Antiplatelet therapy for thromboprophylaxis: the need for careful consideration of the evidence from randomised trials (original) (raw)
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Approach to Outcome Measurement in the Prevention of Thrombosis in Surgical and Medical Patients
Chest, 2012
T his article provides the rationale for the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (AT9) approach to estimating the effect of antithrombotic prophylaxis on patient-important outcomes of pulmonary embolism (PE) and symptomatic venous thrombosis. 1.0 Thromboprophylaxis Reduces Fatal PE in Medical and Surgical Patients Although some studies have limitations of lack of concealment and blinding, evidence from metaanalyses of randomized controlled trials (RCTs) strongly suggests that prophylaxis with an anticoagulant or aspirin reduces symptomatic VTE and fatal This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure effi cacy of the treatment. These trials suggest a benefi t of thromboprophylaxis in reducing fatal PE. In contrast, most of the recent clinical trials comparing the effi cacy of alternative anticoagulants used a surrogate outcome, asymptomatic DVT detected at mandatory venography. This outcome is fundamentally unsatisfactory because it does not allow a trade-off with serious bleeding; that trade-off requires knowledge of the number of symptomatic events that thromboprophylaxis prevents. In this article, we review the merits and limitations of four approaches to estimating reduction in symptomatic thrombosis: (1) direct measurement of symptomatic thrombosis, (2) use of asymptomatic events for relative risks and symptomatic events from randomized controlled trials for baseline risk, (3) use of baseline risk estimates from studies that did not perform surveillance and relative effect from asymptomatic events in randomized controlled trials, and (4) use of available data to estimate the proportion of asymptomatic events that will become symptomatic. All approaches have their limitations. The optimal choice of approach depends on the nature of the evidence available. CHEST 2012; 141(2)(Suppl):e185S-e194S Abbreviations: AT9 5 Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines; IPC 5 intermittent pneumatic compression; LMWH 5 low-molecularweight heparin; PE 5 pulmonary embolism; RCT 5 randomized controlled trial; RR 5 risk ratio; UFH 5 unfractionated heparin; VKA 5 vitamin K antagonist
European Journal of Internal Medicine, 2014
Introduction: Patients with arterial disease receiving antiplatelet agents may develop venous thromboembolism (VTE) and need anticoagulant therapy, although concomitant use of these drugs may increase bleeding risk. We analyzed RIETE data and compared clinical outcomes depending on decision to discontinue or maintain antiplatelet therapy at VTE diagnosis. Methods: Consecutive patients with acute VTE were enrolled in RIETE. Only patients receiving antiplatelet therapy at baseline were included in this analysis. Primary outcomes were: rate of subsequent ischemic events, major bleeding or death during anticoagulation course. Results: 1178 patients who received antiplatelet drugs at VTE diagnosis were included. Antiplatelet therapy was discontinued in 62% of patients. During anticoagulation course, patients also receiving antiplatelet therapy had higher rates of lower limb amputations (2.28 vs. 0.21 events per 100 patients-years; p b 0.01), any ischemic events (5.7 vs. 2.28 events per 100 patients-years; p b 0.05) or death (23.6 vs. 13.9 deaths per 100 patientsyears; p b 0.01). No differences in the rate of major bleeding or recurrent VTE were revealed. In matched analysis, patients on antiplatelet therapy were found to have a significantly higher rate of limb amputations (odds ratio: 15.3; 95% CI: 1.02-229) and an increased number of composite outcomes including all-cause deaths, arterial and VTE events (odds ratio: 1.46; CI: 1.03-2.06), with no differences in major bleeding rate. Conclusion: Concomitant anticoagulant and antiplatelet therapy in patients with VTE and arterial disease is not associated with increased risk for bleeding, recurrent VTE or death. The worse outcome observed in patients who continued antiplatelet therapy requires further investigations.
