Individualized or Uniform De-Escalation Strategies for Antiplatelet Therapy in Acute Coronary Syndrome: A Review of Clinical Trials with Platelet Function Testing and Genetic Testing-Based Protocols.

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.

Prognostic value of right atrial stiffness in systemic sclerosis.

OBJECTIVES: We hypothesised that right atrial (RA) size and mechanics may have prognostic role in systemic sclerosis (SSc) patients without manifest pulmonary arterial hypertension (PAH), thus we aimed to investigate the prognostic power of RA volume, strain and stiffness parameters alone and when added to the echocardiographic marker of RV longitudinal systolic function. METHODS: Seventy SSc patients (57±12 years) were enrolled into our follow-up study. They underwent standard echocardiographic and tissue Doppler measurements at baseline. In addition to maximal RA volume index, RA reservoir, conduit and contractile strain were measured with 2D speckle tracking technique. RA stiffness was calculated as ratio of TriE/e' to reservoir strain. Survival was assessed after 5 years. All-cause mortality was chosen as outcome. Sequential χ2 analysis was used to evaluate the incremental prognostic benefit of adding RA volume, strain or stiffness to tricuspid S (TriS). RESULTS: During the follow-up period of 4.7±0.9 years, 6 patients (8.6%) died. When added to TriS in sequential Cox model, RA stiffness significantly improved the diagnostic performance of the model (Δχ2= 3.950; p=0.047) and remained independent predictor of the outcome (HR 2.460 (1.005-6.021); p=0.049). Vmax index and strain parameters did not show incremental prognostic value over TriS. Using ROC analysis, RA stiffness ≥0.156 was the best predictor of mortality (sensitivity=83.3%, specificity =89.1%, AUC=0.859). CONCLUSIONS: RA stiffness is associated with all-cause mortality in SSc patients without PAH independent of and incremental to the RV longitudinal systolic function. It may be proposed as non-invasive marker for identifying patients with high mortality risk.

Galectin-3 and sST2: associations to the echocardiographic markers of the myocardial mechanics in systemic sclerosis - a pilot study.

BACKGROUND: Progressive cardiac fibrosis is the central aspect of the myocardial involvement in systemic sclerosis (SSc). We hypothesized that circulating biomarkers of the cardiac fibrosis may be useful in the early diagnosis of the cardiac manifestation in this disease. Thus, we investigated the potential correlations between the levels of galectin-3, soluble suppression of tumorigenicity-2 (sST2) and the echocardiographic markers of the myocardial mechanics in SSc patients. METHODS: Forty patients (57.3 ± 13.7 years, 36 female) were investigated. In addition to the conventional echocardiography, tissue Doppler and speckle tracking-derived strain techniques were used to assess the function of both ventricles and atria. To estimate the correlations between galectin-3 and sST2 levels and the echocardiographic variables, partial correlation method was used with age as correcting factor. RESULTS: In age adjusted analysis galectin-3 level showed significant correlation with left ventricular global longitudinal strain (r = 0.460, p = 0.005); grade of left ventricular diastolic dysfunction (r = 0.394, p = 0.013); septal e' (r = - 0.369, p = 0.021); septal E/e' (r = 0.380, p = 0.017) and with the grade of mitral regurgitation (r = 0.323, p = 0.048). No significant correlation was found between sST2 levels and the echocardiographic variables. CONCLUSIONS: Galectin-3 levels, but not sST2 levels show significant correlation with the parameters of the left ventricular systolic and diastolic function. Galectin-3 may be a useful biomarker for the screening and early diagnosis of SSc patients with cardiac involvement.

Network Meta-Analysis of Ticagrelor for Stroke Prevention in Patients at High Risk for Cardiovascular or Cerebrovascular Events.

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.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.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, 0.71­0.89]). Treatment with ticagrelor monotherapy did not significantly affect ischemic stroke (risk ratio, 0.88 [95% CI, 0.77­1.00]; 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, 0.91­1.07]).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.

