Q-wave Myocardial Infarction Research Articles

Contrast Echocardiography with a Quantitative Assessment of Myocardial Perfusion in Patients with Previous Q-Wave Myocardial Infarction

To assess possibilities of contrast echocardiography with quantitative evaluation of myocardial perfusion in patients with previous Q-wave myocardial infarction. We examined 15 men (42-72 years) with coronary artery disease and previous myocardial infarction, and pathological Q-wave in 2 or more ECG leads. Quantification of left ventricular (LV) myocardial perfusion was performed by calculating of the ultrasound signal tissue intensity from the LV myocardial segments during intravenous administration of the ultrasound contrast agent (SonoVue). The Tissue intensive curve (TIC) analysis was done in the end-diastolic period before and on the fourth cardiac cycle after applying the "flash". Changes in the intensity of myocardial perfusion (A4, dB) was estimated as the difference between the intensity values of the ultrasound signal in the myocardial segment during the period of filling the contrast bubbles on 4-th cardiac cycle and before applying the «flash». Measurements were performed in 16 segments of the LV. A contrast cardiac magnetic resonance imaging (contrast MRI) was performed in order to verify the LV scar. Fibrotic changes of 50% of myocardial wall or more were considered as signs of post-infarction scar. The dynamics of perfusion and scar presence in 240 myocardial segments were evaluated. The median A4 was 1 dB (range, -20 to 10 dB). MRI revealed 82 of 240 segments with the large-focal scar. The effectiveness of the diagnostic test (quantitative contrast perfusion echocardiography with A4 assessment) to detect myocardial scar was investigated. ROC curve analysis showed good model quality, AUC=0,787 (0,730-0,837); sensitivity 82.9%; specificity 75.3%; p<0.01. The cut-off point for A4 was -1. A new approach to quantitative contrast assessment of perfusion allows to identify perfusion disorders with high efficiency in patients with previous Q-wave myocardial infarction.

Prognostic value of SPECT myocardial perfusion entropy in high-risk type 2 diabetic patients : The EVADIAB study

Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for the assessment of myocardial ischemia provides valuable prognostic value. However, the risk stratification of patients with type 2 diabetes mellitus (T2D) remains suboptimal. Recent studies have highlighted the role of coronary microvascular disease in the occurrence of coronary symptoms in this population. We hypothesized that enhanced signal analysis from SPECT myocardial perfusion images may allow insights into the status of the coronary microvasculature. More specifically, we hypothesized that myocardial perfusion entropy (MPE) as a surrogate marker of microvascular disease quantified from SPECT myocardial perfusion images may provide an incremental prognostic value in T2D patients independently from the routinely performed assessment of myocardial ischemia. T2D patients with very high cardiovascular risk were studied (n = 166, 65 ± 12 years). Ischemia was assessed by SPECT myocardial perfusion imaging (MPI). In addition, SPECT MPI was used for the quantification of rest and stress MPE using an original algorithm providing a global value of MPE from reconstructed rest and stress SPECT images. The primary end point was major adverse cardiac events (MACEs) defined as cardiac death, Q-wave myocardial infarction (MI) and myocardial revascularization > 3 months after SPECT. Forty-six patients underwent MACEs over a median follow-up of 4.6 years. Significant differences in stress MPE were observed between patients with and without MACEs (4.19 ± 0.46 vs. 3.93 ± 0.39; P ≤ 0.01). By Kaplan-Meier analysis, the risk of MACEs was significantly higher in patients with higher stress MPE (log-rank P ≤ 0.01). Stress MPE was significantly associated with the risk of MACEs (hazard ratio: 2.80, P ≤ 0.01) after adjustment for clinical and imaging risk factors as identified from preliminary, univariate analysis and including age, hypertension and ischemia. The risk of overfitting was controlled by internal validation procedures such as LASSO, stepwise and random forests selections on time-to-MACEs Cox models. A competing risk event (“other deaths”) slightly overestimated Cox estimates. However, the impact of informative censorship was assessed by Fine-Gray subdistribution hazard estimates and proved to be marginal. The incremental prognostic value of MPE over clinical risk factors was quantified using nested models showing improved AIC, reclassification (global continuous Net Reclassification Improvement [NRI]: 70.1, global Integrated Discrimination Improvement [IDI]: 6.6%), discrimination (change in c-statistic: 0.69 vs. 0.74), and time-dependent AUC (0.71 vs. 0.77 at 4 years of follow-up). Stress MPE provided independent and incremental prognostic information for the prediction of MACEs in diabetic patients.

Influence of Bleeding Risk on Outcomes of Radial and Femoral Access for Percutaneous Coronary Intervention: An Analysis From the GLOBAL LEADERS Trial

BackgroundRadial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding. MethodsPatients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days. ResultsIn the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; Pinteraction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; Pinteraction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant. ConclusionsOur findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.

