Duration of dual antiplatelet therapy (DAPT): a call for personalized medicine.
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ABSTRACT:
SUBMITTER: Tahir U
PROVIDER: S-EPMC5107506 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The Dual Antiplatelet Therapy (DAPT) study demonstrated that DAPT beyond 1-year after drug-eluting stent (DES) implantation, as compared with aspirin therapy alone, significantly reduced the risk of major cardiovascular and cerebrovascular events, which was mainly driven by the large risk reduction for myocardial infarction (MI). We sought to compare the largest DAPT study with other trials evaluating DAPT durations after DES implantation.By a systematic literature search, we identified 9 trials comparing prolonged- versus short-DAPT in addition to the DAPT study. The result from the DAPT study (N = 9961) with public-private collaboration was different from the pooled result of the 9 other investigator-driven trials (N = 22174) in terms of the effect of prolonged-DAPT on MI (odds ratio [OR] 0.48 [95%CI 0.38-0.62] versus pooled OR 0.88 [95%CI 0.67-1.15]: P = 0.001 for difference), while the trends for excess risk of prolonged-DAPT relative to short-DAPT for all-cause death (OR 1.31 [95%CI 0.97-1.78] versus pooled OR 1.16 [95%CI 0.92-1.45]: P = 0.53 for difference), and bleeding (OR 1.62 [95%CI 1.21-2.17] versus pooled OR 2.08 [95%CI 1.51-2.84]: P = 0.25 for difference) were consistently seen in both the DAPT and other trials. The annual rate of MI during aspirin mono-therapy in the DAPT study was much higher than that those in the other trials (2.7% versus 0.6-1.6%).Given the difference between the DAPT study and other trials, future studies should focus on certain subgroups of patients that are more or less likely to benefit from longer duration DAPT.
| S-EPMC5607128 | biostudies-literature
Project description:AimsBleeding is a frequent complication in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). An indication for dual antiplatelet therapy due to coronary stent implantation is present in a considerable number of these patients. The objective of this retrospective study was to evaluate if dual antiplatelet therapy (DAPT) significantly increases the high intrinsic bleeding risk in patients on VA-ECMO.Methods and resultsA total of 93 patients were treated with VA-ECMO between October 2010 and October 2013. Average time on VA-ECMO was 58.9 ± 1.7 hours. Dual antiplatelet therapy was given to 51.6% of all patients. Any bleeding was recorded in 60.2% of all patients. There was no difference in bleeding incidence in patients on DAPT when compared to those without any antiplatelet therapy including any bleeding (66.7% vs. 57.1%, p = 0.35), BARC3 bleeding (43.8% vs. 33.3%, p = 0.31) or pulmonary bleeding (16.7% vs. 19.0%, p = 0.77). This holds true after adjustment for confounders. Rate of transfusion of red blood cells were similar in patients with or without DAPT (35.4% vs. 28.6%, p = 0.488).ConclusionsBleeding on VA-ECMO is frequent. This registry recorded no statistical difference in bleeding in patients on dual antiplatelet therapy when compared to no antiplatelet therapy. When indicated, DAPT should not be withheld from VA ECMO patients.
| S-EPMC4965019 | biostudies-literature
Project description:Thienopyridine plus aspirin beyond 1 year after coronary stenting reduces myocardial infarction (MI) risk and increases bleeding risk in comparison with aspirin alone. The hazard associated with late thienopyridine discontinuation and risk factors for MI after discontinuation are poorly defined.In the DAPT Study (Dual Antiplatelet Therapy), after percutaneous coronary intervention and 12 months of thienopyridine (clopidogrel or prasugrel) plus aspirin, eligible patients remained on aspirin and were randomly assigned to continued thienopyridine versus placebo for 18 months. At 30 months, patients stopped the study drug and were observed for 3 months. Cumulative incidence of MI was assessed over 3 months after randomization (months 12-15) and 3 months after study drug discontinuation (months 30-33). The MI hazard for each of these periods was assessed across randomized treatment arms and by DAPT score values <2 or ?2.Among the 11?648 randomly assigned patients, the monthly cumulative incidence of MI was lower with continued thienopyridine versus placebo at 12 to 15 months (0.12% versus 0.37%, P<0.001, in all patients; 0.13% versus 0.27%, P=0.02, in patients not treated with paclitaxel-eluting stents), and higher at 30 to 33 months (0.30% versus 0.15%, P=0.013, in all patients; in patients without paclitaxel-eluting stents, 0.18% versus 0.17%, P=0.91). The majority of MIs in both time periods (74% and 76%) were not related to stent thrombosis. After multivariable adjustment, treatment arm independently predicted MI at months 12 to 15 (P<0.001) and 30 to 33 (P=0.011). During months 12 to 15, patients with DAPT scores <2 or ?2 both had lower rates of MI with continued thienopyridine (MI monthly incidence 0.16% versus 0.51%, P<0.001, for scores ?2; 0.08% versus 0.24%, P=0.012, for scores<2, interaction P=0.064).Discontinuing thienopyridine after either 12 or 30 months is associated with an early increase in MI risk, mainly unrelated to stent thrombosis; the magnitude of risk is highest in the earlier time frame, and lower in patients not treated with paclitaxel-eluting stents. Although higher DAPT scores identify patients with greater absolute ischemic benefit (relative to bleeding harm) with continued thienopyridine therapy, discontinuation at 12 months increases MI hazard regardless of DAPT score group.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938.