Use of drug-eluting stents in elderly patients with acute myocardial infarction: An analysis of the Hungarian Myocardial Infarction Registry.

BACKGROUND: Bare-metal stents (BMS) are frequently implanted in elderly patients instead of drug-eluting stents (DES). We aimed to compare the prognosis of patients treated for myocardial infarction with the two types of stents over the age of 75. METHODS: Data of patients registered in the Hungarian Myocardial Infarction Registry, a mandatory nationwide programme for hospitals treating patients with myocardial infarction were processed. From patients included between January 2014 and December 2017 we created two groups according to DES and BMS implantation. The outcome measures included all-cause mortality, the composite of cardiac events (MACE), repeated revascularisation and transfusion. Propensity score matching was used to balance the groups and Cox proportional hazards' models to estimate the risk during the 1st year after the index event. RESULTS: From 7383 patients (age: 81.08 ± 4.38 years) 3266 (44.2%) patients received DES. The PS-matched cohort included 5780 cases with balanced characteristics. In the DES group, the mortality (HR 0.66 [0.60-0.72]), MACE (HR 0.66 [0.60-0.72]) and the rate of transfusion (HR 0.84 [0.73-0.97]) were significantly lower. The PS-matched cohort showed a similar trend but with a lower rate of benefits with a 21% reduction of mortality and 23% of MACE. Difference in transfusion did not reach the level of significance. In multivariate models, stent type prevailed as an independent predictor of mortality and but not of transfusion. CONCLUSIONS: Based on our analysis of a real-life, high-risk population, implantation of DES seems to be an advantageous strategy for elderly patients.

Oral anticoagulation and outcomes in patients with acute myocardial infarction: Insights from the Hungarian Myocardial Infarction Registry.

INTRODUCTION: Anticoagulation reduces the risk of stroke and embolization and is recommended in most patients with atrial fibrillation. Patients after coronary intervention and acute coronary syndromes require antiplatelet treatment. Although oral anticoagulation (OAC) therapy may interfere with the outcome of patients after coronary intervention, its exact impact remains unclear. Importantly, risk-benefit relations may be considerably different after myocardial infarction. MATERIAL AND METHODS: Data of patients registered from the Hungarian Myocardial Infarction Registry, a mandatory nationwide program for hospitals treating patients with myocardial infarction, were processed. Patients registered between 01.2014. and 12.2017 were included. All-cause mortality, the composite of cardiac events (MACE), and transfusion were compared between patients receiving OAC treatment and a propensity score (PS) matched control group. Subgroup analyses of different anticoagulation and antiplatelet strategies were performed with propensity weighted Cox proportional hazards' models to estimate risk during the first year after the index event. RESULTS: From 30 681 patients 1875 cases received OAC treatment and had apparently worse prognosis. After PS-matching, however, we found no difference regarding mortality (hazard ratio [HR]: 0.91 95% CI 0.77-1.09, P = .303), MACE (HR: 0.92 95% CI 0.78-1.09, P = .335) or transfusion (HR: 1.21, 95% CI 0.97-1.49, P = .086). In PS-adjusted analyses for the OAC group, patients who received aspirin were associated with lower mortality (HR: 0.77, 95% CI: 0.60-0.997, P = .048) and MACE (HR:0.73, 95% CI 0.58-0.92, P = .008) compared to those without aspirin. CONCLUSIONS: In patients with acute myocardial infarction, the prognosis of OAC-treated patients was comparable to the PS matched control; however, the omission of aspirin therapy was associated with unfavorable outcomes.

Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel: a pre-specified exploratory analysis from the TROPICAL-ACS trial.