Thrombosis and Haemostasis, 2019
The double-blind, randomized, AMPLIFY trial compared 6 months' treatment with apixaban (10 mg twice daily for 7 days and 5 mg twice daily thereafter) versus conventional treatment (subcutaneous enoxaparin [1 mg/kg twice daily for ! 5 days] overlapped and followed by warfarin [international normalized ratio ¼ 2.0-3.0]) in patients with acute venous thromboembolism (VTE). This post hoc analysis of AMPLIFY compared outcomes among those taking or not taking concomitant anti-platelet therapy. The primary efficacy outcome was recurrent VTE or VTE-related death; the principal safety outcome was major bleeding. Of 5,365 (apixaban, n ¼ 2,676; enoxaparin/warfarin, n ¼ 2,689) randomized patients, 813 (apixaban, n ¼ 402 [15%]; enoxaparin/warfarin, n ¼ 411 [15%]) took concomitant anti-platelet therapy, of which 92% consisted of low-dose aspirin. Rates of VTE or VTE-related death were similar whether or not anti-platelet agents were taken (apixaban: 3.6 and 2.0%; enoxaparin/warfarin: 3.0 and 2.6%; anti-platelet use: relative risk [RR], 1.23; 95% confidence interval [CI], 0.58-2.62; no anti-platelet use: RR, 0.77; 95% CI, 0.52-1.13); interaction p-value ¼ 0.299. Major bleeding rates were threefold higher in those taking versus those not taking anti-platelet agents (apixaban: 1.2 and 0.4%; enoxaparin/warfarin: 4.1 and 1.4%; anti-platelet use: RR, 0.30; 95% CI, 0.11-0.81; no anti-platelet use: RR, 0.31; 95% CI, 0.15-0.63); interaction p-value ¼ 0.924. Concomitant anti-platelet therapy produced a proportionally similar increase in major bleeding in patients randomized to apixaban or conventional therapy, but there were fewer major bleeds with apixaban. Therefore, the overall safety of apixaban over conventional therapy was maintained in patients receiving anti-platelet therapy. Clinicaltrials.gov: NCT00643201.
Uptake of new treatment strategies for deep vein thrombosis: an international audit
International Journal for Quality in Health Care, 2004
Objective. Study of the uptake of new medical technologies provides useful information on the transfer of published evidence into usual practice. We conducted an audit of selected hospitals in three countries (Canada, France, and Switzerland) to identify clinical predictors of low-molecular-weight (LMW) heparin use and outpatient treatment, and to compare the pace of uptake of these new therapeutic approaches across hospitals.
Fundamental & Clinical Pharmacology, 2008
In a very large number of randomized trials of secondary prevention in cardiovascular disease (CVD), single agent antiplatelet therapy, principally with aspirin, has been shown to reduce the risk of a combined endpoint of important vascular events by about a quarter as well as its components, namely nonfatal myocardial infarction by about a third, nonfatal stroke by about a quarter, and deaths from vascular disease by about one-sixth. Basic research has contributed to an increased understanding of vascular thrombosis. Specifically, research in platelet
Antithrombotic Trialists Collaboration, 2002
Objective To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. Design Collaborative meta-analyses (systematic overviews). Inclusion criteria Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen. Studies reviewed 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens. Main outcome measure "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death. Results Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P = 0.0005), peripheral arterial disease (P = 0.004), and atrial fibrillation (P = 0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial
Dual antiplatelet therapy and antithrombotic treatment: Recommendations and controversies
Cardiology journal, 2009
Dual antiplatelet therapy is currently recommended for all patients with acute coronary syndromes, independent of whether they receive pharmacological treatment or undergo percutaneous coronary intervention. Antiplatelet agents are the cornerstone of pharmacological treatment in interventional cardiology. However, there is a clear need for randomized trials to assess the treatment strategy of dual antiplatelet therapy in patients who also need long-term antithrombotic treatment (such as those with atrial fibrillation, prosthetic heart valve, mitral valve regurgitation or stenosis, deep vein thrombosis, pulmonary embolism, or pulmonary hypertension). In this paper we discuss trials and analyses on the use of dual antiplatelet treatment in combination with antithrombotic therapy in particular diseases, with a focus on the risk of hemorrhagic events connected with this treatment, as well as recent guidelines of the European Society of Cardiology, the American College of Cardiology, and...