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Background: In patients undergoing percutaneous coronary intervention (PCI), the use of anti-inflammatory therapy with colchicine is associated with a reduction of recurrent ischemic events. The mechanisms of such findings are not fully elucidated. Objectives: To investigate the effects of colchicine versus aspirin on inflammation and platelet reactivity in patients with acute coronary syndrome (ACS) undergoing PCI. Methods: This observational study compared laboratory measurements in ACS patients receiving single antiplatelet therapy with ticagrelor or prasugrel plus colchicine (MACT) (n = 185) versus conventional dual-antiplatelet therapy (DAPT) with aspirin plus ticagrelor or prasugrel (n = 497). The primary outcome was the frequency of high residual inflammation, defined as high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L at 1 month post-PCI. Multiple sensitivity analyses were performed for the primary outcome, including multivariable adjustment, propensity-score matching, and inverse-probability weighted methods. Results: One month after PCI, patients treated with MACT had significantly lower levels of hs-CRP compared to those treated with DAPT (0.6 [0.4-1.2] vs. 0.9 [0.6-2.3] mg/L, p < 0.001). The frequency of high residual inflammation was also lower in the MACT group (10.8% vs. 27.2%, p < 0.001) (odds ratio [95% confidence interval] = 0.33 [0.20-0.54], p < 0.001). This effect was consistent across sensitivity analyses. There was no difference in platelet reactivity between MACT and DAPT (49.6 ± 49.0 vs. 51.5 ± 66.4 P2Y12 reaction unit [PRU] measured by VerifyNow, p = 0.776). Conclusion: In ACS patients undergoing PCI, MACT was associated with a lower rate of high residual inflammation without increasing platelet reactivity compared to conventional DAPT. Clinical trial registration: NCT04949516 for MACT pilot trial and NCT04650529 for Gyeongsang National University Hospital registry.
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Intervención Coronaria Percutánea , Humanos , Medición de Riesgo/métodos , Intervención Coronaria Percutánea/efectos adversos , Sistemas de Atención de Punto , Pruebas en el Punto de Atención , Pruebas de Función Plaquetaria/métodos , Activación Plaquetaria/fisiología , Inhibidores de Agregación Plaquetaria/uso terapéuticoRESUMEN
BACKGROUND: Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in coronary artery disease (CAD). Recent trials have introduced a novel approach involving P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel, after a short DAPT. However, the effectiveness and safety of this strategy remains to be established. We aimed to perform a meta-analysis comparing monotherapy with P2Y12 inhibitors versus standard DAPT in patients undergoing PCI at 12 months. METHODS: Multiple databases were searched. Six RCTs with a total of 24877 patients were included. The primary endpoint was all-cause mortality at 12 months of follow-up. The secondary endpoints were cardiovascular mortality, myocardial infarction, probable or definite stent thrombosis, stroke events, and major bleeding. The study is registered with PROSPERO (CRD42024499529). RESULTS: Monotherapy with P2Y12 inhibitor ticagrelor significantly reduced both allcause mortality (HR 0.71, 95 CI [0.55-0.91], P = 0.007) and cardiovascular mortality (HR 0.66, 95% CI [0.49-0.89], P = 0.006) compared to standard DAPT. In contrast, clopidogrel monotherapy did not demonstrate a similar reduction. The decrease in mortality associated with ticagrelor was primarily due to a lower risk of major bleeding (HR 0.56, 95% CI [0.43-0.72], P < 0.001), while the risk of myocardial infarction (MI) remained unchanged (HR 0.90, 95% CI [0.73-1.11], P = 0.32). The risk of stroke was found to be similar across treatments. CONCLUSIONS: In comparison to standard DAPT, P2Y12 inhibitor monotherapy with ticagrelor may lead to a reduced mortality. The clinical benefits are driven by a reduction of bleeding risk without ischemic risk trade-off.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Antagonistas del Receptor Purinérgico P2Y , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Intervención Coronaria Percutánea/métodos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Resultado del Tratamiento , Terapia Antiplaquetaria Doble/métodos , Ticagrelor/uso terapéuticoRESUMEN
