ABSTRACT
BACKGROUND: Incomplete revascularization (ICR) after percutaneous coronary intervention (PCI) is associated with mortality and morbidity. AIM: We sought to investigate whether ICR in the left anterior descending artery (LAD) is worse than ICR of the right coronary artery (RCA) or left circumflex artery (LCX); and whether ICR in patients with a chronic total occlusion (CTO) is worse than in those without. METHODS: In the RIVER-PCI trial, 2651 patients with ICR after PCI were randomly assigned to ranolazine or placebo. Angiograms were assessed at an independent core laboratory in 2501 patients (94.3%). The primary endpoint was the composite of ischemia-driven revascularization or hospitalization. RESULTS: A total of 1664 patients (66.5%) had ICR involving the LAD, whereas 837 (33.5%) had ICR limited to the RCA or LCX. At median follow-up of 643 days, the primary endpoint occurred in 26.9% versus 26.5% of patients (adjusted HR [aHR]: 1.03, 95% confidence interval [CI]: 0.88-1.21). A nonrecanalized CTO was present in 854 patients (34.1%) with ICR after PCI. The primary endpoint occurred in 28.6% versus 25.9% of ICR patients with versus without a CTO (aHR: 1.10, 95% CI: 0.94-1.29). However, patients with a CTO had higher rates of ischemia-driven hospitalization without revascularization (aHR: 1.27, 95% CI: 1.04-1.56), heart failure hospitalization (aHR: 2.69, 95% CI: 1.61-4.59) and myocardial infarction (aHR: 1.46, 95% CI: 1.11-1.92) compared with those without. CONCLUSIONS: The 2-year prognosis was similar in post-PCI patients with ICR whether the LAD was versus was not involved. ICR patients with a CTO had more frequent hospitalizations for ischemia and myocardial infarctions compared with those without.
ABSTRACT
BACKGROUND: Monotherapy with a P2Y12 inhibitor after a minimum period of dual antiplatelet therapy is an emerging approach to reduce the risk of bleeding after percutaneous coronary intervention (PCI). METHODS: In a double-blind trial, we examined the effect of ticagrelor alone as compared with ticagrelor plus aspirin with regard to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. After 3 months of treatment with ticagrelor plus aspirin, patients who had not had a major bleeding event or ischemic event continued to take ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. We also evaluated the composite end point of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, using a noninferiority hypothesis with an absolute margin of 1.6 percentage points. RESULTS: We enrolled 9006 patients, and 7119 underwent randomization after 3 months. Between randomization and 1 year, the incidence of the primary end point was 4.0% among patients randomly assigned to receive ticagrelor plus placebo and 7.1% among patients assigned to receive ticagrelor plus aspirin (hazard ratio, 0.56; 95% confidence interval [CI], 0.45 to 0.68; P<0.001). The difference in risk between the groups was similar for BARC type 3 or 5 bleeding (incidence, 1.0% among patients receiving ticagrelor plus placebo and 2.0% among patients receiving ticagrelor plus aspirin; hazard ratio, 0.49; 95% CI, 0.33 to 0.74). The incidence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97 to 0.84; hazard ratio, 0.99; 95% CI, 0.78 to 1.25; P<0.001 for noninferiority). CONCLUSIONS: Among high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy, ticagrelor monotherapy was associated with a lower incidence of clinically relevant bleeding than ticagrelor plus aspirin, with no higher risk of death, myocardial infarction, or stroke. (Funded by AstraZeneca; TWILIGHT ClinicalTrials.gov number, NCT02270242.).
Subject(s)
Aspirin/therapeutic use , Coronary Disease/therapy , Hemorrhage/chemically induced , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors/therapeutic use , Ticagrelor/therapeutic use , Aged , Aspirin/adverse effects , Coronary Disease/drug therapy , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mortality , Myocardial Infarction/epidemiology , Platelet Aggregation Inhibitors/adverse effects , Risk Factors , Stroke/epidemiology , Ticagrelor/adverse effectsABSTRACT
BACKGROUND: Chronic total occlusions (CTO) are common and are associated with lower percutaneous coronary intervention (PCI) success rates, often due to failure of antegrade guidewire crossing. Local, intralesional delivery of collagenase (MZ-004) may facilitate guidewire crossing in CTO. AIMS: To evaluate the effect of MZ-004 in facilitating antegrade wire crossing in CTO angioplasty. METHODS: A total of 76 patients undergoing CTO PCI were enrolled at 13 international sites: 38 in the randomized training stage (collagenase [MZ-004] 900 or 1200 µg) and 38 in the placebo-controlled stage (MZ-004 900 or 1200 µg or placebo). Patients received the MZ-004 or identical volume saline (placebo group) in a double-blind design, injected via microcatheter directly into the proximal cap of the CTO. The following day patients underwent CTO PCI using antegrade wire techniques only. RESULTS: Patients were generally similar except for a trend for higher Japanese chronic total occlusion (J-CTO) score in the MZ-004 group (MZ-004 J-CTO score 1.9 vs. 1.4, p = 0.07). There was a numerical increase in the rates of guidewire crossing in the MZ-004 groups compared to placebo (74% vs. 63%, p = 0.52). Guidewire crossing with a soft-tip guidewire (≤1.5 g tip load) was significantly higher in the MZ-004 groups (0% in placebo, 17% in 900 µg, and 29% in 1200 µg MZ-004 group, p = 0.03). Rates of the major adverse cardiovascular event were similar between groups. CONCLUSION: Local delivery of MZ-004 into coronary CTOs appears safe and may facilitate CTO crossing, particularly with softer tipped guidewires. These data support the development of a pivotal trial to further evaluate this agent.
