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Background: In the COMPASS trial, the combination of acetylsalicylic acid (ASA) plus 2.5 mg rivaroxaban twice daily (dual-pathway inhibition, DPI) has been shown to be superior to ASA monotherapy for the reduction in ischemic major adverse cardiovascular events (MACEs, i.e., cardiovascular death, stroke, or myocardial infarction). Methods: The international XATOA registry (Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis) is a prospective post-approval registry that investigates the cardiovascular outcomes of patients taking ASA plus 2.5 mg rivaroxaban. The aim of this pre-specified analysis was to determine the net clinical outcome (NCO), i.e., a combination of MACEs and bleeding events, of DPI in patients from daily clinical practice. Results: Among the 5615 patients, the presence of multiple risk factors resulted in an increase in the total risk of experiencing an NCO event, e.g., from 1.27% (one risk factor) to 2.18% (two risk factors) and 4.07% (three or more risk factors), respectively, with ischemic MACE representing the primary driver of bleeding complications. Conclusions: In the real-world XATOA registry, the annual rate of NCO events was low and numerically similar to those seen in the treatment group in the randomized COMPASS trial.
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BACKGROUND: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. METHODS: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. RESULTS: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052-1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454-0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529-0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478-0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231-1.880), ICH (aHR 2.045, 95% CI 1.329-3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB. CONCLUSIONS: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.
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Fibrilación Atrial , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/complicaciones , Warfarina/uso terapéutico , Fibrilación Atrial/complicaciones , Anticoagulantes/uso terapéutico , Fibrinolíticos/uso terapéutico , Estudios de Cohortes , Isquemia Encefálica/tratamiento farmacológico , Constricción Patológica/inducido químicamente , Constricción Patológica/complicaciones , Constricción Patológica/tratamiento farmacológico , Hemorragia/inducido químicamente , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/complicaciones , Hemorragias Intracraneales/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Arterias , Administración OralRESUMEN
BACKGROUND: This study was conducted to assess the net clinical benefit (NCB) for oral anticoagulant (OAC) in atrial fibrillation (AF) patients according to the CHA2DS2-VASc score. METHODS: Patients with AF were prospectively recruited in the COOL AF Thailand registry from 2014 to 2017. The incidence rate of thromboembolic (TE) events and major bleeding (MB) was calculated. Cox proportional hazards model was used to compare the TE and MB rate in patients with and without OACs in CHA2DS2-VASc score of 0-1 and ≥ 2, respectively. The survival analysis was performed based on CHA2DS2-VASc score. The NCB of OACs was defined as the TE rate prevented minus the MB rate increased multiplied by a weighting factor. RESULTS: A total of 3,402 AF patients were recruited. An average age of patients was 67.38 ± 11.27 years. Compared to non-anticoagulated patients, the Kaplan Meier curve showed anticoagulated patients with CHA2DS2-VASc score of 2 or more had the lower thromboembolic events with statistical significance (p = 0.043) and the higher MB events with statistical significance (p = 0.018). In overall AF patients, there were positive NCB in warfarin patients with CHA2DS2-VASc score of 3 or more while there were positive NCB in DOACs patients regardless of CHA2DS2-VASc score. Females with CHA2DS2-VASc score of 3 or more had a positive NCB regardless of OACs type. Good anticoagulation control (TTR ≥65%) improved an NCB in males with CHA2DS2-VASc score of 3 or more. CONCLUSIONS: AF patients with CHA2DS2-VASc score of 3 or more regardless warfarin or DOACs had a positive NCB. The NCB of OACs was more positive for DOACs compared to warfarin and for females compared to males.