Stroke confers a severe global healthcare burden, hence exploring risk factors for stroke occurrence and prognosis is important for stroke prevention and post-stroke management strategies. Endogenous fibrinolysis is a spontaneous physiological protective mechanism that dissolves thrombus to maintain vascular patency. Recently, impaired endogenous fibrinolysis has been considered as a potential novel cardiovascular risk factor, but its link with ischaemic stroke in the past has been underappreciated. In this review, we summarize the latest mechanisms of endogenous fibrinolysis, review the current evidence and data on endogenous fibrinolysis in ischemic stroke. It includes the structure of thrombus in ischemic stroke patients, the effect of fibrin structure on the endogenous fibrinolytic efficiency, and the association between intravenous thrombolytic therapy and endogenous fibrinolysis in ischemic stroke. It also includes the single factors (tissue plasminogen activator, urokinase plasminogen activator, plasminogen activator inhibitor-1, thrombin activatable fibrinolysis inhibitor, complement component 3, complement component 5, alpha-2-antiplasmin, plasmin-alpha-2-antiplasmin complex, and lipoprotein[a]), and the global assessments of endogenous fibrinolysis status (thromboelastography, rotational thromboelastometry, and global thrombosis test), and their potential as predictors to identify occurrence or unfavorable functional outcomes of ischemic stroke. All of these assessments present advantages and limitations, and we suggest that the global thrombosis test may be more appropriate for detecting impaired endogenous fibrinolysis status in ischemic stroke patients.
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Fibrinólisis , Accidente Cerebrovascular Isquémico , Humanos , Fibrinólisis/fisiología , Accidente Cerebrovascular Isquémico/sangre , Pronóstico , Terapia Trombolítica , Trombosis/sangre , Trombosis/etiologíaRESUMEN
BACKGROUND: Impaired endogenous fibrinolysis is adverse cardiovascular risk factor in acute coronary syndrome (ACS) patients. Addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy (DAPT) reduces cardiovascular events but increases bleeding. OBJECTIVE: We aimed to assess whether addition of VLDR to DAPT can enhance endogenous fibrinolysis. METHODS: In a prospective, open-label trial, we assessed endogenous fibrinolysis in whole blood, in 549 patients with ACS using the Global Thrombosis Test (GTT) and Thromboelastography (TEG). Patients (n = 180) who demonstrated impaired endogenous fibrinolysis (lysis time [LT] >2000s with the GTT) were randomised 1:1:1 to (i) clopidogrel 75 mg daily; (ii) clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily; or (iii) ticagrelor 90 mg twice daily, for 30 days, in addition to aspirin. Fibrinolytic status was assessed at 0, 2, 4 and 8 weeks. The primary outcome was the change in LT from admission to week 4. We also measured thrombotic occlusion time (OT) at high shear, and rivaroxaban level. RESULTS: There was no difference between the groups with respect to LT or clot lysis with TEG, and no change in these parameters compared to baseline during study drug allocation. In the rivaroxaban plus clopidogrel group, OT was prolonged compared to the other groups, although rivaroxaban levels were low, suggesting non-compliance. CONCLUSION: Addition of rivaroxaban 2.5 mg twice daily to DAPT does not affect endogenous fibrinolysis of thrombus formed at either high or low shear. Further studies are needed to determine whether higher doses of rivaroxaban can favourably modulate fibrinolysis. CONDENSED ABSTRACT: Impaired endogenous fibrinolysis is a strong risk factor in ACS. We aimed to assess whether adding very low dose rivaroxaban (VLDR) to DAPT can enhance fibrinolysis. Fibrin and clot lysis were assessed in whole blood. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75 mg daily; clopidogrel 75 mg plus VLDR; or ticagrelor 90 mg twice daily, in addition to aspirin. At 30-days, there was no difference in lysis time between the groups, nor change from baseline. VLDR does not improve fibrinolysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic regimens can enhance endogenous fibrinolysis.