AIMS: The value of platelet function testing (PFT) in predicting clinical outcomes and guiding P2Y12-inhibitor treatment is uncertain. In a pre-specified sub-study of the TROPICAL-ACS trial, we assessed ischaemic and bleeding risks according to high platelet reactivity (HPR) and low platelet reactivity (LPR) to ADP in patients receiving uniform prasugrel vs. PFT-guided clopidogrel or prasugrel. METHODS AND RESULTS: Acute coronary syndrome patients with PFT done 14 days after hospital discharge were included with prior randomization to uniform prasugrel for 12 months (control group, no treatment modification) vs. early de-escalation from prasugrel to clopidogrel and PFT-guided maintenance treatment (HPR: switch-back to prasugrel, non-HPR: clopidogrel). The composite ischaemic endpoint included cardiovascular death, myocardial infarction, or stroke, while key safety outcome was Bleeding Academic Research Consortium (BARC) 2-5 bleeding, from PFT until 12 months. We identified 2527 patients with PFT results available: 1266 were randomized to the guided and 1261 to the control group. Before treatment adjustment, HPR was more prevalent in the guided group (40% vs. 15%), while LPR was more common in control patients (27% vs. 11%). Compared to control patients without HPR on prasugrel (n = 1073), similar outcomes were observed in guided patients kept on clopidogrel [n = 755, hazard ratio (HR): 1.06 (0.57-1.95), P = 0.86] and also in patients with HPR on clopidogrel switched to prasugrel [n = 511, HR: 0.96 (0.47-1.96), P = 0.91]. In contrast, HPR on prasugrel was associated with a higher risk for ischaemic events in control patients [n = 188, HR: 2.16 (1.01-4.65), P = 0.049]. Low platelet reactivity was an independent predictor of bleeding [HR: 1.74 (1.18-2.56), P = 0.005], without interaction (Pint = 0.76) between study groups. CONCLUSION: Based on this substudy of a randomized trial, selecting prasugrel or clopidogrel based on PFT resulted in similar ischaemic outcomes as uniform prasugrel therapy without HPR. Although infrequent, HPR on prasugrel was associated with increased risk of ischaemic events. Low platelet reactivity was a strong and independent predictor of bleeding both on prasugrel and clopidogrel.

Age and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: results from the randomized TROPICAL-ACS trial.

Aims: Guided de-escalation of P2Y12-inhibitor treatment was recently identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention. Safety and efficacy of this strategy may differ in relation to patient's age. This pre-specified analysis of the TROPICAL-ACS trial aimed to assess the impact of age on clinical outcomes following guided de-escalation of antiplatelet treatment in ACS patients. Methods and results: Patients were randomly assigned in a 1:1 fashion to either standard treatment with prasugrel for 12 months (control group) or to a guided de-escalation regimen (1 week prasugrel followed by 1 week clopidogrel and platelet function testing guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). We used Cox regression models to assess the associations of age on clinical endpoints and interactions. In younger patients (age ≤70, n = 2240), the 1 year incidence of the primary endpoint (cardiovascular death, myocardial infarction, stroke, or bleeding ≥ grade 2 according to Bleeding Academic Research Consortium criteria) was significantly lower in guided de-escalation vs. control group [5.9% vs. 8.3%; hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.51-0.96; P = 0.03, number needed to treat = 42]. In elderly patients (age >70, n = 370), the absolute risk of events was higher without significant differences between guided de-escalation vs. control group (15.5% vs. 13.6%; HR 1.17, 95% CI 0.69-2.01; P = 0.56). When the impact of age, as a continuous variable, was analysed on outcomes after guided de-escalation vs. control treatment, an increasing relative risk reduction was observed in the primary endpoint by decreasing age (Pint = 0.02), due to significant reductions in bleeding. Conclusion: Treatment effects of guided de-escalation for P2Y12 inhibitors depend on patient's age with younger patients deriving a significant net clinical benefit. Although the safety and efficacy of guided de-escalation in the elderly was similar to uniform prasugrel therapy, this should be further investigated due to the limited sample size of this group.

The role of social support in the dietary behavior of coronary heart patients: an application of the health action process approach.

