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Intra-coronary Imaging for the Evaluation of Plaque Modifications Induced by Drug Therapies for Secondary Prevention.

ABSTRACT: PURPOSE OF REVIEW:Patients diagnosed with coronary artery disease are at a high risk of subsequent cardiovascular events; therefore, secondary prevention in the form of therapeutic lifestyle changes, and drug therapies is vital. This article aims to review potential application of intra-coronary imaging for the evaluation of plaque modifications, induced by medications for secondary prevention for CAD. RECENT FINDINGS:Intra-coronary imaging provides detailed information on the atherosclerotic plaque which is the primary pathological substrate for the recurrent ischemic cardiovascular events. These modalities can detect features associated with high risk and allow serial in vivo imaging of lesions. Therefore, intravascular imaging tools have been used in landmark studies and played a role in improving our understanding of the disease processes. Changes in size and plaque composition over time can be evaluated by these tools and may help understanding the impact of a treatment. Moreover, surrogate imaging end points can be used when testing new drugs for secondary prevention.

SUBMITTER: Kilic ID

PROVIDER: S-EPMC7538414 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Intra-coronary Imaging for the Evaluation of Plaque Modifications Induced by Drug Therapies for Secondary Prevention.

Kilic Ismail Dogu ID Fabris Enrico E Kedhi Elvin E Ghilencea Liviu-Nicolae LN Caiazzo Gianluca G Sherif Sara Abou SA Di Mario Carlo C

Current atherosclerosis reports 20201006 12

<h4>Purpose of review</h4>Patients diagnosed with coronary artery disease are at a high risk of subsequent cardiovascular events; therefore, secondary prevention in the form of therapeutic lifestyle changes, and drug therapies is vital. This article aims to review potential application of intra-coronary imaging for the evaluation of plaque modifications, induced by medications for secondary prevention for CAD.<h4>Recent findings</h4>Intra-coronary imaging provides detailed information on the ath ...[more]

PMID: 33025069

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Project description:BACKGROUND:Atherosclerotic plaque rupture is the culprit event which underpins most acute vascular syndromes such as acute myocardial infarction. Novel biomarkers of plaque rupture could improve biological understanding and clinical management of patients presenting with possible acute vascular syndromes but such biomarker(s) remain elusive. Investigation of biomarkers in the context of de novo plaque rupture in humans is confounded by the inability to attribute the plaque rupture as the source of biomarker release, as plaque ruptures are typically associated with prompt down-stream events of myocardial necrosis and systemic inflammation. METHODS:We developed a novel approach to identify potential biomarkers of plaque rupture by integrating plaque imaging, using optical coherence tomography, with both plaque and plasma proteomic analysis in a human model of angioplasty-induced plaque disruption. RESULTS:We compared two pairs of coronary plaque debris, captured by a FilterWire Device, and their corresponding control samples and found matrix metalloproteinase 9 (MMP9) to be significantly enriched in plaque. Plaque contents, as defined by optical coherence tomography, affect the systemic changes of MMP9. Disruption of lipid-rich plaque led to prompt elevation of plasma MMP9, whereas disruption of non-lipid-rich plaque resulted in delayed elevation of plasma MMP9. Systemic MMP9 elevation is independent of the associated myocardial necrosis and systemic inflammation (measured by Troponin I and C-reactive protein, respectively). This information guided the selection of a subset of subjects of for further label free proteomics analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS). We discovered five novel, plaque-enriched proteins (lipopolysaccharide binding protein, Annexin A5, eukaryotic translocation initiation factor, syntaxin 11, cytochrome B5 reductase 3) to be significantly elevated in systemic circulation at 5 min after plaque disruption. CONCLUSION:This novel approach for biomarker discovery in human coronary artery plaque disruption can identify new biomarkers related to human coronary artery plaque composition and disruption.

Project description:Patients with acute coronary syndrome (ACS) usually receive acetylsalicylic acid plus an adenosine diphosphate (ADP) receptor inhibitor to reduce the long-term risk of recurrent events. However, patients receiving standard antiplatelet prophylaxis still face a substantial risk of recurrent events. Strategies involving 3 antithrombotic agents with different modes of action have now been tested. In Thrombin Receptor Antagonists for Clinical Event Reduction (TRA-CER), compared with standard care alone, bleeding complications including intracranial hemorrhage (ICH) were increased with the addition of vorapaxar, without efficacy benefit. In Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA 2°P-TIMI 50), the addition of vorapaxar reduced recurrent events compared with standard care in stable patients with prior myocardial infarction. This study was terminated early in patients with prior stroke owing to excess ICH, though an increased risk of ICH or fatal bleeding was not detected in patients with prior myocardial infarction. The Apixaban for Prevention of Acute Ischemic and Safety Events 2 (APPRAISE-2) trial of standard-dose apixaban added to standard care in patients with ACS was also stopped early owing to excess serious bleeding. However, in Rivaroxaban in Combination With Aspirin Alone or With Aspirin and a Thienopyridine in Patients With Acute Coronary Syndromes (ATLAS ACS 2 TIMI 51), fatal bleeding or fatal ICH did not increase with low-dose rivaroxaban added to low-dose acetylsalicylic acid-based standard care compared with standard care alone. In that trial, a significant reduction of recurrent vascular events was shown with 3 antithrombotic regimens compared with standard care. Therefore, depending on drug dose and patient population, further reductions in recurrent vascular events after ACS may be possible in future clinical practice, with a favorable benefit-risk profile.

Project description:A combination optical coherence tomography and near-infrared spectroscopy (OCT-NIRS) coronary imaging system is being developed to improve the care of coronary patients. While stenting has improved, complications continue to occur at the stented site and new events are caused by unrecognized vulnerable plaques. An OCT-NIRS device has potential to improve secondary prevention by optimizing stenting and by identifying vulnerable patients and vulnerable plaques. OCT is already in widespread use world-wide to optimize coronary artery stenting. It provides automated lumen detection and can identify features of coronary plaques not accurately identified by angiography or intravascular ultrasound. The ILUMIEN IV study, to be completed in 2022, will determine if OCT-guided stenting will yield better clinical outcomes than angiographic guidance alone. While the superb spatial resolution of OCT enables the identification of many plaque structural features, the detection by OCT of lipids, an important component of vulnerable plaques, is limited by suboptimal specificity and interobserver agreement. In contrast, NIRS has been extensively validated for lipid-rich plaque detection against the gold-standard of histology and is the only FDA-approved method to identify coronary lipids. Studies in patients have demonstrated that NIRS detects lipid in culprit lesions causing coronary events. In 2019, the positive results of the prospective Lipid-Rich Plaque Study led to FDA approval of NIRS for detection of high-risk plaques and patients. The complementarity of OCT for plaque structure and NIRS for plaque composition led to the sequential performance of NIRS and OCT imaging in patients. NIRS identified lipid while OCT determined the thickness of the cap over the lipid pool. The positive results obtained with OCT and NIRS imaging led to development of a prototype combined OCT-NIRS catheter that can provide co-registered OCT and NIRS data in a single pullback. The data will provide structural and chemical information likely to improve stenting and deliver more accurate identification of vulnerable plaques and vulnerable patients. More precise diagnosis will then lead to OCT-NIRS guided treatment trials to improve secondary prevention. Success in secondary prevention will then facilitate development of improved primary prevention with invasive imaging and effective treatment of patients identified by non-invasive methods.

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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Intra-coronary Imaging for the Evaluation of Plaque Modifications Induced by Drug Therapies for Secondary Prevention.

Publications

Intra-coronary Imaging for the Evaluation of Plaque Modifications Induced by Drug Therapies for Secondary Prevention.

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