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Síndrome Coronario Agudo , Trombosis , Humanos , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Rivaroxabán/farmacología , Rivaroxabán/uso terapéutico , Clopidogrel/uso terapéutico , Fibrinólisis , Ticagrelor/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Estudios Prospectivos , Aspirina/farmacología , Aspirina/uso terapéuticoRESUMEN
Patients with transient ST-segment elevation myocardial infarction or spontaneous reperfusion, which occurs in approximately 20% of patients with ST-segment elevation myocardial infarction (STEMI), have smaller infarcts and more favorable clinical outcomes than patients without spontaneous reperfusion. Understanding the mechanisms underlying spontaneous reperfusion is therefore important since this may identify possible novel therapeutic targets to improve outcomes in patients with STEMI. In this review, we discuss some of the possible determinants of spontaneous reperfusion including pro-thrombotic profile, endogenous fibrinolytic status, lipoprotein(a) (Lp[a]), inflammatory markers, and neutrophil extracellular traps (NETs). Effective (rapid) endogenous fibrinolysis, as assessed in whole blood in vitro, using a point-of-care technique assessment of global thrombotic status, has been strongly linked to spontaneous reperfusion. Lp(a), which has a high degree of homology to plasminogen, may impair fibrinolysis through competitive inhibition of tissue plasminogen activator-mediated plasminogen activation as well as tissue plasminogen activator-mediated clot lysis and contribute to pathogenic clot properties by decreasing fibrin clot permeation. NETs appear to negatively modulate clot lysis by increasing thrombin fiber diameter and inhibiting plasmin-driven lysis of plasma clots. There are limited data that oral anticoagulation may modulate endogenous fibrinolysis but antiplatelet agents currently appear to have no impact. Phase III trials involving subcutaneous P2Y12 or glycoprotein IIb/IIIa inhibitors, oral factor XIa inhibitors, interleukin-6 inhibitors, and apolipoprotein(a) antisense oligonucleotides in patients with cardiovascular disease are ongoing. Future studies will be needed to determine the impact of these novel antithrombotic, anti-inflammatory, and lipid-lowering therapies on endogenous fibrinolysis and spontaneous reperfusion.
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Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/fisiopatología , Fibrinólisis , Trampas Extracelulares/metabolismo , Reperfusión Miocárdica , Lipoproteína(a)/metabolismo , Lipoproteína(a)/sangreRESUMEN
BACKGROUND: East Asians (EAs), compared to white Caucasians (W), have a lower risk of ischemic heart disease and a higher risk of bleeding with antithrombotic medications. The underlying mechanisms are incompletely understood. OBJECTIVES: We sought to compare thrombotic profiles of EA and W patients with myocardial infarction (MI) and relate these to cardiovascular outcomes. METHODS: In a prospective study in the United Kingdom and Korea, blood samples from patients (n = 515) with ST- or non-ST-elevation MI (STEMI and NSTEMI) were assessed using the Global Thrombosis Test, measuring thrombotic occlusion (OT) and endogenous fibrinolysis (lysis time [LT]). Patients were followed for 1 year for major adverse cardiovascular events (MACE) and bleeding. RESULTS: EA patients showed reduced OT (longer OT) compared to W (646 seconds [470-818] vs. 436 seconds [320-580], p < 0.001), with similar LT. In STEMI, OT (588 seconds [440-759] vs. 361 seconds [274-462], p < 0.001) and LT (1,854 seconds [1,389-2,729] vs. 1,338 seconds [1,104-1,788], p < 0.001) were longer in EA than W. In NSTEMI, OT was longer (OT: 734 seconds [541-866] vs. 580 seconds [474-712], p < 0.001) and LT shorter (1519 seconds [1,058-2,508] vs. 1,898 seconds [1,614-2,806], p = 0.004) in EA than W patients. MACE was more frequent in W than EA (6.3 vs. 1.9%, p = 0.014) and bleeding infrequent. While OT was unrelated, LT was a strong independent predictor of MACE event after adjustment for risk factors (hazard ratio: 3.70, 95% confidence interval: 1.43-9.57, p = 0.007), predominantly in W patients, and more so in STEMI than NSTEMI patients. CONCLUSION: EA patients exhibit different global thrombotic profiles to W, associated with a lower rate of cardiovascular events.
