post-hoc analysis. METHODS: The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary outcome. We analyzed the primary and secondary outcomes using unadjusted relative risks and performed adjusted analysis for the primary outcome and all-cause mortality using the covariates mean arterial pressure <70 mmHg at inotrope initiation, age, and acute myocardial infarction CS. RESULTS: Among 192 participants in the DOREMI study, 70 patients (36 %) were female. The primary outcome occurred in 38 female patients (54 %) compared to 61 male patients (50 %) [adjusted relative risk (aRR) 1.23; 95 % CI 0.78-1.95, p = 0.97]. When stratified by inotrope, there was no difference in the primary outcome comparing females to males receiving dobutamine (RR 1.14; 95 % CI 0.79-1.65, p = 0.50) nor milrinone (RR 1.03; 95 % CI 0.68-1.57, p = 0.87). There was no difference in all-cause mortality comparing females to males (aRR 1.51; 95 % CI 0.78-2.94, p = 0.88). Additionally, there were no differences in any secondary outcomes between males and females (p > 0.05 for all endpoints). CONCLUSION: In patients presenting with CS treated with milrinone or dobutamine, no differences in clinical outcomes were observed between males and females.

The association of PRECISE-DAPT score with ischaemic outcomes in patients taking dual antiplatelet therapy following percutaneous coronary intervention: a meta-analysis.

AIMS: The PRECISE-DAPT (Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) score identifies patients at high risk of bleeding complications following percutaneous coronary intervention (PCI). International guidelines recommend the PRECISE-DAPT score to identify patients at high risk for bleeding, who may benefit from shortened dual antiplatelet therapy. The association of the PRECISE-DAPT score with ischaemic outcomes remains unclear. We performed a meta-analysis investigating the association between a high PRECISE-DAPT score and ischaemic outcomes. METHODS AND RESULTS: A comprehensive literature search was conducted on articles published between 11 March 2017 and 5 June 2021. Two reviewers independently screened articles for inclusion using pre-defined criteria. The outcome measures extracted included composite ischaemic events, major bleeding events, and all-cause mortality. A random effects model was applied to obtain combined risk estimates for outcomes. From 12 included studies, there were 39 459 patients with PRECISE-DAPT <25 and 14 761 patients with PRECISE-DAPT ≥25. PRECISE-DAPT score ≥25 was associated with increased risk of composite ischaemic events [odds ratio (OR) 2.16; 95% confidence interval (CI) 1.77-2.65], myocardial infarction (OR 2.06; 95% CI 1.38-3.08), and ischaemic stroke (OR 2.90; 95% CI 1.76-4.78). Patients with a PRECISE-DAPT score ≥25 had increased risk of major bleeding (OR 3.62; 95% CI 2.62-4.99). Patients with a PRECISE-DAPT score ≥25 had higher risk of all-cause mortality (OR 5.83; 95% CI 5.37-6.33). CONCLUSION: Patients with a PRECISE-DAPT score ≥25 are at increased risk for ischaemic events, bleeding, and all-cause mortality. Prospective evaluation of a PRECISE-DAPT guided approach to antiplatelet therapy is required to demonstrate benefit in this high-risk population.

Ischemic and bleeding outcomes after coronary artery bypass grafting among patients initially treated with a P2Y12 receptor antagonist for acute coronary syndromes: Insights on timing of discontinuation of ticagrelor and clopidogrel prior to surgery.

