Abstract 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.
Objectives The authors sought to compare the effect on inhibition of platelet aggregation (IPA) of prasugrel therapy versus tirofiban bolus with or without a post-bolus short drug infusion in ...ST-segment elevation myocardial infarction (STEMI) patients. Background The degree and rapidity of IPA after prasugrel alone with or without concomitant glycoprotein IIb/IIIa inhibition in STEMI patients is unknown. Methods A total of 100 STEMI patients randomly received prasugrel 60 mg versus 25 μg/kg tirofiban bolus with or without post-bolus 2-h infusion of tirofiban, with or without concomitant prasugrel. IPA at light transmission aggregometry was performed throughout 24 h. The primary endpoint was IPA stimulated with 20 μmol/l adenosine diphosphate (ADP) at 30 min. Results At 30 min, patients in the prasugrel group showed a significantly lower IPA to 20 μmol/l ADP stimulation as compared with tirofiban-treated patients (36 ± 35 vs. 87 ± 31, p < 0.0001). Similarly, patients taking prasugrel showed a suboptimal degree of platelet inhibition for at least 2 h compared with tirofiban patients. Post-bolus tirofiban infusion was necessary to maintain a high level of IPA beyond 1 h after bolus administration if concomitant clopidogrel was given, whereas the bolus-only tirofiban and concomitant prasugrel led to the higher and more consistent IPA levels after both ADP and thrombin receptor-activating peptide stimuli than either therapy alone. Conclusions Our study shows that prasugrel administration leads to a suboptimal IPA for at least 2 h in STEMI patients. Yet, prasugrel, given in association with a bolus only of glycoprotein IIb/IIIa inhibitor, obviates the need of post-bolus infusion and almost completely abolishes residual variability of IPA after treatment. (Facilitation through Aggrastat By drOpping or shortening Infusion Line in patients with ST-segment elevation myocardial infarction compared to or on top of PRasugrel given at loading dOse The FABOLUS PRO trial; NCT01336348 )
Abstract Background It remains unclear whether radial increases the risk of operator or patient radiation exposure when performed by expert operators Objectives To determine whether radial access ...increases radiation exposure Methods We randomly assigned 8404 patients, with or without ST-segment elevation acute coronary syndrome, to radial or femoral access for coronary angiography and percutaneous intervention, and collected fluoroscopy time and dose area product (DAP). In the radiation sub-study (RAD-MATRIX), we anticipated that 13 or more operators, each wearing a thorax (primary endpoint), wrist and head (secondary endpoints) lithium fluoride thermo luminescent dosimeter and randomizing at least 13 patients per access site were needed to establish non-inferiority of radial versus femoral access. Results Among eighteen operators, performing 777 procedures in 767 patients, the non-inferiority primary endpoint was not achieved (p-value for non-inferiority=0.843). Operator equivalent dose at the thorax was significantly higher with radial than femoral access (77 μSv IQR:40-112 vs. 41 μSv IQR:23-59, p=0.02). After normalization of operator radiation dose by fluoroscopy time or DAP, the difference remained significant. Radiation dose at wrist or head did not differ between radial and femoral access. Thorax operator dose did not differ in the right radial (84 μSv IQR:47-146) compared to the left radial access (52 μSv IQR:33-92; p=0.15) In the overall MATRIX population, fluoroscopy time (10 min; IQR:6-16 vs. 9 min IQR:5-15; p<0.0001 and DAP—available in 7570 procedures and 6902 patients—(65 Gy*cm2 IQR:29-120 vs. 59 Gy*cm2 26-110; p=0.0001) were higher with radial as compared to femoral access. Conclusions Radial, as compared with femoral access is associated with greater operator and patient radiation exposure when performed by expert operators in current practice. Radial operators and institutions should be sensitized towards radiation risks and adopt adjunctive radio-protective measures.
Objectives We assessed the relation between female sex and sirolimus-eluting stent (SES) use on long-term outcomes in acute myocardial infarction. Background There are no data on sex-specific ...differences in long-term benefit of SES use compared with bare-metal stent (BMS) use among patients undergoing primary percutaneous coronary interventions. Methods We performed a post hoc analysis of the MULTISTRATEGY trial. Hazard ratios (HRs) of events with 95% CI for sex and stent type were computed using Cox proportional regression with adjustment for confounders. Results A total of 744 patients, 64 years old (55-73 years old), 179 (24.1%) women, were enrolled. After a follow-up of 1,080 days, SES use was associated with a significant reduction of major adverse cardiovascular events, that is, the composite of all-cause death, reinfarction, or clinically driven target vessel revascularization (TVR) (13.9% vs 23.6%, adjusted HR 0.62, 95% CI 0.41-0.94, P = .026) and of TVR (6.1% vs 15.1%, adjusted HR 0.35, 95% CI 0.19-0.63, P < .001) in men. Conversely, SES use was not associated to a better outcome among women (major adverse cardiovascular events 21.9% in SES vs 18.2% in the BMS group, adjusted HR 1.27, 95% CI 0.53-3.02, P = .59; TVR 6.6% vs 9.1%, adjusted HR 0.62, 95% CI 0.17-2.21, P = .46). Conclusions In this analysis, the clinical benefit of SES use, over BMS, at 3-year follow-up was restricted to men and was not observed among women.