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Síndrome Coronario Agudo , Pueblo Asiatico , Hemorragia , Infarto del Miocardio sin Elevación del ST , Población Blanca , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/etnología , Síndrome Coronario Agudo/epidemiología , Anciano , Infarto del Miocardio sin Elevación del ST/sangre , Infarto del Miocardio sin Elevación del ST/etnología , Hemorragia/sangre , República de Corea/epidemiología , Factores de Riesgo , Reino Unido/epidemiología , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/etnología , Infarto del Miocardio con Elevación del ST/epidemiología , Trombosis/sangre , Trombosis/etiología , Infarto del Miocardio/sangre , Infarto del Miocardio/etnología , Infarto del Miocardio/epidemiología , Fibrinólisis , Pueblos del Este de AsiaRESUMEN
Background: East Asians have shown different risk profiles for both thrombophilia and bleeding than Western counterparts. Objectives: The authors sought to evaluate the effect of low-dose aspirin for primary prevention between these populations. Methods: We searched randomized clinical trials (RCTs) for intervention with low-dose aspirin (≤100 mg once daily) in participants without symptomatic cardiovascular disease until December 31, 2021. The number of events between the arms was extracted for analysis. Pooled risk ratios (RRs) and risk differences (RDs) were analyzed in each population. Outcomes included a major adverse cardiovascular event (MACE), cardiovascular death, myocardial infarction, stroke, and major bleeding (intracranial hemorrhage and major gastrointestinal bleeding). Results: Two RCTs included 17,003 East Asians, and 9 RCTs had 117,467 Western participants. Aspirin treatment showed a similar effect in reducing the MACE rate (RR of East Asians: 0.87; 95% CI: 0.71-1.05; RR of Westerners: 0.90; 95% CI: 0.85-0.95) (Pinteraction = 0.721). In contrast, the risk of major bleeding during aspirin vs control was greater in the East Asian population (RR: 2.48; 95% CI: 1.86-3.30) compared with the Western population (RR: 1.45; 95% CI: 1.26-1.66) (Pinteraction = 0.001), which was driven by more frequent gastrointestinal bleeding (RR of East Asians: 3.29; 95% CI: 2.26-4.80 vs RR of Westerners: 1.56; 95% CI: 1.29-1.88) (Pinteraction < 0.001). The net RDs (RD of MACE plus RD of major bleeding) were 8.04 and 0.72 per 1,000 persons in East Asian and Western participants, indicating 124 and 1,389 of the net number needed to harm, respectively. Conclusions: Low-dose aspirin for primary prevention in East Asians must be cautiously prescribed because of the increased risk of major bleeding relative to Western counterparts.
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BACKGROUND: Myocardial ischemia induces intracellular accumulation of non-glycosylated apolipoprotein J that results in a reduction of circulating glycosylated ApoJ (ApoJ-Glyc). The latter has been suggested to be a marker of transient myocardial ischemia. OBJECTIVE: This proof-of-concept clinical study aimed to assess whether changes in circulating ApoJ-Glyc could detect myocardial ischemia in patients attending the emergency department (ED) with chest pain suggestive of acute coronary syndrome (ACS). METHODS: In suspected ACS patients, EDICA (Early Detection of Myocardial Ischemia in Suspected Acute Coronary Syndromes by ApoJ-Glyc a Novel Pathologically based Ischemia Biomarker), a multicentre, international, cohort study assessed changes in 2 glycosylated variants of ApoJ-Glyc, (ApoJ-GlycA2 and ApoJ-GlycA6), in serum samples obtained at ED admission (0 h), and 1 h and 3 h thereafter, blinded to the clinical diagnosis (i.e. STEMI, NSTEMI, unstable angina, non-ischemic). RESULTS: 404 patients were recruited; 291 were given a clinical diagnosis of "non-ischemic" chest pain and 113 were considered to have had an ischemic event. ApoJ-GlycA6 was lower on admission in ischemic compared with "non-ischemic" patients (66 [46-90] vs. 73 [56-95] µg/ml; P = 0.04). 74% of unstable angina patients (all with undetectable hs-Tn), had ischemic changes in ApoJ-Glyc at 0 h and 89% at 1 h. Initially low ApoJ-Glyc levels in 62 patients requiring coronary revascularization increased significantly after successful percutaneous intervention. CONCLUSIONS: Circulating ApoJ-Glyc concentrations decrease early in ED patients with myocardial ischemia compared with "non-ischemic" patients, even in the absence of troponin elevations. ApoJ-Glyc may be a useful marker of myocardial ischemia in the ED setting.
