Clinical Outcomes Following Stent Thrombosis Occurring In-Hospital Versus Out-of-Hospital Results From the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) Trial

ObjectivesThe study sought to determine whether rapid access to medical care and reperfusion results in a better prognosis in patients with in-hospital compared with out-of-hospital stent thrombosis (ST) in patients with ST-segment elevation myocardial infarction (STEMI) in the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial.BackgroundWhether the prognosis of in-hospital and out-of-hospital ST are similar is uncertain, with conflicting data reported from prior studies.MethodsA total of 3,602 STEMI patients undergoing primary percutaneous coronary intervention (PCI) were randomized to bivalirudin (n = 1,800) versus unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) (UFH+GPI; n = 1,802). Stents were implanted in 3,202 patients, 156 (4.9%) of whom developed Academic Research Consortium definite/probable ST during 3-year follow-up. We investigated the 1-year clinical outcomes after ST in 54 patients with in-hospital ST compared with 102 patients with out-of-hospital ST.ResultsOne year after the ST event, patients with in-hospital compared with out-of-hospital ST had significantly greater mortality (27.8% vs. 10.8%, p < 0.01); most deaths in both groups occurred within 1 week of the ST event. Patients with in-hospital ST also had higher rates of major bleeding (21.2% vs. 6.0%, p < 0.01), but a lower rate of myocardial infarction (56.6% vs. 77.5%, p < 0.01). Subgroup analysis within both in-hospital and out-of-hospital ST groups indicated that subacute ST had the highest mortality. By multivariable analysis, 1-year mortality was significantly increased in patients with in-hospital compared with out-of-hospital ST (adjusted hazard ratio: 4.62, 95% confidence interval: 1.98 to 10.77, p < 0.01). Additional correlates of increased mortality after an ST event included diabetes and randomization to UFH+GPI (vs. bivalirudin).ConclusionsFollowing primary PCI for STEMI, more than one-third of all ST events during 3-year follow-up occurred during the index hospital phase. Mortality and major bleeding were significantly higher after in-hospital ST compared with out-of-hospital ST. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966

Characterization of the Average Daily Ischemic and Bleeding Risk After Primary PCI for STEMI.

BACKGROUND: The risk of recurrent ischemic and bleeding events after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) may not be uniform over time, which may affect the benefit-to-risk ratio of guideline-recommended antithrombotic therapies in different intervals. OBJECTIVES: This study sought to characterize the average daily ischemic rates (ADIRs) and average daily bleeding rates (ADBRs) within the first year after primary PCI for STEMI. METHODS: Among 3,602 patients with STEMI who were enrolled in the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial, all ischemic and bleeding events, including recurrent events, were classified according to the timing of their occurrence as acute (?24 h after PCI), subacute (1 day to 30 days), and late (30 days to 1 year). Patients were treated with aspirin and clopidogrel for the entire year. ADIRs included cardiac death, reinfarction, and definite stent thrombosis. ADBRs included non-coronary artery bypass graft-related Thrombolysis In Myocardial Infarction major and minor bleeding. ADIRs and ADBRs were calculated as the total number of events divided by the number of patient-days of follow-up in each interval assuming a Poisson distribution. Generalized estimating equations were used to test the absolute least square mean differences (LSMD) between ADIRs and ADBRs. RESULTS: The ADIR and ADBR both exponentially decreased from the acute to the late periods (p < 0.0001). Although there were no significant differences in ADIR and ADBR in the acute phase (LSMD: +0.11%; 95% confidence interval [CI]: -0.35% to 0.58%; p = 0.63), the ADBR was greater than the ADIR in the subacute phase (LSMD: -0.39%; 95% CI: -0.58% to -0.20%; p < 0.0001). In the late phase, the ADIR exceeded the ADBR (LSMD: +1.51%; 95% CI: 1.04% to 1.98%; p < 0.0001). CONCLUSIONS: After primary PCI, the ADIR and ADBR both markedly decreased over time. Although the rates for bleeding exceeded those for ischemia within 30 days, the daily risk of ischemia significantly exceeded the daily risk of bleeding beyond 30 days, supporting the use of intensified platelet inhibition during the first year after STEMI

Incidence, Patterns, and Associations Between Dual-Antiplatelet Therapy Cessation and Risk for Adverse Events Among Patients With and Without Diabetes Mellitus Receiving Drug-Eluting Stents: Results From the PARIS Registry.

