The appropriate duration of dual antiplatelet therapy in patients at high risk for bleeding after the implantation of a drug-eluting coronary stent remains unclear.
One month after they had undergone ...implantation of a biodegradable-polymer sirolimus-eluting coronary stent, we randomly assigned patients at high bleeding risk to discontinue dual antiplatelet therapy immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy). The three ranked primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding; cumulative incidences were assessed at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population.
Among the 4434 patients in the per-protocol population, net adverse clinical events occurred in 165 patients (7.5%) in the abbreviated-therapy group and in 172 (7.7%) in the standard-therapy group (difference, -0.23 percentage points; 95% confidence interval CI, -1.80 to 1.33; P<0.001 for noninferiority). A total of 133 patients (6.1%) in the abbreviated-therapy group and 132 patients (5.9%) in the standard-therapy group had a major adverse cardiac or cerebral event (difference, 0.11 percentage points; 95% CI, -1.29 to 1.51; P = 0.001 for noninferiority). Among the 4579 patients in the intention-to-treat population, major or clinically relevant nonmajor bleeding occurred in 148 patients (6.5%) in the abbreviated-therapy group and in 211 (9.4%) in the standard-therapy group (difference, -2.82 percentage points; 95% CI, -4.40 to -1.24; P<0.001 for superiority).
One month of dual antiplatelet therapy was noninferior to the continuation of therapy for at least 2 additional months with regard to the occurrence of net adverse clinical events and major adverse cardiac or cerebral events; abbreviated therapy also resulted in a lower incidence of major or clinically relevant nonmajor bleeding. (Funded by Terumo; MASTER DAPT ClinicalTrials.gov number, NCT03023020.).
Summary Background Cangrelor is a potent, rapid-acting, reversible intravenous platelet inhibitor that was tested for percutaneous coronary intervention (PCI) in three large, double-blind, randomised ...trials. We did a pooled analysis of data from three trials that assessed the effectiveness of cangrelor against either clopidogrel or placebo in PCI. Methods This prespecified, pooled analysis of patient-level data from three trials (CHAMPION-PCI, CHAMPION-PLATFORM, and CHAMPION-PHOENIX) compared cangrelor with control (clopidogrel or placebo) for prevention of thrombotic complications during and after PCI. Trial participants were patients undergoing PCI for ST-elevation myocardial infarction (11·6%), non-ST-elevation acute coronary syndromes (57·4%), and stable coronary artery disease (31·0%). Efficacy was assessed in the modified intention-to-treat population of 24 910 patients, with a prespecified primary efficacy composite of death, myocardial infarction, ischaemia-driven revascularisation, or stent thrombosis at 48 h. The primary safety outcome was non-coronary artery bypass graft-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe or life-threatening bleeding at 48 h. Findings Cangrelor reduced the odds of the primary outcome by 19% (3·8% for cangrelor vs 4·7% for control; odds ratio OR 0·81, 95% CI 0·71–0·91, p=0·0007), and stent thrombosis by 41% (0·5% vs 0·8%, OR 0·59, 95% CI 0·43–0·80, p=0·0008). Cangrelor reduced the odds of the secondary triple composite (all-cause death, myocardial infarction, or ischaemia-driven revascularisation at 48 h) by 19% (3·6% vs 4·4%, OR 0·81, 95% CI 0·71–0·92, p=0·0014). Efficacy outcomes were consistent across the trials and main patient subsets. These benefits were maintained at 30 days. There was no difference in the primary safety outcome (0·2% in both groups), in GUSTO moderate bleeding (0·6% vs 0·4%), or in transfusion (0·7% vs 0·6%), but cangrelor increased GUSTO mild bleeding (16·8% vs 13·0%, p<0·0001). Interpretation Compared with control (clopidogrel or placebo), cangrelor reduced PCI periprocedural thrombotic complications, at the expense of increased bleeding. Funding The Medicines Company.
Summary Background It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. Methods We did a ...randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov , number NCT01433627. Findings We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio RR 0·85, 95% CI 0·74–0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73–0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49–0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53–0·99; p=0·045). Interpretation In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. Funding The Medicines Company and Terumo.
Background Proton pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel, but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the ...association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy (DAPT) with clopidogrel plus aspirin. Methods and results In the PRODIGY trial, 1,970 patients were randomized to 6- or 24-month DAPT at 30 days from index procedure. Among them, 738 patients (37.5%) received PPI (mainly lansoprazole; 90.1%) at the time of randomization. Proton pump inhibitor users were older, were most likely to be woman, had a lower creatinine clearance, presented more frequently with acute coronary syndrome, and had a higher CRUSADE bleeding score. After adjustment, the primary efficacy end point (composite of all-cause death, myocardial infarction, and cerebrovascular accident) was similar between no PPI and PPI users (9.2% vs 11.5%, adjusted hazard ratio HR 1.051, 95% CI 0.788-1.400, P = .736). Bleeding rates did not differ between the 2 groups (Bleeding Academic Research Consortium type 2, 3, or 5: adjusted HR 0.996, 95% CI 0.672-1.474, P = .980). Net clinical adverse events were also similar in no PPI and PPI patients (12.9% vs 14.9%, adjusted HR 0.99, 95% CI 0.772-1.268, P = .93). Results remained consistent at sensitivity analysis when focusing on the 548 patients who remained on PPI for the whole study duration. Conclusions The current findings suggest that the concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcome.