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BACKGROUND: After a brief period of dual antiplatelet therapy, P2Y12 inhibitor monotherapy in the absence of aspirin effectively reduces bleeding without increasing recurrent ischemia in patients undergoing percutaneous coronary intervention (PCI). In addition, early anti-inflammatory therapies may have clinical benefits in acute coronary syndrome (ACS) patients. OBJECTIVES: The aim of this study was to investigate the feasibility of ticagrelor or prasugrel P2Y12 inhibitor monotherapy combined with colchicine immediately after PCI in patients with ACS. METHODS: This was a proof-of-concept pilot trial. ACS patients treated with drug-eluting stents were included. On the day after PCI, low-dose colchicine (0.6 mg daily) was administered in addition to ticagrelor or prasugrel maintenance therapy, whereas aspirin therapy was discontinued. The primary outcome was any stent thrombosis at 3 months. The key secondary outcomes were platelet reactivity measured by the VerifyNow assay (Accriva) before discharge and a reduction in high-sensitivity C-reactive protein (hs-CRP) over 1 month. RESULTS: We enrolled 200 patients, 190 (95.0%) of whom completed the 3-month follow-up. The primary outcome occurred in 2 patients (1.0%): 1 definite and 1 probable stent thrombosis. The level of platelet reactivity overall was 27 ± 42 P2Y12 reaction units, and only 1 patient had high platelet reactivity (>208 P2Y12 reaction units). The hs-CRP levels decreased from 6.1 mg/L (IQR: 2.6-15.9 mg/L) at 24 hours after PCI to 0.6 mg/L (IQR: 0.4-1.2 mg/L) at 1 month (P < 0.001), and the prevalence of high-inflammation criteria (hs-CRP ≥2 mg/L) decreased from 81.8% to 11.8% (P < 0.001). CONCLUSIONS: In ACS patients undergoing PCI, it is feasible to discontinue aspirin therapy and administer low-dose colchicine on the day after PCI in addition to ticagrelor or prasugrel P2Y12 inhibitors. This approach is associated with favorable platelet function and inflammatory profiles. (Mono Antiplatelet and Colchicine Therapy [MACT]; NCT04949516).
