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2.
Nat Rev Cardiol ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953535

RESUMO

Advances in antiplatelet therapies for patients with cardiovascular disease have improved patient outcomes over time, but the challenge of balancing the risks of ischaemia and bleeding remains substantial. Moreover, many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. Therefore, novel strategies are needed to prevent clinical events through mechanisms beyond platelet inhibition and with an acceptable associated risk of bleeding. The advent of non-vitamin K antagonist oral anticoagulants, which attenuate fibrin formation by selective inhibition of factor Xa or thrombin, has renewed the interest in dual-pathway inhibition strategies that combine an antiplatelet agent with an anticoagulant drug. In this Review, we highlight the emerging pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with different manifestations of cardiovascular disease, such as coronary artery disease, cerebrovascular disease and peripheral artery disease.

3.
Thromb Haemost ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31940677

RESUMO

BACKGROUND: Western guidelines recommend an international normalized ratio (INR) range of 2 to 3 when using warfarin for stroke prevention in atrial fibrillation (AF), but lower INR ranges are frequently used in East Asia. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) in AF patients comparing the effect of lower versus standard INR targets on thromboembolism, major bleeding, and mortality. METHODS: We searched Western databases including Cochrane CENTRAL, Medline, and Embase as well as Chinese databases including SinoMed, CNKI, and Wanfang Data. We pooled risk ratios (RRs) using random-effects model. We grouped INR targets in two ways: (1) any study-specific lower versus standard targets and (2) INR ranges of approximately 1.5 to 2 versus 2 to 3. RESULTS: Seventy-nine RCTs (n = 12,928) met eligibility criteria: 74 (n = 11,322) from East Asia and 5 (n = 1,606) from Western countries. Compared with standard targets, lower INR ranges were associated with higher rates of thromboembolism (76 RCTs, n = 12,577: 7.1% vs. 4.4%, RR 1.50, 95% confidence interval [CI] 1.29-1.74, I 2 = 0%), lower rates of major bleeding (61 RCTs, n = 10,815: 2.2% vs. 4.4%, RR 0.54, 95% CI 0.44-0.67, I 2 = 0%), and similar mortality (32 RCTs, n = 7,327: 4.8% vs. 5.2%, RR 1.00, 95% CI 0.85-1.19, I 2 = 0%). Results were similar when comparing target ranges of approximately 1.5 to 2 versus 2 to 3. CONCLUSION: Moderate quality evidence suggests lower INR targets reduce bleeding but increase thromboembolism in AF. The data are dominated by East-Asian studies, limiting generalizability to Western populations. Until higher quality data demonstrate otherwise, an INR range of 2 to 3 should remain standard for thromboembolic prophylaxis in AF.

5.
Gastroenterology ; 158(1): 285-286, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31704300
6.
Circulation ; 140(23): 1933-1942, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31790297

RESUMO

Managing severe valvular heart disease with mechanical valve replacement necessitates lifelong anticoagulation with a vitamin K antagonist. Optimal anticoagulation intensity for patients with mechanical valves remains uncertain; current recommendations are inconsistent across guideline bodies and largely based on expert opinion. In this review, we outline the history of anticoagulation therapy in patients with mechanical heart valves and critically evaluate current antithrombotic guidelines for these patients. We conclude that randomized trials evaluating optimal anticoagulation intensity in patients with mechanical valves are needed, and that future guidelines must better justify antithrombotic treatment recommendations.

7.
Eur J Intern Med ; 70: 1-7, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31679885

RESUMO

The achievements with antithrombotic therapy over the past 50 years have been monumental and the disappointments relatively few. In this review, we will discuss, chronologically, the major developments of the two recognized classes of antithrombotics - anticoagulants and antiplatelet agents.

