Optimal antiplatelet strategy after transcatheter aortic valve implantation: a meta-analysis.
ABSTRACT: Objective:International guidelines recommend the use of dual antiplatelet therapy (DAPT) after transcatheter aortic valve implantation (TAVI). The recommended duration of DAPT varies between guidelines. In this two-part study, we (1) performed a structured survey of 45 TAVI centres from around the world to determine if there is consensus among clinicians regarding antiplatelet therapy after TAVI; and then (2) performed a systematic review of all suitable studies (randomised controlled trials (RCTs) and registries) to determine if aspirin monotherapy can be used instead of DAPT. Methods:A structured electronic survey regarding antiplatelet use after TAVI was completed by 45 TAVI centres across Europe, Australasia and the USA. A systematic review of TAVI RCTs and registries was then performed comparing DAPT duration and incidence of stroke, bleeding and death. A variance weighted least squared metaregression was then performed to determine the relationship of antiplatelet therapy and adverse events. Results:82.2% of centres routinely used DAPT after TAVI. Median duration was 3 months. 13.3% based their practice on guidelines. 11 781 patients (26 studies) were eligible for the metaregression. There was no benefit of DAPT over aspirin monotherapy for stroke (P=0.49), death (P=0.72) or bleeding (P=0.91). Discussion:Aspirin monotherapy appears to be as safe and effective as DAPT after TAVI.
Project description:BACKGROUND:International guidelines do not provide uniform recommendations regarding the use of antiplatelet treatment in the perioperative period in patients undergoing coronary artery bypass grafting (CABG). METHODS:A questionnaire was sent to all 16 cardiothoracic centres in the Netherlands to determine which antiplatelet treatment is used in the perioperative setting. Furthermore, a single-centre prospective observational cohort study was performed which included all patients undergoing isolated CABG in July 2014. RESULTS:Eleven centres responded to the survey. Acetylsalicylic acid monotherapy was discontinued before surgery in 6 centres. In patients with an acute coronary syndrome receiving dual antiplatelet therapy (DAPT), most centres discontinued the P2Y12 inhibitor preoperatively. DAPT was restarted after surgery in 4 centres. However, 6 centres continued DAPT in patients who had undergone coronary stenting within one month of surgery. In patients with coronary stents, variation in the management of antiplatelet therapy increased in proportion to the interval between stenting and surgery. A total of 70 patients were included in the registry. Acetylsalicylic acid monotherapy was discontinued in 51% of patients and restarted in all patients. P2Y12 inhibitor treatment was discontinued before surgery in 70% of patients and re-initiated after CABG in 29%. CONCLUSIONS:Major differences were observed in the preoperative and postoperative management of antiplatelet treatment between different Dutch cardiothoracic centres and within a single centre. Part of this variation is probably due to lack of evidence and differences between the current guidelines; however, many of the strategies were not in accordance with any of these guidelines.
Project description:Monotherapy with antiplatelet agents is only modestly effective in secondary prevention of ischemic stroke (IS), particularly in patients with multiple risk factors such as cervicocephalic arterial stenosis, diabetes, and hypertension. While dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduced IS recurrence, particularly in the early stages after IS, it increased the risk of bleeding. Compared with aspirin, cilostazol prevented IS recurrence without increasing the incidence of serious bleeds. In patients with intracranial arterial stenosis, no significant increase in bleeding events was observed for DAPT with cilostazol and aspirin, compared to that for aspirin monotherapy. DAPT involving cilostazol may therefore be safer than conventional DAPT. These findings prompted us to conduct the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com; ClinicalTrials.gov identifier: NCT01995370) to evaluate the safety and efficacy of DAPT involving cilostazol for secondary IS prevention, in comparison with that of antiplatelet monotherapy.The CSPS.com is a multicenter, randomized, open-label, parallel-group trial. A total of 4000 high-risk patients with noncardioembolic IS will be randomized 8-180 days after onset to receive aspirin or clopidogrel monotherapy, or DAPT with cilostazol and aspirin or clopidogrel for at least one-year.The primary outcome is IS recurrence. Secondary outcomes are composite occurrences of any stroke, death from any cause, myocardial infarction, vascular death, and other vascular events.The CSPS.com is expected to provide evidence indicating whether secondary IS prevention in high-risk patients can be improved by using DAPT involving cilostazol.
