Comparison of mid-term mortality after surgical, supported or unsupported percutaneous revascularization in patients with severely reduced ejection fraction: A direct and network meta-analysis of adjusted observational studies and randomized-controlled.

INTRODUCTION: The optimal revascularization strategy in patients with heart failure with reduced ejection fraction (HFrEF) remains to be elucidated. The aim of this paper is to compare the mid-term mortality rate among patients with severely reduced ejection fraction (EF) and complex coronary artery disease who underwent coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) with Impella support, or without. METHODS: Randomized control trials and propensity-adjusted observational studies including patients with ischemic cardiomyopathy (ICM) and severe EF reduction undergoing revascularization were selected. Different revascularization strategies (CABG, supported PCI, and PCI without Impella) were compared in pairwise and network meta-analysis. The primary endpoint was mid-term mortality (within the first year after revascularization). RESULTS: Fifteen studies, mostly observational (17,841 patients; 6779 patients treated with CABG, 8478 treated with PCI without Impella, and 2584 treated with Impella-supported PCI) were included in this analysis. The median age was 67.8 years (IQR 65-70.1), 21.2% (IQR 16.4-26%) of patients were female sex, and a high prevalence of cardiovascular risk factors was noted across the entire population. At pairwise analysis, CABG and PCI without Impella showed similar one-year all-cause mortality (10.6% [IQR 7.5-12.6%] vs 12% [IQR 8.4-11.5%]) RR 0.85 CI 0.67-1.09, while supported PCI reduced one-year all-cause mortality compared to PCI without Impella (9.4% [IQR 5.7-12.5%] vs 10.6% [IQR 8.9-10.7%]) RR 0.77 CI 0.6-0.89. At network meta-analysis, supported PCI showed better results (RR 0.75, 95% CI 0.59-0.94) compared to CABG. CONCLUSION: Our analysis found that supported PCI may have a benefit over standard PCI in patients in direct comparison, and over CABG from indirect comparison, and with HFrEF undergoing revascularization. Further RCTs are needed to confirm this result. (PROSPERO CRD42023425667).

OCT guided vs. COmplete pci in patieNts with sT segment elevation myocArdial infarCtion and mulTivessel disease: OCT-CONTACT RCT.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion significantly reduces the risk of cardiovascular death. However, the management of non-culprit lesions in patients with the multivessel disease remains a matter of debate in this setting. It's still unclear if a morphological OCT-guided approach, identifying coronary plaque instability, may provide a more specific treatment compared with a standard angiographic/functional approach. METHODS: OCT-Contact is a prospective, multicenter, open-label, non-inferiority randomized controlled trial. Patients with STEMI with successful primary PCI of the culprit lesion will be enrolled after the index PCI. Patients will be deemed eligible if a critical coronary lesion other than the culprit (associated with a diameter of stenosis ≥50%) will be identified during the index angiography. Patients will be randomized in a 1:1 fashion to OCT-guided PCI of non-culprit lesions (Group A) vs. complete PCI (Group B). PCI in group A will be undertaken according to criteria of plaque vulnerability, while in group B the use of fractional flow reserve will be left at the operators' discretion. Major-adverse cardiovascular events (MACE) are a composite of all-cause mortality, non-fatal myocardial infarction (MI) (excluding peri-procedural MI), unplanned revascularization, and NYHA IV heart failure) will be the primary efficacy outcome. Single components of MACE along with cardiovascular mortality will be the secondary endpoints. . Safety endpoints will embrace worsening of renal failure, procedural complications, and bleedings. Patients will be followed for 24 months after randomization. RESULTS: A sample size of 406 patients (203 per group) is required to provide the analysis an 80% power to detect a non-inferiority in the primary endpoint with an alpha error set at 0.05 and a non-inferiority limit of 4%. CONCLUSIONS: A morphological OCT-guided approach may be a more specific treatment compared with the standard angiographic/functional approach in non-culprit lesions of STEMI patients.

In-hospital outcomes in nonagenarian patients undergoing primary percutaneous coronary intervention.