Impact of SYNTAX Score on 10-Year Outcomes After Revascularization for Left Main Coronary Artery Disease

ObjectivesThe aim of this study was to investigate the long-term impact of SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS) on differential outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease. BackgroundThe very long term prognostic effect of SS on mortality and major cardiovascular events after LMCA revascularization is still undetermined. MethodsIn the MAIN-COMPARE (Ten-Year Outcomes of Stents Versus Coronary-Artery Bypass Grafting for Left Main Coronary Artery Disease) registry, patients with baseline SS measurements were analyzed. The 10-year rates of all-cause mortality, the composite of death, Q-wave myocardial infarction, or stroke, and target vessel revascularization after PCI or CABG were compared according to baseline SS. ResultsAmong 1,580 patients with baseline SS, 547 patients (34.6%) had low SS (≤22), 350 (22.2%) had intermediate SS (23 to 32), and 683 (43.2%) had high SS (≥33). In patients with low to intermediate SS, the adjusted 10-year risks for death and serious composite outcome were similar between the PCI group and the CABG group. However, in patients with high SS, PCI with stenting, compared with CABG, was associated with a higher risk for death (hazard ratio: 1.39; 95% confidence interval: 1.00 to 1.92; p = 0.048) and serious composite outcome (hazard ratio: 1.27; 95% confidence interval: 0.94 to 1.74; p = 0.123). In each revascularization group, conventional tertiles of SS had a differential prognostic impact on 10-year clinical outcomes in the PCI arm but not in the CABG arm. ConclusionsIn this 10-year extended follow-up of patients undergoing LMCA revascularization, CABG showed a clear prognostic benefit over PCI in patients with high anatomic complexity measured by SS at baseline. The discriminative capacity of SS on long-term outcomes was relevant in the PCI group but not in the CABG group. (Ten-Year Outcomes of Stents Versus Coronary-Artery Bypass Grafting for Left Main Coronary Artery Disease [MAIN-COMPARE]; NCT02791412)

The association of body mass index with long-term clinical outcomes after ticagrelor monotherapy following abbreviated dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: a prespecified sub-analysis of the GLOBAL LEADERS Trial

BackgroundThe efficacy of antiplatelet therapies following percutaneous coronary intervention (PCI) may be affected by body mass index (BMI).Methods and resultsThis is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m2. Of those, 6973 (43.7%) patients with a BMI < 27 kg/m2 had a higher risk of all-cause mortality at 2 years than those with BMI ≥ 27 kg/m2 (adjusted HR 1.24, 95% CI 1.02–1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (pinteraction = 0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI < 27 kg/m2 (HR 0.69, 95% CI 0.51–0.94), but not in the ones with BMI ≥ 27 kg/m2 (pinteraction = 0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies.ConclusionsOverall, BMI did not influence the treatment effect seen with ticagrelor monotherapy; however, a beneficial effect of ticagrelor monotherapy was seen in ACS patients with BMI < 27 kg/m2.Trial registrationThe trial has been registered with ClinicalTrials.gov, Number NCT01813435.Graphic abstract

Rates and Independent Correlates of 10-Year Major Adverse Events and Mortality in Patients Undergoing Left Main Coronary Arterial Revascularization

Patients who underwent myocardial revascularization for significant left main coronary artery disease (LMCA) are at high risks of ischemic events and death during follow-up. We sought to determine the independent correlates for very long-term outcomes after LMCA revascularization, which would be clinical value for risk stratification in such high-risk patients. The 10-year rates of clinical outcomes and independent correlates of adverse events were evaluated in 2,240 patients with LMCA disease in the MAIN-COMPARE registry, including 1,102 patients who underwent stenting and 1,138 who underwent coronary artery bypass grafting. The primary outcome was the composite of all-cause death, Q-wave myocardial infarction, or stroke. Secondary outcomes were all-cause mortality and target-vessel revascularization (TVR). The 10-year rates of the primary composite outcome, all-cause mortality, and TVR were 24.7%, 22.2%, and 13.6%, respectively. Age >65 years, diabetes, previous heart failure, cerebrovascular disease, peripheral arterial disease, chronic renal failure, atrial fibrillation, ejection fraction <40%, and distal LMCA bifurcation disease were independent correlates of the primary outcome in the overall population. Several clinical and anatomic parameters were also identified as independent correlates of all-cause death and TVR. Interaction analysis showed no heterogeneities of the effects of variables depending on revascularization type. These clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for patients who underwent LMCA revascularization.

