Ticagrelor alone or conventional dual antiplatelet therapy in patients with stable or acute coronary syndromes

AIMS The aim of this study was to investigate the effect of ticagrelor monotherapy after one-month dual antiplatelet therapy (DAPT) or conventional DAPT in patients with or without acute coronary syndrome (ACS) in the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY). METHODS AND RESULTS Risk estimates were expressed as rate ratios (RR) with 95% confidence intervals (CI). A total of 3,840 ACS and 3,745 stable ischaemic heart disease (SIHD) patients were included. At two years, rates of the co-primary efficacy endpoint, a composite of death, myocardial infarction, stroke or urgent target vessel revascularisation, were 7.94% in the experimental and 9.68% in the control group (RR 0.82, 95% CI: 0.66-1.01) among ACS patients and 6.31% in the experimental and 7.14% in the control group (RR 0.89, 95% CI: 0.69-1.13) among SIHD patients (pint=0.63). Trends for lower and higher risk of BARC 3 or 5 bleeding with the experimental strategy in ACS (2.27% vs 3.00%, RR 0.76, 95% CI: 0.51-1.12) and SIHD (2.70% vs 1.96%, RR 1.39, 95% CI: 0.91-2.12) patients, respectively, were observed with significant interaction testing (pint=0.039). A net clinical benefit endpoint, the composite of both co-primary study endpoints, favoured the experimental treatment among ACS patients only. CONCLUSIONS Ticagrelor monotherapy after one-month DAPT provided consistent treatment effects on ischaemic endpoints in patients with or without ACS but only the former experienced a net clinical benefit. ClinicalTrials.gov identifier: NCT03231059

Predictors of Restenosis After Coronary Stent Implantation

AbstractObjectives. We sought to determine predictors of restenosis after coronary stenting (CS) in a consecutive series of patients.Background. Although stenting in highly selected patient groups reduces restenosis, the results of stenting in a heterogeneous patient group and the effects of clinical and procedural factors on stent restenosis are currently unclear.Methods. We analyzed the 6-month angiographic outcome of 500 lesions in 463 consecutive patients undergoing successful CS. Clinical, qualitative and quantitative angiographic variables were correlated with restenosis assessed as both a binary and a continuous variable.Results. Restenosis, defined as the presence of >50% diameter stenosis in the dilated segment, was present in 105 (26%) of the 405 lesions with angiographic follow-up. The mean late lumen loss during the follow-up period was 0.79 ± 0.64 mm. Implantation of multiple stents (p < 0.0001) and a high acute gain (p < 0.0002) were independently associated with a higher late lumen loss. In contrast, the use of high inflation pressure (p < 0.02) and Palmaz-Schatz stents (p < 0.005) was independently associated with a lower late lumen loss. When restenosis was defined as a qualitative variable, implantation of multiple stents (p < 0.001), stenosis length (p < 0.01), small reference diameter (p < 0.02) and stent type other than Palmaz-Schatz (p < 0.01) were independent predictors of restenosis. None of the clinical variables tested was associated with restenosis.Conclusions. Coronary stenting in an unselected patient group is associated with an acceptable restenosis rate. Although some risk factors were identified, the risk of restenosis was not related to most of the variables tested. This suggests that the superiority of CS over balloon angioplasty, in terms of restenosis, might also apply to subgroups of patients that were not included in the recent randomized studies

Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document.

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices

Ticagrelor Alone or Conventional Dual Antiplatelet Therapy in Patients With Stable or Acute Coronary Syndromes

To investigate the effect of ticagrelor monotherapy after 1-month dual antiplatelet therapy (DAPT) or conventional DAPT in patients with or without acute coronary syndrome (ACS) in the GLOBAL LEADERS Adjudication Sub-Study (GLASSY)

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC).

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives

PRECISE-DAPT score for bleeding risk prediction in patients on dual or single antiplatelet regimens: insights from the GLOBAL LEADERS and GLASSY.

AIMS The 5-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally-adjudicated bleeding endpoints. METHODS AND RESULTS The PRECISE-DAPT was calculated in 14,928 and 7,134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict BARC 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally-adjudicated in GLOBAL LEADERS and GLASSY, respectively.At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 (95% confidence interval [CI]:0.63-0.71) vs. 0.63 (95% CI:0.59-0.67) in GLOBAL LEADERS (p = 0.27), and 0.67 (95% CI:0.61-0.73) vs. 0.66 (95% CI:0.61-0.72) in GLASSY (p = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified 4-item PRECISE-DAPT. CONCLUSIONS The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically-relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints