Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients.

Aim: We sought to determine whether the optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) placement varies according to clinical presentation. Methods and Results: We performed an individual patient data pairwise and network meta-analysis comparing short-term (≤6-months) versus long-term (1-year) DAPT as well as 3-month vs. 6-month vs 1-year DAPT. The primary study outcome was the 1-year composite risk of myocardial infarction (MI) or definite/probable stent thrombosis (ST). Six trials were included in which DAPT after DES consisted of aspirin and clopidogrel. Among 11 473 randomized patients 6714 (58.5%) had stable CAD and 4758 (41.5%) presented with acute coronary syndrome (ACS), the majority of whom (67.0%) had unstable angina. In ACS patients, ≤6-month DAPT was associated with non-significantly higher 1-year rates of MI or ST compared with 1-year DAPT (Hazard Ratio (HR) 1.48, 95% Confidence interval (CI) 0.98-2.22; P = 0.059), whereas in stable patients rates of MI and ST were similar between the two DAPT strategies (HR 0.93, 95%CI 0.65-1.35; P = 0.71; Pinteraction = 0.09). By network meta-analysis, 3-month DAPT, but not 6-month DAPT, was associated with higher rates of MI or ST in ACS, whereas no significant differences were apparent in stable patients. Short DAPT was associated with lower rates of major bleeding compared with 1-year DAPT, irrespective of clinical presentation. All-cause mortality was not significantly different with short vs. long DAPT in both patients with stable CAD and ACS. Conclusions: Optimal DAPT duration after DES differs according to clinical presentation. In the present meta-analysis, despite the fact that most enrolled ACS patients were relatively low risk, 3-month DAPT was associated with increased ischaemic risk, whereas 3-month DAPT appeared safe in stable CAD. Prolonged DAPT increases bleeding regardless of clinical presentation. Further study is required to identify the optimal duration of DAPT after DES in individual patients based on their relative ischaemic and bleeding risks.

Effects of statin therapy on platelet reactivity after percutaneous coronary revascularization in patients with acute coronary syndrome.

Statin use is associated with enhanced pharmacodynamic response to clopidogrel in patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI). However, the impact of statin therapy on clopidogrel response profiles in patients with acute coronary syndrome (ACS) undergoing PCI has not been established and represents the objective of this investigation. On-treatment P2Y12 platelet reactivity was measured using the vasodilator stimulated phosphoprotein (VASP) phosphorylation assay before PCI, at hospital discharge, and at 1 month after PCI in ACS patients enrolled in the multicenter, prospective GEne polymorphisms, Platelet Reactivity, and Syntax Score (GEPRESS) study (n = 962). High platelet reactivity (HPR) was defined as platelet reactivity index ≥50%. Statins were prescribed at hospital discharge in 87% (n = 835) of patients. All patients were followed for 1 year. The 1-month HPR rate was lower in statin than in non-statin treated patients (39.6 vs 52%, respectively, p = 0.009). This finding was confirmed also among statin-treated patients with high Syntax score (≥15). After adjustment for differences in baseline characteristics, statin use at discharge was independently associated with 1-month HPR rate (odds ratio, 0.58, 95% confidence interval, 0.38-0.89; p = 0.015). In ACS patients undergoing PCI treated with clopidogrel the use of statins at discharge was associated with significantly lower 1-month HPR rates compared with patients not treated with statins.

Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials.

BACKGROUND: Despite recent studies, the optimum duration of dual antiplatelet therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We performed a meta-analysis with several analytical approaches to investigate mortality and other clinical outcomes with different DAPT strategies. METHODS: We searched Medline, Embase, Cochrane databases, and proceedings of international meetings on Nov 20, 2014, for randomised controlled trials comparing different DAPT durations after drug-eluting stent implantation. We extracted study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes. DAPT duration was categorised in each study as shorter versus longer, and as 6 months or shorter versus 1 year versus longer than 1 year. Analyses were done by both frequentist and Bayesian approaches. FINDINGS: We identified ten trials published between Dec 16, 2011, and Nov 16, 2014, including 31,666 randomly assigned patients. By frequentist pairwise meta-analysis, shorter DAPT was associated with significantly lower all-cause mortality compared with longer DAPT (HR 0·82, 95% CI 0·69-0·98; p=0·02; number needed to treat [NNT]=325), with no significant heterogeneity apparent across trials. The reduced mortality with shorter compared with longer DAPT was attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347), with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also associated with a lower risk of major bleeding, but a higher risk of myocardial infarction and stent thrombosis. We noted similar results in a Bayesian framework with non-informative priors. By network meta-analysis, patients treated with 6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction and stent thrombosis but lower risk of mortality compared with patients treated with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or shorter had similar rates of mortality, myocardial infarction, and stent thrombosis, but lower rates of major bleeding than did patients treated with 1-year DAPT. INTERPRETATION: Although treatment with DAPT beyond 1 year after drug-eluting stent implantation reduces myocardial infarction and stent thrombosis, it is associated with increased mortality because of an increased risk of non-cardiovascular mortality not offset by a reduction in cardiac mortality. FUNDING: None.

Healthcare needs in elderly patients with chronic heart failure in view of a personalized blended collaborative care intervention: a cross sectional study.

Introduction: Few studies explored healthcare needs of elderly heart failure (HF) patients with comorbidities in view of a personalized intervention conducted by Care Managers (CM) in the framework of Blended Collaborative Care (BCC). The aims of the present study were to: (1) identify perceived healthcare needs/preferences in elderly patients with HF prior to a CM intervention; (2) investigate possible associations between healthcare needs/preferences, sociodemographic variables (age; sex) and number of comorbidities. Method: Patients aged 65 years or more affected by HF with at least 2 medical comorbidities were enrolled in the study. They were assessed by structured interviewing with colored cue cards that represented six main topics including education, individual tailoring of treatment, monitoring, support, coordination, and communication, related to healthcare needs and preferences. Results: Thirty-three patients (Italy = 21, Denmark = 7, Germany = 5; mean age = 75.2 ± 7.7 years; males 63.6%) were enrolled from June 2021 to February 2022. Major identified needs included: HF information (education), patients' involvement in treatment-related management (individual tailoring of treatment), regular checks of HF symptoms (monitoring), general practitioner update by a CM about progression of symptoms and health behaviors (coordination), and telephone contacts with the CM (communication). Regarding communication modalities with a CM, males preferred phone calls (χ2 = 6.291, p = 0.043) and mobile messaging services (χ2 = 9.647, p = 0.008), whereas females preferred in-person meetings and a patient dashboard. No differences in needs and preferences according to age and number of comorbidities were found. Discussion: The findings highlight specific healthcare needs and preferences in older HF multimorbid patients, allowing a more personalized intervention delivered by CM in the framework of BCC.

Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis.

BACKGROUND: The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. METHODS: For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. FINDINGS: 49 trials including 50,844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13-0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11-0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08-0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16-0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24-0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10-0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03-0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17-0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19-0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up. INTERPRETATION: In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift. FUNDING: The Cardiovascular Research Foundation.

Successful manual thrombus aspiration in anterior ST-segment elevation myocardial infarction due to cardioembolic obstruction of the left main coronary artery.

Large clinical trials and meta-analyses have shown that thrombus aspiration (TA) in the setting of ST-T segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) does not improve clinical outcome, whilst it may be associated with an increased risk of stroke. Accordingly, in the most recent European Society of Cardiology guidelines the role of routine TA during PPCI has been downgraded to a class III recommendation with level A of evidence. On the other hand, it has been suggested that in case of high thrombus burden a selective use of TA may still play a role. STEMI due to cardioembolism (CE) definitely represents one of these situations. In the present case of an 81-year-old woman presenting with STEMI due to a cardioembolic obstruction of left main coronary artery, we show that TA succeeded, whereas classical angioplasty failed, in promoting a prompt coronary flow restoration in a life-threatening condition. Further, it allowed us not to upgrade the procedure with stent implantation that would have required a triple antithrombotic therapy, significantly increasing the bleeding risk. Visual examination of thrombi retrieved suggested the diagnosis of CE. Finally, we clearly show which is the mechanism linking TA with the risk of stroke. .

Efficacy and safety of thrombus aspiration in ST-segment elevation myocardial infarction: an updated systematic review and meta-analysis of randomised clinical trials.

BACKGROUND:: The role of thrombus aspiration plus primary percutaneous coronary intervention in ST-segment elevation myocardial infarction remains controversial. METHODS:: We performed a meta-analysis of 25 randomised controlled trials in which 21,740 ST-segment elevation myocardial infarction patients were randomly assigned to thrombus aspiration plus primary percutaneous coronary intervention or primary percutaneous coronary intervention. Study endpoints were: death, myocardial infarction, stent thrombosis and stroke. RESULTS:: On pooled analysis, the risk of death (4.3% vs. 4.8%, odds ratio (OR) 0.90, 95% confidence interval (CI) 0.79-1.03; P=0.123), myocardial infarction (2.4% vs. 2.5%, OR 0.95, 95% CI 0.80-1.13; P=0.57) and stent thrombosis (1.3% vs. 1.6%, OR 0.80, 95% CI 0.63-1.01; P=0.066) was similar between thrombus aspiration plus primary percutaneous coronary intervention and primary percutaneous coronary intervention. The risk of stroke was higher in the thrombus aspiration plus primary percutaneous coronary intervention than the primary percutaneous coronary intervention group (0.84% vs. 0.59%, OR 1.401, 95% CI 1.004-1.954; P=0.047). However, on sensitivity analysis after removing the TOTAL trial, thrombus aspiration plus primary percutaneous coronary intervention was not associated with an increased risk of stroke (OR 1.01, 95% CI 0.58-1.78). The weak association between thrombus aspiration and stroke was also confirmed by the fact that the lower bound of the 95% CI was slightly below unity after removing either the study by Kaltoft or the ITTI trial. There was no interaction between the main study results and follow-up, evidence of coronary thrombus, or study sample size. CONCLUSIONS:: In patients with ST-segment elevation myocardial infarction, thrombus aspiration plus primary percutaneous coronary intervention does not reduce the risk of death, myocardial infarction or stent thrombosis. Thrombus aspiration plus primary percutaneous coronary intervention is associated with an increased risk of stroke; however, this latter finding appears weak.

Risk-Benefit Profile of Longer-Than-1-Year Dual-Antiplatelet Therapy Duration After Drug-Eluting Stent Implantation in Relation to Clinical Presentation.