BACKGROUND: The aim of the present analysis was to evaluate the incidence and predictors of in-hospital adverse outcomes in nonagenarian patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). METHODS: Consecutive nonagenarian patients undergoing pPCI for STEMI from 2009 to 2019 were retrospectively included in an international multicenter registry. In-hospital all-cause death was the primary outcome. RESULTS: A total of 308 patients were included (mean age 92.5±2.5 years, 65.6% female). Mean systolic blood pressure (SBP) at hospital admission was 130.7±33.5 mmHg, 46 (17%) patients presented with a Killip class III-IV, mean left ventricle ejection fraction (LVEF) was 40.0±11.5% and 147 (58%) patients were independent in everyday activities. In-hospital death occurred in 99 patients (32%). After multivariate adjustment, lower LVEF (OR per unit reduction 1.08, 95% CI: 1.03-1.11, P value <0.001), lower SBP (OR 1.02 per mmHg reduction, 95% CI: 1.01-1.03, P value 0.001) and being not independent at home (OR 2.56, 95% CI: 1.25-5.26, P value 0.01) resulted independent predictors of in-hospital mortality. A sensitivity analysis performed in final TIMI 3 flow population confirmed the prognostic role of LVEF and independency on in-hospital mortality. CONCLUSIONS: Nonagenarian patients presenting with STEMI and undergoing pPCI have high in-hospital mortality. Independency in everyday life is a strong independent predictor of survival to hospital discharge.

Incidence trends and long-term outcomes of myocardial infarction in young adults: Does gender matter?

AIMS: Data about long-term clinical outcomes of young patients experiencing an acute myocardial infarction (MI) and about the potential impact of gender on juvenile MI incidence and prognosis are scant. METHODS AND RESULTS: Hospital Discharge Register records of Piedmont region (Italy) from 2007 to 2018 were interrogated to identify incident juvenile MI cases and MI recurrences. Patients were considered young if the first MI occurred before or at 47 years of age (5th percentile). Incidence of first juvenile MI event and overall survival were the primary outcomes. Gender differences and survival rate after an MI recurrence were secondary outcomes. Out of 114.816 hospitalizations due to MI, 4482 (3.9%) occurred in people aged ≤47. Average incidence rate of juvenile MI over the study period was 24.5 (23.8-25.2) per 100.000 person-years, with a decline among men and a stable trend among women through the years. The risk of in hospital death was higher for women (1.9% vs. 0.9%, p = 0.02), while the survival rate at 10 years after the first MI was 94.8%, without gender differences (HR 1.05: 0.69-1.60). MI recurrence occurred in 348 (7.8%) and was less common in women (HR 0.72: 0.52-0.99). After multivariate adjustment, MI recurrence was associated with a significantly higher risk of death at follow-up as compared with a single MI episode (HR 3.05: 1.9-4.80, all CI 95%). CONCLUSION: Among young patients with MI, women had a higher in-hospital mortality compared to men, but long-term prognosis after hospital discharge did not differ. MI recurrences were associated with increased mortality at follow up.

Impact of lipid-lowering therapies on cardiovascular outcomes according to coronary artery calcium score. A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Coronary artery calcium (CAC) score improves the accuracy of risk stratification for atherosclerotic cardiovascular disease (ASCVD) events compared with traditional cardiovascular risk factors. We evaluated the interaction of coronary atherosclerotic burden as determined by the CAC score with the prognostic benefit of lipid-lowering therapies in the primary prevention setting. METHODS: We reviewed the MEDLINE, EMBASE, and Cochrane databases for studies including individuals without a previous ASCVD event who underwent CAC score assessment and for whom lipid-lowering therapy status stratified by CAC values was available. The primary outcome was ASCVD. The pooled effect of lipid-lowering therapy on outcomes stratified by CAC groups (0, 1-100,> 100) was evaluated using a random effects model. RESULTS: Five studies (1 randomized, 2 prospective cohort, 2 retrospective) were included encompassing 35 640 individuals (female 38.1%) with a median age of 62.2 [range, 49.6-68.9] years, low-density lipoprotein cholesterol level of 128 (114-146) mg/dL, and follow-up of 4.3 (2.3-11.1) years. ASCVD occurrence increased steadily across growing CAC strata, both in patients with and without lipid-lowering therapy. Comparing patients with (34.9%) and without (65.1%) treatment exposure, lipid-lowering therapy was associated with reduced occurrence of ASCVD in patients with CAC> 100 (OR, 0.70; 95%CI, 0.53-0.92), but not in patients with CAC 1-100 or CAC 0. Results were consistent when only adjusted data were pooled. CONCLUSIONS: Among individuals without a previous ASCVD, a CAC score> 100 identifies individuals most likely to benefit from lipid-lowering therapy, while undetectable CAC suggests no treatment benefit.