Project description:Dual antiplatelet therapy based on the combination of an adenosine diphosphate (ADP)-receptor antagonist plus aspirin has demonstrated to be more effective in reducing the rate of major ischemic vascular events compared to aspirin monotherapy in some clinical settings. The current controversy on the duration of dual antiplatelet therapy should not conceal another major issue: the choice of the more appropriate antiplatelet monotherapy after the dual treatment phase. The aim of this article is to critically analyze the available evidence in this topic. Data from studies like CAPRIE, MATCH, PROFESS, CHANCE, DAPT and others, raise questions as why antiplatelet monotherapy after the dual phase should only be based on aspirin, in spite of a lack of evidence surprisingly not highlighted by key opinion leaders and experts. We conclude that, whether ADP-receptor antagonist rather than aspirin may be proposed as monotherapy seems not only have no answer but also not place in the current specialists' analysis, as if a dogmatic approach were prevalent. Perhaps the time for an open debate on these topics is ripe.
Project description:Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is key for secondary prevention of recurrent coronary ischemic events and stent thrombosis. For this purpose, DAPT showed superior efficacy compared to aspirin alone, but it is also associated with an increased risk of major, and potentially fatal, bleeding. Hence, while secondary prevention with aspirin monotherapy is generally maintained for an indefinite period, the duration of DAPT after the index event is still debated. Multiple trials have challenged the guideline recommended standard of care of 12 months of DAPT duration. These studies tested on one side a treatment reduction to 6 or 3 months, and on the other side an extension of treatment beyond 12 months in order to define the optimal DAPT duration maximizing the anti-ischemic protection and minimizing bleeding. In this document we sought to summarize the existing evidence from more than 18 randomized controlled trials in the field, and discuss the benefit and risks of prolonging/shortening DAPT duration. In addition, a specific focus on treatment individualization will outline the current, evidence-based, decision-making process for optimal DAPT duration selection after coronary stenting.
Project description:Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of pharmacologic management of patients with acute coronary syndrome (ACS) and/or those receiving coronary stents. Long-term (>1 year) DAPT may further reduce the risk of stent thrombosis after a percutaneous coronary intervention (PCI) and may decrease the occurrence of non-stent-related ischaemic events in patients with ACS. Nevertheless, compared with aspirin alone, extended use of aspirin plus a P2Y12 receptor inhibitor may increase the risk of bleeding events that have been strongly linked to adverse outcomes including recurrent ischaemia, repeat hospitalisation and death. In the past years, multiple randomised trials have been published comparing the duration of DAPT after PCI and in ACS patients, investigating either a shorter or prolonged DAPT regimen. Although the current European Society of Cardiology guidelines provide a backup to individualised treatment, it appears to be difficult to identify the ideal patient profile which could safely reduce or prolong the DAPT duration in daily clinical practice. The aim of this consensus document is to review contemporary literature on optimal DAPT duration, and to guide clinicians in tailoring antiplatelet strategies in patients undergoing PCI or presenting with ACS.
Project description:Dual antiplatelet therapy (DAPT) combining aspirin and a P2Y12 receptor inhibitor has been consistently shown to reduce recurrent major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) compared with aspirin monotherapy, but at the expense of an increased risk of major bleeding. Nevertheless, the optimal duration of DAPT for secondary prevention of CAD remains uncertain, owing to the conflicting results of several large randomised trials. Among patients with stable CAD undergoing PCI with drug-eluting stents (DES), shorter durations of DAPT (3-6 months) were shown non-inferior to 12 or 24 months duration with respect to MACE, but reduced the rates of major bleeding. Contrariwise, prolonged DAPT durations (18-48 months) reduced the incidence of myocardial infarction and stent thrombosis, but at a cost of an increased risk of major bleeding and all-cause mortality. Until more evidence becomes available, the choice of optimal DAPT regimen and duration for patients with CAD requires a tailored approach based on the patient clinical presentation, baseline risk profile and management strategy. Future studies are however needed to identify patients who may derive benefit from shortened or extended DAPT courses for secondary prevention of CAD based on their individual ischaemic and bleeding risk. Based on limited evidence, 12 months duration of DAPT is currently recommended in patients with ACS irrespective of their management strategy, but large ongoing randomised trials are currently assessing the efficacy and safety of a short-term DAPT strategy (3-6 months) for patients with ACS undergoing PCI with newer generation DES. Finally, several ongoing, large-scale, randomised trials are challenging the current concept of DAPT by investigating P2Y12 receptor inhibitors as single antiplatelet therapy and may potentially shift the paradigm of antiplatelet therapy after PCI in the near future. This article provides a contemporary state-of-the-art review of the current evidence on DAPT for secondary prevention of patients with CAD and its future perspectives.