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Fibrilación Atrial , Accidente Cerebrovascular , Tromboembolia , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Warfarina/efectos adversos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Factores de Riesgo , Medición de Riesgo , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Tromboembolia/diagnóstico , Tromboembolia/epidemiología , Tromboembolia/etiologíaRESUMEN
BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns. Shared decision-making (SDM) is an approach that involves patients and healthcare providers in making decisions about treatment options. This study aims to assess the effectiveness of a novel SDM tool for anticoagulation management in AF. METHODS: The study will be a prospective, cluster randomized controlled trial involving 440 patients with AF in 8 community health service centers (clusters) in Shanghai, China. The SDM group will receive anticoagulation management through the novel SDM tool, while the control group will receive standard care. The follow-up period will be at least 2 years. The primary outcome will be any bleeding event, while secondary outcomes include the accordance of stroke prophylaxis for AF according to the current guidelines, time in therapeutic range (TTR), the occurrences of major bleeding and thrombosis events, and patient knowledge, adherence, and satisfaction. DISCUSSION: This study will provide evidence of the effectiveness of shared decision-making in improving the appropriateness of OAC use in Chinese AF patients. The findings may inform the development of guidelines and policies for the management of AF and anticoagulation therapy in China and other countries. TRIAL REGISTRATION: ChiCTR ChiCTR2200062123. Registered on 23 July 2022.
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Fibrilación Atrial , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Anticoagulantes/efectos adversos , Estudios Prospectivos , China , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/complicaciones , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non-gender CHA2DS2-VASc scores 0-1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non-gender CHA2DS2-VASc scores 0-1. Methods: This multi-center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-VKA oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0-1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/mL], creatinine clearance [<50 mL/min], and dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT, including composite thrombotic events (ischemic stroke, systemic embolism, and myocardial infarction) and major bleeding events. Results: We included 2465 patients (age 56.2 ± 9.5 years; female 27.0%) followed-up for 4.0 ± 2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. With detailed risk stratification using the ABCD score, NOAC showed a significant positive NCB compared with the other ATTs (SAPT vs. NOAC, NCB 2.01, 95% confidence interval [CI] 0.37-4.66; VKA vs. NOAC, NCB 2.38, 95% CI 0.56-5.40) in ABCD score ≥1. ATT failed to show a positive NCB in patients with truly low stroke risk (ABCD score = 0). Conclusions: In the Korean AF cohort at non-gender CHA2DS2-VASc scores 0-1, NOAC showed significant NCB advantages over VKA or SAPT with ABCD score ≥1.
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Adjusting antiplatelet strategies after antiplatelet-associated gastrointestinal bleeding (GIB) is a complex clinical challenge. To assess the risk of outcomes at different times of resumption of antiplatelet therapy in an attempt to find the optimal time to resume therapy. The study analyzed consecutive patients with antiplatelet-associated GIB from Beijing Friendship Hospital Information System between October 2019 and June 2022. The primary outcomes were recurrent bleeding, major adverse cardiovascular and cerebrovascular events (MACE), and all-cause death. Multivariate-adjusted Cox proportional hazards models were used to evaluate the risks of these outcomes. The receiver operating characteristic curve was used to find the optimal time to resume treatment. Of the 617 patients with GIB after antiplatelet therapy successfully followed up, the median follow-up was 246 (interquartile range: 120-466) days, most patients (87.36%) interrupted therapy after GIB and 45.22% resumed within 90 days, of which 35.13% resumed within 7 days and 64.87% resumed after 7 days. Resumption therapy had a low risk of recurrent bleeding (uninterrupted as a reference: HR 0.32, 95% CI 0.15-0.67, p = 0.003), MACE (no resumption as a reference: HR 0.66, 95% CI 0.45-0.98, p = 0.037), and all-cause death (no resumption as a reference: HR 0.18, 95% CI 0.08-0.40, p < 0.001). And resuming therapy within 7 days had a lower risk of MACE (HR 0.18, 95% CI 0.08-0.44, p < 0.001) than after 7 days without a significantly higher risk of re-bleeding. The optimal time point for resuming therapy in this study was 8.5 days. Resuming antiplatelet therapy after GIB provides better clinical benefits compared to discontinued and uninterrupted therapy, especially compared with resuming after 7 days, resuming within 7 days is associated with a lower risk of MACE and a less significant increased risk of recurrent bleeding, leading to a higher net clinical benefit. China Clinical Trial Registration: ChiCTR2200064063.
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Hemorragia Gastrointestinal , Inhibidores de Agregación Plaquetaria , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/terapia , Riesgo , China , Anticoagulantes/uso terapéuticoRESUMEN
BACKGROUND: The ideal treatment for patent foramen ovale (PFO) in patients with cryptogenic stroke remains controversial and is being evaluated. The objective of this study was to evaluate the net clinical benefit (NCB) between PFO closure and medical treatment. METHODS: We searched three electronic databases from inception until January 2022. The primary outcomes were the NCB-1, defined as the cumulative incidence of stroke, major bleeding, atrial fibrillation/flutter, and serious procedural or device complications; the NCB-2 and NCB-3 were defined as NCB1 but using a weighted factor of 0.5 and 0.25 for atrial fibrillation/flutter events, respectively. We also evaluated each component outcome of NCB as a secondary outcome. Risk ratios (RR) and 95% confidence intervals (CI) of each outcome were calculated (random-effects model). RESULTS: Our analysis included six RCTs (n = 3750 patients). The rates of NCB-1, NCB-2, and NCB-3 were not different between PFO closure and medical treatment. The heterogeneity between trials was low to moderate. Stroke showed a significant relative decrease of 44% (95% CI, 21-60%), favoring the PFO closure arm. Atrial fibrillation/flutter increased by 4.04 times (95% CI, 1.57-8.89) in the PFO closure compared with the medical treatment group. In a meta-regression analysis, the reduction in NCB-1 with PFO closure increased as the proportion of patients treated with the Amplatzer device increased (p = 0.02), and the reduction in NCB-1, NCB-2, and NCB-3 with PFO closure increased as the proportion of patients treated with substantial PFO size increased (p = 0.03). CONCLUSION: The NCB between PFO closure and medical treatment was not different, suggesting individualized treatment to maximize benefit.
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Fibrilación Atrial , Aleteo Atrial , Foramen Oval Permeable , Accidente Cerebrovascular Isquémico , Dispositivo Oclusor Septal , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Recurrencia Local de Neoplasia/complicaciones , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular Isquémico/complicaciones , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/cirugía , Prevención Secundaria , Cateterismo Cardíaco , Aleteo Atrial/etiología , Resultado del Tratamiento , Dispositivo Oclusor Septal/efectos adversos , RecurrenciaRESUMEN
OBJECTIVES: To assess the effect of patient preferences on the net clinical benefit (NCB) of an antiplatelet therapy for the secondary prevention of cardiovascular complications. STUDY DESIGN AND SETTING: Risk equations were developed to estimate the individual predicted risk of key outcomes of antiplatelet treatment in patients with a prior myocardial infarction using the Clinical Practice Research Datalink linked to the Hospital Episode Statistics and UK Office of National Statistics databases. Patient preferences for outcomes of antiplatelet therapies were elicited in a separate discrete choice experiment survey. Trial hazard ratios, relative to placebo, were used to calculate the per-patient NCB using equal or preference weighting of outcomes. RESULTS: Risk equations were estimated using 31,941 adults in the Clinical Practice Research Datalink population, of which 22,125 were included in the benefit-risk assessment. The mean NCB was lower in the preference-weighted than in the equal-weighted analysis (0.040 vs. 0.057; P < 0.0001), but the direction of effect was unchanged by the weighting. In analyses stratified by the presence of bleeding risk factors, including preference weighting altered the ranking of subgroups by NCB. CONCLUSION: Patient preference weighting may have a significant effect on NCB and should be included in personalized benefit-risk assessments.
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Infarto del Miocardio , Inhibidores de Agregación Plaquetaria , Adulto , Hemorragia/inducido químicamente , Humanos , Infarto del Miocardio/tratamiento farmacológico , Prioridad del Paciente , Inhibidores de Agregación Plaquetaria/efectos adversos , Medición de RiesgoRESUMEN
Background: Evidence from recent studies has shown the benefits of colchicine for patients with coronary artery disease. The aim was to assess the effect of colchicine treatment on cardiovascular events, with an estimation of the risk of discontinuation and net clinical benefit. Methods and Results: Fourteen trials with a total of 13,186 patients were selected through a systematic search. Colchicine therapy significantly reduced the relative risk of primary endpoint by about 30% [RR 0.70 (95%CI:0.56-0.88)]. Compared with placebo, colchicine significantly reduced the risk of ischemia-driven revascularization [RR 0.57 (95%CI 0.41-0.80)], ischemia-driven revascularization and resuscitation [RR 0.50 (95%CI 0.34-0.73)], myocardial infarction [RR 0.73 (95%CI 0.57-0.95)], and stroke [RR 0.49 (95%CI 0.30-0.7)]. Patients treated with colchicine in comparison with placebo have a significant increase in the risk of treatment cessation (RR 1.60 95%CI 1.06-2.42). However, in the analysis which excluded studies without placebo, the relative risk of discontinuation was smaller (RR 1.34 95%CI 0.97-1.84) and in the three largest studies, the risk of discontinuation was lower and insignificant [RR 1.26 (95%CI 0.87-1.83)]. The net clinical benefit was 17.8/1,000 patients (p < 0.001). Conclusion: In coronary artery disease, low-dose colchicine significantly reduces the risk of the primary composite endpoint by about 30%. The drug should be considered as part of the preventive treatment in patients with good tolerance.
