Stroke of antiplatelet and anticoagulant therapy in patients with coronary artery disease: a meta-analysis of randomized controlled trials.

BACKGROUND: We performed a meta-analysis sought to investigate the risk of stroke with antiplatelet and anticoagulant therapies among patients with coronary artery disease (CAD). METHODS: We searched PubMed, EMBASE, and Cochrane Library for randomized controlled trials from January 1995 to March 2020. Studies were retrieved if they reported data of stroke for patients with CAD and were randomized to receive intensive versus conservative antithrombotic therapies, including antiplatelet and oral anticoagulant (OAC). Analyses were pooled by random-effects modeling. A total of 42 studies with 301,547subjects were enrolled in this analysis. RESULTS: Intensive antithrombotic therapy significantly reduced risk of all stroke (RR 0.86, 95% CI 0.80-0.94) and ischemic stroke (RR 0.80, 95% CI 0.71-0.91), but increased risk of hemorrhagic stroke (RR 1.36, 95% CI 1.00-1.86) and intracranial hemorrhage (RR 1.46, 95% CI 1.17-1.81). Subgroup analyses indicated that OAC yields more benefit to all stroke than antiplatelet therapy (OAC: RR 0.73, 95% CI 0.58-0.92; Antiplatelet: RR 0.90, 95% CI 0.83-0.97; Between-group heterogeneity P value = 0.030). The benefit of antiplatelet therapy on all stroke and ischemic stroke were mainly driven by the studies comparing longer versus shorter duration of dual antiplatelet therapy (All stroke: RR 0.86, 95% CI 0.78-0.95; ischemic stroke: RR 0.84, 95% CI 0.75-0.94). CONCLUSIONS: Among CAD patients who have already received antiplatelet therapy, either strengthening antiplatelet or anticoagulant treatments significantly reduced all stroke, mainly due to the reduction of ischemic stroke, although it increased the risk of hemorrhagic stroke and intracranial hemorrhage. OAC yields more benefit to all stroke than antiplatelet therapy.

Mortality of Escalation and Modulation Antithrombotic Therapy in Coronary Artery Disease Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The net clinical benefit of antithrombotic therapy (ATT) reflects the concomitant effects of bleeding and ischemic events. OBJECTIVES: We sought to assess the overall effect of the modulation or escalation of ATT on all-cause mortality as well as ischemic and bleeding events. METHODS: We performed a meta-analysis of randomized controlled trials comparing escalation or modulation of ATT versus standard ATT in patients with coronary artery disease. A total of 32 studies with 160,659 subjects were enrolled in this analysis. RESULTS: Neither escalation nor modulation of ATT has significant effect on all-cause mortality (escalation: relative risk [RR]: 0.94, 95% confidence interval [CI]: 0.85-1.04; modulation: RR: 0.90; 95% CI: 0.81-1.01). Compared with standard ATT therapy, escalation of ATT was associated with lower risk of myocardial infarction (MI; RR: 0.84, 95% CI: 0.76-0.94), but had a higher risk of major or minor bleeding (RR: 1.38, 95% CI: 1.15-1.66). Modulation of ATT was associated with a similar risk of MI (RR: 1.07, 95% CI: 0.96-1.19), but a reduced risk for major or minor bleeding (RR: 0.58, 95% CI: 0.51-0.66). Meta-regression combining both escalation and modulation studies found that the heterogeneity of all-cause mortality was mainly attributed to the heterogeneity of major or minor bleeding (adjusted R-squared = 100.00%, p = 0.004), but not to MI. CONCLUSION: Either escalation or modulation of ATT has little benefit in all-cause mortality. The variability of the treatment effects on all-cause mortality was mainly attributed to the variability of major or minor bleeding, but not to MI.

Prognostic significance of multiple triglycerides-derived metabolic indices in patients with acute coronary syndrome.

