Duration of dual antiplatelet therapy (DAPT): a call for personalized medicine.
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ABSTRACT:
SUBMITTER: Tahir U
PROVIDER: S-EPMC5107506 | biostudies-literature | 2016 Oct
REPOSITORIES: biostudies-literature
Publications
Duration of dual antiplatelet therapy (DAPT): a call for personalized medicine.
Journal of thoracic disease 20161001 10
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Project description:AimsThe 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.Methods and resultsBy 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%).ConclusionsGiven 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:BackgroundThienopyridine 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.MethodsIn 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.ResultsAmong 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).ConclusionsDiscontinuing 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.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938.
| S-EPMC5469374 | biostudies-literature
Project description:The prevalence and burden of coronary heart disease (CHD) has increased substantially in India, accompanied with increasing need for percutaneous coronary interventions (PCI). Although a large government-funded insurance scheme in Maharashtra, India covered the cost of PCI for low-income patients, the high cost of post-PCI treatment, especially Dual Antiplatelet Therapy (DAPT), still caused many patients to prematurely discontinue the secondary prevention. Our study aimed to investigate the effectiveness of DAPT adherence on all-cause mortality among post-PCI patients and explore the potential determinants of DAPT adherence in India. We collected clinical data of 4,595 patients undergoing PCI in 110 participating medical centers in Maharashtra, India from 2012 to 2015 by electronic medical records. We surveyed 2527 adult patients who were under the insurance scheme by telephone interview, usually between 6 to 12 months after their revascularization. Patients reporting DAPT continuation in the telephone survey were categorized as DAPT adherence. The outcome of the interest was all-cause mortality within 1 year after the index procedure. Multivariate Cox proportional hazard (PH) model with adjustment of potential confounders and standardization were used to explore the effects of DAPT adherence on all-cause mortality. We further used a multivariate logistic model to investigate the potential determinants of DAPT adherence. Out of the 2527 patients interviewed, 2064 patients were included in the analysis, of whom 470 (22.8%) discontinued DAPT prematurely within a year. After adjustment for baseline confounders, DAPT adherence was associated with lower one-year all-cause mortality compared to premature discontinuation (less than 6-month), with an adjusted hazard ratio (HR) of 0.52 (95% Confidence Interval (CI) = (0.36, 0.67)). We also found younger patients (OR per year was 0.99 (0.97, 1.00)) and male (vs. female, OR of 1.30 (0.99, 1.70)) had higher adherence to DAPT at one year as did patients taking antihypertensive medications (vs. non medication, OR of 1.57 (1.25, 1.95)). These findings suggest the protective effects of DAPT adherence on 1-year mortality among post-PCI patients in a low-income setting and indicate younger age, male sex and use of other preventive treatments were predictors of higher DAPT adherence.
| S-EPMC9125829 | biostudies-literature
Project description:Backgroundwhile the duration of dual antiplatelet therapy (DAPT) following coronary angioplasty for chronic coronary syndrome (CCS) recommended by the European Society of Cardiology has decreased over the last decade, little is known about the adherence to those guidelines in clinical practice in France.AimTo analyze the real duration of DAPT post coronary angioplasty in CCS, as well as the factors affecting this duration.MethodsBetween 2014 and 2019, 8.836 percutaneous coronary interventions for CCS from the France-PCI registry were evaluated, with 1 year follow up, after exclusion of patients receiving oral anticoagulants, procedures performed within one year of an acute coronary syndrome, and repeat angioplasty.ResultsPost-percutaneous coronary intervention (PCI) DAPT duration was > 12 months for 53.1% of patients treated for CCS; 30.5% had a DAPT between 7 and 12 months, and 16.4% a DAPT ≤ 6 months. Patients with L-DAPT (>12 months) were at higher ischemic risk [25.0% of DAPT score ≥2 vs. 18.8% DAPT score ≥2 in S&I-DAPT group (≤12 months)]. The most commonly used P2Y12 inhibitor was clopidogrel (82.2%). The prescription of ticagrelor increased over the period.Conclusionspost-PCI DAPT duration in CCS was higher than international recommendations in the France PCI registry between 2014 and 2019. More than half of the angioplasty performed for CCS are followed by a DAPT > 12 months. Ischemic risk assessment influences the duration of DAPT. This risk is probably overestimated nowadays, leading to a prolongation of DAPT beyond the recommended durations, thus increasing the bleeding risk.
| S-EPMC10080068 | biostudies-literature
Project description:Background Recent guidelines on dual antiplatelet therapy (DAPT) duration after percutaneous coronary intervention (PCI) balance the subsequent risks of major bleeding with ischemic events. Although generally favoring shorter DAPT duration with second-generation drug-eluting stents, the effects on long-term outcomes in the wider population are uncertain. Methods and Results We tracked all patients having PCI with second-generation drug-eluting stents in the Veterans Affairs Healthcare System between 2006 and 2016 for death, myocardial infarction, stroke, and major bleeding up to 13 years. We compared these outcomes with 4 DAPT durations of 1 to 5, 6 to 9, 10 to 12, and 13 to 18 months after the index PCI using hazard ratios (HRs) and 95% CIs from Cox proportional hazards models adjusted by inverse probability weighting. A total of 40 882 subjects with PCI were followed up for a median of 4.3 (25%-75%: 2.4-6.5) years. DAPT discontinuation was rare early after PCI (5.8% at 1-5 months and 6.3% at 6-9 months) but increased (19% and 44%) >9 months. The risk of cardiovascular and noncardiovascular death was higher (HR, 2.03-3.41) with DAPT discontinuation <9 months, likely reflecting premature cessation from factors related to early death. DAPT discontinuation after 9 months following PCI was associated with lower risks of death (HR, 0.93 [95% CI, 0.88-0.99]), cardiac death (HR, 0.79 [95% CI, 0.70-0.90]), myocardial infarction (HR, 0.75 [95% CI, 0.69-0.82]), and major bleeding (HR, 0.82 [95% CI, 0.74-0.91]). Results were similar with an index PCI for an acute coronary syndrome. Conclusions Stopping DAPT after 9 months is associated with lower long-term risks of adverse ischemic and bleeding events and supports recent guidelines of shorter duration DAPT after PCI with second-generation drug-eluting stents.
| S-EPMC9939065 | biostudies-literature
Project description:ImportanceDespite 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.ObjectiveTo 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.Design, setting, and participantsInternational, 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.InterventionsContinued 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.Main outcomes and measuresStent thrombosis, MACCE, and moderate or severe bleeding.ResultsAmong 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).Conclusions and relevanceAmong 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.Trial registrationclinicaltrials.gov Identifier: NCT00977938.
| S-EPMC4481320 | biostudies-literature
Project description: Not available
| S-EPMC9982210 | biostudies-literature
Project description:BackgroundTreatment 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.MethodsWe 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.FindingsIncluding 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.InterpretationExtended 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.FundingNone.
| S-EPMC4386690 | 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