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Síndrome Coronario Agudo , Colchicina , Intervención Coronaria Percutánea , Humanos , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/terapia , Aspirina/administración & dosificación , Proteína C-Reactiva , Colchicina/uso terapéutico , Proyectos Piloto , Clorhidrato de Prasugrel/administración & dosificación , Ticagrelor/administración & dosificación , Resultado del TratamientoRESUMEN
Loss-of-function (LoF) alleles of cytochrome P450 2C19 (CYP2C19), which are prevalent in East Asians, are linked to high platelet reactivity (HPR) phenotype and poor prognosis. We aimed to investigate the incremental predictive value of HPR combined with CYP2C19 genotype in predicting outcomes after drug-eluting stent (DES) implantation. The patients treated with platelet function and genotype-related long-term prognosis in drug-eluting stent (PTRG-DES) consortium enrolled a total of 13,160 Korean patients treated with DES who had platelet function test (PFT) or CYP2C19 genotype, of which, 6,717 patients with PFT and genotype together were categorized. HPR was defined as VerifyNow ≥ 252 P2Y12 reaction unit. The primary outcome was the incidence of major adverse cardiac and cerebrovascular event (MACCE) 5 years after treatment. The patients with both HPR and CYP2C19 LoF/LoF had the highest MACCE rates (6.2%) and increased MACCE risk (adjusted hazard ratio: 1.89, 95% confidence interval: 1.20-2.91, P = 0.006) compared with those without both HPR and CYP2C19 LoF/LoF. There was no effect of interaction between HPR and CYP2C19 genotype on the primary outcome (P = 0.424). Adding combined HPR and CYP2C19 genotype to the conventional model had an incremental influence in predicting MACCE and stent thrombosis. Compared to the model including HPR or CYP2C19 genotype alone, a combination model significantly improved the risk stratification for stent thrombosis but not MACCE. In DES-treated East Asian patients, the combined evaluation of PFT results and CYP2C19 genotyping might improve risk prediction of ischemic events during clopidogrel treatment.
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Thrombus formation in a severely stenosed artery is initiated by high shear activation of platelets, with soluble platelet agonists, such as ADP and thromboxane, playing only a secondary role in the growth and stability of the thrombus. Conventional platelet function tests, however, assess only the soluble agonist-dependent pathway of platelet aggregation. As the thrombus evolves, its stability and ability to withstand dislodgement by arterial flow will determine whether complete and persistent vessel occlusion will occur. The Global Thrombosis Test (GTT), an automated point-of-care technique, simulates the formation of thrombus in whole blood under high shear flow (shear rate >12â 000â s-1) and measures the time for occlusive thrombus formation and spontaneous, endogenous thrombolysis/fibrinolysis. The latest GTT-3 model subjects the growing thrombus to upstream pressure, resembling that in a medium-sized artery, and provides an additional assessment of thrombus stability and fibrinolysis rate. It can be used in 3 programs, including a new "hypershear" mode, whereby repetitive cycles of pressure are applied to the growing thrombus, increasing shear rate to â¼22â 000â s-1, such as that in patients on mechanical circulatory support. In addition to assessing the risk of arterial thrombosis, the GTT-3 could be used to assess the impact of antithrombotic medications on thrombus stability at high shear. Although current antiplatelet medications target the biochemical axis of platelet aggregation (soluble agonists) and also increase bleeding risk, novel shear-selective antiplatelet therapies may prevent thrombosis while preserving hemostasis. Future studies are needed to assess the usefulness of assessing thrombus stability on cardiovascular and pharmacological evaluation.
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Fibrinólisis , Trombosis , Humanos , Fibrinólisis/fisiología , Plaquetas/metabolismo , Agregación Plaquetaria , Inhibidores de Agregación Plaquetaria/uso terapéuticoRESUMEN
Patients with isolated tricuspid valve (TV) disease have poor prognosis with no consensus on their management. Transcatheter TV intervention is emerging as a valid option in patients with prohibitive surgical risk. We analyzed studies of patients who underwent isolated TV surgery to identify the features associated with successful clinical outcomes. We performed a systematic review and meta-analysis of studies reporting clinical outcomes of isolated surgical TV intervention, namely TV repair, TV replacement with a bioprosthetic valve (TVR-B), or TV replacement with a mechanical valve (TVR-M). Twenty-seven studies involving 10,478 patients (4,931 TV repair, 3,821 TVR-B, and 1,713 TVR-M) were included. Early mortality occurred in 9% and did not differ between TV surgical approaches. Late mortality was 27% at a median follow-up of 4 (3 to 6) years and was significantly higher for all-TVR (30% vs 25%, rate ratio 1.18, 95% confidence interval 1.05 to 1.31, p = 0.004) and TVR-B (28% vs 24%, rate ratio 1.15, 95% confidence interval 1.02 to 1.30, p = 0.02) compared with TV repair. Late mortality did not differ between TVR-B and TVR-M. Across all studies, early complications included bleeding (7.4%), acute kidney injury (18.7%), permanent pacemaker (13.7%), cerebrovascular accidents (1.2%), and infection (8.9%). Late clinical outcomes included reintervention (3.7%), structural valve deterioration (2.4%), valve thrombosis (2.6%), and TV regurgitation recurrence after 1 year (15.0%). In conclusion, in isolated TV surgeries, TV repair has favorable long-term mortality compared with TV replacement. This supports the development and refinement of transcatheter TV repair approaches. Future research is recommended to provide comparative data for various transcatheter TV interventions.