Dietary behaviour plays a crucial role in both the onset and the management of coronary artery disease (CAD). To develop effective interventions to modify dietary behaviours of patients, it is fundamental to identify and examine the predictive factors that are relevant to healthy dietary behaviour. The Health Action Process Approach provides a useful framework for understanding and predicting the process of health behaviour. The aim of the current study is to clarify the role and effect of received social support in the HAPA model. A longitudinal sample of 117 CAD patients filled out a questionnaire at three time points. Along with HAPA constructs, dietary behaviour was assessed with a food frequency questionnaire. To investigate the longitudinal associations of the constructs, structural equation modelling with latent variables was employed. In the final model, outcome expectancies and pre-action self-efficacy jointly predicted behavioural intention. In the post-intentional phase, social support served as a mediator between intention and action planning. Moreover, coping planning mediated the relationship between action planning and dietary behaviour. These results confirmed the mediator role of social support in the intention-behaviour relationship. This finding suggests that social support can be a crucial component to facilitate healthy dietary behaviour.

Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial.

BACKGROUND: Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). METHODS: In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. FINDINGS: Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (pnon-inferiority=0·0004; hazard ratio [HR] 0·81 [95% CI 0·62-1·06], psuperiority=0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; pnon-inferiority=0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59-1·13]; p=0·23). INTERPRETATION: Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. FUNDING: Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

Impairment of Left Atrial Mechanics Is an Early Sign of Myocardial Involvement in Systemic Sclerosis.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is common in systemic sclerosis (SSc). Less is known, however, about left atrial (LA) mechanics in this context. The aim of this study was to investigate the correlation between LV diastolic function and LA mechanics in SSc patients with the use of volumetric and 2-dimensional speckle tracking-derived strain techniques and to compare the results with those obtained in healthy subjects. METHODS AND RESULTS: Seventy-two SSc patients and 30 healthy volunteers (H) were investigated. LV diastolic function was classified as normal (I), impaired relaxation (II), and pseudonormal pattern (III). LA reservoir (H: 51.8 ± 7.4%; I: 45.1 ± 8.1%; II: 42.2 ± 6.6%; III: 36.6 ± 7.3%; analysis of variance: P < .001) and contractile strain (H: 24.8 ± 4.9%; I: 18.2 ± 4.4%; II: 21.5 ± 2.8%; III: 16.8 ± 3.6%; P < .001) already showed significant worsening in SSc patients with preserved LV diastolic function compared with healthy subjects. LA conduit strain (H: 27.1 ± 4.6%; I: 26.9 ± 5.7%; II: 20.6 ± 6.1%; III: 19.5 ± 5.3%; P < .001) was preserved in this early phase. Further deterioration of reservoir strain was pronounced in the pseudonormal group only. LA contractile strain increased significantly in the impaired relaxation group and then decreased with the further worsening of the LV diastolic function. Regarding phasic volume indices, the differences between groups were not always statistically significant. CONCLUSION: LA mechanics strongly reflects the changes in LV diastolic function in SSc. On the other hand, strain parameters of the LA reservoir and contractile function already show significant worsening in SSc patients with preserved LV diastolic function, suggesting that impairment of the LA mechanics is an early sign of myocardial involvement in SSc.

Early morphologic and functional changes of atherosclerosis in systemic sclerosis-a systematic review and meta-analysis.