BACKGROUND: We sought to determine whether the risks and benefits of prolonging dual-antiplatelet therapy (DAPT) beyond 1 year after drug-eluting stent implantation depend on clinical presentation in a meta-analysis of randomized controlled trials. METHODS AND RESULTS: Randomized controlled trials comparing ≤1- versus >1-year DAPT after drug-eluting stent placement were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. The primary efficacy end point was myocardial infarction, whereas the primary safety end point was major bleeding. Net clinical benefit was defined as the composite of myocardial infarction or major bleeding. Outcomes were analyzed according to patient presentation with stable ischemic heart disease versus acute coronary syndromes. The meta-analysis included 6 trials with a total of 21 457 patients, including 14 132 with stable ischemic heart disease and 7325 with acute coronary syndrome. After a median follow-up of 19.5 months, ≤1-year DAPT was associated with higher rates of myocardial infarction compared with >1-year DAPT (hazard ratio [HR], 1.63; 95% CI, 1.37-1.95), with no interaction apparent between treatment effect and clinical presentation. Shorter DAPT was associated with reduced rates of major bleeding compared with longer DAPT (HR, 0.64; 95% CI, 0.42-0.99) with no significant interaction between treatment effect and clinical presentation. However, a net clinical benefit of >1-year DAPT was present in patients with acute coronary syndrome (HR of shorter versus longer DAPT, 1.59; 95% CI, 1.24-2.02) but not in those with stable ischemic heart disease (HR, 1.15; 95% CI, 0.89-1.51; Pinteraction=0.04). Shorter DAPT was also associated with lower rates of noncardiac mortality compared with longer DAPT (HR, 0.71; 95% CI, 0.52-0.96), with no significant interaction between treatment effect and clinical presentation ( Pinteraction=0.12). CONCLUSIONS: Compared with ≤1-year DAPT, >1-year DAPT reduces the risk of myocardial infarction but increases the risk of major bleeding and noncardiac mortality. A net clinical benefit of extended DAPT was apparent for patients with acute coronary syndrome but not for those with stable ischemic heart disease.

Prognostic significance of shockable and non-shockable cardiac arrest in ST-segment elevation myocardial infarction patients undergoing primary angioplasty.

OBJECTIVE: To determine, in patients with ST-segment Elevation Myocardial Infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), the prognostic weight of cardiac arrest (CA) according to the type of rhythm (shockable vs. non-shockable). METHODS: We prospectively enrolled 3278 consecutive STEMI patients undergoing PPCI. Multivariable Cox regression was used to establish the relation to 1-year cardiac mortality of both type of CA. In patients suffering from CA we identified predictors of both poor neurological outcome (cerebral performance categories 3-5) and cardiac mortality at 1year. RESULTS: The incidence of CA was 7.26% (n=238). Of these, 196 (5.98%) had an initial shockable rhythm and 42 (1.28%) a non shockable rhythm. During 1-year follow up 311(9.48%) patients died from cardiac causes. Shockable rhythm (adjusted-HR=1.61; 95%CI 1.08-2.43, p=0.02) and non-shockable rhythm (adjusted-HR=3.83; 95%CI 2.36-6.22, p<0.001) were independently associated with 1-year cardiac mortality. Among patients with CA those with shockable rhythm had a lower risk of poor neurological outcome at 1year follow up (adjusted OR=0.22: 95%CI; 0.08-0.55, p=0.001). Independent predictors of 1-y cardiac mortality were: non shockable rhythm (adjusted HR=2.6; 95%CI; 1.48-4.5, p=0.001), crew-witnessed CA, diabetes mellitus, left ventricle ejection fraction and creatinine on admission. There was a significant interaction between type of rhythm and crew-witnessed CA (p=0.026). CONCLUSIONS: In patients with STEMI undergoing PPCI patients with both shockable and non shockable CA are at increased risk of 1-year cardiac mortality. Among patients with CA those with non shockable rhythm have an higher risk of both poor neurological outcome and cardiac mortality at 1year.

Mortality Following Nonemergent, Uncomplicated Target Lesion Revascularization After Percutaneous Coronary Intervention: An Individual Patient Data Pooled Analysis of 21 Randomized Trials and 32,524 Patients.