Association of diabetes with outcomes in patients undergoing contemporary percutaneous coronary intervention: Pre-specified subgroup analysis from the randomized GLOBAL LEADERS study

Background and aimsDiabetes has been well recognized as a strong predictor for adverse outcomes after percutaneous coronary intervention (PCI), however, studies in the era of drug-eluting stent and potent P2Y12 inhibitors have shown conflicting results. We aimed to assess ischemic and bleeding outcomes after contemporary PCI according to diabetic status. MethodsWe studied 15,957 patients undergoing PCI for stable or acute coronary syndrome in the GLOBAL LEADERS study with known baseline diabetic status. The primary endpoint was all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was major bleeding defined as bleeding academic research consortium (BARC) type 3 or 5. ResultsA quarter of the study cohort were diabetic (4038/15,957), and these patients had a significantly higher risk of primary endpoint at 2 years compared to non-diabetics (adjusted hazard ratio [HR] 1.38; 95% confidence interval [CI] 1.17–1.63). The difference was driven by a significantly higher risk of all-cause mortality at 2 years in diabetics (adjusted HR 1.47, 95% CI 1.22–1.78). The risk of BARC 3 or 5 bleeding was comparable between the two groups (adjusted HR 1.09, 95% CI 0.86–1.39). The antiplatelet strategy (experimental versus reference strategy) had no significant effect on the rates of primary endpoint and secondary safety endpoint at 2 years in patients with and without diabetes. ConclusionsDiabetic patients had higher risk of ischemic events after PCI than non-diabetic patients, whilst bleeding risk was comparable. The outcomes of diabetic patients following PCI were not affected by the two different antiplatelet strategies.

Impact of renal function on clinical outcomes after PCI in ACS and stable CAD patients treated with ticagrelor: a prespecified analysis of the GLOBAL LEADERS randomized clinical trial.

Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60ml/min/1.73m2). At 2years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35-1.98, padj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61-1.11, p = 0.192, pint = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, pint = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (pint = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (pint = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. The trial has been registered with ClinicalTrials.gov, number NCT01813435.

Impact of Intravascular Ultrasound on Outcomes Following PErcutaneous Coronary InterventioN in Complex Lesions (iOPEN Complex)

Clinical data support the use of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) as being associated with improved outcomes. Nonetheless, global utilization of IVUS remains low. We hypothesize that, in the revascularization of complex lesions, IVUS use is associated with improved outcomes. All patients with complex lesions treated with PCI at a single center from 2003 to 2016 were stratified by use of IVUS. Complex lesions were defined as follows: American College of Cardiology/American Heart Association type C lesions, in-stent restenosis, long lesions, bifurcations, severe calcification, left main lesions, and chronic total occlusions. The primary end point was the rate of major adverse cardiac events (MACE) at 1-year follow-up, defined as the composite of all-cause mortality, Q-wave myocardial infarction, and target vessel revascularization. Inverse probability weighting was used in the adjusted analysis. A total of 6,855 patients were included in the final analysis, of whom 67.3% had IVUS and 32.7% had angiography alone. The primary end point occurred in 13.4% of patients treated with IVUS and 18.3% of patients treated with angiography alone (P < .001). Inverse probability weighting-adjusted 1-year MACE rates demonstrated significant reduction with IVUS for each complex lesion type. Among patients with complex lesions, the use of IVUS was associated with lower MACE 1 year after PCI than angiography alone was. Because of the increased procedural risk in complex lesions, routine utilization of IVUS-guided PCI should be considered in this subset of patients.

Association of Sex With Outcomes in Patients Undergoing Percutaneous Coronary Intervention

Women experience worse ischemic and bleeding outcomes after percutaneous coronary intervention (PCI). To assess the association of sex with patient outcomes at 2 years after contemporary PCI and with the efficacy and safety of 2 antiplatelet strategies. This study is a prespecified subgroup analysis of the investigator-initiated, prospective, randomized GLOBAL LEADERS study evaluating 2 strategies of antiplatelet therapy after PCI in an unselected population including 130 secondary/tertiary care hospitals in different countries. The main study enrolled 15 991 unselected patients undergoing PCI between July 2013 and November 2015. Patients had an outpatient clinic visit at 30 days and 3, 6, 12, 18, and 24 months after the index procedure. Data were analyzed between January 1, 2019, and March 31, 2019. Eligible patients were randomized to either the experimental or reference antiplatelet strategy. Experimental strategy consisted of 1 month of dual antiplatelet therapy (DAPT) followed by 23 months of ticagrelor monotherapy, while the reference strategy comprised of 12 months of DAPT followed by 12 months of aspirin monotherapy. The primary efficacy end point was the composite of all-cause mortality and new Q-wave myocardial infarction at 2 years. The secondary safety end point was Bleeding Academic Research Consortium type 3 or 5 bleeding. Of the 15 968 patients included in this study, 3714 (23.3%) were women. The risk of the primary end point at 2 years was similar between women and men (adjusted hazard ratio [HR], 1.00; 95% CI, 0.83-1.20). Compared with men, women had higher risk of Bleeding Academic Research Consortium type 3 or 5 bleeding (adjusted HR, 1.32; 95% CI, 1.04-1.67) and hemorrhagic stroke at 2 years (adjusted HR, 4.76; 95% CI, 1.92-11.81). At 2 years, there was no between-sex difference in the efficacy and safety of the 2 antiplatelet strategies. At 1 year, compared with DAPT, ticagrelor monotherapy was associated with a lower risk of bleeding in men (HR, 0.72; 95% CI, 0.53-0.98) but not in women (HR, 1.23; 95% CI, 0.80-1.89; P for interaction = .045). Compared with men, women experienced a higher risk of bleeding and hemorrhagic stroke after PCI. The effect of 2 antiplatelet strategies on death and Q-wave myocardial infarction following PCI did not differ between the sexes at 2 years. ClinicalTrials.gov identifier: NCT01813435.