Performance of Thin-Strut Stents in Non-Left Main Bifurcation Coronary Lesions: A RAIN Subanalysis.

OBJECTIVES: This study assesses the safety and efficacy of thin-strut stents in non-left main (non-LM) bifurcation coronary lesions. BACKGROUND: Thinner struts of recent drug-eluting stent (DES) devices are associated with improved outcomes, but data about their performance in challenging scenarios are scant. METHODS: RAIN was a retrospective multicenter registry enrolling patients with coronary bifurcation lesions or left main (LM) disease treated with thin-strut DESs. Target-lesion revascularization (TLR) was the primary endpoint, while major adverse clinical event (MACE) rate, a composite of all-cause death, myocardial infarction (MI), target-vessel revascularization (TVR), TLR, and stent thrombosis (ST), and its single components were the secondary endpoints. Multivariable analysis was performed to identify predictors of TLR. Outcome incidences according to stenting strategy (provisional vs 2-stent technique), use of final kissing balloon (FKB), and intravascular ultrasound/optical coherence tomography optimization were further investigated in prespecified subanalyses. RESULTS: A total of 1803 patients (59% acute coronary syndrome, 41% stable coronary artery disease) with non-LM bifurcations were enrolled. After a median follow-up of 12 months, TLR incidence was 2.5% (2.2% for provisional stenting and 3.5% for 2-stent technique). MACE rate was 9.4% (all-cause death, 4.1%; MI, 3.2%; TVR, 3.7%; definite ST, 1.1%). After multivariable adjustment, postdilation (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15-0.71; P<.01) and provisional stenting (HR, 0.62; 95% CI, 0.55-0.89; P=.03) were associated with lower TLR rates. FKB was associated with a lower incidence of TLR in the 2-stent subgroup (P=.03). Intracoronary imaging had no significant impact on the primary endpoint. CONCLUSIONS: Thin-strut DES options represent an effective choice in bifurcation lesions. Postdilation and provisional stenting are associated with a reduced risk of TLR. FKB should be recommended in 2-stent techniques.

Ticagrelor versus prasugrel in acute coronary syndrome: sex-specific analysis from the RENAMI Registry.

BACKGROUND: The use of potent P2Y12 inhibitors (ticagrelor & prasugrel) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions (PCI) is a class I recommendation. We performed a sex-specific analysis comparing the difference in efficacy and safety outcomes between ticagrelor and prasugrel in a real-world ACS population. METHODS: Data from the multicenter REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) for 4424 ACS patients who underwent PCI and were treated with ticagrelor or prasugrel between 2012 to 2016 were analyzed. Mean follow-up was 17±9 months. RESULTS: After propensity score matching, there was no significant difference in the occurrence of primary endpoint of net adverse cardiac events between ticagrelor and prasugrel in men (HR: 0.94; 95% CI: 0.69-1.29; P=0.71), or women (HR: 1.17; 95% CI: 0.63-2.20; P=0.62; P interaction [sex] = 0.40). Similarly, no differences were found in the occurrence of any of the secondary endpoints (MACE, all cause death, re-infarction, stent thrombosis, BARC major bleeding and BARC any bleeding) between the two P2Y12 groups between men and women. CONCLUSIONS: In this real-world ACS population, no relative difference in efficacy or safety outcomes were found between ticagrelor and prasugrel between sexes.