8.
Future Cardiol ; 15(6): 395-404, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31668083

RESUMO

Direct oral anticoagulants are associated with lower rates of bleeding than vitamin K antagonists, but life-threatening bleeding still occurs. Andexanet alfa is a catalytically inactive recombinant modified human factor Xa molecule that reverses the anticoagulant effect of direct and indirect acting factor Xa inhibitors. In the ANNEXA-4 study, treatment with andexanet was associated with a 92% reduction in median anti-Xa activity levels and excellent or good hemostasis in 82% of patients presenting with serious bleeding while receiving apixaban or rivaroxaban. In this review, we discuss the burden of bleeding in anticoagulated patients and the need for reversal agents, review the mechanism of action of andexanet and critically evaluate the evidence for its efficacy and safety.

9.
Am Heart J ; 218: 46-56, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706144

RESUMO

Because patients with stable coronary artery disease are at continued risk of major atherosclerotic events despite effective secondary prevention strategies, there is a need to continue to develop additional safe, effective and well-tolerated therapies for secondary prevention of cardiovascular disease. RATIONALE AND DESIGN: The LoDoCo (Low Dose Colchicine) pilot trial showed that the anti-inflammatory drug colchicine 0.5 mg once daily appears safe and effective for secondary prevention of cardiovascular disease. Colchicine's low cost and long-term safety suggest that if its efficacy can be confirmed in a rigorous trial, repurposing it for secondary prevention of cardiovascular disease would have the potential to impact the global burden of cardiovascular disease. LoDoCo2 is an investigator-initiated, international, multicentre, double-blind, event driven trial in which 5522 patients with stable coronary artery disease tolerant to colchicine during a 30-day run-in phase have been randomized to colchicine 0.5 mg daily or matching placebo on a background of optimal medical therapy. The study will have 90% power to detect a 30% reduction in the composite primary endpoint: cardiovascular death, myocardial infarction, ischemic stroke and ischemia-driven coronary revascularization. Adverse events potentially related to the use of colchicine will also be collected, including late gastrointestinal intolerance, neuropathy, myopathy, myositis, and neutropenia. CONCLUSION: The LoDoCo2 Trial will provide information on the efficacy and safety of low-dose colchicine for secondary prevention in patients with stable coronary artery disease.

10.
Stroke ; 50(12): 3347-3354, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31690249

RESUMO

Background and Purpose- Diabetes mellitus (DM) and non-DM patients without coronary artery disease (CAD) have a similar low risk of myocardial infarction after coronary angiography. The risk of ischemic stroke in DM patients dependent on CAD status is less explored. We examined whether DM patients without CAD have a risk of ischemic stroke similar to that in patients with neither DM nor CAD. Methods- We conducted a cohort study of patients who underwent coronary angiography between 2004 and 2012 in Western Denmark. Patients diagnosed with previous ischemic stroke or transient ischemic attack were excluded. Patients were stratified according to the presence of DM and CAD. Follow-up started 30 days after coronary angiography. We computed event rates and adjusted incidence rate ratios using patients without DM or CAD as reference. We examined the trend between CAD extent and ischemic stroke in patients with DM. Results- A total of 81 909 patients were included. Median follow-up was 3.8 years. Patients with both DM and CAD were at the highest risk of ischemic stroke (1.32 events per 100 person-years; adjusted incidence rate ratio, 2.00 [95% CI, 1.72-2.32]). Patients with CAD alone (0.77 events per 100 person-years; adjusted incidence rate ratio, 1.27 [95% CI, 1.12-1.44]) or DM alone (0.95 events per 100 person-years; adjusted incidence rate ratio, 1.74 [95% CI, 1.42-2.15]) were at intermediate risk, whereas patients with neither DM nor CAD (0.52 events per 100 person-years) were at the lowest risk. Among patients with DM, extent of CAD was further predictive of risk (Ptrend<0.001). Conclusions- Not only CAD but also DM are associated with the risk of ischemic stroke after coronary angiography. Their combination further increases the risk of ischemic stroke depending on the extent of CAD.