Arterial hypertension in elderly and senile patients: clinical characteristics and treatment quality (according to the national register of arterial hypertension)

Introduction. The importance of studying treatment in older hypertensive patients is underlined by the tendency to aging of the population as a whole. During recent years, the approach to therapy of older patients changed. The guidelines on management of arterial hypertension recommend lower target blood pressure values and earlier start of the treatment.Aim. To study the quality of arterial hypertension treatment and clinical characteristics in older patients (≥65 years).Material and Methods. The Russian national registry of hypertension was conducted in 22 regions of the Russian Federation since 2012. It included 53 city primary health care centers and five cardiology clinics. The data were analyzed in two groups comprised of 65 to 79-year-old individuals and patients older than 80 years. Data on physical, instrumental, and laboratory examinations, as well as data regarding antihypertensive and lipid-lowering therapy and comorbidities, were analyzed.Results: Patients aged 65 to 79 years and those older than 80 years had coronary artery disease (42.7% and 55.5%), chronic heart failure (CHF) (46.8% and 55.7%), history of Q-wave myocardial infarction (MI) (6.4% and 5.9%), stroke (5.5% and 5.7%), atrial fibrillation/flutter (3.7% and 6.5%), chronic kidney disease (CKD) stage 3–5 (36.6% and 48.4%), and diabetes mellitus (19.4% and 13.4%). Following the guidelines on management of arterial hypertension 2013, the target values of systolic blood pressure were achieved in 30% of patients; target values of diastolic blood pressure were reached in 60% of patients. Decreases in systolic blood pressure lower than &lt;120 mmHg and in diastolic blood pressure lower than 70 mmHg were found in 3% of patients. In accordance with Guidelines 2018, target values of systolic blood pressure were achieved in 21–24% of patients; target values of diastolic blood pressure were achieved in 12–13% patients. Ambulatory 24-h blood pressure monitoring was performed only in 2.8% of 65–79-year-old patients and in 1.9% of patients older than 80 years. Data on antihypertensive therapy were absent in 13% of medical records of patients who had indications for it. Medical records of 20% of patients with history of Q-wave MI, CHF, diabetes mellitus, and CKD did not contain data on administration of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Administration of beta-blockers and mineralocorticoid receptor antagonists in patients with hypertension and chronic heart failure was insufficient. Achievement of target cholesterol levels was insufficient in both age groups.

Ticagrelor Alone Versus Dual Antiplatelet Therapy From 1 Month After Drug-Eluting Coronary Stenting

BackgroundThe GLOBAL LEADERS (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) study randomly assigned 15,991 patients undergoing percutaneous coronary intervention to 1-month dual antiplatelet therapy (DAPT) followed by 23-month ticagrelor monotherapy or conventional 12-month DAPT followed by 12-month aspirin. Apart from Q-wave myocardial infarction (MI), all study endpoints were analyzed as investigator reported. ObjectivesThis was a pre-specified ancillary study assessing whether experimental therapy is noninferior, and if met, superior, to conventional treatment for the coprimary efficacy endpoint of all-cause death, nonfatal MI, nonfatal stroke, or urgent target vessel revascularization and superior in preventing BARC 3 (Bleeding Academic Research Consortium) or 5 bleeding (coprimary safety endpoint) at 2 years with a 0.025 significance level to preserve nominal 5% alpha error. MethodsAn independent clinical event committee adjudicated investigator-reported and eventually unreported events of 7,585 patients from the 20 top-enrolling participating sites. ResultsThe 2-year coprimary efficacy endpoint occurred in 271 (7.14%) and in 319 (8.41%) patients in the experimental and conventional groups, respectively (rate ratio [RR]: 0.85; 95% confidence interval [CI]: 0.72 to 0.99), fulfilling noninferiority (p noninferiority <0.001), but not superiority (p superiority = 0.0465). The rates of BARC 3 or 5 bleeding did not differ (RR: 1.00; 95% CI: 0.75 to 1.33; p = 0.986). A time-dependent treatment effect was observed with the experimental strategy being associated with a lower risk of MI (RR: 0.54; 95% CI: 0.33 to 0.88; p interaction = 0.062) and definite stent thrombosis (RR: 0.14; 95% CI: 0.03 to 0.63; p interaction = 0.007) after 1-year post-percutaneous coronary intervention. ConclusionsTicagrelor monotherapy after 1-month DAPT was noninferior, but not superior, to conventional treatment in the prevention of ischemic events, and it did not decrease major bleeding risk as compared with conventional treatment. (GLOBAL LEADERS Adjudication Sub-Study [GLASSY]; NCT03231059).

