Projected impact of pharmacogenomic testing on medications beyond antiplatelet therapy in percutaneous coronary intervention patients.
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ABSTRACT:
SUBMITTER: Black RM
PROVIDER: S-EPMC7252508 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo investigate the relation of annual household income to antiplatelet adherence following PCI.BackgroundTreatment with 6-12 months of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) is a Class I recommendation. Adherence to these medications is essential to reduce risk of stent thrombosis and recurrent ischemic events. Social risk factors like household income modify how patients access and adhere to essential pharmacologic therapies such as antiplatelet agents.MethodsWe identified individuals presenting with PCI in an administrative claims database of commercially insured and Medicare Advantage beneficiaries from 2017 to 2019. We collected data on age, sex, race, ethnicity, educational attainment, and covariates (prevalent coronary disease, medications, healthcare visits, insurance type, copay, antiplatelet medications, and Elixhauser Comorbidity Index conditions). We related annual household income, categorized as <$40,000; $40-49,999; $50-59,999; $60-74,999; $75-99,999; and ≥$100 K, to proportion of days covered (PDC) in multivariable-adjusted regression models. We defined non-adherence as PDC <80%.ResultsOur dataset included 90,163 individuals (age 69.0 ± 10.9 years, 33.1% women, 25.1% non-White race) who underwent PCI. We observed graded, decreased antiplatelet adherence across income categories: rates of PDC≥80% decreased with successively lower income. Individuals with annual income <$40,000 had 1.5-fold higher odds of non-adherence (95% CI, 1.40-1.56) compared to those with income ≥$100,000 after multivariable adjustment.ConclusionsIn a claims-based analysis, we determined that lower income is associated with decreased likelihood of adherence to antiplatelet agents following PCI. Our results indicate the importance of considering social risk factors in the evaluation of barriers to antiplatelet adherence following PCI.
| S-EPMC9434414 | biostudies-literature
Project description:Antianginal medications (AAMs) can be perceived to be less important after percutaneous coronary intervention (PCI) and may be de-escalated after revascularization. We examined the frequency of AAM de-escalation at discharge post-PCI and its association with follow-up health status.In a 10-center PCI registry, the Seattle Angina Questionnaire was assessed before and 6 months post-PCI. AAM de-escalation was defined as fewer AAMs at discharge versus admission or >25% absolute dose decrease. Of 2743 PCI patients (70% male), AAM were de-escalated, escalated, and unchanged in 299 (11%), 714 (26%), and 1730 (63%) patients, respectively. Patients whose AAM were de-escalated were more likely to report angina at 6 months, compared with unchanged or escalated AAM (34% versus 24% versus 21%; P<0.001). The association of AAM de-escalation with health status was examined using multivariable models adjusting for the predicted risk of post-PCI angina, completeness of revascularization, and the interaction of AAM de-escalation×completeness of revascularization. There was a significant interaction between AAM de-escalation and completeness of revascularization (P<0.001), suggesting that AAM de-escalation was associated with greater impairment of health status among patients with incomplete revascularization. In patients with incomplete revascularization, de-escalation of AAM at discharge was associated with 43% increased angina risk (relative risk, 1.43; 95% confidence interval, 1.26-1.63) and worse angina-related health status at 6 months post-PCI.De-escalation of AAM occurs in 1 in 10 patients post-PCI, and it is associated with an increased risk of angina and worse health status, particularly among those with incomplete revascularization.
| S-EPMC5721850 | biostudies-other
Project description:IntroductionClopidogrel is commonly prescribed with aspirin to reduce the risk for adverse cardiovascular events after percutaneous coronary intervention (PCI). However, there is significant inter-patient variability in clopidogrel response. The CYP2C19 enzyme is involved in the biotransformation of clopidogrel to its pharmacologically active form, and variation in the CYP2C19 gene contributes to clopidogrel response variability. Areas covered. This article describes the impact of CYP2C19 genotype on clopidogrel pharmacokinetics, pharmacodynamics, and effectiveness. Examples of clinical implementation of CYP2C19 genotype-guided antiplatelet therapy for patients undergoing PCI are also described as are emerging outcomes data with this treatment approach. Expert commentary. A large clinical trial evaluating outcomes with CYP2C19 genotype-guided antiplatelet therapy after PCI is on-going. In the meantime, data from pragmatic and observational studies and smaller trials support improved outcomes with genotyping after PCI and use of alternative antiplatelet therapy in patients with a CYP2C19 genotype associated with reduced clopidogrel effectiveness.
