Display omitted
•Recommendations for aspirin in patients with no apparent CV were downgraded in recent guidelines.•Patients with advanced underlying subclinical atherosclerosis are at higher CV ...risk.•A personalized approach balancing CV and bleeding risks identifies patients who may need aspirin.
Cardiovascular disease (CVD) remains the leading cause of death worldwide. The risk of a cardiovascular (CV) event is not static and increases along a continuum, making identification and management complex.
Aspirin has been the cornerstone of antiplatelet therapy in CV risk reduction and remains the only antiplatelet agent with current guideline recommendations throughout the CV risk continuum. In light of recent trials, the role of aspirin in CVD prevention in asymptomatic patients has been downgraded in clinical guidelines. However, a substantial proportion of asymptomatic patients have underlying conditions, such as advanced subclinical atherosclerosis that are associated with high CV risk. Advanced subclinical atherosclerosis has not been extensively investigated in patients in clinical trials but in the absence of significant bleeding risks, patients with subclinical atherosclerosis may particularly benefit from preventive aspirin therapy.
Recent studies and clinical guidelines support the need for a personalized treatment approach for these patients, balancing their risk of future CV events against their relative bleeding risk. In this commentary, we first discussed various tools and strategies currently available for assessing CV and bleeding risks; we then provided two hypothetical cases to outline how these tools can be implemented for optimal management of patients with no prior CV events who, nonetheless, are susceptible to CVD.
The first case details a young and apparently healthy patient with underlying advanced subclinical atherosclerosis; whereas the second case describes a patient with recently diagnosed type 2 diabetes mellitus who is at higher risk of CVD than their non-diabetic counterparts. For both cases, we considered patient clinical characteristics, CV and bleeding risks, as well as other risk factors to evaluate the appropriate treatment strategy and determine whether patients would obtain a net clinical benefit from low-dose aspirin therapy. These cases can serve as examples to guide clinical decision-making on the use of low-dose aspirin for primary CVD prevention and improve CVD management via a personalized approach.
Abstract
There are clinical scenarios where the balance between the risk of ischemic and bleeding events leads to the clinical decision to reverse the antiplatelet effect of P2Y
12
receptor ...inhibitors. These scenarios comprise emergency situations such as active severe bleeding, urgent procedures with presumed high bleeding risk, or major trauma with (anticipated) bleeding. Supplementation of platelets has been investigated in ex vivo as well as in in vivo studies. These studies indicate that the inhibition of adenosine diphosphate-induced aggregation by the irreversibly binding thienopyridine derivatives clopidogrel and prasugrel can be reversed by administration of platelet concentrates. Supplementation of platelets in patients on prasugrel is more effective if this can be transfused > 6 hours after last dosing. Studies on the reversal effect obtained by administration of platelet concentrates in patients on ticagrelor show conflicting results. Experimental data suggest that administration of serum albumin might increase the reversal effect. A monoclonal antibody fragment (PB2452) for neutralizing ticagrelor is currently in clinical development. A recently published first in man study shows that reversal of platelet inhibition occurs within 5 minutes after start of administration and the effect is maintained for 20 to 24 hours after a 16-hour infusion which is by far the most effective approach for reversal of ticagrelor.
Traditionally, guidelines divide patients into primary and secondary prevention for atherosclerotic cardiovascular disease (ASCVD) risk management. However, the modern understanding of the biological ...progression of atherosclerosis is inconsistent with this binary approach. Therefore, a new approach demonstrating both atherosclerosis and ASCVD risk as a continuum is needed to give clinicians a framework for better matching risk and intensity of therapy. Advances in coronary imaging have most clearly brought this problem into view, as for example coronary artery calcium (CAC) scoring has shown that some individuals in the primary prevention have equal or higher ASCVD risk as certain subgroups in secondary prevention. This article introduces “advanced subclinical atherosclerosis” as a new and distinct clinical group that sits between the traditional groups of primary and secondary prevention. Importantly, this article also introduces a new graphic to visualize this intermediate population that is explicitly based on plaque burden. The aim of the graphic is both to educate and to allow for better identification of a patient's cardiovascular risk and guide more effective risk-based management.
In acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), treatment with the P2Y12 inhibitors ticagrelor or prasugrel is recommended over clopidogrel due to a ...better efficacy, albeit having more bleeding complication. These higher bleeding rates have provoked trials investigating de-escalation from ticagrelor or prasugrel to clopidogrel in the hope of reducing bleeding without increasing thrombotic event rates. In this review, we sought to present an overview of the major trials investigating several different options for de-escalation; unguided, platelet function testing- and genotype-guided. Based on these results, and on other established literature sources, such as guidelines and expert consensus papers, we provide an overview to help decide when and how to de-escalate antiplatelet therapy in ACS patients undergoing PCI.
Abstract
Objectives
This prespecified analysis of the TROPICAL-ACS trial aimed to assess the impact of gender on clinical outcomes and platelet reactivity (PR) following guided de-escalation of dual ...antiplatelet treatment (DAPT) in acute coronary syndrome (ACS) patients.
Background
Guided de-escalation of DAPT was recently identified as an effective alternative treatment strategy in ACS.
Methods
We used Cox proportional hazards models and linear regression analysis to assess the interaction of gender with clinical endpoints and PR.