OBJECTIVES: This study sought to investigate the impact of nonemergent, uncomplicated target lesion revascularization (TLR) on the risk of long-term mortality after percutaneous coronary intervention (PCI). BACKGROUND: Restenosis requiring TLR after PCI is generally considered a benign event. METHODS: The study pooled patient-level data from 21 randomized trials. Subjects dying the same day as or the day after the TLR procedure as well as those with myocardial infarction (MI) the day before, the same day as or the day after TLR were excluded. The primary endpoint of the study was all-cause mortality. RESULTS: The dataset included 32,524 patients who were stratified according to whether repeat TLR was performed during follow-up. During a median follow-up of 37 months, 2,330 (7.2%) patients underwent a nonemergent, uncomplicated TLR procedure. After adjusting for potential confounders, TLR was an independent predictor of mortality (hazard ratio: 1.23, 95% confidence interval: 1.04 to 1.45; p = 0.02). Patients undergoing nonemergent, uncomplicated TLR had significantly higher rates of non-procedure-related MI compared with those without TVR. Among patients undergoing elective TLR, MI occurring after TLR was an independent predictor of mortality (hazard ratio: 3.82; 95% confidence interval: 2.44 to 5.99; p < 0.0001). CONCLUSIONS: Nonemergent, uncomplicated TLR after PCI is an independent predictor of long-term mortality, an association in part explained by higher rates of MI occurring after TLR. Efforts aimed at reducing TLR risk may translate into prognostic benefits including reduced rates of MI and survival.

Prodromal angina and risk of 2-year cardiac mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention.

We sought to investigate the prognostic significance of prodromal angina (PA) in unselected patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) and its additive predictive value to the GRACE score.We prospectively enrolled 3015 consecutive STEMI patients undergoing PPCI. Patients were divided in 2 groups according to the presence or absence of PA. Multivariable Cox regression was used to establish the relation to 2-year cardiac mortality of PA.The mean age of the study population was 68 (±14) years; 2178 patients (72%) were male. During follow-up, 395 (13%) patients died with 278 of these (9.2%) suffering from cardiac mortality. Kaplan-Meier estimates showed a survival rate of 95% and 87% for patients with PA and no PA, respectively (log rank test < 0.001). After multivariable analysis, patients with PA had still a lower risk of 2 years' cardiac mortality compared with patients without PA (adjusted hazard ratio = 0.50; 95% confidence interval [CI] 1.06-1.81, P = .001). Evaluation of net reclassification improvement showed that reclassification improved by 0.16% in case patients, whereas classification worsened in control patients by 1.08% leading to a net reclassification improvement of -0.93% (95% CI: -0.98, -0.88).In patients with STEMI undergoing PPCI the presence of PA is independently associated with a lower risk of 2-year cardiac mortality. However, the incorporation of this variable to the GRACE score slightly worsened the classification of risk. Accordingly, it seems unlikely that the evaluation of PA may be useful in clinical practice.

High sensitive TROponin levels In Patients with Chest pain and kidney disease: A multicenter registry - The TROPIC study.

BACKGROUND: Accuracy of high sensitive troponin (hs-cTn) to detect coronary artery disease (CAD) in patients with renal insufficiency is not established. The aim of this study was to evaluate the prognostic role of hs-cTn T and I in patients with chronic kidney disease (CKD). METHODS: All consecutive patients with chest pain, renal insufficiency (eGFR < 60 mL/min/1.73 m2) and high sensitive troponin level were included. The predictive value of baseline and interval troponin (hs-cTnT and hs-cTnI) for the presence of CAD was assessed. RESULTS: One hundred and thirteen patients with troponin I and 534 with troponin T were included, with 95 (84%) and 463 (87%) diagnosis of CAD respectively. There were no differences in clinical, procedural and outcomes between the two assays. For both, baseline hs-cTn values did not differ be-tween patients with/without CAD showing low area under the curve (AUC). For interval levels, hs-cTnI was significantly higher for patients with CAD (0.2 ± 0.8 vs. 8.9 ± 4.6 ng/mL; p = 0.04) and AUC was more accurate for troponin I than hs-cTnT (AUC 0.85 vs. 0.69). Peak level was greater for hs-cTnI in patients with CAD or thrombus (0.4 ± 0.6 vs. 15 ± 20 ng/mL; p = 0.02; AUC 0.87: 0.79-0.93); no differences were found for troponin T assays (0.8 ± 1.5 vs. 2.2 ± 3.6 ng/mL; p = 1.7), with lower AUC (0.73: 0.69-0.77). Peak troponin levels (both T and I) independently predicted all cause death at 30 days. CONCLUSIONS: Patients with CKD presenting with altered troponin are at high risk of coronary disease. Peak level of both troponin assays predicts events at 30 days, with troponin I being more accurate than troponin T. (Cardiol J 2017; 24, 2: 139-150).

Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting.

BACKGROUND: Although some randomized controlled trials (RCTs) and meta-analyses have suggested that prolonged dual-antiplatelet therapy (DAPT) may be associated with increased mortality, the mechanistic underpinnings of this association remain unclear. OBJECTIVES: The aim of this study was to analyze the associations among bleeding, mortality, and DAPT duration after drug-eluting stent implantation in a meta-analysis of RCTs. METHODS: RCTs comparing different DAPT durations after drug-eluting stent placement were sought through the MEDLINE, Embase, and Cochrane databases and the proceedings of international meetings. Deaths were considered possibly bleeding related if occurring within 1 year of the episodes of bleeding. Primary analysis was by intention-to-treat. Secondary analysis was performed in a modified intention-to-treat population in which events occurring when all patients were on DAPT were excluded. RESULTS: Individual patient data were obtained for 6 RCTs, and aggregate data were available for 12 RCTs. Patients with bleeding had significantly higher rates of mortality compared with those without, and in a time-adjusted multivariate analysis, bleeding was an independent predictor of mortality occurring within 1 year of the bleeding episode (hazard ratio: 6.93; 95% confidence interval: 4.53 to 10.60; p < 0.0001). Shorter DAPT was associated with lower rates of all-cause death compared with longer DAPT (hazard ratio: 0.85; 95% confidence interval: 0.73 to 1.00; p = 0.05), which was driven by lower rates of bleeding-related deaths with shorter DAPT compared with prolonged DAPT (hazard ratio: 0.65; 95% confidence interval: 0.43 to 0.99; p = 0.04). Mortality unrelated to bleeding was comparable between the 2 groups. Similar results were apparent in the modified intention-to-treat population. CONCLUSIONS: Bleeding was strongly associated with the occurrence of mortality within 1 year after the bleeding event. Shorter compared with longer DAPT was associated with lower risk for bleeding-related death, a finding that may underlie the lower all-cause mortality with shorter DAPT in the RCTs of different DAPT durations after DES.

Relationship between diabetes, platelet reactivity, and the SYNTAX score to one-year clinical outcome in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention.

AIMS: In patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) treated with PCI, high (H) platelet reactivity (PR) significantly affects one-year outcome. The aim of this report was to analyse the relationships between HPR, the SYNTAX score (SS) and one-year major adverse cardiac events (MACE: cardiac death, myocardial infarction, stent thrombosis) according to diabetes mellitus (DM) status in patients included in the GEne Polymorphism, Platelet REactivity, and the Syntax Score (GEPRESS) study. METHODS AND RESULTS: PR was measured using the vasodilator-stimulated phosphoprotein (VASP) assay at three time points (before PCI, at hospital discharge and at one month after PCI), with HPR defined as >50% PR index in 1,042 patients treated with aspirin and clopidogrel for one year after PCI. Patients with DM and an SS ≥15 had the highest MACE rate between one month and one year, further increased by the presence of HPR (16.4%). On the other hand, among all patients with an SS <15, MACE rates remained low (<3%), irrespective of DM status and PR. CONCLUSIONS: Among NSTE-ACS patients treated with PCI, the combination of DM, an SS ≥15 and HPR characterised a cohort with the highest MACE rate from one month to one year. In such high-risk patients, careful clinical monitoring and implementation of secondary prevention measures, including the use of potent P2Y12 inhibitors, are strongly advised.

Long-Term Safety of Drug-Eluting and Bare-Metal Stents: Evidence From a Comprehensive Network Meta-Analysis.