OBJECTIVE: Cardiopulmonary manifestations have an important impact on the life expectancy of SSc patients. Functional and morphological macrovascular changes may appear early before the development of ischaemic symptoms. Several non-invasive methods are used in cardiovascular risk assessment. Heterogeneous data are available regarding these in SSc. We aimed to perform a systematic review and meta-analysis to characterize the importance of atherosclerosis in SSc. METHODS: A systematic literature search was performed to identify controlled studies on carotid intima-media thickness, flow- or nitrate-induced vasodilatation (flow-mediated dilatation, nitroglycerine-mediated dilatation), pulse wave velocity, augmentation index and ankle-brachial pressure index. Outcomes were pooled with the random-effects model. RESULTS: Thirty-five studies comprising a total of 1292 SSc patients qualified. Intima-media thickness, pulse wave velocity and ankle-augmentation index were higher and flow-mediated dilatation lower in SSc patients [standardized mean difference (SMD) 0.65 (95% CI: 0.29, 1.01), 0.62 (95% CI: 0.35, 0.88), 0.96 (95% CI: 0.45, 1.47) and -0.68 (95% CI: -1.39, -0.34), respectively, P < 0.01 for each]. Nitroglycerine-mediated dilatation and ankle-brachial pressure index were lower, but not significantly [SMD: -0.16 (95% CI: -0.50, 0.18) and -0.39 (95% CI: -0.91, 0.13), respectively]. Data showed high to moderate inconsistency and significant heterogeneity. Meta-regression analysis of the SMD and the disease duration found a regression coefficient of 0.086, P = 0.014, confirming that parameters of the included SSc population may have contributed to the heterogeneity. CONCLUSION: Meta-analysis of the published observational studies confirms that abnormalities attributable to macrovascular involvement are significantly more prevalent in SSc patients compared with controls. Considering the increasing importance of cardiovascular disease in SSc, a more widespread use of cardiovascular risk assessment is warranted.

Diastolic Dysfunction Is a Contributing Factor to Exercise Intolerance in COPD.

Right ventricular (RV) systolic failure is rare in patients with COPD, but they often develop RV diastolic dysfunction. Left ventricular (LV) diastolic dysfunction is also common in this population. Nevertheless, data are scarce regarding the effect of diastolic dysfunction on the functional capacity in patients with COPD. We investigated the correlation between echocardiographic parameters of RV and LV diastolic function and the exercise capacity in COPD, by using conventional echocardiographic methods and tissue Doppler imaging. 65 patients with COPD (61 ± 9 years) in stages GOLD II-IV were investigated. Functional capacity was measured with 6-minute walk test (6MWT). Right (RA) and left atrial (LA) area index were measured; collapsibility index inferior vena cava was calculated. Parameters of the mitral and tricuspid inflow (E, A) as well as annular systolic (S), early- (e') and late- (a') diastolic myocardial longitudinal velocities were measured. E/A, E/e' and e'/a' ratios were calculated. 6MWT distance was 330 ± 76 m. LV diastolic dysfunction was found in 48 (74%) patients. LV and RV filling pressures were elevated in 28 (43%) and in 29 (45%) patients, respectively. In the left heart, LA area index showed significant correlation with the functional capacity (r = -0.319; p = 0.011). In stepwise multiple linear regression analysis tricuspid e'/a' (r = 0.611; p = 0.000), collapsibility index (r = 0.505; p = 0.000), RA area index (r = -0.445; p = 0.000) and body surface area (r = 0.314; p = 0.011) were independent predictors of 6MWT distance. Right ventricular diastolic function and filling pressure have strong influence on the functional capacity in patients with COPD.

Apixaban and risk of myocardial infarction: meta-analysis of randomized controlled trials.

The coagulation system contributes greatly to the evolution of myocardial infarction (MI). Anticoagulation may reduce the occurrence of MI as monotherapy or with concomitant use of aspirin. Activated factor X antagonists (anti-Xa) and direct thrombin inhibitors have promising results in various indications in non-inferiority trials. However, results regarding their cardiovascular safety are heterogeneous. We systematically evaluated the risk of MI and mortality in patients receiving the new-generation oral anti-Xa agent apixaban. Electronic databases were searched to find prospective, randomized, controlled clinical trials (RCT) that evaluated the clinical impact of apixaban. Efficacy measures included frequency of MI, cardiovascular and overall mortality. Outcome parameters of RCTs were pooled with a random-effects model. Between January 2000 and December 2013, 12 RCTs comprising 54,054 patients were identified. Based on the pooled results, there was no increase in the risk of MI in patients treated with apixaban [odds ratio (OR) 0.90; 95 % confidence interval (CI) 0.77-1.05; p = 0.17] compared to different controls. Cardiovascular and overall mortality with apixaban was comparable to the control groups (OR 0.88; 95 % CI 0.72-1.06; p = 0.18, OR 0.89; 95 % CI 0.77-1.03; p = 0.11, respectively). The pooled risk of major bleeding was lower in the apixaban treated groups (OR 0.84; 95 % CI 0.62-1.12; p = 0.23) however this reached significant level only in subgroup analysis of trials with anticoagulant regimes in the control (OR 0.66; 95 % CI 0.51-0.87; p = 0.003). In a broad spectrum of patients and compared to different controls apixaban treatment was not associated with an increase in MI or mortality.