11.
Am Heart J ; 218: 100-109, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31715433

RESUMO

For 4 decades, antithrombotic therapy with aspirin has been a cornerstone of secondary prevention for patients with chronic atherosclerotic cardiovascular disease (ASCVD). Unfortunately, despite the use of evidence-based therapies, patients with ASCVD continue to have recurrent major adverse cardiovascular events including death, myocardial infarction, and stroke-at a rate of approximately 2%-4% per year. To combat this continuing risk, several recent trials have evaluated the efficacy and safety of more intensive antithrombotic strategies through prolonged dual antiplatelet therapy (DAPT), combining a P2Y12 receptor antagonists and low-dose aspirin, or alternatively applying a dual pathway inhibition approach, combining low-dose non-vitamin K antagonist anticoagulant and low-dose aspirin. Both combination strategies have been shown to reduce recurrent ischemic events but at the cost of increased bleeding events. The clinical application of these antithrombotic strategies requires clinicians to assess and balance the risk of recurrent ischemic and bleeding events in an individual patient. Furthermore, clinicians may also need to adapt their antithrombotic strategies to achieve best patient outcomes, as ASCVD is a progressive disease and the risks of cardiovascular ischemic and bleeding events may shift over time. This state-of-the-art article reviews evidence from the trials and provides a practical approach to the application of DAPT and dual pathway antithrombotic therapy in the long-term management of patients with chronic ASCVD.

13.
Eur J Prev Cardiol ; : 2047487319882154, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615291

RESUMO

AIMS: Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease. METHODS AND RESULTS: We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8-2.6) and cardiovascular death (hazard ratio 2.0; 1.5-2.7) were more than twofold higher in patients with 4-6 compared with 0-1 risk factors (p < 0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors (p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors. CONCLUSION: More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events.

14.
BMJ ; 367: l5476, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601578

RESUMO

OBJECTIVE: To assess the effects of different oral antithrombotic drugs that prevent saphenous vein graft failure in patients undergoing coronary artery bypass graft surgery. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, Web of Science, CINAHL, and the Cochrane Library from inception to 25 January 2019. ELIGIBILITY CRITERIA: for selecting studies Randomised controlled trials of participants (aged ≥18) who received oral antithrombotic drugs (antiplatelets or anticoagulants) to prevent saphenous vein graft failure after coronary artery bypass graft surgery. MAIN OUTCOME MEASURES: The primary efficacy endpoint was saphenous vein graft failure and the primary safety endpoint was major bleeding. Secondary endpoints were myocardial infarction and death. RESULTS: This review identified 3266 citations, and 21 articles that related to 20 randomised controlled trials were included in the network meta-analysis. These 20 trials comprised 4803 participants and investigated nine different interventions (eight active and one placebo). Moderate certainty evidence supports the use of dual antiplatelet therapy with either aspirin plus ticagrelor (odds ratio 0.50, 95% confidence interval 0.31 to 0.79, number needed to treat 10) or aspirin plus clopidogrel (0.60, 0.42 to 0.86, 19) to reduce saphenous vein graft failure when compared with aspirin monotherapy. The study found no strong evidence of differences in major bleeding, myocardial infarction, and death among different antithrombotic therapies. The possibility of intransitivity could not be ruled out; however, between-trial heterogeneity and incoherence were low in all included analyses. Sensitivity analysis using per graft data did not change the effect estimates. CONCLUSIONS: The results of this network meta-analysis suggest an important absolute benefit of adding ticagrelor or clopidogrel to aspirin to prevent saphenous vein graft failure after coronary artery bypass graft surgery. Dual antiplatelet therapy after surgery should be tailored to the patient by balancing the safety and efficacy profile of the drug intervention against important patient outcomes. STUDY REGISTRATION: PROSPERO registration number CRD42017065678.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Fibrinolíticos/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Trombose/prevenção & controle , Humanos , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
J Am Coll Cardiol ; 74(14): 1760-1768, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31582135