BACKGROUND: Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety and efficacy of these devices are unknown. Many recent studies have now reported extended follow-up data. OBJECTIVES: This study sought to investigate the long-term safety and efficacy of durable polymer-based DES, bioabsorbable polymer-based biolimus-eluting stents (BES), and BMS by means of network meta-analysis. METHODS: Randomized controlled trials comparing DES to each other or to BMS were searched through MEDLINE, EMBASE, and Cochrane databases and proceedings of international meetings. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. RESULTS: Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target-vessel revascularization were reduced with all DES compared with BMS, with cobalt-chromium EES, platinum chromium-EES, SES, and BES also having lower target-vessel revascularization rates than PES. CONCLUSIONS: After a median follow-up of 3.8 years, all DES demonstrated superior efficacy compared with BMS. Among DES, second-generation devices have substantially improved long-term safety and efficacy outcomes compared with first-generation devices.

Short- versus long-term dual antiplatelet therapy after drug-eluting stent implantation: an individual patient data pairwise and network meta-analysis.

BACKGROUND: Randomized controlled trials comparing short- (≤6 months) with long-term (≥1 year) dual antiplatelet therapy (DAPT) after drug-eluting stent(s) (DES) placement have been insufficiently powered to detect significant differences in the risk of major adverse cardiac events (MACE). OBJECTIVES: This study sought to compare clinical outcomes between short- (≤6 months) and long-term (1 year) DAPT and among 3 months, 6 months, and 1 year of DAPT post-DES placement by performing an individual patient data pairwise and network meta-analysis. METHODS: Randomized controlled trials comparing DAPT durations after DES placement were searched through the MEDLINE, EMBASE, and Cochrane databases and in international meeting proceedings. The primary study outcome was 1-year risk of MACE (cardiac death, myocardial infarction, or definite/probable stent thrombosis). RESULTS: Four trials including 8,180 randomized patients were identified. At 1-year follow-up, short-term DAPT was associated with similar rates of MACE (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.86 to 1.43; p = 0.44), but significantly lower rates of bleeding (HR: 0.66; 95% CI: 0.46 to 0.94; p = 0.03) versus prolonged DAPT. Comparable results were apparent in the landmark period between DAPT discontinuation and 1-year follow-up (for MACE: HR: 1.20; 95% CI: 0.77 to 1.89; p = 0.42) (for bleeding: HR: 0.44; 95% CI: 0.21 to 0.91; p = 0.03). There were no significant differences in 1-year rates of MACE among 3-month versus 1-year DAPT, 6-month versus 1-year DAPT, or 3-month versus 6-month DAPT. CONCLUSIONS: Compared with prolonged DAPT, short-term DAPT is associated with similar rates of MACE but lower rates of bleeding after DES placement.

Percutaneous coronary intervention versus coronary artery bypass graft for stable angina: meta-regression of randomized trials.

AIMS: Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) perform similarly in terms of lowering mortality and myocardial infarction rates in patients with stable angina, except in subjects with high-risk lesions. PCI is burdened from higher rates of revascularization, but offers a reduction in stroke. To date, the impact of clinical variables on the risk-benefit assessment has not been established. METHODS AND RESULTS: Using event rates as a dependent variable, meta-regression was performed to test whether an interaction existed between baseline clinical features (age, gender, diabetes mellitus, previous myocardial infarction and ejection fraction) and choice of revascularization, focusing on death, myocardial infarction, repeat revascularization and stroke. 20 randomized clinical trials (RCT) including 12,844 patients with stable angina were included. Compared to CABG, PCI significantly reduced the risk of stroke, both at 30 days (odds ratio [OR] 0.36 [95% confidence interval: 0.20-0.62]) and at follow up (median=12 months, OR=0.57 [0.41-0.80]). This reduction in stroke was significantly higher in females (B=-0.12, p=0.03). For repeat revascularization, PCI performed worse than CABG, both in the overall population and in patients with multivessel disease (OR=4.71 [3.17-7.01]) and (OR=7.18 [4.32-11.93]). Women (B=3.4, p=0.01) and those with diabetes mellitus (B=1.8, p=0.002) were at increased risk of subsequent revascularization after PCI. CONCLUSION: PCI significantly reduces the risk of stroke compared to CABG particularly in female patients: however the risk of revascularization is increased with PCI, especially in women and in those with diabetes.

