Background and Purpose: Preventive antiplatelet therapy is recommended for patients with cardiac or cerebrovascular atherosclerosis. Ticagrelor has an improved safety and efficacy profile in patients with acute coronary syndrome; however, data regarding stroke prevention remain controversial. We conducted a network meta-analysis to compare ticagrelor with other receptor antagonists (P2Y12) inhibitors and aspirin in monotherapy or combination in the treatment of patients with high risk for cardiovascular or cerebrovascular disease, defined as coronary artery disease, acute coronary syndrome, stroke or transient ischemic attack, or peripheral artery disease. Methods: Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted until August 1, 2020. Search terms included ticagrelor, AZD 6140, and stroke. The risk of bias was assessed using the Cochrane Collaboration assessment tool. Random-effects model was used to combine risk estimates across trials and risk ratio with 95% CIs served as summary statistics. The influence of individual components was evaluated in an additive network meta-analysis model. The primary efficacy end point was the occurrence of stroke. The safety end points included bleeding and all-cause mortality. Results: Twenty-six randomized clinical trials comprising 124 495 patients were analyzed. When compared with controls, ticagrelor plus aspirin significantly reduced the risk of ischemic stroke by 20% (risk ratio, 0.80 [95% CI, 0.71–0.89]). Treatment with ticagrelor monotherapy did not significantly affect ischemic stroke (risk ratio, 0.88 [95% CI, 0.77–1.00]; P =0.05). Compared with aspirin alone, major bleeding was in similar ranges with antiplatelet monotherapies while the relative risk was twice higher with combined antiplatelet therapies. There was no considerable difference in the risk of mortality with ticagrelor plus aspirin (risk ratio, 0.99 [95% CI, 0.91–1.07]). Conclusions: Ticagrelor on top of aspirin may provide more favorable outcomes on secondary stroke prevention in patients with vascular risk factors; however, this benefit may come with the price of increased bleeding risk including intracranial bleeding.

Objective: As stroke represents one of the leading causes of mortality and disability worldwide, we aimed to determine the preventive effect of different antiplatelet therapies after an ischemic stroke or transient ischemic attack. Methods: Network meta-analysis evaluating antiplatelet regimes after an ischemic stroke or transient ischemic attack. Searches were conducted in MEDLINE, EMBASE, and Cochrane Library databases until Nov. 23, 2021, for randomized controlled trials. Direct comparisons within trials were combined with indirect evidence from other trials by using a frequentist model. An additive network meta-analysis model was used to evaluate the influence of individual components. The primary efficacy endpoint was a recurrent stroke, the main safety outcomes were the risk of major bleeding and mortality at the longest available follow-up. Results: 58 randomized controlled trials (175,730 patients) were analyzed. The analysis involved 20 antithrombotic strategies including different antiplatelet agents, combinations with aspirin, and anticoagulant therapies. Cilostazol proved to be the most efficacious in reducing stroke recurrence and the risk of bleeding (RR = 0.66, 95%CI = 0.55–0.80 and RR = 0.39, 95%CI = 0.08–2.01) compared to aspirin, respectively. Intensification with combinations of aspirin with ticagrelor or clopidogrel resulted in a lower risk of stroke recurrence (RR = 0.79, 95%CI = 0.67–0.93 and RR = 0.79, 95%CI = 0.72–0.87) but carried a higher bleeding risk (RR = 3.01, 95%CI = 1.65–5.49 and RR = 1.78 95%CI = 1.49–2.13). Conclusion: The prognosis of patients with an ischemic stroke or transient ischemic attack is improved with antiplatelets. Cilostazol showed the best risk-benefit characteristics without trade-off with the risk of major bleeding. Improved stroke recurrence with intensified antiplatelet regimens is counterbalanced with higher bleeding risk, and consequently, mortality remains unaffected. Treatment decisions in stroke survivals should integrate the assessment of bleeding risk for better identification of patients with the highest benefit of treatment intensification. Systematic review registration: Prospero registration number: CRD42020197143, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=197143.

Background: Endovascular therapy offers an alternative for treating femoropopliteal (FP) and infrapopliteal (IP) lesions related to occlusive lower extremity artery disease. Despite numerous trials, the effectiveness of restenosis prevention using local drug delivery devices remains a topic of debate. Objectives: An updated systematic review and network meta-analysis was conducted. Our overall aim was to summarize the most recent clinical evidence regarding endovascular approaches for FP and IP atherosclerotic lesions. Methods: We conducted a search for randomized trials in the MEDLINE database, and extracted data related to clinical endpoints. Our primary focus was on the rate of major adverse events (MAEs), including mortality, amputation, and target lesion revascularization (TLR). A multiple treatment network meta-analysis supplemented with component network analyses was performed to examine the impact of combined treatment. Results: Our search yielded 33 randomized controlled trials encompassing 5766 patients. This included 19 studies focused on femoropopliteal and 14 on IP lesions, accounting for 3565 and 2201 patients, respectively. Drug-coated balloons (DCBs) and drug-eluting stents (DESs) displayed a reduced MAE risk in comparison to plain old balloon angioplasty (POBA)—RR for DCB: 0.64 (95% CI: 0.52–0.77) and for DES: 0.71 (95% CI: 0.51–0.99). The bare-metal stent (BMS) group manifested the most substantial MAE risk, being 59% higher relative to the DCB cohort (BMS vs. DCB RR: 1.59; 95% CI: 1.03–2.47). For FP lesions, DES was the standout performer, curtailing MAE risk by 55% relative to POBA. Within IP lesions, DES mitigated the MAE risk by 25% versus POBA. DCB did not exhibit any notable MAE reduction when pitted against POBA. Conclusion: In FP arteries, both DESs and DCBs yielded significantly diminished MAEs, thus outpacing other techniques. Regarding IP arteries, only DESs resulted in significantly fewer MAEs. In alignment with contemporary research, our findings revealed no signs of elevated mortality in patients undergoing treatment with drug-eluting apparatuses.