RESUMO

BACKGROUND: Dabigatran and idarucizumab, its reversal agent, are renally cleared. OBJECTIVES: The purpose of this study was to determine the extent of reversal and outcomes according to baseline renal function in dabigatran-treated nondialysis patients receiving idarucizumab. METHODS: In 503 patients in RE-VERSE AD (Reversal of Effects of Idarucizumab in Patients on Active Dabigatran), the extent of dabigatran reversal and clinical outcomes were compared according to baseline renal function (creatinine clearance: normal ≥80, mild 50 to <80, moderate 30 to <50, and severe <30 ml/min). RESULTS: Compared with patients with normal renal function, those with impaired renal function were older, were more often women, and had lower body mass indexes, more comorbidities, higher CHADS2 scores, and higher dabigatran plasma levels despite more frequent use of lower-dose dabigatran regimens. Regardless of renal function, median reversal measured by dilute thrombin time was 100% within 4 h of idarucizumab administration, and over 98% of patients achieved this with corresponding undetectable levels of unbound dabigatran. By 12 or 24 h, 56% of patients with severe, 29.1% with moderate, and 9.2% with mild renal impairment had dabigatran levels >20 ng/ml compared with 8.3% of patients with normal renal function at baseline. Time to cessation of bleeding and the proportion with normal hemostasis with procedures were similar regardless of renal function, but patients with severe renal impairment had higher 30- and 90-day mortality rates. CONCLUSIONS: Idarucizumab completely reverses dabigatran in >98% of patients regardless of renal function. Although re-elevation of dabigatran levels within 12 to 24 h is more common with renal impairment, the time to bleeding cessation and the extent of hemostasis during procedures are similar. (Reversal of Dabigatran Anticoagulant Effect With Idarucizumab; NCT02104947).

16.
Circ Arrhythm Electrophysiol ; 12(10): e007545, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31610718

RESUMO

BACKGROUND: Oral anticoagulant use is common among patients undergoing pacemaker or defibrillator surgery. BRUISE CONTROL (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial; NCT00800137) demonstrated that perioperative warfarin continuation reduced clinically significant hematomas (CSH) by 80% compared with heparin bridging (3.5% versus 16%). BRUISE-CONTROL-2 (NCT01675076) observed a similarly low risk of CSH when comparing continued versus interrupted direct oral anticoagulant (2.1% in both groups). Using patient level data from both trials, the current study aims to: (1) evaluate the effect of concomitant antiplatelet therapy on CSH, and (2) understand the relative risk of CSH in patients treated with direct oral anticoagulant versus continued warfarin. METHODS: We analyzed 1343 patients included in BRUISE-CONTROL-1 and BRUISE-CONTROL-2. The primary outcome for both trials was CSH. There were 408 patients identified as having continued either a single or dual antiplatelet agent at the time of device surgery. RESULTS: Antiplatelet use (versus nonuse) was associated with CSH in 9.8% versus 4.3% of patients (P<0.001), and remained a strong independent predictor after multivariable adjustment (odds ratio, 1.965; 95% CI, 1.202-3.213; P=0.0071). In multivariable analysis, adjusting for antiplatelet use, there was no significant difference in CSH observed between direct oral anticoagulant use compared with continued warfarin (odds ratio, 0.858; 95% CI, 0.375-1.963; P=0.717). CONCLUSIONS: Concomitant antiplatelet therapy doubled the risk of CSH during device surgery. No difference in CSH was found between direct oral anticoagulant versus continued warfarin. In anticoagulated patients undergoing elective or semi-urgent device surgery, the patient specific benefit/risk of holding an antiplatelet should be carefully considered. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00800137, NCT01675076.