OBJECTIVES: The aim of this study was to examine the frequency and clinical impact of different cessation patterns of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents among patients with and those without diabetes mellitus (DM). BACKGROUND: Early DAPT suspension after percutaneous coronary intervention increases the risk for major adverse cardiac events. However, temporal variability in risk and relation to DAPT cessation patterns among patients with DM remain unclear. METHODS: Using data from the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients) registry, 1,430 patients with DM (34%) and 2,777 without DM (66%) treated with drug-eluting stents were identified. DAPT cessation modes were classified as temporary interruption (<14 days), disruption because of bleeding or poor compliance, and physician-recommended discontinuation. RESULTS: During 2-year follow-up, DM was associated with an increased risk for thrombotic events but a similar risk for bleeding. The cumulative incidence of DAPT cessation was significantly lower in patients with versus those without DM (50.1% vs. 55.4%; p < 0.01), driven largely by less frequent physician-guided discontinuation beyond 1 year. In contrast, 2-year rates of interruption and disruption were similar between groups. When DAPT was interrupted or discontinued under physician guidance, the risk for major adverse cardiac events was unchanged compared with patients with DM on uninterrupted DAPT. Conversely, when DAPT was disrupted, the risk for major adverse cardiac events increased compared with uninterrupted DAPT, regardless of diabetic status, with no evidence of statistical interaction. CONCLUSIONS: DAPT cessation patterns vary according to diabetic status, with less frequent physician-guided discontinuation among patients with DM. The presence of DM does not emerge as a modifier of cardiovascular risk after DAPT cessation

Causes, Timing, and Impact of Dual Antiplatelet Therapy Interruption for Surgery (From the PARIS Registry)

Temporary interruption of dual antiplatelet therapy (DAPT) is not infrequently required in patients undergoing percutaneous coronary intervention (PCI). We sought to describe the procedures and outcomes associated with DAPT interruption in patients treated with DAPT following successful PCI from the Patterns of non-adherence to anti-platelet regimens in stented patients registry (n = 5018). DAPT interruption was prespecified as physician recommended cessation forcohort, 490 patients (9.8%) experienced 594 DAPT interruptions over 2 years following PCI. Only 1 antiplatelet agent was interrupted in 57.2% cases and interruption was frequently recommended by noncardiologists (51.3%). Where type of surgery was reported, majority of DAPT interruptions occurred for minor surgery (68.4% vs 31.6%) and a similar cessation pattern of single versus dual antiplatelet cessation was observed regardless of minor or major surgery. Subsequent to DAPT interruption, 12 patients (2.4%) experienced 1 thrombotic event each, of which 5 (1.0%) occurred during the interruption period. All events occurred in patients who either stopped both agents (8 of 12) or clopidogrel-only (4 of 12), with no events occurring due to aspirin cessation alone. In conclusion, in the Patterns of Non-adherence to Anti-platelet Regiments in Stented Patients registry, 1 in 10 patients were recommended DAPT interruption for surgery within 2 years of PCI. Interruption was more common for a single agent rather than both antiplatelet agents regardless of severity of surgery, and was frequently recommended by noncardiologists. Only 1% of patients with DAPT interruption experienced a subsequent thrombotic event during the interruption period, which mainly occurred in patients stopping both antiplatelet agents

Prospective Study of TMVR Using Balloon-Expandable Aortic Transcatheter Valves in MAC: MITRAL Trial 1-Year Outcomes