BACKGROUND: Clinical outcomes in acute coronary syndrome patients treated with P2Y12 inhibitors who require urgent coronary artery bypass grafting (CABG) have not been well studied. METHODS: We examined clinical outcomes in acute coronary syndrome patients in relation to the timing of CABG following P2Y12 inhibitor discontinuation (<72 h, 72 h to five days, >5 days). The primary ischemic outcome was a composite of death, reinfarction, need for revascularization, or stroke. The primary safety outcome was bleeding of at least moderate severity as defined by a Universal Definition of Perioperative Bleeding class ≥2. RESULTS: Among 508 patients (95 ticagrelor, 413 clopidogrel), the timing of CABG following P2Y12 inhibitor discontinuation was <72 h in 32.1%, 72 h to five days in 23.2% and >5 days in 44.7%. Compared with CABG within 72 h, CABG 72 h to five days (adjusted odds ratio (OR) 0.35; 95% confidence interval (CI) 0.14-0.85; p=0.02) but not >5 days (adjusted OR 0.62; 95% CI 0.33-1.16; p=0.14) after P2Y12 inhibitor discontinuation was associated with lower odds of the primary ischemic outcome. Compared with CABG within 72 h, CABG 72 h to five days (adjusted OR 0.38; 95% CI 0.22-0.66; p=0.001) and >5 days (adjusted OR 0.33; 95% CI 0.20-0.53; p<0.001) after P2Y12 inhibitor discontinuation were associated with lower rates of Universal Definition of Perioperative Bleeding class ≥2 bleeding. CONCLUSIONS: CABG within 72 h after P2Y12 inhibitor discontinuation is associated with excess ischemia and bleeding. The rates of ischemic and bleeding events were comparable in patients undergoing CABG 72 h to five days compared with >5 days after P2Y12 inhibitor discontinuation.

Statin therapy in the treatment of active cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Preclinical evidence suggests statins may have anti-tumor properties. Large observational studies are also consistent with improved survival and cancer-specific outcomes among cancer patients on statins. We sought to evaluate the randomized controlled trials of statins in addition to usual anti-cancer therapy. METHODS: A systematic search of MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, Papers First and Clinicaltrials.gov was performed from inception through to July 4, 2017 to identify randomized clinical trials that investigated statin therapy in cancer patients. Our primary outcome was overall survival and our secondary outcome was progression-free survival. We calculated summary hazard ratio's (HR) and 95% confidence intervals (CI) based on random-effects models using aggregate data. PROSPERO (CRD42017065503). RESULTS: Ten studies with 1,881 individuals were included with 1,572 deaths and a median follow-up of 23 months. All trials included patients with advanced (stage 3 or higher) disease. There was minimal between-study statistical heterogeneity (I2 = 1.8%, for OS; I2 = 0%, for PFS). The pooled HR for overall survival in patients randomized to statins plus standard anti-cancer therapy versus standard therapy alone was 0.94 (95% CI, 0.85 to 1.04). In the 9 studies that reported progression-free survival (1,798 participants), the pooled HR for statin plus standard therapy versus standard therapy alone was 0.97 (95% CI, 0.87 to 1.07). CONCLUSIONS: In patients with advanced cancer and a prognosis <2 years, the addition of statins to standard anti-cancer therapy does not appear to improve overall survival or progression-free survival. Future research should assess if cancer patients with better prognosis benefit from longer-term statin therapy.

Ticagrelor in Triple Antithrombotic Therapy: Predictors of Ischemic and Bleeding Complications.

BACKGROUND: Patients on dual antiplatelet therapy following percutaneous coronary intervention often have indications for concurrent oral anticoagulation or triple antithrombotic therapy (TT). Although TT may decrease ischemic complications, it may confer increased bleeding risk. HYPOTHESIS: We hypothesize that the use of ticagrelor in TT is associated with higher risk of complications; accordingly, we sought to determine predictors of complications in patients on TT. METHODS: Patients discharged on TT after percutaneous coronary intervention were followed prospectively for 12 months. The primary endpoint was a composite of ischemic (death, myocardial infarction, stroke) and major bleeding complications or net adverse clinical event (NACE). A major secondary endpoint was BARC (Bleeding Academic Research Consortium) types 2, 3, or 5 bleeding. Outcomes were compared between ticagrelor- and clopidogrel-treated patients. Multivariable analyses were performed to elucidate predictors of complications. RESULTS: Twenty-seven of 152 patients discharged on TT were on ticagrelor. NACE occurred in 52% of patients and BARC 2, 3, or 5 bleeding occurred in 18%. There was no difference in the primary or secondary outcome between ticagrelor vs clopidogrel subgroup. On logistic regressions, use of TT in patients with acute coronary syndrome (P = 0.002) and bridging in with ticagrelor (P = 0.02) were associated with increased NACE. Low estimated glomerular filtration rate was an independent predictor of bleeding (P = 0.03). CONCLUSIONS: The risk of bleeding and ischemic complications among patients on TT is similar between those on ticagrelor and clopidogrel. However, caution with use of bridging anticoagulation should be taken when using ticagrelor.