17.
J Am Coll Cardiol ; 74(12): 1519-1528, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31537259

RESUMO

BACKGROUND: In patients with coronary or peripheral artery disease, the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events and mortality and increased bleeding. OBJECTIVES: This study sought to explore the effects of the combination of rivaroxaban and aspirin compared with aspirin on sites, timing, severity, and management of bleeding in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) study. METHODS: This study reports, by treatment group, the number and proportion of patients; hazard rate ratios for bleeding according to site and severity; the timing of bleeding using landmark analyses; and the number and proportion of patients who received blood products and other hemostatic treatments. RESULTS: Of 27,395 patients enrolled (mean age 68 years, 22% women), 18,278 were randomized to the combination of rivaroxaban and aspirin or to aspirin alone and followed for a mean of 23 months. Compared with aspirin alone, the combination increased modified International Society on Thrombosis and Hemostasis major bleeding (288 of 9,152 [3.1%] vs. 170 of 9,126 [1.9%]), (HR: 1.70; 95% CI: 1.40 to 2.05; p < 0.001), International Society on Thrombosis and Hemostasis major bleeding (206 of 9,152 [2.3%] vs. 116 of 9,126 [1.3%]), (HR: 1.78; 95% CI: 1.41 to 2.23; p < 0.0001), and minor bleeding (838 of 9,152 [9.2%] vs. 503 of 9,126 [5.5%]), (HR: 1.70; 95% CI 1.52 to 1.90; p < 0.0001); the combination also increased the need for any red cell transfusion (87 of 9,152 [1.0%] vs. 44 of 9,126 [0.5%]), (HR: 1.97; 95% CI 1.37 to 2.83, p = 0.0002). The gastrointestinal (GI) tract was the most common site of increased major bleeding (140 of 9,152 [1.5%] vs. 65 of 9,126 [0.7%]), (HR: 2.15; 95% CI: 1.60 to 2.89; p < 0.001), and the increase in bleeding was predominantly in the first year after randomization. Approximately one-third of major GI bleeding was gastric or duodenal, one-third was colonic or rectal, and one-third was from an unknown GI site. The study investigators reported that approximately three-quarters of major bleeding episodes were of mild or moderate intensity. A similar proportion of patients in each treatment group who experienced major bleeding received platelets, clotting factors, or other hemostatic agents. CONCLUSIONS: The combination of rivaroxaban and aspirin compared with aspirin alone increased major bleeding, mainly from the GI tract. Most excess bleeding occurred during the first year after randomization, was of mild or moderate intensity, and was managed with conventional supportive therapy. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease [COMPASS]; NCT01776424).

18.
Circulation ; 140(18): 1451-1459, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31510769

RESUMO

BACKGROUND: Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer. METHODS: We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites. RESULTS: Of 27 395 patients enrolled (mean age, 68 years; women, 21%), 2678 (9.8%) experienced any (major or minor) bleeding, 713 (2.6%) experienced major bleeding, and 1084 (4.0%) were diagnosed with cancer during a mean follow-up of 23 months. Among 2678 who experienced bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Gastrointestinal bleeding was associated with a 20-fold higher hazard of new gastrointestinal cancer diagnosis (7.4% versus 0.5%; hazard ratio [HR], 20.6 [95% CI, 15.2-27.8]) and 1.7-fold higher hazard of new nongastrointestinal cancer diagnosis (3.8% versus 3.1%; HR, 1.70 [95% CI, 1.20-2.40]). Genitourinary bleeding was associated with a 32-fold higher hazard of new genitourinary cancer diagnosis (15.8% versus 0.8%; HR, 32.5 [95% CI, 24.7-42.9]), and urinary bleeding was associated with a 98-fold higher hazard of new urinary cancer diagnosis (14.2% versus 0.2%; HR, 98.5; 95% CI, 68.0-142.7). Nongastrointestinal, nongenitourinary bleeding was associated with a 3-fold higher hazard of nongastrointestinal, nongenitourinary cancers (4.4% versus 1.9%; HR, 3.02 [95% CI, 2.32-3.91]). CONCLUSIONS: In patients with atherosclerosis treated with antithrombotic drugs, any gastrointestinal or genitourinary bleeding was associated with higher rates of new cancer diagnosis. Any gastrointestinal or genitourinary bleeding should prompt investigation for cancers at these sites. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