| S-EPMC5628391 | biostudies-literature
Project description:IntroductionDual antiplatelet therapy (DAPT) is routinely given to patients after percutaneous coronary intervention (PCI) with stenting; however, there is ongoing debate about the optimal duration, especially in specific patient groups. In the proposed systematic review, we intend to assess the optimal duration of DAPT following PCI with stenting, with a focus on clinically relevant patient subgroups.Methods and analysisWe will perform a comprehensive search of the published literature for randomised controlled trials (RCTs) assessing the benefits and harms of extended DAPT (>12 months) compared with short-term DAPT (6-12 months) following PCI with stenting (bare metal or drug eluting). ClinicalTrials.gov and ICTRP will also be searched to identify ongoing and completed clinical trials. Two independent reviewers will select studies for inclusion, and the risk of bias will be assessed by use of Cochrane's Risk of Bias tool. The primary outcome of interest is death (all-cause, cardiovascular, non-cardiovascular). Secondary outcomes are bleeding (major, minor, gastrointestinal), urgent target vessel revascularisation, major adverse cardiovascular events, myocardial infarction, stroke and stent thrombosis. Subgroup data will be sought for patients with prior myocardial infarction, acute coronary syndrome at presentation and diabetes, and based on smoking status and age group. Data will be analysed by random-effects meta-analysis, and separate analyses will be performed for patient subgroups. Bayesian network meta-analysis will be performed to investigate the effect of individual P2Y12 inhibitors at different DAPT durations longer than 6 months.Ethics and disseminationThis review will provide a comprehensive overview of the available evidence of the benefits and harms associated with extending DAPT beyond 12 months following PCI with stenting and the effects on clinically important subgroups. The results of this review will inform clinical and policy decisions regarding the optimal treatment duration of DAPT following PCI with stenting.Systematic review registrationPROSPERO no. CRD42018082587.
| S-EPMC6588972 | biostudies-literature
Project description:ObjectiveTo evaluate the clinical utility of individualising dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in an all-comers population, including ST-elevation myocardial infarction (STEMI) patients.SettingTertiary care single centre registry.Participants1008 consecutive PCI patients with stent implantation, without exclusion criteria.InterventionPeri-interventional individualisation of DAPT, guided by multiple electrode aggregometry (MEA), to overcome high on-treatment platelet reactivity (HPR) to ADP-induced (≥50 U) and arachidonic acid (AA)-induced aggregation (>35 U).Outcome measuresThe primary efficacy end point was definite stent thrombosis (ST) at 30 days. The primary safety end point was thrombolysis in myocardial infarction (TIMI) major and minor bleeding. Secondary end points were probable ST, myocardial infarction, cardiovascular death and the combined end point: major cardiac adverse event (MACE).Results53% of patients presented with acute coronary syndrome (9% STEMI, 44% non-ST-elevation). HPR to ADP after 600 mg clopidogrel loading occurred in 30% of patients (73±19 U vs 28±11 U; p<0.001) and was treated by prasugrel or ticagrelor (73%), or clopidogrel (27%) reloading (22±12 U; p<0.001). HPR to ADP after prasugrel loading occurred in 2% of patients (82±26 U vs 19±10 U; p<0.001) and was treated with ticagrelor (34±15 U; p=0.02). HPR to AA occurred in 9% of patients with a significant higher proportion in patients with HPR to ADP (22% vs 4%, p<0.001) and was treated with aspirin reloading. Definite ST occurred in 0.09% of patients (n=1); probable ST, myocardial infarction, cardiovascular death and MACE occurred in 0.19% (n=2), 0.09% (n=1) and 1.8% (n=18) of patients. TIMI major and minor bleeding did not differ between patients without HPR and individualised patients (2.6% for both).ConclusionsIndividualisation of DAPT with MEA minimises early thrombotic events in an all-comers PCI population to an unreported degree without increasing bleeding. A randomised multicentre trial utilising MEA seems warranted.Trial registration numberhttp://www.clinicaltrials.gov; NCT01515345.