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Background: Venous thromboembolism (VTE) is highly prevalent in cancer patients. Recent guidelines recommend considering direct oral anticoagulants (DOACs) for the treatment of cancer-associated thrombosis (CAT). However, direct head-to-head comparisons among DOACs are lacking, and almost no net clinical benefit (NCB) analysis has been performed in patients with CAT. Methods: We systematically searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) reporting on recurrent VTE, major bleeding, or clinically relevant bleeding events in patients with CAT who received DOACs and low-molecular-weight heparins. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using a random-effect model. Surface under the cumulative ranking curve (SUCRA) values were calculated, and a trade-off analysis was performed to estimate the NCB. Results: Overall, four RCTs involving 2,894 patients were enrolled. DOACs were more effective than dalteparin in reducing the risk of recurrent VTE (RR: 0.62, 95% CI: 0.44-0.87), with a comparative risk of major bleeding (RR: 1.33, 95% CI: 0.84-2.11) and an increased risk of clinically relevant bleeding (RR: 1.45, 95% CI: 1.05-1.99). No significant difference was observed among individual anticoagulants in terms of recurrent VTE and major bleeding. With respect to the ranking of each anticoagulant for the primary outcome, edoxaban (SUCRA: 69.2) was more effective than dalteparin (SUCRA: 60.7), rivaroxaban (SUCRA: 60.7), and apixaban (SUCRA: 25.5) in reducing VTE recurrence. For major bleeding, apixaban (SUCRA: 76.3) had the highest cumulative ranking probability, followed by edoxaban (SUCRA: 66.4), dalteparin (SUCRA: 28.8), and rivaroxaban (SUCRA: 28.5). Similar results were observed for clinically relevant bleeding. In terms of both benefit and safety outcomes, DOACs, especially edoxaban, seemed to confer a better NCB profile than dalteparin. Conclusions: DOACs are a safe and effective alternative therapy to dalteparin in patients with CAT. Among them, edoxaban might provide a good risk-to-benefit balance. However, because of the lack of head-to-head studies, further investigations are needed to confirm our findings.
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BACKGROUND: Ambulatory cancer patients carry a high risk of venous thromboembolism (VTE). However, the optimal prophylaxis strategy remains controversial. This meta-analysis compared the effectiveness and safety of apixaban, rivaroxaban, low molecular weight heparin (LMWH), semuloparin, aspirin, and warfarin for the prevention of VTE in ambulatory cancer patients. METHODS: A systematic review and network meta-analysis was performed. PubMed, the Cochrane Central Register of Controlled Trails (CENTRAL) and EMBASE electronic databases were searched from inception to 26 April 2019. In the meta-analysis, 19 randomized controlled trials (RCTs) in ambulatory cancer patients administrated venous thromboprophylaxis agents were included. The primary outcome was the risk of VTE. Safety outcomes included the occurrence of major-bleeding. Two investigators identified the studies and performed data extraction. A network meta-analysis was performed and agents were ranked using cumulative ranking (SUCRA) probabilities. RESULTS: We identified 19 studies, including 11,430 patients comparing 10 interventions. Compared to placebo controls, apixaban (5 mg) showed the highest efficacy for the prevention of VTE [odds ratio (OR) 0.36, 95% confidence interval (CI): 0.18-0.71, SUCRA=69.5] and was more effective than LMWH (OR 0.5, 0.39-0.63; SUCRA=52.1) or warfarin (OR 0.75, 95% CI: 0.35-1.59; SUCRA=25.6). Moreover, the safety of apixaban (5 mg) (OR 1.41, 95% CI: 0.33-5.93; SUCRA=58.5) was higher than LMWH (OR 1.96, 95% CI: 0.99-3.86; SUCRA=44.1) or warfarin (OR 3.06, 95% CI: 1.03-9.08; SUCRA=29.1). There were no significant differences between placebo and experimental groups in terms of patient deaths. CONCLUSIONS: Anticoagulation therapies in ambulatory cancer patients can significantly reduce the risk of VTE. However, this protective effect was associated with a significantly increased risk of major bleeding. Apixaban at the appropriate dose can decrease the risk of VTE without increasing the bleeding risk. These findings require validation in larger study cohorts.