Association of Pulse Pressure With Clinical Outcomes in Patients Under Different Antiplatelet Strategies After Percutaneous Coronary Intervention: Analysis of GLOBAL LEADERS

BackgroundWe evaluated the association of pulse pressure (PP) and different antiplatelet regimes with clinical and safety outcomes in an all-comers percutaneous coronary intervention (PCI) population. MethodsIn this analysis of GLOBAL LEADERS (n = 15,936) we compared the experimental therapy of 23 months of ticagrelor after 1 month of dual-antiplatelet therapy (DAPT) vs standard DAPT for 12 months followed by aspirin monotherapy in subjects who underwent PCI and were divided into 2 groups according to the median PP (60 mm Hg). The primary end point (all-cause death or new Q-wave myocardial infarction) and the composite end points: patient-oriented composite end points (POCE), Bleeding Academic Research Consortium (BARC) 3 or 5, and net adverse clinical events (NACE) were evaluated. ResultsAt 2 years, subjects in the high-PP group (n = 7971) had similar rates of the primary end point (4.3% vs 3.9%; P = 0.058), POCE (14.9% vs 12.7%; P = 0.051), and BARC 3 or 5 (2.5% vs 1.7%; P = 0.355) and higher rates of NACE (16.4% vs 13.7%; P = 0.037) compared with the low-PP group (n = 7965). Among patients with PP < 60 mm Hg, the primary end point (3.4% vs 4.4%, adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.96), POCE (11.8% vs 13.5%, aHR 0.86, 95% CI 0.76-0.98), NACE (12.8% vs 14.7%, aHR 0.85, 95% CI 0.76-0.96), and BARC 3 or 5 (1.4% vs 2.1%, aHR 0.69, 95% CI 0.49-0.97) were lower with ticagrelor monotherapy compared with DAPT. The only significant interaction was for BARC 3 or 5 (P = 0.008). ConclusionsAfter contemporary PCI, subjects with high PP levels experienced high rates of NACE at 2 years. In those with low PP, ticagrelor monotherapy led to a lower risk of bleeding events compared with standard DAPT.

P2812Ischemic efficacy and bleeding safety of ticagrelor monotherapy in patients with multivessel percutaneous coronary intervention: insights from the Global Leaders trial

Abstract Background/Introduction The optimal duration of DAPT after coronary stent implantation remains a matter of debate and a novel antiplatelet regimen without an increased risk of bleeding while maintaining an anti-ischemic efficacy is of paramount importance in patients at higher risk of ischemia. Purpose The aim of the present sub-study of the Global Leaders trial is to evaluate the efficacy and safety of the experimental antiplatelet strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) vs. the reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) in patients with multivessel percutaneous coronary intervention (PCI). Methods The Global Leaders trial enrolled 15,991 patients treated by default with a biolimus A-9 eluting stent. The present sub-study of the trial sought to evaluate the impact of the long-term ticagrelor monotherapy on the primary endpoint (composite of all-cause death and new Q-wave myocardial infarction [MI] centrally adjudicated with the Minnesota code) at two years. In addition, the patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, and any revascularization) and the net adverse clinical events (NACE) (composite of POCE and Bleeding Academic Research Consortium [BARC] type 3 or 5 bleeding) were also evaluated at two years. Results A total of 15,845 patients was included in this analysis, of whom 3,576 patients received multivessel PCI. At two years, the experimental strategy significantly reduced a risk of the primary endpoint (the composite of all-cause death and new Q-wave myocardial infarction [MI]) (3.05% vs. 4.85%, HR: 0.62, 95% CI: 0.44–0.88, p=0.006, Pinteraction=0.031) in patients with multivessel PCI. Similarly, the experimental treatment had a significant risk reduction in the patient-oriented composite endpoint (POCE), defined as the composite of all-cause death, any stroke, any MI, and any revascularization (13.37% vs. 16.74%, HR: 0.78, 95% CI: 0.66–0.93, p=0.005, Pinteraction=0.020) and the net adverse clinical events (NACE), defined as the composite of POCE and Bleeding Academic Research Consortium [BARC] defined bleeding type 3 or 5 (14.65% vs. 18.38%, HR: 0.78, 95% CI: 0.66–0.92, p=0.003, Pinteraction=0.014) at two years. There was no significant difference in BARC type 3 or 5 bleeding (2.44% vs. 2.65%, HR: 0.92, 95% CI: 0.61–1.39, p=0.685, Pinteraction=0.754) at two years between the two regimens. KM in patients with multivessel PCI Conclusion The present study has demonstrated the experimental antiplatelet strategy, when compared with the reference regimen, could potentially have a favourable balance between ischemic efficacy and bleeding safety in patients who underwent multivessel PCI. Acknowledgement/Funding The Global Leaders trial was supported by unrestricted grants from AstraZeneca, Biosensors, and The Medicines Company. ECRI (European Cardiovascular R

P2531Impact of age on clinical outcomes after PCI in patients with ACS and stable CAD treated with 23-month ticagrelor monotherapy following 1-month DAPT in the randomized GLOBAL LEADERS study