Stroke embodies one of the leading causes of death and disability worldwide. We aimed to provide a comprehensive insight into the effectiveness and safety of antiplatelet agents and anticoagulants in the secondary prevention of ischemic stroke or transient ischemic attack. A systematic search for randomized controlled trials, comparing antiplatelet or anticoagulant therapy versus aspirin or placebo among patients with ischemic stroke or transient ischemic attack, was performed in order to summarize data regarding the different regimens. Keyword-based searches in the MEDLINE, EMBASE, and Cochrane Library databases were conducted until the 1st of January 2021. Our search explored 46 randomized controlled trials involving ten antiplatelet agents, six combinations with aspirin, and four anticoagulant therapies. The review of the literature reflects that antiplatelet therapy improves outcome in patients with ischemic stroke or transient ischemic attack. Monotherapy proved to be an effective and safe choice, especially in patients with a high risk of bleeding. Intensified antiplatelet regimens further improve stroke recurrence; however, bleeding rate increases while mortality remains unaffected. Supplementing the clinical judgment of stroke treatment, assessment of bleeding risk is warranted to identify patients with the highest benefit of treatment intensification.

This comprehensive literature review assessed the effectiveness of precision medicine approaches in individualizing P2Y12 de-escalation strategies, such as platelet function testing guidance, genetic testing guidance, and uniform de-escalation, for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Analyzing six trials with a total of 13,729 patients, the cumulative analyses demonstrated a significant reduction in major adverse cardiac events (MACE), net adverse clinical events (NACE), and major and minor bleeding events with P2Y12 de-escalation. Specifically, the analysis found a 24% reduction of MACE and a 22% reduction of adverse event risk (relative risk (RR) 0.76, 95% confidence interval (CI): 0.71–0.82, and RR: 0.78, 95% CI 0.67–0.92, respectively). Reductions in bleeding events were highest with uniform unguided de-escalation, followed by guided de-escalations, while ischemic event rates were similarly lower across all three strategies. Although the review highlights the potential of individualized P2Y12 de-escalation strategies to offer a safer alternative to the long-term potent P2Y12 inhibitor-based dual antiplatelet therapy, it also indicates that laboratory-guided precision medicine approaches may not yet offer the expected benefits, necessitating further research to optimize individualized strategies and evaluate the potential of precision medicine approaches in this context.

Trans -radial access (TRA) is the primary arterial approach for percutaneous coronary intervention (PCI) in ST -elevation myocardial infarction (STEMI). However, occasionally, a crossover to trans -femoral access is necessary because of unsuccessful TRA. The impact of failed TRA on the prognosis in STEMI patients and the utility of predictive models for TRA failure remains uncertain. Data from the Hungarian Myocardial Infarction Registry (January 2014 to December 2020) were analyzed. Primary endpoints were 1 -year mortality and major adverse cardiovascular events. Propensity score matching was employed to create a balanced cohort for comparing successful and failed TRA. The impact of unsuccessful TRA on prognosis was evaluated using Cox regression analysis. Machine learning techniques were applied to predict TRA failure. The performance and the clinical applicability of the novel and previous prediction models were comprehensively evaluated. Of 76,625 registered patients, 34,293 (69.8 13.4 years, male/female: 21,893/12,400) underwent TRA (33,573) or failed TRA (720) PCI for STEMI. After propensity score matching, in the unsuccessful TRA group, the risk of mortality (34.3% vs 22.5%, hazard ratio 1.6, 95% confidence interval 1.3 to 2.0, p < 0.001) and major adverse cardiovascular events (37.4% vs 26.8%, hazard ratio 1.5, 95% confidence interval 1.3 to 1.8, p < 0.001) were significantly higher. Door -to -balloon time did not differ significantly (p = 0.835). In predictive analysis, Regularized Discriminant Analysis emerged as the most promising model, surpassing previous prediction models (area under the curve: 0.66, sensitivity: 0.32, specificity: 0.86). Nevertheless, Global Registry of Acute Coronary Events (GRACE) 2.0 score demonstrated a remarkable performance (area under the curve: 0.65, sensitivity: 0.51, specificity: 0.73). This study underscores the pivotal role of successful TRA in enhancing outcomes in STEMI cases, advocating for its prioritization. The inability to conclude interventions through this approach is linked to a poorer prognosis, even in risk -adjusted analyses. Our findings indicate that prediction models utilizing clinical parameters do not outperform the established GRACE 2.0 algorithm, questioning their utility. In conclusion, the results emphasize the significance of TRA success and the continued relevance of the GRACE score in clinical decision -making to optimize patient outcomes. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY -NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) (Am J Cardiol 2024;220:23 - 32)