Abstract Background Optimal upfront dual antiplatelet therapy (DAPT) duration after complex percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear. Objectives This ...study investigated the efficacy and safety of long- (≥12 months) versus short-term (3 or 6 months) DAPT with aspirin and clopidogrel according to PCI complexity. Methods We pooled patient-level data from 6 randomized controlled trials investigating DAPT durations after PCI. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. The primary safety endpoint was major bleeding. Intention-to-treat was the primary analytic approach. Results Of 9,577 patients included in the pooled dataset for whom procedural variables were available, 1,680 (17.5%) underwent complex PCI. Overall, 85% of patients received new-generation DES. At a median follow-up time of 392 days (interquartile range: 366 to 710 days), patients who underwent complex PCI had a higher risk of MACE (adjusted hazard ratio HR: 1.98; 95% confidence interval CI: 1.50 to 2.60; p < 0.0001). Compared with short-term DAPT, long-term DAPT yielded significant reductions in MACE in the complex PCI group (adjusted HR: 0.56; 95% CI: 0.35 to 0.89) versus the noncomplex PCI group (adjusted HR: 1.01; 95% CI: 0.75 to 1.35; pinteraction = 0.01). The magnitude of the benefit with long-term DAPT was progressively greater per increase in procedural complexity. Long-term DAPT was associated with increased risk for major bleeding, which was similar between groups (pinteraction = 0.96). Results were consistent by per-treatment landmark analysis. Conclusions Alongside other established clinical risk factors, procedural complexity is an important parameter to take into account in tailoring upfront duration of DAPT.
Abstract 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.
Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study Martine Gilard, Bertrand Arnaud, ...Jean-Christophe Cornily, Grégoire Le Gal, Karine Lacut, Geneviève Le Calvez, Jacques Mansourati, Dominique Mottier, Jean-François Abgrall, Jacques Boschat In a previous observational study, we found the effect of clopidogrel as tested by vasodilator-stimulated phosphoprotein (VASP) phosphorylation to be diminished in patients receiving proton pump inhibitor treatment. In this double-blind placebo-controlled trial, 124 consecutive patients were randomized to receive either associated omeprazole (20 mg/day) or placebo for 7 days. The clopidogrel effect was tested on Day 1 and Day 7 in both groups by measuring platelet phosphorylated VASP. Our main end point was to compare platelet activation in the 2 groups. Omeprazole significantly decreased the antiplatelet effect of clopidogrel as assessed by a VASP phosphorylation test (p < 0.0001).
Dual antiplatelet therapy is commonly used in patients undergoing transcatheter aortic valve implantation (TAVI), but the optimal antiplatelet regimen is uncertain and remains to be determined. The ...objective of this study was to compare 2 strategies of antiplatelet therapy in patients undergoing TAVI. A strategy using monoantiplatelet therapy (group A, n = 164) was prospectively compared with a strategy using dual antiplatelet therapy (group B, n = 128) in 292 consecutive patients undergoing TAVI. The primary end point was a combination of mortality, major stroke, life-threatening bleeding (LTB), myocardial infarction, and major vascular complications at 30 days. All adverse events were adjudicated according to the Valve Academic Research Consortium. The primary end point occurred in 22 patients (13.4%) in the group A and in 30 patients (23.4%) in the group B (hazard ratio 0.51, 95% confidence interval 0.28 to 0.94, p = 0.026). LTB (3.7% vs 12.5%, p = 0.005) and major bleedings (2.4% vs 13.3%, p <0.0001) occurred less frequently in the group A, whereas the incidence of stroke (1.2% vs 4.7%, p = 0.14) and myocardial infarction (1.2% vs 0.8%, p = 1.0) was not significantly different between the 2 groups. The benefit of a strategy using mono versus dual antiplatelet therapy persisted after multivariate adjustment and propensity score analysis (hazard ratio 0.53, 95% confidence interval 0.28 to 0.95, p = 0.033). In conclusion, a strategy using mono versus dual antiplatelet therapy in patients undergoing TAVI reduces LTB and major bleedings without increasing the risk of stroke and myocardial infarction. The results of our study question the justification of dual antiplatelet therapy and require confirmation in a randomized trial.