Abstract Background The efficacy and safety of ticagrelor monotherapy in elderly patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) or stable coronary artery disease (CAD) has not been evaluated. Purpose To evaluate the efficacy and safety of ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after PCI in relation to age and clinical presentation in the GLOBAL LEADERS study cohort. Methods This is a subanalysis of the randomized multicentre GLOBAL LEADERS study, comparing the experimental strategy of 23-month ticagrelor monotherapy after 1 month of ticagrelor and aspirin with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy in 15991 patients undergoing PCI. Patients were categorized into elderly and very elderly according to a pre-specified cut-off of 75 years and a post-hoc defined cut-off of 80 years. Impact of age and clinical presentation (ACS versus stable CAD) on clinical outcome at 2 years was evaluated. The primary endpoint was a composite of all-cause mortality or nonfatal, centrally adjudicated, new Q-wave myocardial infarction. Results In the overall elderly (&gt;75 years) population (n=2565), primary endpoint occurred in 7.2% of patients in the experimental group and in 9.4% of patients in the reference group (p=0.041) at 2 years (p int =0.23). Elderly patients in the experimental group had a lower rate of definite stent thrombosis (ST) (0.2% vs. 0.9%, p=0.043, p int=0.03), definite or probable ST (0.4 vs. 1.3%, p=0.015, p int=0.01) and a numerically higher rates of BARC 3 or 5 type bleeding (5.0% vs. 3.9%, p=0.192, p int=0.06), when compared to the reference arm. Among elderly patients presenting with ACS both treatment groups did not differ in the rates of primary endpoint (9.1% vs. 10.8%, p=0.367) and BARC 3 or 5 type bleeding (4.7% vs. 5.7%, p=0.458), whereas among elderly patients with stable CAD the experimental strategy was associated with numerically lower rates of the primary endpoint (5.7% vs. 8.4%, p=0.046) (p int =0.42) and a higher rate of BARC 3 or 5 type bleedings (5.3% vs. 2.6%, p=0.012) (p int =0.02) at 2 years. Exploratory analyses among very elderly (≥80 years) patients (n=1169) indicated no significant differences between treatment groups in the rates of the primary endpoint (10.2% vs. 11.7% p=0.411, p int=0.940) and BARC 3 or 5 type bleeding (6.0% vs. 5.3%, p=0.630, p int=0.514) at 2 years. Conclusions The efficacy and safety of the experimental treatment strategy of 23-month ticagrelor monotherapy after 1-month DAPT following PCI was not identified as age-dependent. Among elderly patients the anti-ischemic benefit was derived at the expense of increased rate of BARC 3 or 5 type bleeding in stable CAD subgroup, but not in ACS subgroup. Acknowledgement/Funding European Clinical Research Institute, which received unrestricted grants from Biosensors International, AstraZeneca, and the Medicines Company.

Efficacy and Safety of Ticagrelor Monotherapy in Patients Undergoing Multivessel PCI

BackgroundData on optimal antiplatelet treatment regimens in patients who undergo multivessel percutaneous coronary intervention (PCI) are sparse. ObjectivesThis post hoc study investigated the impact of an experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus a reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) according to multivessel PCI. MethodsThe GLOBAL LEADERS trial is a prospective, multicenter, open-label, randomized controlled trial, allocating all-comer patients in a 1:1 ratio to either the experimental strategy or the reference regimen. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was Bleeding Academic Research Consortium type 3 or 5 bleeding. ResultsAmong the overall study population (n=15,845), 3,576 patients (22.4%) having multivessel PCI experienced a significantly higher risk of ischemic and bleeding events at 2 years, compared to those having single-vessel PCI. There was an interaction between the experimental strategy and multivessel PCI on the primary endpoint (hazard ratio: 0.62; 95% confidence interval: 0.44 to 0.88; pinteraction = 0.031). This difference was largely driven by a lower risk of all-cause mortality. In contrast, the risk of Bleeding Academic Research Consortium type 3 or 5 bleeding was statistically similar between the 2 regimens (hazard ratio: 0.92; 95% confidence interval: 0.61 to 1.39; pinteraction = 0.754). ConclusionsLong-term ticagrelor monotherapy following 1-month DAPT can favorably balance ischemic and bleeding risks in patients with multivessel PCI. These findings should be interpreted as hypothesis-generating and need to be replicated in future dedicated randomized trials. (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation; NCT01813435).