A pharmacodynamic comparison of a personalized strategy for anti-platelet therapy versus ticagrelor in achieving a therapeutic window.

BACKGROUND: A therapeutic window in antiplatelet treatment has been associated with concurrent lowering of bleeding and ischemic risks. Prasugrel and ticagrelor provide potent platelet inhibition, but may increase bleeding. No study has evaluated a personalized therapy with selective use of novel P2Y12 inhibitory agents compared to empiric ticagrelor use. The objective of this study was to compare a personalized anti-platelet therapy strategy to empiric ticagrelor in achieving a therapeutic window. METHODS: Using the CAPITAL registry, we performed a retrospective analysis to evaluate a personalized anti-platelet therapy (PAT) strategy, using a pharmacogenetic approach, and compared it to empiric ticagrelor. In the PAT group, carriers of CYP2C19*2 received prasugrel and non-carriers received clopidogrel. The primary outcome was the proportion of patients within a validated therapeutic window, after a steady state treatment (≥48h) of antiplatelet therapy, as measured by a P2Y12 reaction unit (PRU) >85 and <208. RESULTS: Of 199 patients with platelet function measurements, 150 received PAT, while 49 received ticagrelor. Significantly more patients on PAT achieved the primary outcome (50.0% vs. 4.1%, p<0.0001). This was predominantly driven by an increase in low on-treatment reactivity with ticagrelor (95.9% vs. 37.3%, p<0.0001). Multivariable analysis demonstrated PAT to be the strongest predictor of achieving PRU values within the therapeutic window (odds ratio 20.27; 95% CI: 4.33-94.82, p=0.0001). CONCLUSION: Patients treated with PAT were more likely to achieve a therapeutic window compared to a strategy of ticagrelor. Future prospective evaluation of novel PAT strategies will be required to prove clinical utility.

A review of patient-reported outcomes for children and adolescents with obesity.

INTRODUCTION: Obesity is a chronic condition that can impact the physical, emotional, mental and social elements that encompass a child's life. The objectives of this study were to identify which generic and obesity-specific patient-reported outcome (PRO) instruments are used in obesity literature, as well as review their conceptual approach, health and health-related content, ethical content and psychometric properties. METHOD: PubMed, CINAHL, EMBASE and PsycINFO were searched from the inception of each database to May 2012 to identify all studies using multi-dimensional PRO instruments with children who are overweight or obese. The most common generic and all obesity-specific instruments were analyzed according to the study objectives. RESULTS: From 4,226 articles identified by our search, 70 articles used 6 generic and 4 obesity-specific PRO instruments. While the most commonly used PRO instrument was the generic PedsQL 4.0 (used in 53 studies), many health domains were found in the obesity-specific instruments that are not measured by the PedsQL 4.0. Summary of the development and psychometric properties of the generic and obesity PROs identified that no one instrument meets all the guideline criteria for instrument development and validation, e.g., only one instrument included qualitative input from children with obesity in the content development phase. DISCUSSION: This comprehensive review provides information to aid in selecting multi-dimensional PRO instruments in children with obesity according to various aspects of content as well as psychometric properties. The conceptual analysis shows that the reviewed PRO instruments contain inconsistencies in their conceptual approaches. Also, certain relevant health domains to children and youth with obesity were not included in the most commonly used generic instrument. The obesity-specific instruments require further validation before they can be used in intervention studies.