The “obesity paradox” that patients with high body mass index (BMI) have good prognoses remains controversial. This study aimed to assess the impact of BMI on clinical outcomes in patients who ...underwent transcatheter aortic valve implantation (TAVI). Data from the French national TAVI registry were collected for 3,072 patients who underwent TAVI from January 2010 to October 2011. The patients were categorized into 4 groups according to BMI (kg/m2 ): underweight (<18.5 kg/m2 ), normal weight (18.5 to 25 kg/m2 ), overweight (25 to 30 kg/m2 ), and obese (>30 kg/m2 ). Thereafter, clinical outcomes were compared among the 4 groups. The BMI distribution was 3.1% (n = 95), 44.1% (n = 1,355), 34.2% (n = 1,050), and 18.6% (n = 572). Although the 4 groups greatly differed in baseline clinical background, they had similar procedural success rates (95.8%, 97.1%, 97.3%, and 95.6%, p = 0.23). Major vascular complication was significantly associated with the underweight patients after adjusting for the other potential confounders (odds ratio 2.33, 95% confidence interval 1.17 to 4.46, p = 0.016). The cumulative postoperative survival rates were increasing across the 4 groups at 30 days (83.2%, 88.9%, 91.6%, and 93.0%, p = 0.003) and 1 year (67.9%, 73.6%, 77.4%, and 80.3%, p = 0.006). In a multivariate Cox regression analysis, the overweight and obese patients were independently associated with superior cumulative survival rate at 1 year (hazard ratios 0.74 and 0.71, 95% confidence intervals 0.57 to 0.97 and 0.59 to 0.87, p = 0.050 and 0.029, respectively). In conclusion, major morbidity and 1-year mortality were less in overweight and obese patients than those classified as normal weight even in a TAVI cohort.
Background Although transcatheter aortic valve implantation has been developing as an alternative treatment in elderly patients with high surgical risk, age-specific differences in clinical outcome ...have not been fully validated. Methods Data were analyzed for 2,254 patients at least 80 years old who were enrolled between January 2010 and October 2011 in the French national transcatheter aortic valve implantation registry, FRANCE-2. Procedural and clinical outcomes defined according to the Valve Academic Research Consortium criteria were compared among subjects in three age groups: 80 to 84 years (n = 867), 85 to 89 years (n = 1,064), and at least 90 years (n = 349; range, 90 to 101 years). Results The self-expandable prosthesis was implanted in 710 patients, and the balloon-expandable prosthesis was implanted in 1,544 patients. No differences were observed in rates of procedural success, Valve Academic Research Consortium–defined complications, and length of hospitalization among groups. Cumulative 30-day mortalities did not change among the three groups (80 to 84 years, 10.3% versus 85 to 89 years, 9.5% versus ≥90 years, 11.2%; p = 0.53). Cumulative 1-year mortalities also showed no statistical differences, although the mortality rate was higher in patients 85 to 89 years old and at least 90 years old compared with those 80 to 84 years old (19.8% versus 26.1% versus 27.7%; p = 0.16). After adjustment for differential baseline characteristics and potential confounders, patient age (85 to 89 years and ≥90 years compared with 80 to 84 years) was not associated with increasing risk of 30-day mortality (hazard ratio, 0.92, 1.26; 95% confidence interval, 0.66 to 1.27, 0.83 to 1.94; p = 0.38, 0.28, respectively) and 1-year mortality (hazard ratio, 1.16, 1.36; 95% confidence interval, 0.90 to 1.49, 0.97 to 1.89; p = 0.25, 0.073, respectively). Conclusions This study revealed acceptable clinical results of transcatheter aortic valve implantation even in very elderly populations.
The purposes of the present study were to determine the impact of chronic obstructive pulmonary disease (COPD) on Valve Academic Research Consortium–defined outcomes in patients undergoing ...transcatheter aortic valve implantation (TAVI). A total of 3,933 consecutive patients underwent TAVI from January 2010 to December 2011 in 34 centers and were included in the French national TAVI registry “FRANCE 2”; 895 (22.7%) had concomitant COPD, 3,038 (77.3%) did not. There were no significant differences in procedural characteristics or 30-day Valve Academic Research Consortium–defined outcomes between those with and without COPD. Multivariate regression analysis showed COPD to be an independent predictor of 1-year mortality and combined efficacy end point after adjustment for concomitant co-morbidities (hazard ratio 1.19, 95% confidence interval 1.005 to 1.41, p = 0.03 and hazard ratio 1.52, 95% confidence interval 1.29 to 1.79, p <0.001, respectively). The higher mortality rate at 1 year in patients with COPD was related to cardiovascular deaths (COPD 10.0% vs non-COPD 6.2%, p = 0.008). Subgroup analysis found that the effect of COPD on 1-year mortality rate was constant across different subgroups, especially the type of approach and the type of anesthesia subgroups. In conclusion, concomitant COPD in patients referred for TAVI characterizes a high-risk population. The excess in mortality is largely determined by a higher rate of cardiovascular deaths and exists regardless of the type of procedure performed and its results.