Accuracy of the PARIS score and PCI complexity to predict ischemic events in patients treated with very thin stents in unprotected left main or coronary bifurcations.

BACKGROUND: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed. METHODS: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents. RESULTS: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI. CONCLUSIONS: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

Cerebral protection in left atrial appendage closure in the presence of appendage thrombosis.

BACKGROUND: Presence of thrombus in the left atrial appendage (LAA) remains a severe contraindication to the percutaneous left atrial appendage closure procedure (LAAC), due to increased embolic risk. Recently, the experience developed in cerebral protection device in transcatheter aortic valve implantation (TAVI) procedure was translated in LAAC to address this issue. AIM: To evaluate efficacy and safety of Sentinel cerebral protection system (CPS) in supporting LAAC in real-world patient with persistent LAA thrombus. METHODS AND RESULTS: The study retrospectively enrolled consecutive patients with non-valvular atrial fibrillation (NVAF) and thrombus in LAA who underwent LAAC supported by Sentinel CPS in seven European high-volume centres. Twenty-seven patients were included with a median age of 69.1 ± 9.7 years old, with median CHA2 DS2 -VASc and HAS-BLEED scores 3 [2-5] and 3 [2.75-4], respectively. Technical and procedural success was achieved in all patients. No periprocedural TIA, stroke, or supra-aortic trunks dissection was recorded. CONCLUSIONS: In this multicenter registry, LAAC supported by Sentinel CPS in patients with LAA persistent thrombus seems to be a safe and efficacious treatment.

Impact of stent thickness on clinical outcomes in small vessel and bifurcation lesions: a RAIN-CARDIOGROUP VII sub-study.

BACKGROUND: The clinical impact of stent strut thickness in coronary bifurcation lesions in small vessels has not been assessed in a real-world population. METHODS: All 506 patients enrolled in the RAIN study, undergoing PCI in a vessel with a diameter 2.5 mm or less were retrospectively evaluated and divided into two groups according to stent strut thickness: 74 µm (n = 206) versus 81 µm (n = 300); 87.1% of the lesions involved bifurcations. TLF [defined as a composite of myocardial infarction (MI) and target lesion revascularization (TLR)] was the primary endpoint, with MACE (a composite of death, MI and TLR), its components and stent thrombosis the secondary endpoint. RESULTS: After 16 (14-18) months, a lower incidence of TLF (4.3 vs. 9.8%, P = 0.026) and ST (1.0 vs. 3.0%, P = 0.042) was seen in the 74 µm group, whereas MACE occurred in 60 of 506 patients, with no statistical difference between the two groups (9.7 vs. 13.3%, P = 0.070). At multivariate analysis, chronic renal failure increased the risk of TLF while thinner strut was an independent protective factor (hazard ratio 0.51, CI 0.17-0.85, P = 0.005). CONCLUSION: In this real-world population, patients being treated for small vessels lesions with thinner strut stents had lower rates of TLF, MI and ST.

A Sex-Based Analysis From the RAIN-CARDIOGROUP VII Study (VeRy Thin Stents for Patients With Left MAIn or BifurcatioN in Real Life) on Left Main Stenting.