Abstract Objectives The aim of this study was to provide a quantitative appraisal of the effects on clinical outcomes of radial access for coronary interventions in patients with coronary artery ...disease (CAD). Background Randomized trials investigating radial versus femoral access for percutaneous coronary interventions have provided conflicting evidence. No comprehensive quantitative appraisal of the risks and benefits of each approach is available across the whole spectrum of patients with stable or unstable CAD. Methods The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for randomized trials comparing radial versus femoral access for coronary interventions. Data were pooled by meta-analysis using a fixed-effects or a random-effects model, as appropriate. Pre-specified subgroup analyses according to clinical presentation, in terms of stable CAD, non–ST-segment elevation acute coronary syndromes, or ST-segment elevation myocardial infarction were performed. Results Twenty-four studies enrolling 22,843 participants were included. Compared with femoral access, radial access was associated with a significantly lower risk for all-cause mortality (odds ratio OR: 0.71; 95% confidence interval CI: 0.59 to 0.87; p = 0.001, number needed to treat to benefit NNTB = 160), major adverse cardiovascular events (OR: 0.84; 95% CI: 0.75 to 0.94; p = 0.002; NNTB = 99), major bleeding (OR: 0.53; 95% CI: 0.42 to 0.65; p < 0.001; NNTB = 103), and major vascular complications (OR: 0.23; 95% CI: 0.16 to 0.35; p < 0.001; NNTB = 117). The rates of myocardial infarction or stroke were similar in the 2 groups. Effects of radial access were consistent across the whole spectrum of patients with CAD for all appraised endpoints. Conclusions Compared with femoral access, radial access reduces mortality and MACE and improves safety, with reductions in major bleeding and vascular complications across the whole spectrum of patients with CAD.
Abstract Objectives The aim of this study was to investigate the clinical correlates and prognostic impact of coronary artery calcification (CAC) in women undergoing percutaneous coronary ...intervention with drug-eluting stents (DES). Background The clinical correlates and the prognostic significance of CAC in women undergoing percutaneous coronary intervention with DES remain unclear. Methods Patient-level data from female participants in 26 randomized trials of DES were pooled. Study population was categorized according to the presence of moderate or severe versus mild or no target lesion CAC, assessed through coronary angiography. Co–primary endpoints of interest were the composite of death, myocardial infarction (MI), or target lesion revascularization and death, MI, or stent thrombosis at 3-year follow-up. Results Among 11,557 women included in the pooled dataset, CAC status was available in 6,371 women. Of these, 1,622 (25.5%) had moderate or severe CAC. In fully adjusted models, independent correlates of CAC were age, hypertension, hypercholesterolemia, smoking, previous coronary artery bypass graft surgery, and worse left ventricular and renal function. At 3 years, women with CAC were at higher risk for death, MI, or target lesion revascularization (18.2% vs. 13.1%; adjusted hazard ratio: 1.56; 95% confidence interval: 1.33 to 1.84; p < 0.0001) and death, MI, or stent thrombosis (12.7% vs. 8.6%; adjusted hazard ratio: 1.48; 95% confidence interval: 1.21 to 1.80; p = 0.0001). The adverse effect of CAC on ischemic outcomes appeared to be consistent across clinical and angiographic subsets of women, including new-generation DES. Conclusions Women undergoing PCI of calcified lesions tend to have worse clinical profile and remain at increased ischemic risk, irrespective of new-generation DES.
Objectives This study sought to assess whether intracoronary adenosine or nitroprusside following thrombus aspiration (TA) is superior to TA alone for the prevention of microvascular obstruction ...(MVO) in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). Background MVO, due to its multifactorial pathogenesis, still occurs after TA in a sizeable portion of patients. Methods We performed a placebo-controlled, randomized, open-label, blind-examination, multicenter trial. A total of 240 STEMI patients with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0/1 were randomly allocated 1:1:1 to receive adenosine (n = 80), nitroprusside (n = 80), or saline (n = 80) given distal to the occluded site after TA. The primary endpoint was the incidence of ST-segment resolution (STR) >70% on surface electrocardiogram at 90 min after PCI. Secondary endpoints were angiographic MVO incidence (TIMI flow grade ≤2 or 3 with a myocardial blush grade <2) and major adverse cardiac event (MACE) rate at 30 days as a composite of cardiac death, myocardial infarction, target lesion revascularization, and heart failure requiring hospitalization. Results STR >70% occurred in in 71% of adenosine-treated patients, in 54% of nitroprusside-treated patients, and in 51% of saline-treated patients (p = 0.009 and p = 0.75, respectively, vs. saline). Angiographic MVO occurred in 18% of adenosine-treated patients, in 24% of nitroprusside-treated patients, and in 30% of saline-treated patients (p = 0.06 and p = 0.37, respectively, vs. saline). MACE occurred in 10%, 14%, and 20% of patients, respectively (p = 0.08 and p = 0.29 vs. saline). Conclusions In STEMI patients treated by PCI and TA, the additional intracoronary administration of adenosine, but not that of nitroprusside, results in a significant improvement of MVO, as assessed by STR.