| S-EPMC4216867 | biostudies-literature
Project description:The objective was to assess the impact of baseline anemia on all-cause mortality and whether 12-month dual antiplatelet therapy (DAPT) affects 1-year mortality linked to anemia in patients after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). 4109 enrolled patients divided into three groups based on their pre-procedural hemoglobin (Hb) level: Hb < 100 mg/L represented moderate-severe anemia; 100 mg/L ≤ Hb < 120 mg/L for women and 100 mg/L ≤ Hb < 130 mg/L for men represented mild anemia; Hb ≥ 20 mg/L for women and Hb ≥ 130 mg/L for men represented no anemia. DAPT medications were prescribed when patients were discharged. There were significant differences in 30-day and 1-year mortality between moderate-severe anemia and no anemia patients (HR 8.05, 95% CI 1.46 to 44.33, P = 0.017; HR 3.93, 95% CI 1.11 to 13.98, P = 0.034), and in long-term mortality between anemia and no anemia groups (HR 1.82, 95% CI 1.17 to 2.83, P = 0.008 for mild anemia; HR 3.19,95% CI 1.29 to 7.86, P = 0.012 for moderate-severe anemia). There was not significant interaction between 12-month DAPT and anemia on mortality in anemic patients (P for interaction > 0.05). Anemia shows association with increased all-cause mortality in patients undergoing PCI. Twelve-month DAPT does not show synergy with anemia to increase the risk of all-cause 1-year mortality in anemic patients after PCI.
| S-EPMC4658638 | biostudies-other
Project description:BACKGROUND:Several antiplatelet medications used during and after percutaneous coronary intervention (PCI) are contraindicated for specific patient groups. A broad assessment of contraindicated medication use and associated clinical outcomes is not well described. METHODS AND RESULTS:Using national Veterans Affairs Clinical Assessment, Reporting, and Tracking Program data for all PCI between 2007 and 2013, we evaluated patients with contraindications to commonly used antiplatelet medications during and after PCI, defined in accordance with package inserts. Adjusted association between contraindicated medication use and outcomes of periprocedural bleeding and 30-day mortality were assessed using Cox proportional hazards with inverse probability weighting. Among 64?294 patients undergoing PCI, 11?315(17.6%) had a contraindication to a common antiplatelet medication and 737 (6.5%) of these patients received a contraindicated medication. In unadjusted analyses, any contraindicated medication use was associated with both increased bleeding and 30-day mortality. In adjusted models, contraindicated abciximab use in patients with thrombocytopenia (hazard ratio, 2.23; 95% confidence interval, 1.58-3.16) and in patients with a previous stroke (hazard ratio, 1.93; 95% confidence interval, 1.37-2.71) remained significantly associated with increased bleeding. Contraindicated abciximab use was not significantly associated with 30-day mortality in adjusted models. Use of eptifibatide in dialysis patients was not significantly associated with an increased risk of bleeding or mortality. CONCLUSIONS:In this national cohort, ?18% of patients undergoing PCI had contraindications to common antiplatelet medications. Approximately 6% of those patients received a contraindicated medication with attendant bleeding risk, although this did not translate into significantly higher risk of 30-day mortality. Continued efforts to reduce contraindicated medication use may help avoid periprocedural complications.