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Neoplasias , Tromboembolia Venosa , Anticoagulantes/efectos adversos , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Neoplasias/tratamiento farmacológico , Metaanálisis en Red , Tromboembolia Venosa/prevención & controlRESUMEN
Atrial fibrillation is defined as subclinical (SAF) when occurs without symptoms and is discovered only during the interrogation of permanent or temporary cardiac implantable devices. The significant interest in this condition derives from the fact that could easily be otherwise undiagnosed, portending to a potential serious neurological and cardiovascular consequences. The diagnosis of SAF is important for both the primary form and for patients after a stroke, and an appropriate management of antithrombotic treatment becomes a central instrument of prevention. Atrial fibrillation carries a five times increase in the thromboembolic risk. The subclinical asymptomatic forms of atrial tachyarrhythmias and fibrillation, diagnosed by interrogation of implantable cardiac devices, foretell a non-irrelevant risk of stroke, significantly higher than the one for patients without rhythm disturbances. Regardless the cause, the long-lasting asymptomatic arrhythmias, in patients with a significant risk profile, predict more important consequences and can justify anticoagulant treatment, also in primary prevention settings.
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BACKGROUND: Heart failure (HF) is associated with an increased incidence of thromboembolic events. Antithrombotic treatment could reduce the stroke risk, whereas increase the bleeding risk. Whether antithrombotic treatment should be a routine therapy for HF and sinus rhythm (SR) patients remains unanswered. METHODS: We systematically searched Medline, Embase, Cochrane Library databases, and ClinicalTrials.gov Website for randomized controlled trials (RCTs) studying antithrombotic therapy in HF and SR patients. The primary outcomes of efficacy and safety were defined as stroke and major bleeding, respectively. The network meta-analysis was conducted. The results were expressed as relative risks (RRs) with 95% confidence intervals (95% CIs), and pooled using a random-effects model. The surface under the cumulative ranking curves (SUCRA) was calculated and trade-off analysis of net clinical benefit (NCB) was estimated. RESULTS: Five studies totally involving 9390 patients were included. A significantly decreased risk of stroke was found for patients with HF and SR, when rivaroxaban was compared with placebo (RR: 0.67, 95%CI: 0.47-0.96) and warfarin was compared with antiplatelets (RR: 0.49, 95%CI: 0.33-0.73). Warfarin (RR: 7.96, 95%CI: 1.06-59.88) and rivaroxaban (RR: 1.65, 95%CI: 1.16-2.33) were associated with a significant increase in the risk of major bleeding when compared with placebo. Considering the ranking of each antithrombotic therapy for primary outcomes, warfarin (SUCRA: 78.2) emerged with the highest cumulative ranking probability for stroke, with rivaroxaban (SUCRA: 73.9) and antiplatelet agents (SUCRA: 19.6) ranked behind. In terms of major bleeding, rivaroxaban (SUCRA: 57.6) was the safer intervention compared with antiplatelet agents (SUCRA: 43.5) or warfarin (SUCRA: 2.9). No difference was observed considering all-cause death, MI and hospitalization of HF among all different antithrombotic regimens. Rivaroxaban was considered as a reasonably effective and the safe antithrombotic agent for HF and SR patients. CONCLUSIONS: Rivaroxaban might the optimal antithrombotic regimen balancing stroke and major bleeding for HF patients with SR. The results might support the attempt to anticoagulation on HF and SR patients. However, further specialized designs of RCTs are necessary to draw a robust conclusion.