Objectives The purpose of the study was to systematically evaluate the significance of platelet reactivity on clopidogrel treatment on adverse cardiovascular events using a collaborative ...meta-analysis using patient-level data for the VerifyNow P2Y12 assay (Accumetrics, San Diego, California). Background Clinical evidence has been controversial regarding the influence of clopidogrel on treatment platelet reactivity and ischemic outcomes. Methods MEDLINE, Scopus, and the Cochrane library databases were searched through January 2010. A database containing individual patient-level time-to-event data was generated from identified studies. The primary outcome of interest was a composite of death, myocardial infarction (MI), or stent thrombosis. Secondary outcomes included the incidence of: 1) death; 2) MI; and 3) stent thrombosis. Results A total of 6 studies with 3,059 patients was included. In each study, clopidogrel responsiveness was assessed using the same point-of-care assay after percutaneous coronary intervention. The primary endpoint occurred more frequently in higher quartiles of P2Y12 reaction unit (PRU) values: quartile I, 5.8%; quartile II, 6.9%; quartile III, 10.9%; quartile IV, 15.8% (p < 0.001). Taking quartile I as referent, the hazard ratios (HRs) for the primary endpoint were as follows: quartile II, HR: 1.13 (95% confidence interval CI: 0.72 to 1.78; p = 0.60); quartile III, HR: 1.82 (95% CI: 1.20 to 2.75; p = 0.005); quartile IV, HR: 2.62 (95% CI: 1.78 to 3.87; p < 0.001). On a continuous scale, every 10-U increase in PRU was associated with a significantly higher rate of the primary endpoint (HR: 1.04; 95% CI: 1.03 to 1.06; p < 0.0001). According to receiver-operating characteristic curve analysis, a PRU value of 230 appeared to best predict death, MI, or stent thrombosis (p < 0.001). A PRU value ≥230 was associated with a higher rate of the composite primary endpoint (HR: 2.10; 95% CI: 1.62 to 2.73; p < 0.0001), as well as the individual endpoints of death (HR: 1.66; 95% CI: 1.04 to 2.68; p = 0.04), MI (HR: 2.04; 95% CI: 1.51 to 2.76; p < 0.001), and stent thrombosis (HR: 3.11; 95% CI: 1.50 to 6.46; p = 0.002). Conclusions In this collaborative meta-analysis, the level of on-treatment platelet reactivity according to the P2Y12 assay is associated with long-term cardiovascular events after percutaneous coronary intervention, including death, MI, and stent thrombosis.
Abstract Objectives The purpose of this study was to investigate the safety and efficacy of new-generation drug-eluting stents (DES) versus early-generation DES in women undergoing complex ...percutaneous coronary intervention (CPCI). Background Whether the benefits of new-generation DES are preserved in women undergoing complex percutaneous revascularization is unknown. Methods We pooled patient-level data from women enrolled in 26 randomized trials of DES. Study population was categorized according to the presence or absence of CPCI, which was defined as the composite of total stent length >30 mm, ≥2 stents implanted, ≥2 lesions treated, or bifurcation lesion as target vessel. The primary endpoint was major adverse cardiovascular events (MACE) defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. Results Of 10,241 women included in the pooled database, 4,629 (45%) underwent CPCI. Compared with non-CPCI, women who underwent CPCI had a higher 3-year risk of MACE (adjusted hazard ratio HR: 1.63; 95% confidence interval CI: 1.45 to 1.83; p < 0.0001). In women who underwent CPCI, use of new-generation DES was associated with significantly lower 3-year risk of MACE (adjusted HR: 0.81; 95% CI: 0.68 to 0.96), target lesion revascularization (adjusted HR: 0.74; 95% CI: 0.57 to 0.95), and definite or probable stent thrombosis (ST) (adjusted HR: 0.50; 95% CI: 0.30 to 0.83). The benefit of new-generation DES on efficacy and safety outcomes was uniform between CPCI and non-CPCI groups, without evidence of interaction. By landmark analysis, new-generation DES were associated with low rates (≤0.4%) of very-late ST irrespective of procedural complexity. Conclusions Women undergoing CPCI remain at higher risk of adverse events. The long-term ischemic benefits of new-generation DES platforms are uniform among complex and non-complex percutaneous revascularization procedures in women.
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