INTRODUCTION: There is a lack of data on clinical outcomes of percutaneous coronary intervention (PCI) with ultrathin stents on unprotected left main (ULM) coronary artery comparing women and men. METHODS: All patients treated with ULM-PCI with ultrathin stents (struts ≤81 µm) enrolled in the RAIN-CARDIOGROUP VII study were analyzed according to a sex-assessment evaluation. Major adverse cardiovascular event (MACE, a composite of all-cause death, myocardial infarction, target-lesion revascularization [TLR], and stent thrombosis) was the primary endpoint, whereas single components of MACE were the secondary endpoints. RESULTS: Out of a cohort of 793 patients, a total of 172 women (21.7%) and 621 men (78.3%) were included. Compared with men, women were older and less frequently smokers, had more frequently a history of previous PCI, and presented more frequently with an acute coronary syndrome. Among women, ostial lesions were more prevalent and mean stent diameter was lower compared with men. After 13.4 months (range, 8.4-21.6 months), 32 women (18.6%) and 106 men (17.1%) experienced MACE (P=.64). Censoring follow-up data at 3 years, no differences were observed in MACE (16.9 vs 14.7 per 100•patient-years; log-rank P=.61) and their single components between women and men. At multivariate analysis, chronic kidney disease (hazard ratio [HR], 1.91: 95% confidence interval [CI], 1.23 to -2.95; P<.01) and acute coronary syndrome presentation (HR, 1.84; 95% CI, 1.22-2.77; P=.01) were independent predictors of MACE overall. Larger stent size (HR, 0.65; 95% CI, 0.48-0.89; P<.01) and longer dual-antiplatelet therapy duration (HR, 0.95; 95% CI, 0.90-0.99; P=.03) were associated with a reduced risk of MACE during the subsequent follow-up. CONCLUSION: Ultrathin stents offer low rates of MACE and TLR in the overall population without significant differences between sexes.

Comparison of bioresorbable vs durable polymer drug-eluting stents in unprotected left main (from the RAIN-CARDIOGROUP VII Study).

BACKGROUND: There are limited data regarding the impact of bioresorbable polymer drug eluting stent (BP-DES) compared to durable polymer drug eluting stent (DP-DES) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. METHODS: In the RAIN registry (ClinicalTrials NCT03544294, june 2018 retrospectively registered) patients with a ULM or bifurcation stenosis treated with PCI using ultrathin stents (struts thinner than 81 µm) were enrolled. The primary endpoint was the rate of target lesion revascularization (TLR); major adverse cardiovascular events (MACE, a composite of all-cause death, myocardial infarction, TLR and stent thrombosis) and its components, along with target vessel revascularization (TVR) were the secondary ones. A propensity score with matching analysis to compare patients treated with BP-DES versus DP-DES was also assessed. RESULTS: From 3001 enrolled patients, after propensity score analysis 1400 patients (700 for each group) were selected. Among them, 352 had ULM disease and 1048 had non-LM bifurcations. At 16 months (12-22), rates of TLR (3.7% vs 2.9%, p = 0.22) and MACE were similar (12.3% vs. 11.6%, p = 0.74) as well as for the other endpoints. Sensitivity analysis of outcomes after a two-stents strategy, showed better outcome in term of MACE (20.4% vs 10%, p = 0.03) and TVR (12% vs 4.6%, p = 0.05) and a trend towards lower TLR in patients treated with BP-DES. CONCLUSION: In patients with bifurcations or ULM treated with ultrathin stents BP-DES seems to perform similarly to DP-DES: the trends toward improved clinical outcomes in patients treated with the BP-DES might potentially be of value for speculating the stent choice in selected high-risk subgroups of patients at increased risk of ischemic events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03544294. Retrospectively registered June 1, 2018.

Real-world reasons and outcomes for 1-month versus longer dual antiplatelet therapy strategies with a polymer-free BIOLIMUS A9-coated stent.

BACKGROUND: A large trial established the favorable profile of a new polymer-free biolimus A9-eluting stent (PF-BES) with a 1-month dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients. This is the first study comparing outcomes for a 1-month versus longer DAPT strategies following PF-BES-percutaneous coronary intervention (PCI). METHODS: All patients undergoing PF-BES-PCI (January 2016 to July 2018) were included in the multicenter CHANCE registry. Patients were stratified according to DAPT strategy at discharge (planned 1-month vs. planned >1-month). Primary outcomes were the 390-day estimates of a patient-oriented and of a device-oriented composite endpoints (POCE: death, myocardial infarction [MI] or target vessel revascularization; DOCE: cardiac death, target vessel-MI or ischemia-driven target lesion revascularization). Landmark analyses from 1-month post-PCI were carried. RESULTS: Following PF-BES-PCI, 328(40.3%) and 485(59.6%) patients were discharged with 1-month and longer DAPT (12 months [6-12]), respectively. Patients with a previous or index MI were less likely to be discharged on 1-month DAPT. Patients prescribed with 1-month DAPT were more likely to be at HBR than those with longer DAPT (90.2% vs. 69.9%, p = .001). No between-groups differences in the primary outcomes (planned 1-month vs. planned >1-month DAPT: POCE 11.9% vs. 13.2%, p = .747; DOCE: 4.8% vs. 8.1%, p = .500) were observed, also after adjusting for confoundings (POCE: adjusted-hazard ratio [adj-HR] 1.26, 95%CI 0.74-2.13; DOCE: adj-HR 1.00, 95%CI 0.49-1.99). Landmark analyses showed similar results. CONCLUSIONS: In a large all-comers registry of PF-BES PCI, no interaction of planned DAPT strategy (1-month vs. >1-month) with outcomes was found. This observation warrants investigation in adequately powered randomized studies (ClinicalTrials.gov NCT03622203).