Results
In both male (
n
= 2,052) and female (
n
= 558) patients, the 1-year incidence of the primary endpoint did not differ in guided de-escalation versus control group patients (male: 7.0% vs. 9.0%; hazard ratio HR, 0.78, 95% confidence interval CI, 0.57–1.06,
p
= 0.11; female: 8.4% vs. 9.2%; HR, 0.92, 95% CI, 0.53–1.62,
p
= 0.76,
p
int
= 0.60). The 1-year incidence of combined ischemic events (male: 2.5% vs. 3.3%; HR, 0.76, 95% CI, 0.46–1.26,
p
= 0.29; female: 2.2% vs. 2.8%; HR, 0.78,95% CI, 0.27–2.25,
p
= 0.65,
p
int
= 0.96) as well as Bleeding Academic Research Consortium ≥ 2 bleeding (male: 4.6% vs. 6.0%; HR, 0.77, 95% CI, 0.52–1.12,
p
= 0.17; female: 6.2% vs. 6.4%; HR, 0.99, 95% CI, 0.51–1.92,
p
= 0.97,
p
int
= 0.51) was similar in the guided de-escalation versus control group for both male and female patients. Interaction testing revealed no significant impact of gender on PR levels (prasugrel or clopidogrel) across treatment groups (
p
int
= 0.72).
Conclusion
Guided de-escalation of DAPT appears to be equally safe and effective in women and men. Especially in patients with increased bleeding risk and independent from gender, a guided DAPT de-escalation strategy may be used as an alternative treatment strategy.
Clinical Trial Registration
URL:
http://https//www.clinicaltrials.gov
. Unique Identifier: NCT: 01959451.
Inflammatory processes in the vessel wall are associated with progression of atherosclerosis and myocardial infarction. Both high levels of C-reactive protein (CRP)and high on-clopidogrel treatment ...platelet reactivity (HPR) have been linked to an increased risk of ischaemic events after percutaneous coronary intervention (PCI). The aim of this study was to explore the association between biomarker levels of inflammation and platelet reactivity. Stable patients (n=1,223) eligible for this study were under chronic antiplatelet treatment with aspirin and clopidogrel due to prior coronary stent placement. ADP-induced platelet aggregation (in AU*min) was measured on a Multiplate analyser. The primary outcome measure of this retrospective study was the ADP-induced platelet aggregation in patients with versus those without elevated CRP levels. Of the patients15.5% (n=189) showed elevated CRP levels (≥5 mg/l). Platelet aggregation (median interquartile range) was significantly higher in patients with elevated CRP levels compared to patients with normal (<5 mg/l) CRP levels (305 202–504 AU*min vs. 218 144–384 AU*min; p<0.001).A multivariable linear regression model that adjusted for known predictors of HPR confirmed a significant independent association between elevated CRP levels and high ADP-induced platelet aggregation values (p=0.0002).Elevated WBC count and fibrinogen levels were also associated with higher platelet aggregation values (p<0.001 for both). In conclusion, elevated levels of CRP, WBC count and fibrinogen were significantly associated with high platelet reactivity in patients under chronic clopidogrel treatment. Whether a direct relation between platelets and inflammation exists, as well as the clinical impact of our results, warrants further investigations.
Objectives The goal of this study was to assess whether a platelet rebound exists and whether it can be attenuated by clopidogrel tapering. Background Clinical studies have reported a clustering of ...thrombotic events after stopping clopidogrel treatment. The hypothesis of a rebound phenomenon of platelets has been declared causative, but its existence has never been confirmed. Tapering of clopidogrel over a certain period of time before stopping the drug completely might provide a way to attenuate this supposed phenomenon. Methods Patients (n = 69) receiving clopidogrel treatment due to prior drug-eluting stent placement and planning to stop clopidogrel were recruited in a double-blind, randomized trial. Patients were randomized to either receive a pre-specified tapering regimen (tapering group; n = 35) for 4 weeks with complete discontinuation of clopidogrel thereafter or continue a daily clopidogrel intake for 4 more weeks with abrupt discontinuation afterwards (off group; n = 34). Platelet aggregation (PA) was assessed with light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) simultaneously at study inclusion and at weeks 2 to 8 after randomization. The primary end point was the highest value of adenosine diphosphate–induced PA measured with LTA in the weeks after complete cessation of clopidogrel in both groups. Results The highest values of adenosine diphosphate–induced PA after complete cessation of clopidogrel were similar between both groups (p = 0.21 with LTA, and p = 0.55 with MEA). Conclusions Tapering of clopidogrel does not result in lower PA values after clopidogrel withdrawal. The course of PA values after clopidogrel cessation provides no evidence for the existence of a rebound phenomenon of platelets.
...determination of a single genotype is only a small extract from the entire genetic basis that determines drug response.11 Other factors including age, bodyweight, diabetes, and renal insufficiency ...can contribute to drug response and integration of these clinical variables with genetic data might enhance the accuracy by which drug response is determined. ...CYP2C19 genotype data have taught us that heterozygous loss-of-function (CYP2C19*2) allele carriers show a broad distribution of drug response ranging from enhanced to low responders.12 Second, the timepoint for testing is set in a randomised trial, but the optimal timing for testing in a real-life setting could differ across clinical scenarios (eg, escalation vs de-escalation, acute coronary syndrome vs chronic coronary syndromes) and patient subgroups. While escalation of dual antiplatelet therapy usually requires early testing after the index procedure when the risk of stent thrombosis or reinfarction is highest, a de-escalation strategy may take place early but also in distance to PCI. ...de-escalation of dual antiplatelet therapy may follow (1) a proactive approach (in line with clinical trial designs) with treatment de-escalation before the occurrence of a bleeding event in patients with a presumed high bleeding risk, or (2) a reactive approach with a change of treatment in reaction to the occurrence of adverse events (eg, side-effects on ticagrelor or prasugrel or bleeding). ...any desired guided de-escalation of dual antiplatelet therapy entails the risk that test results with confirmation of either high on-treatment platelet reactivity or CYP2C19*2 allele carriage might consequently lead to an escalation back to potent P2Y12 inhibitors.
PDF
