Update on Dual Antiplatelet Therapy for Secondary Stroke Prevention.
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ABSTRACT:
SUBMITTER: Stringberg A
PROVIDER: S-EPMC6699814 | biostudies-literature | 2019 Jul-Aug
REPOSITORIES: biostudies-literature
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Update on Dual Antiplatelet Therapy for Secondary Stroke Prevention.
Stringberg Alexandria A Camden Ryan R Qualls Kathryn K Naqvi Syed H SH
Missouri medicine 20190701 4
Aspirin is recommended for patients with acute ischemic stroke within 24 hours of symptom onset. It may be beneficial for dual antiplatelet therapy including clopidogrel and aspirin to be administered in patients with minor stroke or transient ischemic attack for early secondary prevention, however, bleeding risk remains uncertain. This article will review the published literature concerning the role of dual antiplatelet therapy for secondary stroke prevention with focus on balancing both risk a ...[more]
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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.
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Project description:Stroke exacts a huge toll physically, mentally and economically. Antiplatelet therapy is the cornerstone of secondary stroke prevention, and proven drugs available to successfully realize this therapeutic strategy for the long term include aspirin, dipyridamole plus aspirin and clopidogrel. However, government agencies, corporations, health plans and patients desire more information about the clinical- and cost-effectiveness of these established therapies in real-world settings. This paper provides an update on evidence-based secondary stroke prevention with antiplatelet medications, discusses cost-related issues and offers perspective about the future.
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Project description:Our objective is to provide the reader with an overview as well as an update on current antiplatelet therapy for secondary stroke prevention. Relevant journals were hand-searched by the authors to compile a broad but by far not comprehensive summary of innovative and clinically relevant studies. Aspirin, clopidogrel and the combination of dipyridamole plus aspirin are the cornerstone therapy in secondary prevention after non-cardio-embolic stroke or transient ischaemic attack. A head-to-head comparison showed no difference in the prevention of recurrent stroke between dipyridamole plus aspirin and clopidogrel. More potent antiplatelet drugs or the combination of aspirin and clopidogrel prevent more ischaemic events, but also lead to more bleeding complications. For secondary stroke prevention in patients with atrial fibrillation, oral anticoagulation is more effective than aspirin or the combination of aspirin and clopidogrel.
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Project description:Antiplatelet agents are a cornerstone in the treatment of acute arterial thrombotic events and in the prevention of thrombus formation. However, existing antiplatelet agents (mainly aspirin, the combination of aspirin and dipyridamole and clopidogrel) reduce the risk of vascular events only by about one quarter compared with placebo. As a consequence, more efficacious antiplatelet therapies with a reduced bleeding risk are needed. We give an overview of several new antiplatelet agents that are currently investigated in secondary stroke prevention: adenosine 5'-diphosphonate receptor antagonists, cilostazol, sarpogrelate, terutroban and SCH 530348. There are unique features in secondary stroke prevention that have to be taken into account: ischaemic stroke is a heterogeneous disease caused by multiple aetiologies and the blood-brain barrier is disturbed after stroke which may result in a higher intracerebral bleeding risk. Several small randomized trials indicated that the combination of aspirin and clopidogrel might be superior to antiplatelet monotherapy in the acute and early post-ischaemic phase. There is an ongoing debate about antiplatelet resistance. Decreasing response to aspirin is correlated independently with an increased risk of cardiovascular events. However, there is still no evidence from randomized trials linking aspirin resistance and recurrent ischaemic events. Similarly, randomized trials have not demonstrated a clinical significantly decreased antiplatelet effect by the concomitant use of clopidogrel and proton pump inhibitors. Nevertheless, a routine use of this drug combination is not recommended.
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Project description:ObjectivePatients who have an ischemic stroke (IS) or transient ischemic attack (TIA) are at risk of having a secondary stroke. Single antiplatelet therapy (SAPT) or dual antiplatelet therapy (DAPT) may be recommended for secondary stroke prevention (SSP), depending on severity and etiology. This study evaluated outpatient antiplatelet treatment patterns for SSP and outcomes after first hospitalization for IS/TIA among adults without atrial fibrillation in the United States.Materials and methodsThis retrospective observational study utilized data from an adjudicated administrative health claims database. Eligible patients had an imputed National Institutes of Health Stroke Scale index event score ≤7. Over-the-counter medication use (eg, aspirin) was not captured.ResultsOf 154,273 patients, 41,622 (27%) were prescribed antiplatelet therapy within 90 days of the event; 93.8% received SAPT, 6.1% received DAPT. The first line of antiplatelet therapy after discharge was started a mean of 17.0 days after the event; mean treatment duration was 61.9 days. The incidence rate for secondary IS was 5.53, 2.03, and 1.17 per person-year 90-days, 1-year, and 3-years following treatment initiation, respectively. Among patients matched for demographic and clinical characteristics, the risk of secondary IS was increased with DAPT versus SAPT (hazard ratio [95% CI]: 1.27 [1.20-1.34]; p < 0.0001).ConclusionsMany patients were not prescribed or discontinued antiplatelet therapy within 90 days of hospitalization for IS/TIA and, in most cases, prescriptions were not compliant with SSP consensus guidelines. Patients remained at risk for IS, which was highest within 90 days. More effective strategies for SSP are needed to improve outcomes in this patient population.