Objectives This study sought to review cardiac troponin (cTn) trends during non–ST-segment elevation acute coronary syndrome (NSTE ACS) in patients undergoing percutaneous coronary intervention (PCI) ...in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Non–ST-Segment Elevation Acute Coronary Syndromes) and SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors) studies and to study the relationship between post-PCI cTn and mortality. Background The prognostic value of cTn post-PCI is controversial. In patients with NSTE ACS, it is especially difficult to distinguish between cTn elevations due to PCI or index myocardial infarction (MI). Methods Time and cTn (indexed by upper limit of normal ULN) data pairs were plotted for 10,199 patients and independently reviewed by 2 physicians to identify patients in whom post-PCI cTn elevation could be distinguished from that of index MI. Post-PCI cTn peak was identified for each plot, and its relationship with 1-year mortality was evaluated using Cox modeling, correcting for 15 clinical variables from the EARLY ACS 1-year mortality model (including baseline cTn). We used an identical methodology to assess the association between creatine kinase-myocardial band and 1-year mortality. Results Patients with cTn (re-)elevation post-PCI not evaluable were identified and excluded from further analysis (4,198 41% with cTn rising prior to PCI; 229 2% with missing cTn). Among the remainder (n = 5,772 57%), in the multivariable model, peak cTn post-PCI was associated with a 7% increase in mortality (hazard ratio HR for 10× ULN increase: 1.07, 95% confidence interval CI: 1.02 to 1.11; p = 0.0038). Peak post-PCI creatine kinase-myocardial band was significantly associated with 1-year mortality (HR for 1× ULN increase: 1.13, 95% CI: 1.05 to 1.21; p = 0.0013). Conclusions We used a methodology that differentiated post-PCI cTn (re-)elevation from that of presenting MI in more than one-half of patients with NSTE ACS undergoing PCI. This identified a highly significant relationship between post-PCI cTn and 1-year mortality, with implications for both incorporating a cTn post-PCI MI definition and preventing PCI-related myonecrosis.
Cangrelor is an intravenously administered P2Y
receptor antagonist, which has been approved for adult patients undergoing percutaneous coronary intervention and, due to its unique pharmacokinetics, ...it allows effective and controllable peri-procedural platelet inhibition. We report the case of a 6-year-old child with anomalous origin of right coronary artery from aortic left coronary sinus, who underwent elective surgical replacement of stenotic and calcified conduit between the right ventricle and the main pulmonary artery. The surgery was complicated by acute myocardial infarction secondary to coronary extrinsic compression. The patient was successfully treated with urgent percutaneous coronary intervention (simultaneous V-stenting) and cangrelor infusion, subsequently switched to clopidogrel therapy.
It is currently unclear if the location of coronary artery disease affects decision making with regard to dual antiplatelet therapy (DAPT). We investigated if the presence of at least 30% luminal ...narrowing in the left main (LM) and/or proximal left anterior descending (pLAD) coronary arteries on angiography is an outcome modifier with respect to DAPT duration.
In the Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia (PRODIGY) study, 953 (54.3%) patients with and 801 (45.7%) without LM/pLAD lumen narrowing at the qualifying coronary intervention were randomised to six or 24 months of DAPT. Twenty-four month as compared to six-month DAPT reduced the occurrence of definite, probable or possible stent thrombosis by 50% in patients with (2.8% vs. 5.6%; HR 0.45, 95% CI: 0.23-0.89; p=0.02) but not in those without LM/pLAD lumen narrowing, with a highly significant interaction testing (PINT= 0.002). This result remained consistent irrespective of whether stenting was (PINT: 0.01) or was not (PINT: 0.02) performed in the LM/pLAD.
Left main and/or proximal LAD lumen narrowing may be a treatment modifier with respect to the duration of DAPT. Patients fulfilling these angiographic characteristics seem to benefit from a prolonged dual antiplatelet treatment. Trial registration: ClinicalTrials.gov Identifier: NCT00611286
Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing ...percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy-three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow-up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio HR, 0.66 95% CI, 0.51-0.85), first HF hospitalization (adjusted HR, 0.67 95% CI, 0.49-0.90) along with all-cause death and cardiovascular death alone (adjusted HR, 0.74 95% CI, 0.56-0.97 and HR, 0.56 95% CI, 0.38-0.84, respectively). The results were consistent in the propensity-score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 95% CI, 0.39-0.89 for ST-segment elevation myocardial infarction and HR, 0.71 95% CI, 0.50-0.99 for non-ST-elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 95% CI, 0.37-0.72), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 95% CI, 0.37-1.10,
for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST-segment elevation myocardial infarction and non-ST-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895176.
Background and Objectives. Recent guidelines have downgraded the routine use of the intra-aortic balloon pump (IABP) in patients with cardiogenic shock (CS) due to ST-elevation myocardial infarction ...(STEMI). Despite this, its use in clinical practice remains high. The aim of this study was to evaluate the prognostic impact of the IABP in patients with STEMI complicated by CS undergoing primary PCI (pPCI), focusing on patients with anterior MI in whom a major benefit has been previously hypothesized. Materials and Methods. We enrolled 2958 consecutive patients undergoing pPCI for STEMI in our department from 2005 to 2018. Propensity score matching and mortality analysis were performed. Results. CS occurred in 246 patients (8.3%); among these patients, 145 (60%) had anterior AMI. In the propensity-matched analysis, the use of the IABP was associated with a lower 30-day mortality (39.3% vs. 60.9%, p = 0.032) in the subgroup of patients with anterior STEMI. Conversely, in the whole group of CS patients and in the subgroup of patients with non-anterior STEMI, IABP use did not have a significant impact on mortality. Conclusions. The use of the IABP in cases of STEMI complicated by CS was found to improve survival in patients with anterior infarction. Prospective studies are needed before abandoning or markedly limiting the use of the IABP in this clinical setting.
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