| S-EPMC4956561 | biostudies-literature
Project description:BackgroundThere are no data on comparison between clopidogrel monotherapy and prolonged dual antiplatelet therapy (DAPT) in patients at high-risk undergoing percutaneous coronary intervention (PCI).MethodsOf 2,082 consecutive patients undergoing PCI using second-generation drug-eluting stent (DES), we studied 637 patients at high-risk either angiographically or clinically who received clopidogrel longer than 24 months and were event-free at 12 months after index PCI. Patients were divided into 2 groups: the clopidogrel monotherapy group and the prolonged DAPT group. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction (MI), definite or probable stent thrombosis, or stroke between 12 months and 36 months after the index PCI.ResultsIn propensity score-matched population (246 pairs), the cumulative rate of primary outcome was 4.5% in the clopidogrel monotherapy group and 4.9% in the prolonged DAPT group (hazard ratio, 1.21; 95% confidence interval, 0.54-2.75; P = 0.643). There was no significant difference in all-cause death, MI, stent thrombosis, stroke between the clopidogrel monotherapy group and the prolonged DAPT group.ConclusionCompared with prolonged DAPT, clopidogrel monotherapy showed similar long-term outcomes in patients at high-risk after second-generation DES implantation.
| S-EPMC8076847 | biostudies-literature
Project description:ImportanceDual antiplatelet therapy after percutaneous coronary intervention (PCI) reduces ischemia but increases bleeding.ObjectiveTo develop a clinical decision tool to identify patients expected to derive benefit vs harm from continuing thienopyridine beyond 1 year after PCI.Design, setting, and participantsAmong 11,648 randomized DAPT Study patients from 11 countries (August 2009-May 2014), a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI. Validation was internal via bootstrap resampling and external among 8136 patients from 36 countries randomized in the PROTECT trial (June 2007-July 2014).ExposuresTwelve months of open-label thienopyridine plus aspirin, then randomized to 18 months of continued thienopyridine plus aspirin vs placebo plus aspirin.Main outcomes and measuresIschemia (myocardial infarction or stent thrombosis) and bleeding (moderate or severe) 12 to 30 months after PCI.ResultsAmong DAPT Study patients (derivation cohort; mean age, 61.3 years; women, 25.1%), ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had c statistics of 0.70 and 0.68, respectively. The prediction rule assigned 1 point each for myocardial infarction at presentation, prior myocardial infarction or PCI, diabetes, stent diameter less than 3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; -1 point for age 65 to younger than 75 years; and -2 points for age 75 years or older. Among the high score group (score ≥2, n = 5917), continued thienopyridine vs placebo was associated with reduced ischemic events (2.7% vs 5.7%; risk difference [RD], -3.0% [95% CI, -4.1% to -2.0%], P < .001) compared with the low score group (score <2, n = 5731; 1.7% vs 2.3%; RD, -0.7% [95% CI, -1.4% to 0.09%], P = .07; interaction P < .001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among the high score group (1.8% vs 1.4%; RD, 0.4% [95% CI, -0.3% to 1.0%], P = .26) compared with the low score group (3.0% vs 1.4%; RD, 1.5% [95% CI, 0.8% to 2.3%], P < .001; interaction P = .02). Among PROTECT patients (validation cohort; mean age, 62 years; women, 23.7%), ischemia occurred in 79 patients (1.0%) and bleeding in 37 (0.5%), with a c statistic of 0.64 for ischemia and 0.64 for bleeding. In this cohort, the high-score patients (n = 2848) had increased ischemic events compared with the low-score patients and no significant difference in bleeding.Conclusion and relevanceAmong patients not sustaining major bleeding or ischemic events 1 year after PCI, a prediction rule assessing late ischemic and bleeding risks to inform dual antiplatelet therapy duration showed modest accuracy in derivation and validation cohorts. This rule requires further prospective evaluation to assess potential effects on patient care, as well as validation in other cohorts.Trial registrationclinicaltrials.gov Identifier: NCT00977938.
| S-EPMC5408574 | biostudies-literature
Project description:Reperfusion therapy for patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) involves primary percutaneous coronary intervention (PPCI) and concomitant oral antiplatelet and intravenous antithrombotic pharmacotherapy. There is a conflict between the desire to reduce the time between first medical contact and coronary re-canalisation and achieving effective platelet inhibition with oral antiplatelet agents. This review outlines the currently available antiplatelet treatments, and their place within the therapeutic timeline of a patient presenting with STEMI. Additionally, we focus on current challenges associated with effective antiplatelet treatment, including acute stent thrombosis (AST), the effect of morphine, platelet function assessment and concomitant anticoagulant therapy.
| S-EPMC5808489 | biostudies-literature