P2811Impact of ticagrelor monotherapy on two-year clinical outcomes in patients with long stenting: insights from the Global Leaders trial

Abstract Background/Introduction Data on the efficacy and safety of different antiplatelet regimens are limited in patients with increasing total stent length (TSL). Purpose To evaluate the impact of the experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) vs. the reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) in patients with increasing TSL. Methods The present post-hoc analysis of the Global Leaders trial evaluated the primary endpoint (the composite of the all-cause death and new Q-wave myocardial infarction [MI]) at two years in patients with increasing TSL. In addition, the patient-oriented composite endpoint (POCE) (the composite of all-cause death, any stroke, any MI, and any revascularization) and the net adverse clinical events (NACE) (the composite of POCE and Bleeding Academic Research Consortium [BARC] type 3 or 5 bleeding) were also assessed. Results The cohort of 15,450 patients treated with a biolimus-eluting biodegradable polymer stents were included in this analysis. In the longer TSL group (≥46mm), the experimental strategy significantly reduced the risk of the primary endpoint (3.78% vs. 5.68%, hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.49–0.90, p=0.008, P interaction=0.042) as well as POCE (14.57% vs. 18.11%, HR: 0.79, 95% CI: 0.67–0.92, p=0.003, P interaction=0.010) and NACE (16.07% vs. 19.64%, HR: 0.80, 95% CI: 0.69–0.93, p=0.004, P interaction=0.012) at two years. The risk of BARC type 3 or 5 bleeding at two years was similar between the two antiplatelet regimens. KM in patients with long stenting Conclusion Ticagrelor monotherapy significantly reduced the risk of the primary endpoint, POCE and NACE with a similar risk of BARC type 3 or 5 bleeding at two years in patients with the longer TSL. Acknowledgement/Funding The Global Leaders trial was supported by unrestricted grants from AstraZeneca, Biosensors, and The Medicines Company. ECRI (European Cardiovascular R

P6411Dyspnea in ticagrelor treated patients in the all-comer randomized GLOBAL LEADERS study and its association with clinical outcomes

Abstract Background Dyspnea represents a drug adverse effect reported with a higher frequency for ticagrelor, as compared with other P2Y12 antagonists. The impact of dyspnea on clinical outcomes has not been yet evaluated in the context of aspirin-free therapies after percutaneous coronary intervention (PCI). Purpose The study aimed to evaluate the incidence of dyspnea and its associations with demographic characteristics and clinical outcomes in patients undergoing PCI treated with ticagrelor either as monotherapy or as a part of a dual antiplatelet therapy (DAPT) in the GLOBAL LEADERS cohort. Methods This is a sub-analysis of the randomized all-comer GLOBAL LEADERS study (n=15991), comparing the experimental strategy of ticagrelor monotherapy following one-month DAPT after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. The incidence of dyspnea reported as adverse event (AE) and its relation to demographic characteristics and 2-year clinical outcomes was evaluated (intention-to-treat analysis). Multivariable Cox proportional hazards models were performed, including randomized treatment and incidence of first dyspnea event as a time-dependent covariate. The primary endpoint was a composite of 2-year all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction (MI). Patient-oriented clinical endpoints (POCE) comprised all-cause death, any stroke, MI or revascularization, whereas net adverse clinical events (NACE) included POCE and Bleeding Academic Research Consortium (BARC)-defined bleeding type 3 or 5. Results Overall, dyspnea was reported as an AE in 2101 patients (13.2%) up to two years of follow-up, with a higher frequency in the experimental arm (16.4%) as compared with the reference group (11.1%) (hazard ratio [HR]1.70, 95% confidence interval [CI] 1.56–1.86, p=0.001). Predictors of dyspnea AE up to 2 years by multivariate analyses were: chronic obstructive pulmonary disease (HR1.71, 95% CI 1.56–1.87, p=0.001), female gender (HR1.31, 95% CI 1.18–1.44, p=0.001), hypertension (HR1.31, 95% CI 1.19–1.44, p=0.001, prior coronary artery bypass grafting (HR1.30, 95% CI 1.10–1.54, p=0.003), left ventricle ejection fraction below 40% (HR1.22, 95% CI 1.04–1.42, p=0.012), presentation with acute coronary syndrome (HR1.19, 95% CI 1.09–1.29, p=0.001) and body mass index (≥27kg/m2) (HR1.17, 95% CI 1.08–1.28, p=0.001). In patients who reported dyspnea AE, the two-year rates of the efficacy and safety endpoints in the experimental and reference arm were: for the primary endpoint 3.4% vs. 4.3% (p adjusted=0.807), for POCE 15.8% vs. 17.6% (p adjusted=0.218), for NACE 17.2% vs. 19.6% (p adjusted=0.082), for BARC 3 or 5 type bleeding 17.2% vs. 19.6% (p adjusted=0.082), respectively. Conclusions The occurrence of dyspnea AE up to two years after PCI appeared not to affect the safety of the experimental treatment strategy of 23-month ticagrelor monotherapy following one-month DAPT after PCI. Acknowledgement/Funding Study founded by European Cardiovascular Research Institute, which received unrestricted grants from Biosensors Int., AstraZeneca, Medicines Company.