Subject(s)
Coronary Occlusion , Percutaneous Coronary Intervention , Chronic Disease , Collagenases , Coronary Angiography/methods , Coronary Occlusion/surgery , Coronary Occlusion/therapy , Coronary Vessels , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Treatment OutcomeABSTRACT
AIMS: Patients at high bleeding risk (HBR) represent a prevalent subgroup among those undergoing percutaneous coronary intervention (PCI). Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy. The aim of this study was to assess the effects of ticagrelor monotherapy after 3-month DAPT in a contemporary HBR population. METHODS AND RESULTS: This prespecified analysis of the TWILIGHT trial evaluated the treatment effects of early aspirin withdrawal followed by ticagrelor monotherapy in HBR patients undergoing PCI with drug-eluting stents. After 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. A total of 1064 (17.2%) met the Academic Research Consortium definition for HBR. Ticagrelor monotherapy reduced the incidence of the primary endpoint of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding compared with ticagrelor plus aspirin in HBR (6.3% vs. 11.4%; hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.35-0.82) and non-HBR patients (3.5% vs. 5.9%; HR 0.59, 95% CI 0.46-0.77) with similar relative (Pinteraction = 0.67) but a trend towards greater absolute risk reduction in the former [-5.1% vs. -2.3%; difference in absolute risk differences (ARDs) -2.8%, 95% CI -6.4% to 0.8%, P = 0.130]. A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in HBR patients (-3.5% vs. -0.5%; difference in ARDs -3.0%, 95% CI -5.2% to -0.8%, P = 0.008). There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status. CONCLUSIONS: Among HBR patients undergoing PCI who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin. The absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.
Subject(s)
Percutaneous Coronary Intervention , Drug Therapy, Combination , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Percutaneous Coronary Intervention/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Ticagrelor/adverse effects , Treatment OutcomeABSTRACT
AIMS: The aim of this study was to assess the impact of chronic kidney disease (CKD) on the safety and efficacy of ticagrelor monotherapy among patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In this prespecified subanalysis of the TWILIGHT trial, we evaluated the treatment effects of ticagrelor with or without aspirin according to renal function. The trial enrolled patients undergoing drug-eluting stent implantation who fulfilled at least one clinical and one angiographic high-risk criterion. Chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, was a clinical study entry criterion. Following a 3-month period of ticagrelor plus aspirin, event-free patients were randomly assigned to aspirin or placebo on top of ticagrelor for an additional 12 months. Of the 6835 patients randomized and with available eGFR at baseline, 1111 (16.3%) had CKD. Ticagrelor plus placebo reduced the primary endpoint of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding as compared with ticagrelor plus aspirin in both patients with [4.6% vs. 9.0%; hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.80] and without (4.0% vs. 6.7%; HR 0.59, 95% CI 0.47-0.75; Pinteraction = 0.508) CKD, but the absolute risk reduction was greater in the former group. Rates of death, myocardial infarction, or stroke were not significantly different between the two randomized groups irrespective of the presence (7.9% vs. 5.7%; HR 1.40, 95% CI 0.88-2.22) or absence of (3.2% vs. 3.6%; HR 0.90, 95% CI 0.68-1.20; Pinteraction = 0.111) CKD. CONCLUSION: Among CKD patients undergoing PCI, ticagrelor monotherapy reduced the risk of bleeding without a significant increase in ischaemic events as compared with ticagrelor plus aspirin.
Subject(s)
Drug-Eluting Stents , Percutaneous Coronary Intervention , Renal Insufficiency, Chronic , Drug Therapy, Combination , Humans , Platelet Aggregation Inhibitors/therapeutic use , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Ticagrelor/therapeutic use , Treatment OutcomeABSTRACT
AIMS: The aim of this study was to determine the effect of ticagrelor monotherapy on clinically relevant bleeding and major ischaemic events in relation to clinical presentation with and without non-ST elevation acute coronary syndromes (NSTE-ACS) among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS AND RESULTS: We conducted a pre-specified subgroup analysis of The Ticagrelor With Aspirin or Alone in High Risk Patients After Coronary Intervention (TWILIGHT) trial, which enrolled 9006 patients with high-risk features undergoing PCI with DES. After 3 months of dual antiplatelet therapy (DAPT) with ticagrelor plus aspirin, 7119 adherent and event-free patients were randomized in a double-blind manner to ticagrelor plus placebo versus ticagrelor plus aspirin for 12 months. The primary outcome was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding while the composite of all-cause death, myocardial infarction (MI), or stroke was the key secondary outcome. Among patients with NSTE-ACS (n = 4614), ticagrelor monotherapy reduced BARC 2, 3, or 5 bleeding by 53% [3.6% vs. 7.6%; hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.36-0.61; P < 0.001) and in stable patients (n = 2503) by 24% (4.8% vs. 6.2%; HR 0.76; 95% CI 0.54-1.06; P = 0.11; nominal Pint = 0.03). Rates of all-cause death, MI, or stroke among those with (4.3% vs. 4.4%; HR 0.97; 95% CI 0.74-1.28; P = 0.84) and without (3.1% vs. 3.2%; HR 0.96; 95% CI 0.61-1.49; P = 0.85) NSTE-ACS were similar between treatment arms irrespective of clinical presentation (Pint = 0.96). CONCLUSION: Among patients with or without NSTE-ACS who have completed an initial 3-month course of DAPT following PCI with DES, ticagrelor monotherapy reduced clinically meaningful bleeding events without increasing ischaemic risk as compared with ticagrelor plus aspirin. The benefits of ticagrelor monotherapy with respect to bleeding events were more pronounced in patients with NSTE-ACS. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02270242.