| S-EPMC5469374 | biostudies-literature
Project description:Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown.To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) treatment duration effect within the combined cohorts of randomized patients treated with DES or BMS as prespecified secondary analyses.International, multicenter, randomized, double-blinded, placebo-controlled trial comparing extended (30-months) thienopyridine vs placebo in patients taking aspirin who completed 12 months of DAPT without bleeding or ischemic events after receiving stents. The study was initiated in August 2009 with the last follow-up visit in May 2014.Continued thienopyridine or placebo at months 12 through 30 after stent placement, in 11,648 randomized patients treated with aspirin, of whom 1687 received BMS and 9961 DES.Stent thrombosis, MACCE, and moderate or severe bleeding.Among 1687 patients treated with BMS who were randomized to continued thienopyridine vs placebo, rates of stent thrombosis were 0.5% vs 1.11% (n?=?4 vs 9; hazard ratio [HR], 0.49; 95% CI, 0.15-1.64; P?=?.24), rates of MACCE were 4.04% vs 4.69% (n?=?33 vs 38; HR, 0.92; 95% CI, 0.57-1.47; P?=?.72), and rates of moderate/severe bleeding were 2.03% vs 0.90% (n?=?16 vs 7; P?=?.07), respectively. Among all 11,648 randomized patients (both BMS and DES), stent thrombosis rates were 0.41% vs 1.32% (n?=?23 vs 74; HR, 0.31; 95% CI, 0.19-0.50; P?<?.001), rates of MACCE were 4.29% vs 5.74% (n?=?244 vs 323; HR, 0.73; 95% CI, 0.62-0.87; P?<?.001), and rates of moderate/severe bleeding were 2.45% vs 1.47% (n?=?135 vs 80; P?<?.001).Among patients undergoing coronary stent placement with BMS and who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months compared with placebo did not result in statistically significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding. However, the BMS subset may have been underpowered to identify such differences, and further trials are suggested.clinicaltrials.gov Identifier: NCT00977938.
| S-EPMC4481320 | biostudies-literature
Project description:Since their discovery and the advent of RNA interference, microRNAs have drawn enormous attention because of their ubiquitous involvement in cellular pathways from life to death, from metabolism to communication. It is also widely accepted that they possess an undeniable role in cancer both as tumor suppressors and tumor promoters modulating cell proliferation and migration, epithelial-mesenchymal transition and tumor cell invasion and metastasis. Moreover, microRNAs can even affect the tumor surrounding environment influencing angiogenesis and immune system activation and recruitment. The tight association of microRNAs with several cancer-related processes makes them undoubtedly connected to the effect of specific cancer drugs inducing either resistance or sensitization. In this context, personalized medicine through microRNAs arose recently with the discovery of single nucleotide polymorphisms in the target binding sites, in the sequence of the microRNA itself or in microRNA biogenesis related genes, increasing risk, susceptibility and progression of multiple types of cancer in different sets of the population. The depicted scenario implies that the overall variation displayed by these small non-coding RNAs have an impact on patient-specific pharmacokinetics and pharmacodynamics of cancer drugs, pushing on a rising need of personalized treatment. Indeed, microRNAs from either tissues or liquid biopsies are also extensively studied as valuable biomarkers for disease early recognition, progression and prognosis. Despite microRNAs being intensively studied in recent years, a comprehensive review describing these topics all in one is missing. Here we report an up-to-date and critical summary of microRNAs as tools for better understanding personalized cancer biogenesis, evolution, diagnosis and treatment.