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Procedimientos Quirúrgicos Cardíacos , Enfermedades de las Válvulas Cardíacas , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Tricúspide , Humanos , Válvula Tricúspide/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Resultado del Tratamiento , Insuficiencia de la Válvula Tricúspide/complicaciones , Enfermedades de las Válvulas Cardíacas/complicaciones , Estudios RetrospectivosRESUMEN
Conventional dual antiplatelet therapy (DAPT) for patients with acute coronary syndromes undergoing percutaneous coronary intervention comprises aspirin with a potent P2Y purinoceptor 12 (P2Y12) inhibitor (prasugrel or ticagrelor) for 12 months. Although this approach reduces ischaemic risk, patients are exposed to a substantial risk of bleeding. Strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. Either strategy requires assessment of the ischaemic and bleeding risks of each individual. De-escalation of DAPT intensity can reduce bleeding without increasing ischaemic events and can be guided by platelet function testing or genotyping. Abbreviation of DAPT duration after 1-6 months, followed by monotherapy with aspirin or a P2Y12 inhibitor, reduces bleeding without an increase in ischaemic events in patients at high bleeding risk, particularly those without high ischaemic risk. However, these two strategies have not yet been compared in a head-to-head clinical trial. In this Consensus Statement, we summarize the evidence base for these treatment approaches, provide guidance on the assessment of ischaemic and bleeding risks, and provide consensus statements from an international panel of experts to help clinicians to optimize these DAPT approaches for individual patients to improve outcomes.
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Síndrome Coronario Agudo , Trombosis Coronaria , Intervención Coronaria Percutánea , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Clorhidrato de Prasugrel/efectos adversos , Trombosis Coronaria/etiología , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/etiología , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Aspirina/efectos adversos , Hemorragia/inducido químicamente , Intervención Coronaria Percutánea/efectos adversos , Resultado del TratamientoRESUMEN
Percutaneous ventricular assist devices (pVADs) are increasingly being used because of improved experience and availability. The Impella (Abiomed), a percutaneous microaxial, continuous-flow, short-term ventricular assist device, requires meticulous postimplantation management to avoid the 2 most frequent complications, namely, bleeding and hemolysis. A standardized approach to the prevention, detection, and treatment of these complications is mandatory to improve outcomes. The risk for hemolysis is mostly influenced by pump instability, resulting from patient- or device-related factors. Upfront echocardiographic assessment, frequent monitoring, and prompt intervention are essential. The precarious hemostatic balance during pVAD support results from the combination of a procoagulant state, due to critical illness and contact pathway activation, together with a variety of factors aggravating bleeding risk. Preventive strategies and appropriate management, adapted to the impact of the bleeding, are crucial. This review offers a guide to physicians to tackle these device-related complications in this critically ill pVAD-supported patient population.