BACKGROUND: Triglyceride (TG) and its related metabolic indices, all recognized as surrogates of insulin resistance, have been demonstrated to be relevant to clinical prognosis. However, the relative value of these TG-related indices for predicting cardiovascular events among patients with acute coronary syndrome (ACS) has not been examined. METHODS: The TG, the triglyceride-glucose (TyG) index, the atherogenic index of plasma, TG to high-density lipoprotein cholesterol ratio, and the lipoprotein combine index were assessed in 1694 ACS patients undergoing percutaneous coronary intervention. The primary endpoint was major adverse cardiovascular event (MACE), which was the composite of all-cause mortality, stroke, myocardial infarction, or unplanned repeat revascularization. RESULTS: During a median follow-up of 31 months, 345 patients (20.4%) had MACE. The risk of the MACE was increased with higher TG and the four TG-derived metabolic indices [TG-adjusted hazard ratio (HR) = 1.002, 95% CI: 1.001-1.003; TyG index-adjusted HR = 1.736, 95% CI: 1.398-2.156; atherogenic index of plasma-adjusted HR = 2.513, 95% CI: 1.562-4.043; TG to high-density lipoprotein cholesterol ratio-adjusted HR = 1.148, 95% CI: 1.048-1.258; and lipoprotein combine index-adjusted HR = 1.009, 95% CI: 1.004-1.014; P < 0.001 for all indices]. TG and all the four indices significantly improved the predictive ability for MACE in addition to the baseline model. Among them, TyG index showed the best ability for predicting MACE compared with the other three indices from all the three measurements ( P < 0.05 for all comparison). CONCLUSIONS: TG and TG-derived metabolic indices were all strongly associated with MACE among ACS patients undergoing percutaneous coronary intervention. Among all the indices, TyG index showed the best ability to predict the risk of MACE.

Association of serum complement C1q with cardiovascular outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention.

OBJECTIVE: To determine the association of serum complement C1q levels with cardiovascular outcomes among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), and evaluate the value of C1q modified by high-sensitivity C-reactive protein (hs-CRP) levels as an independent predictor. METHODS: As a single-center prospective observational study, we analyzed 1701 patients who had received primary or elective PCI for ACS at Beijing Anzhen Hospital, Capital Medical University, Beijing, China between June 1, 2016 and November 30, 2017. The associations of C1q modified by hs-CRP with major adverse cardiovascular events (MACE) were determined in survival analysis. RESULTS: Patients with the lowest C1q tertile had the highest cumulative risk of MACE (log-rank P = 0.007). In fully adjusted Cox regression models, stratifying the total population according to hs-CRP dichotomy, C1q was significantly associated with MACE in patients with hs-CRP levels less than 2 mg/L but not in those with 2 mg/L or more (P interaction = 0.02). In patients with hs-CRP levels less than 2 mg/L, with the lowest C1q tertile as reference, the risk of MACE was reduced by 40.0% in the middle C1q tertile [hazard ratio (HR) = 0.600, 95% CI: 0.423-0.852, P = 0.004] and by 43.9% in the highest C1q tertile (HR = 0.561, 95% CI: 0.375-0.840, P = 0.005). CONCLUSIONS: Serum complement C1q is significantly associated with cardiovascular outcomes in patients with ACS undergoing PCI, only when hs-CRP levels are less than 2 mg/L. This finding implicates the usefulness of C1q for the risk stratification in ACS patients with reduced systemic inflammation.

Nutritional Risk Index Improves the GRACE Score Prediction of Clinical Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Background: Malnutrition has been shown to be associated with adverse cardiovascular outcomes in many patient populations. Aims: To investigate the prognostic significance of malnutrition as defined by nutritional risk index (NRI) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and whether NRI could improve the GRACE score based prognostic models. Methods: This study applied NRI among 1,718 patients with ACS undergoing PCI. Patients were divided into three nutritional risk groups according to their baseline NRI: no nutritional risk (NRI ≥ 100), mild nutritional risk (97.5 ≤ NRI <100), and moderate-to-severe nutritional risk (NRI <97.5). The primary endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, non-fatal stroke, non-fatal myocardial infarction, or unplanned repeat revascularization. Results: During a median follow-up of 927 days, 354 patients developed MACE. In the overall population, compared with normal nutritional status, malnutrition was associated with increased risk for MACE [adjusted HR for mild and moderate-to-severe nutritional risk, respectively: 1.368 (95%CI 1.004-1.871) and 1.473 (95%CI 1.064-2.041)], and NRI significantly improved the predictive ability of the GRACE score for MACE (cNRI: 0.070, P = 0.010; IDI: 0.005, P < 0.001). In the diabetes subgroup, malnutrition was associated with nearly 2-fold high adjusted risk of MACE, and the GRACE score combined with NRI appeared to have better predictive ability than that in the overall population. Conclusion: Malnutrition as defined by NRI was independently associated with MACE in ACS patients who underwent PCI, especially in individuals with diabetes, and improved the predictive ability of the GRACE score based prognostic models.