| S-EPMC5614923 | biostudies-literature
Project description:Treatment with aspirin and a P2Y12 inhibitor is commonly used in patients with cardiovascular disorders. The overall effect of such treatment on all-cause mortality is unknown. In the Dual Antiplatelet Therapy (DAPT) Study, continuation of dual antiplatelet therapy beyond 12 months after coronary stenting was associated with an unexpected increase in non-cardiovascular death. In view of the potential public health importance of these findings, we aimed to assess the effect of extended duration dual antiplatelet therapy on mortality by doing a meta-analysis of all randomised, controlled trials of treatment duration in various cardiovascular disorders.We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomised controlled trials assessing the effect of extended duration versus no or short duration dual antiplatelet therapy, published before Oct 1, 2014. We did a meta-analysis to pool results with a hierarchical Bayesian random-effects model. The primary outcomes were hazard ratios comparing rates of all-cause, cardiovascular, and non-cardiovascular death.Including the DAPT Study, we identified 14 eligible trials that randomly assigned 69,644 participants to different durations of dual antiplatelet therapy. Compared with aspirin alone or short duration dual antiplatelet therapy (?6 months), continued treatment was not associated with a difference in all-cause mortality (hazard ratio [HR] 1·05, 95% credible interval [CrI] 0·96-1·19; p=0·33). Similarly, cardiovascular (1·01, 0·93-1·12; p=0·81) and non-cardiovascular mortality (1·04, 0·90-1·26; p=0·66) were no different with extended duration versus short duration dual antiplatelet therapy or aspirin alone.Extended duration dual antiplatelet therapy was not associated with a difference in the risk of all-cause, cardiovascular, or non-cardiovascular death compared with aspirin alone or short duration dual antiplatelet therapy.None.
| S-EPMC4386690 | biostudies-literature
Project description:OBJECTIVE:To explore how the results from the 2014 dual antiplatelet therapy (DAPT) trial were disseminated to the scientific community and online media. DESIGN:A a systematic review of scholarly and public attention surrounding the DAPT study. SETTINGS:Data were collected from the ISI Web of Knowledge, Google Scholar, PubMed Commons, EurekAlert, the DAPT study website (www.daptstudy.org) and the New England Journal of Medicine website (for scholarly attention) and Altmetric Explorer, Snap Bird, YouTube (for public attention) citing DAPT study results appearing from 16 November 2014 to 10 June 2015. PARTICIPANTS:No participants were involved in this study. MAIN OUTCOME MEASURE:Proportion of contents highlighting the increased risk of mortality and critical to the author's interpretation of the results. RESULTS:We identified 425 items reported by seven sources; 164 (39%) disseminated the authors' interpretation via an electronic link or a reference, with no additional text. Among 81 items (19 %), the message favoured prolonged treatment and consequently overstated the article conclusions. Among 119 items (28 %), the text was uncertain about the benefit of prolonged treatment but was reported with no or inappropriate mention of increased risk of mortality. Only 34 items (8 %) were uncertain about the benefit of prolonged treatment and mentioned increased risk of mortality. In all, 27 items (6 %) did not favour prolonged treatment, and only 12 of these (3 %) clearly raised some concerns about the reporting of increased risk of death. CONCLUSION:Dissemination of the DAPT study results to the scientific community and on different media sources rarely criticised the interpretation of the study results.