P2817Efficacy and safety of ticagrelor monotherapy in patients with complex percutaneous coronary intervention: insights from the Global Leaders trial

Abstract Background/Introduction Optimal dual antiplatelet therapy (DAPT) in patients with complex percutaneous coronary intervention (PCI) with drug-eluting stents (DES) has not been fully investigated. Purpose To evaluate the efficacy and safety of 1-month DAPT followed by 23-month ticagrelor monotherapy in patients who underwent complex PCI. Methods The Global Leaders trial recruited 15,991 patients treated by default with a biolimus A9-eluting stent, and randomised in a 1:1 ratio either to the experimental strategy (1-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) or to the reference regimen (12-month DAPT followed by 12-month aspirin monotherapy). Complex PCI includes at least one of the following characteristics; left main and/or multivessel PCI, long stenting (defined as total stent length≥46mm), and bifurcation treatment with two stents. The present sub-analysis of the trial evaluated at two years the primary endpoint (composite of all-cause death and new Q-wave myocardial infarction [MI] centrally adjudicated with the Minnesota code). In addition, the patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, and any revascularization) and the net adverse clinical events (NACE) (composite of POCE and Bleeding Academic Research Consortium [BARC] type 3 or 5 bleeding) were also evaluated at two years. Results Of 15,450 patients included in the present analysis, 5,188 (26.7%) patients underwent complex PCI. The experimental strategy, when compared with the reference one, had a significantly lower risk of the primary endpoint (3.56% vs. 5.33%, HR: 0.66; 95% CI: 0.51–0.86; p-value= 0.002; p-value for interaction= 0.019) in patients with complex PCI. Similarly, the experimental treatment was associated with a significantly reduced risk of POCE (14.41% vs. 16.88%, HR: 0.84; 95% CI: 0.74–0.97; p=0.016, p-value for interaction= 0.099) and NACE (15.77% vs. 18.37%, HR: 0.85; 95% CI: 0.74–0.97; p=0.014; p-value for interaction= 0.096). The reduction in ischemic events was predominantly observed in patients with 2 or more characteristics of complex PCI (Figure). In contrast, there was no significant difference in the risk of BARC type 3 or 5 bleeding between the two regimens (2.40% vs. 2.38%, HR: 1.01; 95% CI: 0.71–1.44; p-value=0.956; p-value for interaction= 0.935). Central illustration Conclusion Together with other well-established clinical risk factors, the extent and complexity of stenting should be taken into account in tailoring antiplatelet regimens for secondary prevention. The 1-month DAPT followed by 23-month ticagrelor monotherapy reduced the ischemic events without increasing the risk of bleeding in patients who underwent complex PCI, when compared with the conventional DAPT. Acknowledgement/Funding The Global Leaders trial was supported by the resource from AstraZeneca, Biosensors, and The Medicines Company.

5194Impact of established cardiovascular disease on outcomes in the Global Leaders trial

Abstract Objectives To investigate the impact of ticagrelor monotherapy following one-month dual antiplatelet therapy (DAPT) on clinical outcomes after percutaneous coronary intervention (PCI) in patients with established cardiovascular disease (CVD) who were enrolled in the Global Leaders Trial. Background The impact of prolonged monotherapy with P2Y12 inhibitors after PCI in patients with CVD is undetermined. Methods GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing one-month DAPT with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. The cohort was stratified according to those with- and without established CVD, defined as a history of ≥1 prior myocardial infarction (MI), PCI, coronary artery bypass operation, stroke or peripheral vascular disease. The degree of CVD was defined according to the number of vascular territories effected (1, 2, ≥3). The primary endpoint was a composite of all-cause death or new Q-wave MI at 2-years. Secondary endpoints were the patient orientated composite endpoint (POCE) of death, stroke, MI and any revascularization; definite stent thrombosis and net adverse cardiovascular events a composite of POCE and BARC 3 or 5 bleeding. Results Amongst the 15,761 patients included in this cohort were 6693 patients (42.5%) with- and 9068 patients without established CVD. Patients with CVD were older, and had significantly higher rates of diabetes, hypertension, and hypercholesterolaemia (P&lt;0.01). The incidence of the primary endpoint was significantly higher in patients with established CVD (5.1% vs. 3.3%, P&lt;0.001) as were all secondary endpoints and their individual components. There was a trend for a reduction in the primary endpoint in patients with established CVD receiving the experimental treatment (4.6% vs. 5.6%, HR0.82 [0.66–1.02], p=0.07), which was not seen in those without prior CVD (3.2% vs. 3.3%, HR 0.95 [0.76–1.19, p=0.66; p(interaction)=0.37). Compared with patients without CVD the incidence of the primary and second endpoints and all their individual components, other than BARC 3/5 bleeding, rose significantly with an increasing degree of CVD. In an unadjusted model, compared with patients without CVD, the hazard ratio for the primary endpoint rose from 1.5 (1.21–1.81) to 3.0 (2.32–4.00) in patients with one and three territories of CVD, respectively. Similar rises were seen in models adjusted by age (1.3 [1.01–1.60] to 2.56 [1.94–3.38]) and age, left ventricular ejection fraction, clinical presentation and anti-platelet strategy (1.4 [1.10–1.68] to 2.26 [1.69–3.02]). Conclusions PCI outcomes are poorer in patients with increasing degrees of CVD compared to those without. Prolonged monotherapy with ticagrelor does not mitigate this risk suggesting a greater need to focus on modifiable risk factors