Prognosis Impact and Prediction of Trans-Radial Access Failure in Patients With STEMI, A Nationwide Observational Study.

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.

Comparing Endovascular Approaches in Lower Extremity Artery Disease: Insights from a Network Meta-Analysis.

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.

The pressure-derived microvascular resistance reserve and its correlation to Doppler MRR measurement-a proof of concept study.

Background: Microvascular resistance reserve (MRR) is a recently introduced specific index of coronary microcirculation. MRR calculation can utilize parameters deriving from coronary flow reserve (CFR) assessment, provided that intracoronary pressure data are also available. The previously proposed pressure-bounded CFR (CFRpb) defines the possible CFR interval on the basis of resting and hyperemic pressure gradients in the epicardial vessel, however, its correlation to the Doppler wire measurement was reported to be rather poor without the correction for hydrostatic pressure. Purpose: We aimed to determine the pressure-bounded coronary MRR interval with hydrostatic pressure correction according to the previously established equations of CFRpb adapted for the MRR concept. Furthermore, we also aimed to design a prediction model using the actual MRR value within the pressure-bounded interval and validate the results against the gold-standard Doppler wire technique. Methods: Hydrostatic pressure between the tip of the catheter and the sensor of the pressure wire was calculated by height difference measurement from a lateral angiographic view. In the derivation cohort the pressure-bounded MRR interval (between MRRpbmin and MRRpbmax) was determined solely from hydrostatic pressure-corrected intracoronary pressure data. The actual MRR was calculated by simple hemodynamic equations incorporating the anatomical data of the three-dimensionally reconstructed coronary artery (MRRp-3D). These results were analyzed by regression analyses to find relations between the MRRpb bounds and the actual MRRp-3D. Results: In the derivation cohort of 23 measurements, linear regression analysis showed a tight relation between MRRpbmax and MRRp-3D (r 2 = 0.74, p < 0.0001). Using this relation (MRRp-3D = 1.04 + 0.51 × MRRpbmax), the linear prediction of the MRR was tested in the validation cohort of 19 measurements against the gold standard Doppler wire technique. A significant correlation was found between the linearly predicted and the measured values (r = 0.54, p = 0.01). If the area stenosis (AS%) was included to a quadratic prediction model, the correlation was improved (r = 0.63, p = 0.004). Conclusions: The MRR can be predicted reliably to assess microvascular function by our simple model. After the correction for hydrostatic pressure error, the pressure data during routine FFR measurement provides a simultaneous physiological assessment of the macro- and microvasculature.

Simplified coronary flow reserve calculations based on three-dimensional coronary reconstruction and intracoronary pressure data.

BACKGROUND: Measurements of fractional flow reserve (FFR) and/or coronary flow reserve (CFR) are widely used for hemodynamic characterization of coronary lesions. The frequent combination of the epicardial and microvascular disease may indicate a need for complex hemodynamic evaluation of coronary lesions. This study aims at validating the calculation of CFR based on a simple hemodynamic model to detailed computational fluid dynamics (CFD) analysis. METHODS: Three-dimensional (3D) morphological data and pressure values from FFR measurements were used to calculate the target vessel. Nine patients with one intermediate stenosis each, measured by pressure wire, were included in this study. RESULTS: A correlation was found between the determined CFR from simple equations and from a steady flow simulation (r = 0.984, p < 10-5). There was a significant correlation between the CFR values calculated by transient and steady flow simulations (r = 0.94, p < 10-3). CONCLUSIONS: Feasibility was demonstrated of a simple hemodynamic calculation of CFR based on 3D-angiography and intracoronary pressure measurements. A simultaneous determination of both the FFR and CFR values provides the capability to diagnose microvascular dysfunction: the CFR/FFR ratio characterizes the microvascular reserve.

Angiography-based coronary microvascular assessment with and without intracoronary pressure measurements: a systematic review.

BACKGROUND: In recent years, several indices have been proposed for quantifying coronary microvascular resistance. We intended to conduct a comprehensive review that systematically evaluates indices of microvascular resistance derived from angiography. OBJECTIVE: The objective of this study was to identify and analyze angiography-derived indices of microvascular resistance that have been validated against an invasive reference method. We aimed to compare their limits of agreement with their reference methods and explore their advantages and inherent limitations. METHODS AND RESULTS: We searched PubMed from inception until 2022 for studies on different techniques for quantifying microvascular resistance. Seven studies met the inclusion criteria. Five studies included techniques that applied calculations based solely on invasive angiography, and were validated against invasively measured thermodilution-derived index of microvascular resistance. The remaining two studies combined angiography with invasively measured intracoronary pressure data, and were validated against invasive Doppler measurements. We converted the ± 1.96 standard deviation limits of agreement with the reference method from the seven studies into percentages relative to the cut-off value of the reference method. The lower limits of agreement for angiography-based methods ranged from - 122 to - 60%, while the upper limits ranged from 74 to 135%. The range of the limits of agreement was considerably lower for the two combined angiography- and pressure-based methods, standing at - 52 to 60% and - 25 to 27%. CONCLUSION: Our findings suggest that combined angiography- and pressure-based methods provide a more reliable assessment of microvascular resistance compared to methods relying solely on angiography. Central illustration. Comparative assessment of image-based methods quantifying microvascular resistance with and without intracoronary pressure measurements. Angiography-based methods rely on angiography alone to calculate the microvascular resistance by utilizing angiographic frame counting to extrapolate coronary flow (Q) and subsequently deriving distal coronary pressure using fluid dynamic equations. Combined angiography- and pressure-based methods utilize invasive intracoronary pressure gradients measured during rest and maximal vasodilation to determine coronary flow in their calculation of microvascular resistance. The combined methods showed more acceptable levels of agreement with their reference methods compared to angiography-based methods alone.

Increased risk of adverse events in patients with low-on clopidogrel platelet reactivity after percutaneous coronary intervention: A systematic review and meta-analysis.

BACKGROUND: Clinical evidence has been controversial regarding the influence of low platelet reactivity (LPR), ischemic and bleeding outcomes among patients receiving coronary stent implantation. Hence, the present study performed a meta-analysis to systematically evaluate the significance of LPR on adverse cardiovascular events. METHODS: MEDLINE, EMBASE and CENTRAL databases were searched up to November 2020 for relevant studies including patients with acute coronary syndrome undergoing percutaneous coronary intervention. LPR was the exposed arm while the non-LPR group represented the control. The primary outcome of interest was bleeding risk including major and minor bleeding events. Secondary outcomes included all-cause mortality, repeated revascularization, nonfatal myocardial infarction, and stent thrombosis. Study-level outcomes were evaluated in random-effect models. RESULTS: A total of 20 studies with 19,064 patients were included. Pooled analysis showed that LPR was associated with an increased bleeding risk (relative risk [RR] 2.80, 95% confidence interval [CI] 1.95-4.02, p < 0.01). Patients with LPR had a lower risk of non-fatal myocardial infarction (RR 0.59, 95% CI 0.38-0.91, p < 0.05) and of serious vascular events (RR 0.50, 95% CI 0.30-0.84, p < 0.01). CONCLUSIONS: Low platelet reactivity is associated with an increased bleeding risk of patients who underwent coronary stent implantation. The results suggest possible benefits of this marker in risk stratification, with potential improvement in risk prediction. There are potential advantages using combinations with other factors in prediction models, however, they require further study. PROSPERO registration number: CRD42019136393).