19.
JAMA Neurol ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31524941

RESUMO

Importance: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized clinical trial was stopped early owing to the efficacy of low-dose rivaroxaban plus aspirin in preventing major cardiovascular events. The main reason for early trial termination was the effect of combination therapy on reducing ischemic strokes. Objective: To analyze the association between low-dose rivaroxaban with or without aspirin and different ischemic stroke subtypes. Design, Setting, and Participants: This is a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study that was performed in 33 countries from March 12, 2013, to May 10, 2016. Patients with stable atherosclerotic vascular disease were eligible, and a total of 27 395 participants were randomized and followed up to February 6, 2017. All first ischemic strokes and uncertain strokes that occurred by this date were adjudicated using TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. The analysis of ischemic stroke subtypes was evaluated using an intention-to-treat principle. Statistical analysis was performed from March 12, 2013, to February 6, 2017. Interventions: Participants received rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban (5 mg twice a day), or aspirin (100 mg once a day). Main Outcomes and Measures: Risk of ischemic stroke subtypes during follow-up. Results: A total of 291 patients (66 women; mean [SD] age, 69.4 [8.5] years; 43 [14.8%] had a previous nonlacunar stroke) experienced an ischemic stroke. During the study, 49 patients (16.8%) received a diagnosis of atrial fibrillation. Applying TOAST criteria, 59 strokes (20.3%) were cardioembolic, 54 strokes (18.6%) were secondary to greater than 50% stenosis of the ipsilateral internal carotid artery, 42 strokes (14.4%) had a negative evaluation that met criteria for embolic stroke of undetermined source, and 21 strokes (7.2%) were secondary to small vessel disease. There were significantly fewer cardioembolic strokes (hazard ratio [HR], 0.40 [95% CI, 0.20-0.78]; P = .005) and embolic strokes of undetermined source (HR, 0.30 [95% CI, 0.12-0.74]; P = .006) in the combination therapy group compared with the aspirin-only group. A trend for reduction in strokes secondary to small vessel disease (HR, 0.36 [95% CI, 0.12-1.14]; P = .07) was not statistically significant. No significant difference was observed between the 2 groups in strokes secondary to greater than 50% carotid artery stenosis (HR, 0.85 [95% CI, 0.45-1.60]; P = .61). Rivaroxaban, 5 mg, twice daily showed a trend for reducing cardioembolic strokes compared with aspirin (HR, 0.57 [95% CI, 0.31-1.03]; P = .06) but was not associated with reducing other stroke subtypes. Conclusions and Relevance: For patients with systemic atherosclerosis, low-dose rivaroxaban plus aspirin was associated with large, significant reductions in cardioembolic strokes and embolic strokes of undetermined source. However, these results of exploratory analysis need to be independently confirmed before influencing clinical practice. Trial Registration: ClinicalTrials.gov identifier: NCT01776424.

20.
Eur Heart J ; 40(46): 3771-3778a, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31504399

RESUMO

AIMS : Adding rivaroxaban to aspirin in patients with stable atherosclerotic disease reduces the recurrence of cardiovascular disease (CVD) but increases the risk of major bleeding. The aim of this study was to estimate the individual lifetime treatment benefit and harm of adding low-dose rivaroxaban to aspirin in patients with stable cardiovascular disease. METHODS AND RESULTS : Patients with established CVD from the COMPASS trial (n = 27 390) and SMART prospective cohort study (n = 8139) were used. Using the pre-existing lifetime SMART-REACH model for recurrent CVD, and a newly developed Fine and Gray competing risk-adjusted lifetime model for major bleeding, individual treatment effects from adding low-dose rivaroxaban to aspirin in patients with stable CVD were estimated, expressed in terms of (i) life-years free of stroke or myocardial infarction (MI) gained; and (ii) life-years free from major bleeding lost. Calibration of the SMART-REACH model for prediction of recurrent CVD events in the COMPASS study was good. The major bleeding risk model as derived in the COMPASS trial showed good external calibration in the SMART cohort. Predicted individual gain in life expectancy free of stroke or MI from added low-dose rivaroxaban had a median of 16 months (range 1-48 months), while predicted individualized lifetime lost in terms of major bleeding had a median of 2 months (range 0-20 months). CONCLUSION : There is a wide distribution in lifetime gain and harm from adding low-dose rivaroxaban to aspirin in individual patients with stable CVD. Using these lifetime models, benefits and bleeding risk can be weighed for each individual patient, which could facilitate treatment decisions in clinical practice.

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