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Project description:Stroke is one of the leading causes of disability and death. Ischemic stroke is a syndrome with heterogeneous mechanisms and multiple etiologies, rather than a singularly defined disease. Approximately one third of ischemic strokes are preceded by another cerebrovascular ischemic event. Stroke survivors are at high risk of vascular events (i.e., cerebrovascular and cardiovascular events), particularly during the first several months after the ischemic event. The use of antiplatelet agents remains the fundamental component of secondary stroke prevention. Based on the available data, antiplatelet agents should be used for patients with noncardioembolic stroke. The use of combination therapy (aspirin plus clopidogrel) has not been proven to be effective or safe to use for prevention of early stroke recurrence or in long-term treatment. There is no convincing evidence that any of the available antiplatelet agents are superior for a given stroke subtype. Currently, the uses of aspirin, clopidogrel, or aspirin combined with extended release dipyridamole are all valid alternatives after an ischemic stroke or transient ischemic attack. However, to maximize the effects of these agents, the treatment should be initiated as early as possible and be continued on a lifelong basis.
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Project description:UnlabelledAB OBJECTIVE: We aimed to investigate whether the efficacy and safety of clopidogrel plus aspirin vs aspirin alone were consistent between patients with and without intracranial arterial stenosis (ICAS), in the Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial.MethodsWe assessed the interaction of the treatment effects of the 2 antiplatelet therapies among patients with and without ICAS, identified by magnetic resonance angiography (MRA) in CHANCE (ClinicalTrials.gov identifier NCT00979589).ResultsOverall, 1,089 patients with MRA images available in CHANCE were included in this subanalysis, 608 patients (55.8%) with ICAS and 481 (44.2%) without. Patients with ICAS had higher rates of recurrent stroke (12.5% vs 5.4%; p<0.0001) at 90 days than those without. But there was no statistically significant treatment by presence of ICAS interaction on either the primary outcome of any stroke (hazard ratio for clopidogrel plus aspirin vs aspirin alone: 0.79 [0.47-1.32] vs 1.12 [0.56-2.25]; interaction p=0.522) or the safety outcome of any bleeding event (interaction p=0.277).ConclusionsThe results indicated higher rate of recurrent stroke in minor stroke or high-risk TIA patients with ICAS than in those without. However, there was no significant difference in the response to the 2 antiplatelet therapies between patients with and without ICAS in the CHANCE trial. Classification of evidence: This study provides Class II evidence that for patients with acute minor stroke or TIA with and without ICAS identified by MRA, clopidogrel plus aspirin is not significantly different than aspirin alone in preventing recurrent stroke.
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Project description:BackgroundThe potential benefit of long-term dual antiplatelet therapy (DAPT) for secondary prevention of atherothrombotic events is unclear. Data from different randomized controlled trials (RCT) using different agents in different subgroups showed inconsistent results.MethodsWe performed a systematic review and meta-analysis from RCTs that tested different prolonged durations of DAPT for secondary prevention. Long term DAPT arm was defined as those receiving DAPT for more than 12months. Long-term aspirin arm was defined as those receiving either aspirin alone long term or DAPT for less than 12months.ResultsThe use of long term DAPT was associated with a significant decrease in composite of death, myocardial infarction (MI) and stroke (6.08% vs. 6.71%; odds ratio OR=0.86 [0.78-0.94]; P=0.001). This reduction of death, MI and stroke was mainly noticed in patients with prior MI or stroke, but not with PAD or multiple risk factors. The reduction was seen with post PCI patients with prasugrel and only in those with prior MI with clopidogrel and ticagrelor. Long-term use of DAPT was associated with significant increase in major bleeding (1.47% vs. 0.88%; OR=1.65 [1.23-2.21]; P=0.001).ConclusionLong-term use of DAPT for secondary prevention is associated with lower risk of death, MI and stroke beneficial especially in patients with prior MI and stroke, but it is associated with increased risk of bleeding. Prolonging DAPT requires careful assessment of the trade-off between ischemic and bleeding complications and should probably be reserved for patients with higher risk for atherothrombotic events.
| S-EPMC5250594 | biostudies-literature