Incidence of Adverse Events at 3 Months Versus at 12 Months After Dual Antiplatelet Therapy Cessation in Patients Treated With Thin Stents With Unprotected Left Main or Coronary Bifurcations.

Incidence and predictors of adverse events after dual antiplatelet therapy (DAPT) cessation in patients treated with thin stents (<100 microns) in unprotected left main (ULM) or coronary bifurcation remain undefined. All consecutive patients presenting with a critical lesion of an ULM or involving a main coronary bifurcation who were treated with very thin strut stents were included. MACE (a composite end point of cardiovascular death, myocardial infarction [MI], target lesion revascularization [TLR], and stent thrombosis [ST]) was the primary endpoint, whereas target vessel revascularization (TVR) was the secondary endpoint, with particular attention to type and occurrence of ST and occurrence of ST, CV death, and MI during DAPT or after DAPT discontinuation. All analyses were performed according to length of DAPT dividing the patients in 3 groups: Short DAPT (3-months), intermediate DAPT (3 to 12 months), and long DAPT (12-months). A total of 117 patients were discharged with an indication for DAPT ≤3 months (median 1: 1 to 2.5), 200 for DAPT between 3 and 12 months (median 8: 7 to 10), and 1,958 with 12 months DAPT. After 12.8 months (8 to 20), MACE was significantly higher in the 3-month group compared with 3 to 12 and 12-month groups (9.4% vs 4.0% vs 7.2%, p ≤0.001), mainly driven by MI (4.4% vs 1.5% vs 3%, p ≤0.001) and overall ST (4.3% vs 1.5% vs 1.8%, p ≤0.001). Independent predictors of MACE were low GFR and a 2 stent strategy. Independent predictors of ST were DAPT duration <3 months and the use of a 2-stent strategy. In conclusion, even stents with very thin strut when implanted in real-life ULM or coronary bifurcation patients discharged with short DAPT have a relevant risk of ST, which remains high although not significant after DAPT cessation.

Long versus short dual antiplatelet therapy in acute coronary syndrome patients treated with prasugrel or ticagrelor and coronary revascularization: Insights from the RENAMI registry.