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Insuficiencia Cardíaca , Tromboembolia , Anticoagulantes/efectos adversos , Fibrinolíticos/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Metaanálisis en Red , Inhibidores de Agregación Plaquetaria , Tromboembolia/tratamiento farmacológico , Tromboembolia/prevención & controlRESUMEN
BACKGROUND: Rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid (aspirin; ASA) 100 mg reduced the risk of cardiovascular events as compared with ASA monotherapy in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) but increased the risk of major bleedings. Analysis of net clinical benefit (NCB) is of key clinical relevance and represents an integrated measure of overall patient outcome. METHODS: The current prespecified analysis was performed to assess the NCB of adding rivaroxaban 2.5 mg twice daily to ASA monotherapy in patients with chronic vascular disease in the COMPASS study cohort (intention-to-treat study population), with a specific focus on high-risk subgroups. The predefined NCB outcome was the composite of cardiovascular death, stroke, myocardial infarction, fatal bleeding, or symptomatic bleeding into a critical organ. RESULTS: A lower number of NCB adverse outcomes was observed with rivaroxaban 2.5 mg twice daily plus ASA versus ASA alone (hazard ratio, 0.80 [95% CI, 0.70-0.91], P=0.0005), which became increasingly favorable with longer treatment duration. The main drivers of NCB outcomes were "efficacy" events, in particular stroke (0.5%/y versus 0.8%/y; hazard ratio, 0.58 [95% CI, 0.44-0.76], P<0.0001) and cardiovascular death (0.9%/y versus 1.2%/y; hazard ratio, 0.78 [95% CI, 0.64-0.96], P=0.02), whereas the bleeding components of the NCB, in particular fatal bleeding (0.09%/y versus 0.06%/y; hazard ratio, 1.49 [95% CI 0.67-3.33], P=0.32), only represented a minority of NCB events. In selected high-risk subgroups, including patients with polyvascular disease (≥2 vascular beds affected with atherosclerosis), impaired renal function, heart failure, and/or diabetes mellitus, a larger absolute risk reduction for experiencing a NCB event was observed. CONCLUSIONS: Compared with ASA monotherapy, the combination of rivaroxaban 2.5 mg twice daily plus ASA resulted in fewer NCB events primarily by preventing adverse efficacy events, particularly stroke and cardiovascular mortality, whereas severe bleedings were less frequent and with less clinical impact. The NCB was particularly favorable in high-risk subgroups and those with multiple risk characteristics. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01776424.
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Aspirina/administración & dosificación , Rivaroxabán/administración & dosificación , Enfermedades Vasculares/tratamiento farmacológico , Anciano , Enfermedad Crónica , Manejo de la Enfermedad , Quimioterapia Combinada , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del Tratamiento , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/epidemiología , Enfermedades Vasculares/etiologíaRESUMEN
AIMS: A number of studies have attempted to demonstrate the benefits associated with personalized antiplatelet therapy guided by platelet function testing, which has led to disappointing findings. In this study, we used a new platelet function test to guide antiplatelet therapy in stable coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the present randomized controlled trial, a total of 2237 patients with stable CAD undergoing PCI were randomly chosen to be administered personalized antiplatelet therapy (personalized group; n = 1123) or standard antiplatelet treatment (standard group; n = 1114). The patients in the standard therapy group, without detecting the platelet aggregation rate, were administered a 75 mg/day clopidogrel maintenance dosage plus 100 mg/day of aspirin for at least 6 months after the procedure. For the patients in the personalized therapy group, the antiplatelet strategy was performed according to the maximum aggregation rate (MAR), determined using a novel platelet analyser, PL-12. If MAR > 55%, 90 mg ticagrelor was administered twice daily plus 100 mg/day of aspirin after PCI. If MAR ≤55%, 75 mg/day clopidogrel plus 100 mg/day of aspirin was administered after PCI. The primary endpoint was net clinical adverse events, which were a composite of cardiac death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding [Bleeding Academic Research Consortium (BARC) definitions, Type 2, 3, or 5], in the 180-day period after randomization. The primary endpoint was reached in 58 patients in the personalized group, compared with 85 patients in the standard group [5.1% vs. 7.5%, hazard ratio (HR) 0.678, 95% confidence interval (CI) 0.486-0.947, P = 0.023], on intention-to-treat analysis. We also found that the net clinical adverse events (including ischaemic and bleeding events) were significantly reduced in the personalized group at 30 days after PCI compared to the standard group (1.5% vs. 3.0%, HR 0.510, 95% CI 0.284-0.915, P = 0.020). We did not find a significant difference in major bleeding events at either the 30-day (0.5% vs. 0.3%, P = 0.322) or the 180-day follow-up (2.1% vs. 1.6%, P = 0.364) between the two groups. CONCLUSION: The present study suggests that personalized antiplatelet therapy according to MAR can significantly improve the net clinical benefit 180 days after PCI.