Subject(s)
Acute Coronary Syndrome , Percutaneous Coronary Intervention , Acute Coronary Syndrome/drug therapy , Aspirin/therapeutic use , Drug Therapy, Combination , Humans , Platelet Aggregation Inhibitors/therapeutic use , Ticagrelor/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVES: We sought to compare clinical outcomes after percutaneous coronary intervention (PCI) in patients on versus not on hemodialysis (HD) and examine whether high on-treatment platelet reactivity (HPR) further impacts outcomes among patients on HD. BACKGROUND: Both chronic kidney disease (CKD) and HPR are predictors of major adverse cardiac events (MACE) after PCI. METHODS: Two-year outcomes of patients from the prospective, multicenter ADAPT-DES study (N = 8,582) were analyzed according to HD status at enrollment. All patients underwent platelet function testing with the VerifyNow assay; HPR on clopidogrel was defined as P2Y12 reaction units (PRU) >208. RESULTS: Compared with non-HD patients, patients on HD (n = 85) had significantly higher baseline PRU (median 254 vs. 188, p = .001) and more frequently had HPR (61.7% vs. 42.5%, p < .001). HD was associated with increased 2-year rates of MACE (death, myocardial infarction (MI) or definite stent thrombosis (ST); 23.4% vs. 10.7%, p < .001). HD was also strongly associated with 2-year overall mortality, cardiac death, MI, target vessel revascularization, major bleeding, stroke and ST. Following adjustment for HPR and other covariates, HD was independently associated with overall mortality, MI, ST, and major bleeding at 2 years. The relationship between HD status and 2-year MACE was consistent in patients with and without HPR (Pinteraction = .78). CONCLUSIONS: Nearly two-thirds of patients on HD exhibited HPR on clopidogrel, and both HD and HPR were independently associated with 2-year adverse outcomes after DES implantation. However, the deleterious impact of HD on clinical outcomes was present in both patients with and without HPR.
Subject(s)
Aspirin/therapeutic use , Clopidogrel/therapeutic use , Coronary Artery Disease/therapy , Dual Anti-Platelet Therapy , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors/therapeutic use , Renal Dialysis , Renal Insufficiency, Chronic/therapy , Aged , Aspirin/adverse effects , Clopidogrel/adverse effects , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Coronary Thrombosis/mortality , Coronary Thrombosis/prevention & control , Drug-Eluting Stents , Dual Anti-Platelet Therapy/adverse effects , Dual Anti-Platelet Therapy/mortality , Female , Germany , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/mortality , Platelet Aggregation Inhibitors/adverse effects , Platelet Function Tests , Prospective Studies , Registries , Renal Dialysis/adverse effects , Renal Dialysis/mortality , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/mortality , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) typically requires a greater number of stents and longer stent length than non-CTO PCI, placing these patients at greater risk for adverse ischemic events. We sought to determine whether the association between high platelet reactivity (HPR) and the risk of ischemic events is stronger after CTO than non-CTO PCI. METHODS: Patients undergoing successful PCI in the multicenter ADAPT-DES study were stratified according to whether they underwent PCI of a CTO. HPR was defined as VerifyNow platelet reaction units >208. The study primary endpoint was the 2-year risk target vessel failure ([TVF] defined as cardiac death, myocardial infarction, or target lesion revascularization). RESULTS: CTO PCI was performed in 400 of 8448 patients. HPR was present in 34.5% of CTO PCI patients and 43.1% of non-CTO PCI patients (P = .0007). Patients undergoing CTO PCI with versus without HPR had significantly higher 2-year rates of TVF (15.0% versus 8.3%, P = .04) without significant differences in bleeding. HPR was an independent predictor of 2-year TVF (adjusted HR 1.16, 95% CI 1.02-1.34, P = .03) whereas CTO PCI was not (adjusted HR 0.89, 95% CI 0.65-1.22, P = .48). There was a significant interaction between CTO versus non-CTO PCI and PRU as a continuous variable for 2-year TVF (Pinteraction = 0.02). CONCLUSIONS: In ADAPT-DES, HPR was associated with an increased 2-year risk of TVF after PCI, an association that was at least as strong after CTO PCI compared with non-CTO PCI.