OBJECTIVES: The aim of this study was to evaluate 1-year outcomes of valve-in-mitral annular calcification (ViMAC) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial. BACKGROUND: The MITRAL trial is the first prospective study evaluating the feasibility of ViMAC using balloon-expandable aortic transcatheter heart valves. METHODS: A multicenter prospective study was conducted, enrolling high-risk surgical patients with severe mitral annular calcification and symptomatic severe mitral valve dysfunction at 13 U.S. sites. RESULTS: Between February 2015 and December 2017, 31 patients were enrolled (median age 74.5 years [interquartile range (IQR): 71.3 to 81.0 years], 71% women, median Society of Thoracic Surgeons score 6.3% [IQR: 5.0% to 8.8%], 87.1% in New York Heart Association functional class III or IV). Access was transatrial (48.4%), transseptal (48.4%), or transapical (3.2%). Technical success was 74.2%. Left ventricular outflow tract obstruction (LVOTO) with hemodynamic compromise occurred in 3 patients (transatrial, n = 1; transseptal, n = 1; transapical, n = 1). After LVOTO occurred in the first 2 patients, pre-emptive alcohol septal ablation was implemented to decrease risk in high-risk patients. No intraprocedural deaths or conversions to open heart surgery occurred during the index procedures. All-cause mortality at 30 days was 16.7% (transatrial, 21.4%; transseptal, 6.7%; transapical, 100% [n = 1]; p = 0.33) and at 1 year was 34.5% (transatrial, 38.5%; transseptal, 26.7%; p = 0.69). At 1-year follow-up, 83.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.1 mm Hg (IQR: 5.6 to 7.1 mm Hg), and all patients had ≤1+ mitral regurgitation. CONCLUSIONS: At 1 year, ViMAC was associated with symptom improvement and stable transcatheter heart valve performance. Pre-emptive alcohol septal ablation may prevent transcatheter mitral valve replacement-induced LVOTO in patients at risk. Thirty-day mortality of patients treated via transseptal access was lower than predicted by the Society of Thoracic Surgeons score. Further studies are needed to evaluate safety and efficacy of ViMAC

Dual-Antiplatelet Therapy Cessation and Cardiovascular Risk in Relation to Age: Analysis From the PARIS Registry.

OBJECTIVES: The aim of this study was to examine the association between dual-antiplatelet therapy (DAPT) cessation and cardiovascular risk after percutaneous coronary intervention in relation to age. BACKGROUND: Examination of outcomes by age after percutaneous coronary intervention is relevant given the aging population. METHODS: Two-year clinical outcomes, incidence, and effect of DAPT cessation on outcomes were compared by ages ≤55, 56 to 74, and ≥75 years from the PARIS (Patterns of Non-Adherence to Antiplatelet Regimens in Stented Patients) registry. DAPT cessation included physician-recommended discontinuation, interruption for surgery, and disruption (from noncompliance or bleeding). Clinical endpoints were major adverse cardiac events (MACE) (a composite of cardiac death, definite or probable stent thrombosis, spontaneous myocardial infarction, or clinically indicated target lesion revascularization), a secondary restrictive definition of MACE (MACE2) excluding target lesion revascularization, and bleeding. RESULTS: A total of 1,192 patients (24%) were ≤55 years, 2,869 (57%) were 56 to 74 years, and 957 (19%) were ≥75 years of age. Patients ≥75 years of age had higher DAPT cessation rates and increased risk for MACE2, death, cardiac death, and bleeding compared with younger patients. Discontinuation and interruption were not associated with increased cardiovascular risk across age groups, whereas disruption was associated with increased risk for MACE and MACE2 in younger patients but not in patients ≥75 years of age (p for trend <0.05). CONCLUSIONS: Nonadherence and outcomes vary by age, with patients ≥75 years having the highest DAPT cessation rates. We observed no association between outcomes and DAPT cessation in patients ≥75 years, whereas discontinuation was associated with lower MACE rates and disruption with increased MACE rates in patients <75 years

P2Y12 inhibitor monotherapy or dual antiplatelet therapy after coronary revascularisation: individual patient level meta-analysis of randomised controlled trials