INTRODUCTION: The benefits of short versus long-term dual antiplatelet therapy (DAPT) based on the third generation P2Y12 antagonists prasugrel or ticagrelor, in patients with acute coronary syndromes treated with percutaneous coronary intervention remain to be clearly defined due to current evidences limited to patients treated with clopidogrel. METHODS: All acute coronary syndrome patients from the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) undergoing percutaneous coronary intervention and treated with aspirin, prasugrel or ticagrelor were stratified according to DAPT duration, that is, shorter than 12 months (D1 group), 12 months (D2 group) and longer than 12 months (D3 group). The three groups were compared before and after propensity score matching. Net adverse clinical events (NACEs), defined as a combination of major adverse cardiac events (MACEs) and major bleedings (including therefore all cause death, myocardial infarction and Bleeding Academic Research Consortium (BARC) 3-5 bleeding), were the primary end points, MACEs (a composite of all cause death and myocardial infarction) the secondary one. Single components of NACEs were co-secondary end points, along with BARC 2-5 bleeding, cardiovascular death and stent thrombosis. RESULTS: A total of 4424 patients from the RENAMI registry with available data on DAPT duration were included in the model. After propensity score matching, 628 patients from each group were selected. After 20 months of follow up, DAPT for 12 months and DAPT for longer than 12 months significantly reduced the risk of NACE (D1 11.6% vs. D2 6.7% vs. D3 7.2%, p = 0.003) and MACE (10% vs. 6.2% vs. 2.4%, p < 0.001) compared with DAPT for less than 12 months. These differences were driven by a reduced risk of all cause death (7.8% vs. 1.3% vs. 1.6%, p < 0.001), cardiovascular death (5.1% vs. 1.0% vs. 1.2%, p < 0.0001) and recurrent myocardial infarction (8.3% vs. 5.2% vs. 3.5%, p = 0.002). NACEs were lower with longer DAPT despite a higher risk of BARC 2-5 bleedings (4.6% vs. 5.7% vs. 6.2%, p = 0.04) and a trend towards a higher risk of BARC 3-5 bleedings (2.4% vs. 3.3% vs. 3.9%, p = 0.06). These results were not consistent for female patients and those older than 75 years old, due to an increased risk of bleedings which exceeded the reduction in myocardial infarction. CONCLUSION: In unselected real world acute coronary syndrome patients treated with percutaneous coronary intervention, DAPT with prasugrel or ticagrelor prolonged beyond 12 months markedly reduces fatal and non-fatal ischaemic events, offsetting the increased risk deriving from the higher bleeding risk. On the contrary, patients >75 years old and female ones showed a less favourable risk-benefit ratio for longer DAPT due to excess of bleedings.

P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects.

AIMS: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. METHODS AND RESULTS: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985). CONCLUSION: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Average daily ischemic versus bleeding risk in patients with ACS undergoing PCI: Insights from the BleeMACS and RENAMI registries.

BACKGROUND: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Impact of structural features of very thin stents implanted in unprotected left main or coronary bifurcations on clinical outcomes.

OBJECTIVES: To evaluate the independent clinical impact of stent structural features in a large cohort of patients undergoing unprotected left main (ULM) or coronary bifurcation percutaneous coronary intervention (PCI) with a range of very thin strut stents. BACKGROUND: Clinical impact of structural features of contemporary stents remains to be defined. METHODS: All consecutive patients enrolled in the veRy thin stents for patients with left mAIn or bifurcatioN in real life (RAIN) registry were included. The following stent structural features were studied: antiproliferative drugs (everolimus vs. sirolimus vs. zotarolimus), strut material (platinum-chromium vs. cobalt-chromium), polymer (bioresorbable vs. durable), number of crowns (<8 vs. ≥8) and number of connectors (<3 vs. ≥3). For small diameter stents (≤2.5 mm), struct thickness (74 vs. 80/81 µm) was also tested. Target lesion failure (TLF), a composite of target lesion revascularization and stent thrombosis, was the primary endpoint. Multivariate analysis was performed with Cox regression models. RESULTS: Out of 2,707 patients, 110 (4.1%) experienced a TLF event after 16 months (12-18). After adjustment for confounders, an increased number of connectors (adjusted hazard ratio [adj-HR] 0.62, 95% confidence interval (CI) 0.39-0.99, p = .04) reduced risk of TLF, driven by stents with ≥2.5 mm diameter (HR 0.54, 95% CI 0.32-0.93, p = .02). This independent relationship was lost for stents with diameter <2.5 mm, where only strut thickness appeared to impact. Conversely, no independent relationship of polymer type, number of crowns, and the specific limus-family eluted drug with outcomes was observed. CONCLUSIONS: Among a range of contemporary very thin stent models, an increased number of connectors improved device-related outcomes in this investigated high-risk procedural setting.

Efficacy and Safety of Clopidogrel, Prasugrel and Ticagrelor in ACS Patients Treated with PCI: A Propensity Score Analysis of the RENAMI and BleeMACS Registries.

INTRODUCTION: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. METHODS: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. RESULTS: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events. CONCLUSION: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.