Subject(s)
Blood Platelets/physiology , Coronary Occlusion/blood , Coronary Occlusion/surgery , Drug-Eluting Stents/adverse effects , Myocardial Ischemia/etiology , Percutaneous Coronary Intervention/adverse effects , Aged , Aspirin/therapeutic use , Female , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Postoperative Complications , Prospective Studies , Prosthesis DesignABSTRACT
AIMS: Lead perforation is a rare, well-known complication of cardiac implantable electronic device (CIED) implants, whose management is mostly not evidence-based. Main management strategies include conservative approach based on clinical and lead function follow-up vs. routine invasive lead revision approach. This study compared the complications of both strategies by composite endpoint, including recurrent perforation-related symptoms, recurrent pericardial effusion (PEf), lead dysfunction, and device infection during 12 month follow-up. METHODS AND RESULTS: Multicentre retrospective analysis, inquiring data from imaging studies, device interrogation, pericardiocentesis, and clinical charts of patients with suspected perforating leads between 2007 and 2014 in five hospitals. All cases were reviewed by electrophysiologist and defined as definite perforations by suggestive symptoms along with lead perforation on imaging, bloody PEf on pericardiocentesis shortly after implant, or right ventricular (RV) lead non-capture along with diaphragmatic stimulation upon bipolar pacing. Clinical outcomes associated with both management approaches were compared, with respect to the composite endpoint. The study included 48 definitive perforation cases: 22 managed conservatively and 26 via lead revision. Conservative management was associated with an increased composite endpoint compared with lead revision (8/22 vs. 1/26; P = 0.007). The dominant complication among the conservative cohort was appearance of cardiac tamponade during follow-up; 5/6 occurring in cases which presented with no or only mild PEf and were treated by antiplatelets/coagulants during or shortly after CIED implantation. CONCLUSION: A conservative management of CIED lead perforation is associated with increased complications compared with early lead revision. Lead revision may be the preferred management particularly in patients receiving antiplatelets/coagulants.
Subject(s)
Cardiac Resynchronization Therapy Devices/adverse effects , Heart Injuries/etiology , Heart Injuries/therapy , Aged , Cardiac Tamponade/etiology , Cardiac Tamponade/therapy , Device Removal , Female , Humans , Male , Pericardial Effusion/etiology , Pericardial Effusion/therapy , Pericardiocentesis , Prosthesis-Related Infections/etiology , Prosthesis-Related Infections/therapy , Retreatment , Retrospective StudiesABSTRACT
BACKGROUND: There is a paucity of data from large contemporary cohorts of patients with in-stent restenosis (ISR) treated with drug-eluting stents (DESs), and no studies have examined the impact of high platelet reactivity (HPR) on the occurrence of ischemic events after ISR percutaneous coronary intervention (PCI) with DESs. We sought to report outcomes after PCI of ISR lesions and its association with HPR. METHODS: Patients in the prospective, multicenter ADAPT-DES study were stratified according to whether they had ISR versus non-ISR PCI. Two-year outcomes were compared between the groups using Cox proportional hazards models. HPR was defined as on-clopidogrel P2Y12 platelet reaction units >208 as measured by the VerifyNow assay; target vessel failure (TVF) was defined as the composite of all-cause death, myocardial infarction, or ischemia-driven target vessel revascularization. RESULTS: Among the 8,582 patients included in the ADAPT-DES study, 840 (9.8%) patients underwent successful ISR PCI. ISR PCI was independently associated with a higher 2-year risk of TVF (adjusted hazard ratio [HR] 1.95; 95% CI 1.68-2.27; P<.001) and stent thrombosis (adjusted HR 1.95; 95% CI 1.08-3.51; P=.027) but not bleeding (adjusted HR 0.94; 95% CI 0.73-1.21; P=.64). There was no statistical interaction between HPR and ISR versus non-ISR PCI in regard to TVF (adjusted Pinteraction=.81). CONCLUSIONS: ISR PCI is associated with a considerably higher risk of 2-year adverse ischemic events, with HPR conferring similar risk in ISR and non-ISR PCI. More effective therapeutic strategies for managing ISR lesions are necessary.
Subject(s)
Aspirin , Clopidogrel , Coronary Restenosis , Drug-Eluting Stents/adverse effects , Myocardial Infarction , Percutaneous Coronary Intervention/adverse effects , Platelet Activation/drug effects , Aged , Aspirin/administration & dosage , Aspirin/adverse effects , Clopidogrel/administration & dosage , Clopidogrel/adverse effects , Coronary Restenosis/diagnosis , Coronary Restenosis/etiology , Coronary Restenosis/mortality , Coronary Restenosis/surgery , Female , Humans , Male , Middle Aged , Mortality , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiology , Myocardial Infarction/etiology , Myocardial Infarction/surgery , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Platelet Function Tests/methods , Registries/statistics & numerical data , Reoperation/statistics & numerical data , Risk Assessment/methods , Risk FactorsABSTRACT
BACKGROUND: Whether high on-aspirin platelet reactivity (HAPR) confers an increased risk of adverse outcomes after percutaneous coronary intervention (PCI) remains unclear. We sought to examine the specific relationship between HAPR and clinical outcomes in ADAPT-DES. METHODS: A total of 8,526 "all-comer" patients in the ADAPT-DES registry who underwent placement of drug-eluting stents (DES) and were treated with aspirin and clopidogrel were assessed to measure platelet reactivity. HAPR was characterized as ≥550 aspirin reaction units and high on-clopidogrel platelet reactivity as >208 P2Y12 reaction units. Univariable and propensity-adjusted multivariable analyses were used to assess the relationship between HAPR and clinical outcomes. RESULTS: HAPR was present in 478 (5.6%) patients. Patients with HAPR were older and had more comorbid illnesses and more complex coronary anatomy. During 2-year follow-up, HAPR was not associated with increased rates of major adverse cardiac events (MACE), stent thrombosis, myocardial infarction, or all-cause mortality. In propensity-adjusted multivariable analyses, HAPR was not an independent predictor of MACE after successful PCI (multivariable adjusted hazard ratio: 1.04; 95% CI 0.64-1.69, P = .87). Nor was HAPR associated with reduced bleeding. Even among patients with concomitant high on-clopidogrel platelet reactivity, HAPR was not associated with worse ischemic outcomes (adjusted hazard ratio for 2-year MACE: 1.06; 95% CI 0.55-2.00, P = .87). CONCLUSIONS: HAPR was infrequently present in a large registry of patients undergoing PCI. There was no clear relationship between HAPR and 2-year clinical outcomes. Investigations of antiplatelet regimens without aspirin after DES implantation are ongoing and should inform future management of patients undergoing PCI.