| S-EPMC5695450 | biostudies-literature
Project description:IntroductionMinority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers of CYP2C19 variants has been reported in patients with either coronary artery disease (CAD) or acute coronary syndrome (ACS) after the percutaneous coronary intervention (PCI). Previous studies have evaluated CYP2C19 genotyping-guided antiplatelet therapy in selected populations; however, this has yet to be tested among Hispanics. Given the paucity of clinical research on CYP2C19 and antiplatelet clinical outcomes in Hispanics, our study will test the safety and efficacy of a genetic-driven treatment algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics.Methods and analysisThis is a multicentre, prospective, non-randomised clinical trial that proposes an assessment of pharmacogenomic-guided DAPT in post-PCI Caribbean Hispanic patients with ACS or CAD. We will recruit 250 patients to be compared with a matched non-concurrent cohort of 250 clopidogrel-treated patients (standard-of-care). Major adverse cardiovascular events (MACEs) such as all-cause death, myocardial infarction (MI), stroke, coronary revascularisation, stent thrombosis and bleedings over 6 months will be the study endpoints. Among the recruited, high-risk patients will be escalated to ticagrelor and low-risk patients will remain on clopidogrel. The primary objective is to determine whether genetic-guided therapy is superior to standard of care. The secondary objective will determine if clopidogrel treatment in low-risk patients is not associated with a higher rate of MACEs compared with escalated antiplatelet therapy in high-risk patients. Patients will be enrolled up to the group's completion.Ethics and disseminationApproval was obtained from the Institutional Review Board of the University of Puerto Rico Medical Sciences Campus (protocol # A4070417). The study will be carried out in compliance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice Guidelines. Findings will be published in a peer-reviewed journal and controlled access to experimental data will be available.Trial registration numberNCT03419325; Pre-results.
| S-EPMC7412606 | biostudies-literature
Project description:Purpose of reviewDual antiplatelet therapy (DAPT)-aspirin in conjunction with a P2Y12 inhibitor-is the cornerstone of managing patients with acute coronary syndromes post-revascularization, but the clinical response is highly variable, with potentially devastating consequences. Herein, we review the mechanisms underpinning said variability and explore emerging approaches to normalizing therapeutic benefit.Recent findingsThe potent P2Y12 inhibitors, prasugrel and ticagrelor, exhibit minimal inter-individual variability, replacing clopidogrel in DAPT and achieving greater rates of therapeutic response. However, these benefits decline in later phases when bleeding risk begins to supersede that of ischemia. Guided de-escalation of P2Y12 inhibition as well as shortening DAPT duration have emerged as strategies that retain antithrombotic efficacy while reducing bleeding risk. Aspirin is the other component of DAPT but is also used in isolation for secondary prevention of thrombotic disease. In contrast to the P2Y12 inhibitors, genetic influences on aspirin non-response appear to be outweighed by a triad of clinical factors: non-adherence, enteric aspirin use, and inappropriate dosing according to bodyweight and BMI. Multiple de-escalation strategies for DAPT have been shown to mitigate bleeding risk, but it remains unclear which approach is ideal, necessitating head-to-head investigations to determine which exhibits the most favorable cost-to-benefit ratio. However, there is likely a role for more than one approach in clinical practice, depending on patient risk profile. Our approach to aspirin use is also in need of reassessment: strategies to improve adherence, avoidance of enteric aspirin in cardiac patients, and dose adjustment according to bodyweight and/or BMI are all likely to improve rates of therapeutic response. Moreover, platelet function testing may have a role in identifying patients expected to benefit from primary prophylactic aspirin.
| S-EPMC10307718 | biostudies-literature
Project description:Use of dual antiplatelet therapy (DAPT; the combination of aspirin and an inhibitor of platelet P2Y12) is the key pharmacological component in the management of acute coronary syndrome and percutaneous coronary intervention (PCI) with stent implantation, but the optimal treatment duration is still unclear. Although current guidelines recommend prescription of DAPT for at least 12 months after implantation of drug-eluting stents (DES) if patients are not at high risk of bleeding, several studies showed conflicting results. Observational studies have shown inconsistent findings (i.e., some studies suggested longer duration would be better, and others vice versa) and small-to-moderate sized randomized clinical trials suggested that prolonged use of DAPT beyond 12 months would not be more beneficial and could be detrimental in safety outcomes. However, these studies suffer from insufficient statistical power, data from old version of DES, and non-uniform duration of DAPT. Given there might be the relative risk and benefit associated with combination of DES use and DAPT prescription, the optimal decision making with regard to DAPT duration would be essential for patients who underwent PCI with DES. Thus, by understanding and comparing the evidences of recent studies that support for shorter and longer duration of DAPT, we sought to guide the treating physician in deciding optimal duration of DAPT in such patients. Up to now, there is no strong evidence supporting that longer duration of DAPT is better than shorter duration of DAPT in terms of efficacy and safety outcomes after DES placement.
| S-EPMC4265232 | biostudies-literature