Clinical outcomes with bioabsorbable polymer- versus durable polymer-based drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis.

OBJECTIVES: This study sought to investigate the relative safety and efficacy of bioabsorbable polymer (BP)-based biolimus-eluting stents (BES) versus durable-polymer (DP)-drug-eluting stents (DES) and bare-metal stents (BMS) by means of a network meta-analysis. BACKGROUND: Studies have suggested that BP-BES might reduce the risk of stent thrombosis (ST) and late adverse outcomes compared with first-generation DES. However, the relative safety and efficacy of BP-BES versus newer-generation DES coated with more biocompatible DP have not been investigated in depth. METHODS: Randomized controlled trials comparing BP-BES versus currently U.S.-approved DES or BMS were searched through MEDLINE, EMBASE, and Cochrane databases. Information on study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. RESULTS: Data from 89 trials including 85,490 patients were analyzed. At 1-year follow-up, BP-BES were associated with lower rates of cardiac death/myocardial infarction (MI), MI, and target vessel revascularization (TVR) than BMS and lower rates of TVR than fast-release zotarolimus-eluting stents. The BP-BES had similar rates of cardiac death/MI, MI, and TVR compared with other second-generation DP-DES but higher rates of 1-year ST than cobalt-chromium everolimus-eluting stents (CoCr-EES). The BP-BES were associated with improved late outcomes compared with BMS and paclitaxel-eluting stents, considering the latest follow-up data available, with nonsignificantly different outcomes compared with other DP-DES although higher rates of definite ST compared with CoCr-EES. CONCLUSIONS: In this large-scale network meta-analysis, BP-BES were associated with superior clinical outcomes compared with BMS and first-generation DES and similar rates of cardiac death/MI, MI, and TVR compared with second-generation DP-DES but higher rates of definite ST than CoCr-EES.

Impact of gene polymorphisms, platelet reactivity, and the SYNTAX score on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention: the GEPRESS study.

OBJECTIVES: The aim of this study was to investigate the association between high on-treatment platelet reactivity (HPR) and the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS) for risk prediction of major adverse cardiovascular events (MACE) in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Platelet function testing may be used to optimize antiplatelet therapy in high-risk patients, but identification of this category of patients remains challenging. METHODS: The GEPRESS (Gene Polymorphism, Platelet Reactivity, and the Syntax Score) study was a prospective, multicenter, observational study enrolling 1,053 patients with NSTEACS undergoing PCI and treated with clopidogrel. The platelet reactivity index (PRI) was measured at 3 time points: before PCI, at hospital discharge, and 1 month after PCI. Genetic variants of clopidogrel metabolism were determined in 750 patients. Patients were stratified by the presence of HPR (PRI >50%) and by tertile of the SS (upper SS tertile ≥15). The primary objective of this study was the risk of MACE in the period between 1 month and 1 year. RESULTS: Between 1 month and 1 year, 1-month HPR was an independent predictor of MACE in patients with an SS ≥15, but not in those with an SS <15, displaying a 5-fold increase in event rates (10.4% vs. 2.5%; p < 0.0001). CYP2C19*2 was the only single nucleotide polymorphism associated with HPR, but it was not associated with MACE. Although there was a significant variability in the PRI across the 1-month period, predischarge HPR and SS effectively stratified the risk of subsequent MACE up to 1-year follow-up. CONCLUSIONS: In clopidogrel-treated patients with NSTEACS undergoing PCI, HPR was independently associated with an increased risk of MACE only in the presence of a high SS.