Subject(s)
Clopidogrel/administration & dosage , Coronary Artery Disease/surgery , Drug-Eluting Stents , Percutaneous Coronary Intervention/methods , Platelet Activation/drug effects , Registries , Aged , Coronary Artery Disease/drug therapy , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Injections, Intravenous , Male , Middle Aged , Platelet Aggregation Inhibitors/administration & dosage , Prospective Studies , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Intravascular imaging with intravascular ultrasound (IVUS) and optical coherence tomography (OCT) is an important adjunct to invasive coronary angiography. OBJECTIVES: The primary objective was to examine the frequency of intravascular coronary imaging, trends in imaging use, and outcomes of patients undergoing angiography and/or percutaneous coronary intervention (PCI) in the United States. METHODS: Adult patients ≥18 years of age undergoing in-hospital cardiac catheterization from January 2004 to December 2014 were identified from the National Inpatient Sample (NIS). International Classification of Diseases, Ninth Revision (ICD-9) diagnosis and procedure codes were used to identify IVUS and OCT use during diagnostic angiography and PCI. RESULTS: Among 3,211,872 hospitalizations with coronary angiography, intracoronary imaging was performed in 88,775 cases (4.8% of PCI and 1.0% of diagnostic procedures), with IVUS in 98.9% and OCT in 1.1% of cases. Among patients undergoing PCI, the rate of intravascular coronary imaging increased from 2.1% in 2004-2005 to 6.6% in 2013-2014 (P < 0.001 for trend). Use of intravascular coronary imaging was associated with lower in-hospital mortality in patients undergoing PCI (adjusted OR 0.77; 95% CI 0.71-0.83). There was marked variability in intravascular imaging by hospital, with 63% and 13% of facilities using intravascular imaging in <5% and >15% of PCIs, respectively. CONCLUSIONS: In a large administrative database from the United States, intravascular imaging use was low, increased over time, and imaging was associated with reduced in-hospital mortality. Substantial variation in the frequency of intravascular imaging by hospital was observed. Additional investigation to determine clinical benefits of IVUS and OCT are warranted.
Subject(s)
Coronary Angiography/trends , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Percutaneous Coronary Intervention/trends , Practice Patterns, Physicians'/trends , Tomography, Optical Coherence/trends , Ultrasonography, Interventional/trends , Coronary Artery Disease/mortality , Databases, Factual , Hospital Mortality/trends , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Predictive Value of Tests , Time Factors , Treatment Outcome , United StatesABSTRACT
BACKGROUND: Angina often persists or returns in populations following percutaneous coronary intervention (PCI). We hypothesized that ranolazine would be effective in reducing angina and improving quality of life (QOL) in incomplete revascularization (ICR) post-PCI patients. METHODS AND RESULTS: In RIVER-PCI, 2604 patients with a history of chronic angina who had ICR post-PCI were randomized 1:1 to oral ranolazine versus placebo; QOL analyses included 2389 randomized subjects. Angina and QOL questionnaires were collected at baseline and months 1, 6, and 12. Ranolazine patients were more likely than placebo to discontinue study drug by month 6 (20.4% versus 14.1%, P<0.001) and 12 (27.2% versus 21.3%, P<0.001). Following qualifying index PCI, the primary QOL outcome (Seattle Angina Questionnaire [SAQ] angina frequency score) improved markedly, but similarly, in the ranolazine and placebo groups, respectively, from baseline (67.3±24.5 versus 69.7±24.0, P=0.01) to month 1 (86.6±18.1 versus 85.8±18.5, P=0.27) and month 12 (88.4±17.8 versus 88.5±17.8, P=0.94). SAQ angina frequency repeated measures did not differ in adjusted analysis between groups post baseline (mean difference 1.0; 95% CI -0.2, 2.2; P=0.11). Improvement in SAQ angina frequency was observed with ranolazine at month 6 among diabetics (mean difference 3.3; 95% CI 0.6, 6.1; P=0.02) and those with more angina (baseline SAQ angina frequency ≤60; mean difference 3.4; 95% CI 0.6, 6.2; P=0.02), but was not maintained at month 12. CONCLUSIONS: Despite ICR following PCI, there was no incremental benefit in angina or QOL measures by adding ranolazine in this angiographically-identified population. These measures markedly improved within 1 month of PCI and persisted up to 1 year in both treatment arms. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442038.