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Corazón Auxiliar , Intervención Coronaria Percutánea , Humanos , Resultado del Tratamiento , Hemólisis , Intervención Coronaria Percutánea/efectos adversos , Corazón Auxiliar/efectos adversos , Hemorragia/diagnóstico por imagen , Hemorragia/etiología , Hemorragia/prevención & control , Choque CardiogénicoRESUMEN
BACKGROUND: Spontaneous reperfusion, seen in â¼20% of patients with ST-segment elevation myocardial infarction (STEMI), manifests as normal epicardial flow in the infarct-related artery, with or without ST-segment resolution, before percutaneous coronary intervention (PCI). The drivers mediating this are unknown. OBJECTIVES: The authors sought to relate spontaneous reperfusion to the thrombotic profile. METHODS: In a prospective study, blood from STEMI patients (n = 801) was tested pre-PCI to assess in vitro, point-of-care, occlusion times (OT) and endogenous lysis times (LT). Spontaneous reperfusion was defined as infarct-related artery Thrombolysis In Myocardial Infarction flow grade 3 before PCI. Patients were followed for major cardiovascular events (death, myocardial infarction, or stroke). RESULTS: Spontaneous reperfusion was associated with a longer OT (435 seconds vs 366 seconds; P < 0.001) and a shorter LT (1,257 seconds vs 1,616 seconds; P < 0.001), lower troponin, and better left ventricular function. LT was superior to OT for predicting spontaneous reperfusion (area under the curve for LT: 0.707; 95% CI: 0.661-0.753; area under the curve for OT: 0.629; 95% CI: 0.581-0.677). Among patients with spontaneous reperfusion, those with complete, vs partial ST-segment resolution, had a longer OT (P = 0.002) and a shorter LT (P < 0.001). Spontaneous reperfusion was unrelated to clinical characteristics or pain-to-angiography times. Over 4 years, patients with spontaneous reperfusion experienced fewer major adverse cardiovascular events than those without (4.1% vs 10.6%; P = 0.013), especially in those with both spontaneous reperfusion and complete ST-segment resolution (1.5% vs 10.1%; P = 0.029). CONCLUSIONS: We demonstrate a novel hematological signature in STEMI patients with spontaneous reperfusion, namely, decreased platelet reactivity and faster endogenous fibrinolysis, relating to smaller infarcts and improved survival. This finding indicates a role for modulating thrombotic status early after STEMI onset, to facilitate spontaneous reperfusion and improve outcomes.
Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Trombosis , Humanos , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/cirugía , Intervención Coronaria Percutánea/efectos adversos , Estudios Prospectivos , Infarto del Miocardio/etiología , Trombosis/etiología , Biomarcadores , Reperfusión , Resultado del Tratamiento , Reperfusión MiocárdicaRESUMEN
BACKGROUND: Uncertainty exists whether coronary revascularization plus medical therapy (MT) is associated with an increase in noncardiac mortality in chronic coronary syndrome (CCS) when compared with MT alone, particularly following recent data from the ISCHEMIA-EXTEND (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. OBJECTIVES: This study conducted a large-scale meta-analysis of trials comparing elective coronary revascularization plus MT vs MT alone in patients with CCS to determine whether revascularization has a differential impact on noncardiac mortality at the longest follow-up. METHODS: We searched for randomized trials comparing revascularization plus MT vs MT alone in patients with CCS. Treatment effects were measured by rate ratios (RRs) with 95% CIs, using random-effects models. Noncardiac mortality was the prespecified endpoint. The study is registered with PROSPERO (CRD42022380664). RESULTS: Eighteen trials were included involving 16,908 patients randomized to either revascularization plus MT (n = 8,665) or to MT alone (n = 8,243). No significant differences were detected in noncardiac mortality between the assigned treatment groups (RR: 1.09; 95% CI: 0.94-1.26; P = 0.26), with absent heterogeneity (I2 = 0%). Results were consistent without the ISCHEMIA trial (RR: 1.00; 95% CI: 0.84-1.18; P = 0.97). By meta-regression, follow-up duration did not affect noncardiac death rates with revascularization plus MT vs MT alone (P = 0.52). Trial sequential analysis confirmed the reliability of meta-analysis, with the cumulative Z-curve of trial evidence within the nonsignificance area and reaching futility boundaries. Bayesian meta-analysis findings were consistent with the standard approach (RR: 1.08; 95% credible interval: 0.90-1.31). CONCLUSIONS: In patients with CCS, noncardiac mortality in late follow-up was similar for revascularization plus MT compared with MT alone.