Previous coronary artery bypass grafting (CABG) increases operative risk in conventional valve replacement. Transcatheter aortic valve implantation (TAVI) has been shown to be successful in high-risk ...patient subgroups. The present study compared outcome and overall survival in patients who underwent TAVI with and without history of CABG. From January 2010 to December 2011, 683 of the 3,761 patients selected for TAVI in 34 French centers (18%) had a history of CABG. Outcomes (mortality and complications) were collected prospectively according to the Valve Academic Research Consortium (VARC) criteria. Patients with previous CABG were younger, with higher rates of diabetes and vascular disease and higher logistic European System for Cardiac Operative Risk Evaluation (29.8 ± 16.4 vs 20.1 ± 13.0, p <0.001) but lower rates of pulmonary disease. Two types of valve (Edwards SAPIEN and Medtronic CoreValve) were implanted in equal proportions in the 2 groups. The 30-day and 1-year mortality rates from all causes on Kaplan-Meier analysis (9.2% vs 9.7%, p = 0.71; and 19.0% vs 20.2%, p = 0.49, respectively) did not differ according to the history of CABG. There were no significant differences in the Valve Academic Research Consortium complications (myocardial infarction, stroke or vascular, and bleeding complications). On multivariate analysis, CABG was not associated with greater 1-year post-TAVI mortality. In conclusion, previous CABG did not adversely affect outcome in patients who underwent TAVI, which may be an alternative to surgery in high-risk patients with severe aortic stenosis and history of CABG.
Background Fractional flow reserve (FFR) measured by coronary computed tomography angiography (FFRCT ) has been validated against invasive FFR. However, there are no data on how the use of FFRCT ...affects patient care and outcomes. The aim of this study is to compare standard practice guided by usual care testing to FFRCT -guided management in symptomatic subjects with suspected coronary artery disease (CAD). Methods In this prospective nonrandomized trial, symptomatic patients with suspected CAD will be enrolled in 2 consecutive cohorts: a usual care-guided pathway (cohort 1) and an FFRCT -guided pathway (cohort 2). Each cohort is divided into 2 groups according to whether noninvasive or invasive diagnostic testing was planned before enrollment. In all subjects, the patient's clinical team will review all diagnostic test results and determine a treatment strategy. A total sample size of 580 subjects will be enrolled and followed up for 12 months. Results The primary end point is the comparison of the percentage of patients with planned invasive testing who have a catheterization (invasive coronary angiography) within 90 days from initial assessment, which does not show a significant stenosis (defined as coronary artery stenosis >50% or invasive FFR ≤0.80). Secondary end points include the rate of invasive coronary angiography without obstructive CAD in those with planned noninvasive testing and, in all groups, noninferiority of resource use, quality of life, medical radiation exposure, and major adverse cardiac events up to 365 days of follow-up. Conclusions The study compares clinical and economic outcomes based on diagnostic evaluation using FFRCT with that based on standard diagnostic strategies
Double Antiplatelet Therapy Duration Gilard, Martine, MD, PhD; Morice, Marie Claude, MD
Journal of the American College of Cardiology,
05/2015, Letnik:
65, Številka:
20
Journal Article
Recenzirano
Odprti dostop
Of 11,648 patients randomized in the DAPT trial, 3,576 (30.7%) presented with acute MI; 1,680 of the MI patients (47%) presented with initial ST-segment elevation MI and the remainder with ...non-ST-segment elevation MI. Because this variable was not factored in the randomization, the characteristics of the 2 groups differed: non-MI patients were older; more often female; and showed higher rates of diabetes, peripheral disease, and prior percutaneous coronary intervention. According to the investigators, this increase in noncardiovascular mortality was not exclusively caused by an increase in bleeding-related death.
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