Subject(s)
Angina Pectoris/diagnostic imaging , Angina Pectoris/drug therapy , Cardiovascular Agents/therapeutic use , Percutaneous Coronary Intervention/trends , Quality of Life , Ranolazine/therapeutic use , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Middle Aged , Myocardial Revascularization/methods , Myocardial Revascularization/trends , Percutaneous Coronary Intervention/methods , Radiography , Treatment OutcomeABSTRACT
BACKGROUND: Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events. We aimed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention. METHODS: We performed this multicentre, randomised, parallel-group, double-blind, placebo-controlled, event-driven trial at 245 centres in 15 countries in Europe, Israel, Russia, and the USA. Patients (aged ≥18 years) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention (defined as one or more lesions with ≥50% diameter stenosis in a coronary artery ≥2 mm diameter) were randomly assigned (1:1), via an interactive web-based block randomisation system (block sizes of ten), to receive either twice-daily oral ranolazine 1000 mg or matching placebo. Randomisation was stratified by diabetes history (presence vs absence) and acute coronary syndrome presentation (acute coronary syndrome vs non-acute coronary syndrome). Study investigators, including all research teams, and patients were masked to treatment allocation. The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT01442038. FINDINGS: Between Nov 3, 2011, and May 27, 2013, we randomly assigned 2651 patients to receive ranolazine (n=1332) or placebo (n=1319); 2604 (98%) patients comprised the full analysis set. After a median follow-up of 643 days (IQR 575-758), the composite primary endpoint occurred in 345 (26%) patients assigned to ranolazine and 364 (28%) patients assigned to placebo (hazard ratio 0·95, 95% CI 0·82-1·10; p=0·48). Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups. 189 (14%) patients in the ranolazine group and 137 (11%) patients in the placebo group discontinued study drug because of an adverse event (p=0·04). INTERPRETATION: Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention. Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population. FUNDING: Gilead Sciences, Menarini.
Subject(s)
Angina Pectoris/therapy , Percutaneous Coronary Intervention , Ranolazine/therapeutic use , Sodium Channel Blockers/therapeutic use , Aged , Coronary Artery Disease/therapy , Coronary Stenosis/therapy , Double-Blind Method , Female , Hospitalization/statistics & numerical data , Humans , Ischemic Attack, Transient/epidemiology , Male , Myocardial Infarction/epidemiology , Myocardial Ischemia/epidemiology , Myocardial Ischemia/therapy , Myocardial Revascularization/statistics & numerical data , Stroke/epidemiologyABSTRACT
OBJECTIVES: We sought to identify angiographic predictors of 2-year stent thrombosis (ST) in the ADAPT-DES study. BACKGROUND: A strong relationship between platelet reactivity and ST after implantation of drug-eluting stents (DES) was recently confirmed in the prospective, multicenter ADAPT-DES study. METHODS: In a pre-specified analysis of patients enrolled in ADAPT-DES, an independent angiographic core laboratory performed detailed angiographic analyses for all cases of ST. Patients with Academic Research Consortium definite/probable target-lesion ST were matched with controls in a 1:2 ratio, and multivariable Cox regression models identified angiographic predictors of 2-year ST. RESULTS: Among 8,582 patients who had successful percutaneous coronary intervention (PCI) and were included in the ADAPT-DES study, 92 (1.1%) patients had ST at 2-year follow-up. Target lesion-related ST was identified in 77 patients (82 lesions) who were clinically matched with 153 patients (196 lesions) without ST. Patients with ST were more likely to have longer target lesions, thrombus, moderate/severe calcification, American College of Cardiology/American Heart Association (ACC/AHA) type C lesions, and saphenous vein grafts. After adjustment for clinical covariates the angiographic variables that predicted ST were lesion complexity (ACC/AHA type C lesion, adjusted HR: 1.97, 95% CI: 1.19 to 3.26, P = 0.01) and presence of thrombus on index PCI (HR: 2.25, 95% CI: 1.40 to 3.59, P < 0.01). CONCLUSIONS: Anatomically complex lesions and the presence of thrombus are strong predictors of 2-year ST in the DES era. © 2016 Wiley Periodicals, Inc.
Subject(s)
Coronary Angiography , Coronary Artery Disease/therapy , Coronary Thrombosis/etiology , Drug-Eluting Stents , Percutaneous Coronary Intervention/instrumentation , Aged , Case-Control Studies , Coronary Artery Disease/blood , Coronary Artery Disease/diagnostic imaging , Coronary Thrombosis/blood , Coronary Thrombosis/diagnostic imaging , Drug Therapy, Combination , Female , Germany , Humans , Male , Middle Aged , Multivariate Analysis , Percutaneous Coronary Intervention/adverse effects , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Function Tests , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies , Registries , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United StatesABSTRACT
BACKGROUND: Prior small to modest-sized studies suggest a benefit of intravascular ultrasound (IVUS) guidance in noncomplex lesions. Whether IVUS guidance is associated with improved clinical outcomes after drug-eluting stent (DES) implantation in an unrestricted patient population is unknown. METHODS AND RESULTS: Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a prospective, multicenter, nonrandomized "all-comers" study of 8583 consecutive patients at 11 international centers designed to determine the frequency, timing, and correlates of stent thrombosis and adverse clinical events after DES. Propensity-adjusted multivariable analysis was performed to examine the relationship between IVUS guidance and 1-year outcomes. IVUS was utilized in 3349 patients (39%), and larger-diameter devices, longer stents, and/or higher inflation pressures were used in 74% of IVUS-guided cases. IVUS guidance compared with angiography guidance was associated with reduced 1-year rates of definite/probable stent thrombosis (0.6% [18 events] versus 1.0% [53 events]; adjusted hazard radio, 0.40; 95% confidence interval, 0.21-0.73; P=0.003), myocardial infarction (2.5% versus 3.7%; adjusted hazard radio, 0.66; 95% confidence interval, 0.49-0.88; P=0.004), and composite adjudicated major adverse cardiac events (ie, cardiac death, myocardial infarction, or stent thrombosis) (3.1% versus 4.7%; adjusted hazard radio, 0.70; 95% confidence interval, 0.55-0.88; P=0.002). The benefits of IVUS were especially evident in patients with acute coronary syndromes and complex lesions, although significant reductions in major adverse cardiac events were present in all patient subgroups those with including stable angina and single-vessel disease. CONCLUSIONS: In ADAPT-DES, the largest study of IVUS use to date, IVUS guidance was associated with a reduction in stent thrombosis, myocardial infarction, and major adverse cardiac events within 1 year after DES implantation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.