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Enfermedad de la Arteria Coronaria/terapia , Monitoreo de Drogas/métodos , Terapia Antiplaquetaria Doble , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Agregación Plaquetaria/efectos de los fármacos , Recuento de Plaquetas , Anciano , Trastornos Cerebrovasculares/etiología , Trastornos Cerebrovasculares/mortalidad , Trastornos Cerebrovasculares/prevención & control , China , Toma de Decisiones Clínicas , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/mortalidad , Terapia Antiplaquetaria Doble/efectos adversos , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Trombosis/etiología , Trombosis/mortalidad , Trombosis/prevención & control , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: The publication of new trials brought additional data to the controversial topic of aspirin use in diabetic patients for primary prevention. Therefore, we aimed to systematically review all randomized controlled trials evaluating the clinical impact of aspirin in this setting. METHODS: We searched for randomized controlled trials (RCTs) evaluating the impact of aspirin in patients with diabetes in primary prevention, in MEDLINE, EMBASE, CENTRAL (November/2018). The primary outcomes were all-cause mortality and the composite outcome of major adverse cardiovascular events (MACE). A meta-analysis was performed deriving risk ratios (RR) and 95% confidence intervals (CI). RESULTS: All-cause mortality was not significantly reduced with RR 0.96 (95% CI 0.90-1.03; 7RCT; 27,595 patients). Regarding MACE, there was an 8% risk reduction (RR 0.92, 95% CI 0.84-0.999; I2=0%; 8RCT; 29,814 patients). The risks of major bleeding (RR 1.30, 95% CI 1.10-1.53; 2RCTs, 18,019 patients), and major GI bleeding (RR 1.39, 95% CI 1.08-1.80; 2RCTs, 18,019 patients) were significantly increased. The risks of cardiovascular mortality, myocardial infarction, stroke and amputation were not significantly different from control arm. CONCLUSIONS: Aspirin use among diabetic patients in primary prevention appears was associated with increased risk of major bleeding, a modest decrease of MACE and lack of mortality benefit.
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Aspirina/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus/terapia , Prevención Primaria/métodos , Enfermedades Cardiovasculares/etiología , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéuticoRESUMEN
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and its prevalence increases with age. Few data are available about the clinical performance of direct oral anticoagulant (DOACs) in patients aged ≥ 80 years with AF. The aim of our propensity score matched cohort study was to compare the safety and efficacy of DOACs versus well-controlled VKA therapy among octogenarians with AF in real life setting. Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation Research Database (NCT03760874), which includes all AF patients followed by the participating centers, through outpatient visits every 3 to 6 months. The database was queried for AF patients aged ≥ 80 years who received DOACs or VKAs treatment. The primary effectiveness endpoint was the occurrence of thromboembolic events (a composite of stroke, transient ischemic attack, systemic embolism); the primary safety endpoint was the occurrence of major bleeding; the secondary endpoint was all-cause mortality. The database query identified 774 AF patients aged ≥ 80 years treated with VKAs and 279 with DOACs. Propensity score (2:1) matching selected 252 DOAC and 504 VKA recipients. The mean follow-up was 31.07 ± 14.09 months. The incidence rate of thromboembolic events was 13.79 per 1000 person-years [14.80 in DOAC vs 13.34 in VKA group, Hazard Ratio 1.10; 95% confidence interval (CI) 0.49 to 2.45; P = 0.823]. The incidence rate of intracranial hemorrhage (ICH) was 8.06 per 1000 person-years (3.25 in DOAC vs 10.23 in VKA group, HR 0.33; 95% CI 0.07 to 1.45; P = 0.600). Through these incidence rates, we found a positive net clinical benefit (NCB) of DOACs over VKAs, equal to + 9.01. The incidence rate of all-cause mortality was 105.05 per 1000 person-years (74.67 in DOAC vs 118.67 in VKA group, Hazard Ratio 0.65; 95% CI 0.47 to 0.90; P = 0.010). The concomitant use of antiinflammatory drugs (HR 7.90; P < 0.001) were found to be independent predictor of major bleeding. Moreover, age (HR 1.17; P < 0.002) and chronic kidney disease (HR 0.34; P = 0.019) were found to be independently associated with thromboembolic events. In our study no significant difference in terms of both thromboembolic and major bleeding events, but a significant lower incidence of all-cause mortality, was detected in AF patients aged ≥ 80 years treated with DOACs vs VKAs.