Project description:BACKGROUND:The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; midterm (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after percutaneous coronary intervention with drug-eluting stents. METHODS:Twenty-four randomized, controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The coprimary end points were myocardial infarction and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with a random-effects model. RESULTS:In 79?073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of myocardial infarction in comparison with 12-month DAPT (absolute risk difference, -3.8 incident cases per 1000 person-years; relative risk, 0.68 [95% CI, 0.54-0.87]), midterm DAPT (absolute risk difference, -4.6 incident cases per 1000 person-years; relative risk, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (absolute risk difference, -6.1 incident cases per 1000 person-years; relative risk, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (absolute risk difference, -3.7 incident cases per 1000 person-years; relative risk, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding than all other DAPT groups. In comparison with 12-month DAPT, no significant differences in the risks of ischemic end points or major bleeding were observed with midterm or short-term DAPT followed by aspirin monotherapy, with the exception that short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome, extended-term in comparison with 12-month DAPT was associated with a reduced risk of myocardial infarction without a significant increase in the risk of major bleeding. CONCLUSIONS:The present network meta-analysis suggests that, in comparison with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after percutaneous coronary intervention with drug-eluting stents, whereas extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.
Project description:There is wide variability in prescribing of antiplatelet regimens following transcatheter aortic valve implantation (TAVI). The objective of this review was to evaluate published and unpublished reports regarding the efficacy and safety of dual antiplatelet therapy (DAPT) compared with a single antiplatelet agent in patients undergoing TAVI. We searched MEDLINE, CENTRAL, Embase, and unpublished sources of literature from inception to December 2014 using terms synonymous with TAVI and DAPT. We included randomized controlled trials (RCTs) and cohort or case-control studies that compared DAPT with a single antiplatelet agent post-TAVI. Four articles met the inclusion criteria (2 RCTs, 2 cohort studies), of which all were deemed to be at high risk of bias, for a total of 662 patients. Compared with a single antiplatelet agent, DAPT did not significantly reduce all-cause mortality (risk ratio: 1.22, 95% confidence interval: 0.72-2.09, I(2) = 0%). Due to selective outcome reporting and variable follow-up, other outcomes of interest could not be meta-analyzed; however, evaluation of individual studies demonstrated no significant reduction in thrombotic events with DAPT and a similar or higher risk of bleeding. Current evidence, though limited by low methodological quality, suggests a lack of benefit and potential harm with DAPT compared with a single antiplatelet agent in patients post-TAVI. Therefore, clinicians should evaluate the use of DAPT in patients post-TAVI on a case-by-case basis until more robust evidence is available to guide practice.
Project description:Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is essential after percutaneous coronary intervention (PCI), while many studies have focused on determining the optimal degree of platelet inhibition and optimal DAPT duration to minimize complications after PCI. Current guidelines developed by the American College of Cardiology/American Heart Association and the European Society of Cardiology summarize previous studies and provide recommendations. However, these guidelines are mainly based on Western patients, and their characteristics might differ from those of East Asian patients. Previous data suggested that East Asian patients have unique features with regard to the response to antiplatelet agents. On comparing Western and East Asian patients, it was found that East Asian patients have a lower rate of ischemic events and higher rate of bleeding events after PCI, despite a higher on-treatment platelet reactivity, which is referred to as the "East Asian paradox." As the main purpose of DAPT is to minimize ischemic and bleeding complications after PCI, these differences should be clarified before adopting the guidelines for East Asian patients. Therefore, in this article, we will review various issues regarding DAPT in East Asian patients, with a focus on the unique characteristics of East Asian patients, previous studies regarding antiplatelet agents in East Asian patients, and a guideline from an East Asian perspective.
Project description:PURPOSE: To assess current antithrombotic treatment strategies in the Netherlands in patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: For every Dutch hospital performing TAVI (n?=?14) an interventional cardiologist experienced in performing TAVI was interviewed concerning heparin, aspirin, thienopyridine and oral anticoagulation treatment in patients undergoing TAVI. RESULTS: The response rate was 100 %. In every centre, a protocol for antithrombotic treatment after TAVI was available. Aspirin was prescribed in all centres, concomitant clopidogrel was prescribed 13 of the 14 centres. Duration of concomitant clopidogrel was 3 months in over two-thirds of cases. In 2 centres, duration of concomitant clopidogrel was based upon type of prosthesis: 6 months versus 3 months for supra-annular and intra-annular prostheses, respectively. CONCLUSIONS: Leaning on a small basis of evidence and recommendations, the antithrombotic policy for patients undergoing TAVI is highly variable in the Netherlands. As a standardised regimen might further reduce haemorrhagic complications, large randomised clinical trials may help to establish the most appropriate approach.