Subject(s)
Coronary Angiography , Coronary Artery Disease/therapy , Drug-Eluting Stents , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/therapeutic use , Ultrasonography, Interventional , Aged , Coronary Artery Disease/diagnostic imaging , Coronary Vessels/diagnostic imaging , Female , Humans , Incidence , Male , Middle Aged , Multivariate Analysis , Myocardial Infarction/epidemiology , Prospective Studies , Risk Factors , Thrombosis/epidemiology , Treatment OutcomeABSTRACT
OBJECTIVES: To evaluate the impact of robotic-assisted percutaneous coronary intervention (RA-PCI) versus manual PCI (M-PCI) on the incidence of Longitudinal Geographic Miss (LGM). BACKGROUND: The safety and feasibility of RA-PCI has been established in preclinical animal trials and human clinical trials. Patients with LGM have been shown to have worse clinical outcomes including significantly increased incidences of MACE. METHODS: Patients with significant coronary artery disease underwent RA-PCI in the PRECISE study (n=164) and standard M-PCI in the STLLR trial (n = 1,509). Longitudinal geographic miss was defined as cases where the entire length of the injured or stenotic segment was not fully covered by the total length of the stent. The incidence of LGM was compared between RA-PCI and M-PCI cohorts. RESULTS: The RA-PCI cohort had a significantly greater prevalence of previous MI, previous coronary revascularization, and unstable angina. The robotic cohort exhibited a lower incidence of LGM when compared to the M-PCI patients, 12.2% to 43.1%, respectively (P < 0.0001). To account for the differences in baseline characteristics between the two studies, a propensity score analysis was conducted. The propensity modeling showed similar rates of LGM in both a larger group of patients that met key PRECISE study inclusion/exclusion criteria adjusted for propensity score (9.3% vs 55.0%; P < 0.0001) and in a smaller, matched on propensity score, subset of patients (10.3% vs 64.1%; P < 0.0001). CONCLUSION: Robotic-assisted PCI had significantly lower incidence of LGM compared to standard M-PCI. Reducing LGM potentially improves long-term clinical outcomes through reduction in MACE.
Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , Prosthesis Failure/etiology , Robotic Surgical Procedures , Stents/adverse effects , Aged , Comparative Effectiveness Research , Coronary Angiography/methods , Coronary Angiography/statistics & numerical data , Coronary Artery Disease/diagnosis , Coronary Artery Disease/surgery , Female , Humans , Incidence , Israel , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/methods , Propensity Score , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Robotics , Treatment Outcome , United StatesABSTRACT
AIM: We sought to examine the short- and long-term outcomes of patients who developed contrast-induced acute kidney injury (CI-AKI; defined as an increase in serum creatinine of ≥0.5 mg/dL or a 25% relative rise within 48 h after contrast exposure) from the large-scale HORIZONS-AMI trial. METHODS AND RESULTS: Multivariable analyses were used to identify predictors of CI-AKI, as well predictors of the primary and secondary endpoints. The incidence of CI-AKI in this cohort of ST-segment elevation myocardial infarction (STEMI) patients was 16.1% (479/2968). Predictors of CI-AKI were contrast volume, white blood cell count, left anterior descending infarct-related artery, age, anaemia, creatinine clearance <60 mL/min, and history of congestive heart failure. Patients with CI-AKI had higher rates of net adverse clinical events [NACE; a combination of major bleeding or composite major adverse cardiac events (MACE; consisting of death, reinfarction, target vessel revascularization for ischaemia, or stroke)] at 30 days (22.0 vs. 9.3%; P < 0.0001) and 3 years (40.3 vs. 24.6%; P < 0.0001). They also had higher rates of mortality at 30 days (8.0 vs. 0.9%; P < 0.0001) and 3 years (16.2 vs. 4.5%; P < 0.0001). Multivariable analysis confirmed CI-AKI as an independent predictor of NACE [hazard ratio ([HR), 1.53; 95% confidence interval (CI), 1.23-1.90; P = 0.0001], MACE (HR, 1.56; 95% CI, 1.23-1.98; P = 0.0002), non-coronary artery bypass grafting major bleeding (HR, 2.07; 95% CI, 1.57-2.73; P < 0.0001), and mortality (HR, 1.80; 95% CI, 1.19-2.73; P = 0.005) at 3-year follow-up. CONCLUSION: Contrast-induced acute kidney injury is associated with poor short- and long-term outcomes after primary percutaneous coronary intervention in STEMI.