Asunto(s)
Anticoagulantes , Fibrilación Atrial , Bases de Datos Factuales , Hemorragia , Tromboembolia , Vitamina K , Administración Oral , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/mortalidad , Supervivencia sin Enfermedad , Estudios de Seguimiento , Hemorragia/inducido químicamente , Hemorragia/mortalidad , Humanos , Incidencia , Puntaje de Propensión , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia , Tromboembolia/mortalidad , Tromboembolia/prevención & control , Vitamina K/administración & dosificación , Vitamina K/efectos adversosRESUMEN
Background: Anticoagulation for patients with atrial fibrillation (AF) complicated by left atrial thrombi (LAT) is a frequent cause of bleeding complications, but risk factors remain unknown. MethodsâandâResults: Of 3,139 AF patients who underwent transesophageal echocardiography, 82 with LAT under anticoagulation were included in this study. Patients treated with combination antiplatelet and anticoagulant therapy (n=31) were compared with those receiving anticoagulant monotherapy (n=51) to investigate the effects of antiplatelet agents during anticoagulation on bleeding complications. Over a mean (±SD) follow-up of 878±486 days, bleeding events occurred more frequently in the combination therapy than monotherapy group (58% vs. 20%; P<0.001), but there was no significant difference in embolic events (6.5% vs. 3.9%; P=0.606). Kaplan-Meier analysis also showed a significantly higher rate of bleeding events in the combination therapy group, but no significant difference in the rate of embolic events. Inverse probability of treatment weighting revealed that combination therapy was independently associated with an increased risk of bleeding (hazard ratio [HR] 2.98, 95% confidence interval [CI] 1.14-7.89, P=0.026), but not with the risk of embolic events (HR 0.30, 95% CI 0.04-2.59, P=0.275). Net clinical benefit analysis was almost negative for combination therapy vs. monotherapy. Conclusions: In patients with AF and LAT, combination therapy was significantly associated with an increased risk of bleeding events, but not with a reduced risk of embolic events.
RESUMEN
BACKGROUND: Two methods combining survival and health-related quality of life (HRQoL) data in glioma trials to calculate the "net clinical benefit" were evaluated: Quality-adjusted effect sizes (QASES) and joint modeling (JM). METHODS: The net clinical benefit in two trials was calculated as proof of concept for other trials. With the QASES method, effect sizes for differences in progression-free survival (PFS) or overall survival (OS) and HRQoL between the experimental arm and standard treatment arm were calculated, while the relative emphasis placed on survival/HRQoL varied. JM allows simultaneous modeling of HRQoL and OS/PFS. RESULTS: In the EORTC 26951 trial, combined radiochemotherapy significantly prolonged OS (difference 11.7 months), but also resulted in more patients experiencing clinically relevant worsening (≥10 points) in appetite loss and nausea/vomiting shortly after treatment. Using QASES, the survival benefit of additional procarbazine, lomustine, and vincristine (PCV) decreased from 42.3 months to 29.5 and 28.2 months when accounting for appetite loss and nausea/vomiting, respectively. JM analyses resulted in a loss of the beneficial effect of additional PCV between 13% and 24% when adjusting for different HRQoL parameters. The EORTC 22033 trial showed no significant PFS difference between radiotherapy or temozolomide alone (46 vs 39 months), nor clinically relevant differences in HRQoL. JM analyses also showed no significant association between PFS and HRQoL scales/items, whereas QASES showed that temozolomide alone was more favorable when considering symptom burden (47-49 instead of 39 months). CONCLUSIONS: Both methods resulted in different outcomes, but adjusting for the impact of treatment on HRQoL resulted in theoretically reduced survival benefits.