Objective: To assess the risks and benefits of P2Y12 inhibitor monotherapy compared with dual antiplatelet therapy (DAPT) and whether these associations are modified by patients' characteristics. Design: Individual patient level meta-analysis of randomised controlled trials. Data sources: Searches were conducted in Ovid Medline, Embase, and three websites (www.tctmd.com, www.escardio.org, www.acc.org/cardiosourceplus) from inception to 16 July 2020. The primary authors provided individual participant data. Eligibility criteria: Randomised controlled trials comparing effects of oral P2Y12 monotherapy and DAPT on centrally adjudicated endpoints after coronary revascularisation in patients without an indication for oral anticoagulation. Main outcome measures: The primary outcome was a composite of all cause death, myocardial infarction, and stroke, tested for non-inferiority against a margin of 1.15 for the hazard ratio. The key safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or type 5 bleeding. Results: The meta-analysis included data from six trials, including 24 096 patients. The primary outcome occurred in 283 (2.95%) patients with P2Y12 inhibitor monotherapy and 315 (3.27%) with DAPT in the per protocol population (hazard ratio 0.93, 95% confidence interval 0.79 to 1.09; P=0.005 for non-inferiority; P=0.38 for superiority; τ2=0.00) and in 303 (2.94%) with P2Y12 inhibitor monotherapy and 338 (3.36%) with DAPT in the intention to treat population (0.90, 0.77 to 1.05; P=0.18 for superiority; τ2=0.00). The treatment effect was consistent across all subgroups, except for sex (P for interaction=0.02), suggesting that P2Y12 inhibitor monotherapy lowers the risk of the primary ischaemic endpoint in women (hazard ratio 0.64, 0.46 to 0.89) but not in men (1.00, 0.83 to 1.19). The risk of bleeding was lower with P2Y12 inhibitor monotherapy than with DAPT (97 (0.89%) v 197 (1.83%); hazard ratio 0.49, 0.39 to 0.63; P&lt;0.001; τ2=0.03), which was consistent across subgroups, except for type of P2Y12 inhibitor (P for interaction=0.02), suggesting greater benefit when a newer P2Y12 inhibitor rather than clopidogrel was part of the DAPT regimen. Conclusions: P2Y12 inhibitor monotherapy was associated with a similar risk of death, myocardial infarction, or stroke, with evidence that this association may be modified by sex, and a lower bleeding risk compared with DAPT. Registration: PROSPERO CRD42020176853

Comparison of Double Kissing Crush Versus Culotte Stenting for Unprotected Distal Left Main Bifurcation Lesions Results From a Multicenter, Randomized, Prospective DKCRUSH-III Study

ObjectivesThe study aimed to investigate the difference in major adverse cardiac event (MACE) at 1-year after double kissing (DK) crush versus Culotte stenting for unprotected left main coronary artery (UPLMCA) distal bifurcation lesions.BackgroundDK crush and Culotte stenting were reported to be effective for treatment of coronary bifurcation lesions. However, their comparative performance in UPLMCA bifurcation lesions is not known.MethodsA total of 419 patients with UPLMCA bifurcation lesions were randomly assigned to DK (n = 210) or Culotte (n = 209) treatment. The primary endpoint was the occurrence of a MACE at 1 year, including cardiac death, myocardial infarction, and target vessel revascularization (TVR). In-stent restenosis (ISR) at 8 months was secondary endpoint, and stent thrombosis (ST) served as a safety endpoint. Patients were stratified by SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) and NERS (New Risk Stratification) scores.ResultsPatients in the Culotte group had significant higher 1-year MACE rate (16.3%), mainly driven by increased TVR (11.0%), compared with the DK group (6.2% and 4.3%, respectively; all p < 0.05). ISR rate in side branch was 12.6% in the Culotte group and 6.8% in the DK group (p = 0.037). Definite ST rate was 1.0% in the Culotte group and 0% in the DK group (p = 0.248). Among patients with bifurcation angle ≥70°, NERS score ≥20, and SYNTAX score ≥23, the 1-year MACE rate in the DK group (3.8%, 9.2%, and 7.1%, respectively) was significantly different to those in the Culotte group(16.5%, 20.4%, and 18.9%, respectively; all p < 0.05).ConclusionsCulotte stenting for UPLMCA bifurcation lesions was associated with significantly increased MACEs, mainly due to the increased TVR. (Double Kissing [DK] Crush Versus Culotte Stenting for the Treatment of Unprotected Distal Left Main Bifurcation Lesions: DKCRUSH-III, a Multicenter Randomized Study Comparing Double-Stent Techniques; ChiCTR-TRC-00000151