Subject(s)
Acute Kidney Injury/chemically induced , Contrast Media/adverse effects , Myocardial Infarction/therapy , Percutaneous Coronary Intervention , Aged , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Osmolar Concentration , Postoperative Hemorrhage/chemically induced , Recurrence , Stents , Stroke/chemically induced , Treatment OutcomeABSTRACT
BACKGROUND: The relation between platelet reactivity and stent thrombosis, major bleeding, and other adverse events after coronary artery implantation of drug-eluting stents has been incompletely characterised. We aimed to determine the relation between platelet reactivity during dual therapy with aspirin and clopidogrel and clinical outcomes after successful coronary drug-eluting stent implantation. METHODS: ADAPT-DES was a prospective, multicentre registry of patients successfully treated with one or more drug-eluting stents and given aspirin and clopidogrel at 10-15 US and European hospitals. We assessed platelet reactivity in those patients after successful percutaneous coronary intervention using VerifyNow point-of-care assays, and assigned different cutoffs to define high platelet reactivity. The primary endpoint was definite or probable stent thrombosis; other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. We did a propensity-adjusted multivariable analysis to determine the relation between platelet reactivity and subsequent adverse events. This study is registered with ClinicalTrials.gov, number NCT00638794. FINDINGS: Between Jan 7, 2008, and Sept 16, 2010, 8665 patients were prospectively enrolled at 11 sites, of which 8583 were eligible. At 1-year follow-up, stent thrombosis had occurred in 70 (0·8%) patients, myocardial infarction in 269 (3·1%), clinically relevant bleeding in 531 (6·2%), and death in 161 (1·9%) patients. High platelet reactivity on clopidogrel was strongly related to stent thrombosis (adjusted HR 2·49 [95% CI 1·43-4·31], p=0·001) and myocardial infarction (adjusted HR 1·42 [1·09-1·86], p=0·01), was inversely related to bleeding (adjusted HR 0·73 [0·61-0·89], p=0·002), but was not related to mortality (adjusted HR 1·20 [0·85-1·70], p=0·30). High platelet reactivity on aspirin was not significantly associated with stent thrombosis (adjusted HR 1·46 [0·58-3·64], p=0·42), myocardial infarction, or death, but was inversely related to bleeding (adjusted HR 0·65 [0·43-0·99], p=0·04). INTERPRETATION: The findings from this study emphasise the counter-balancing effects of haemorrhagic and ischaemic complications after stent implantation, and suggest that safer drugs or tailored strategies for the use of more potent agents must be developed if the benefits of greater platelet inhibition in patients with cardiovascular disease are to be realised. FUNDING: Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics.
Subject(s)
Coronary Disease/surgery , Drug-Eluting Stents , Percutaneous Coronary Intervention , Platelet Aggregation/drug effects , Aspirin/therapeutic use , Blood Coagulation Tests , Clopidogrel , Coronary Disease/drug therapy , Coronary Stenosis/etiology , Coronary Stenosis/prevention & control , Drug-Eluting Stents/adverse effects , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/therapeutic use , Point-of-Care Systems , Prospective Studies , Registries , Risk Factors , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic use , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The safety and efficacy of drug-eluting stents (DES) in the treatment of coronary artery disease have been assessed in several randomised trials. However, none of these trials were powered to assess the safety and efficacy of DES in women because only a small proportion of recruited participants were women. We therefore investigated the safety and efficacy of DES in female patients during long-term follow-up. METHODS: We pooled patient-level data for female participants from 26 randomised trials of DES and analysed outcomes according to stent type (bare-metal stents, early-generation DES, and newer-generation DES). The primary safety endpoint was a composite of death or myocardial infarction. The secondary safety endpoint was definite or probable stent thrombosis. The primary efficacy endpoint was target-lesion revascularisation. Analysis was by intention to treat. FINDINGS: Of 43,904 patients recruited in 26 trials of DES, 11,557 (26·3%) were women (mean age 67·1 years [SD 10·6]). 1108 (9·6%) women received bare-metal stents, 4171 (36·1%) early-generation DES, and 6278 (54·3%) newer-generation DES. At 3 years, estimated cumulative incidence of the composite of death or myocardial infarction occurred in 132 (12·8%) women in the bare-metal stent group, 421 (10·9%) in the early-generation DES group, and 496 (9·2%) in the newer-generation DES group (p=0·001). Definite or probable stent thrombosis occurred in 13 (1·3%), 79 (2·1%), and 66 (1·1%) women in the bare-metal stent, early-generation DES, and newer-generation DES groups, respectively (p=0·01). The use of DES was associated with a significant reduction in the 3 year rates of target-lesion revascularisation (197 [18·6%] women in the bare-metal stent group, 294 [7·8%] in the early-generation DES group, and 330 [6·3%] in the newer-generation DES group, p<0·0001). Results did not change after adjustment for baseline characteristics in the multivariable analysis. INTERPRETATION: The use of DES in women is more effective and safe than is use of bare-metal stents during long-term follow-up. Newer-generation DES are associated with an improved safety profile compared with early-generation DES, and should therefore be thought of as the standard of care for percutaneous coronary revascularisation in women. FUNDING: Women in Innovation Initiative of the Society of Cardiovascular Angiography and Interventions.