Year : 2021 | Volume
: 6 | Issue : 1 | Page : 1--3
Precision medicine in coronary artery disease: Time for implementation into practice
Yu-Xiang Dai, Jun-Bo Ge
Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai, China
Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, Shanghai
|How to cite this article:|
Dai YX, Ge JB. Precision medicine in coronary artery disease: Time for implementation into practice.Cardiol Plus 2021;6:1-3
|How to cite this URL:|
Dai YX, Ge JB. Precision medicine in coronary artery disease: Time for implementation into practice. Cardiol Plus [serial online] 2021 [cited 2021 Apr 16 ];6:1-3
Available from: https://www.cardiologyplus.org/text.asp?2021/6/1/1/312600
Coronary artery disease (CAD) has been viewed largely using a reductionist approach; management is thus primarily evidence-based. However, recent advances in biological, genetic, and molecular technologies and big-data analysis suggested that traditional approach is too simple to capture the complexity at an individual level and thus holds only limited potential for further improvement. Understanding of individual differences in patients with similar clinical presentation is critical for effective risk stratification, diagnosis, and therapeutic decision. We believe that we have now accumulated sufficient knowledge and information to implement the concept of precision medicine in the management of CAD.
Percutaneous Coronary Intervention Based on Intravascular Imaging and Physiological Evaluation
Coronary angiography is the gold standard to evaluate the suitability of CAD patients for percutaneous coronary intervention (PCI) but is limited in acquiring comprehensive geographic features. Intravascular imaging with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) could provide precise assessment of plaque size, morphology, burden, distribution, and composition, lesion length, reference vessel size and the presence of dissections and guide stent sizing, assessing residual narrowing and stent apposition and expansion., The most recently released data from the PROSPECT II study showed that near-infrared spectroscopy IVUS imaging could help identify angiographically nonflow limiting but vulnerable lesions with high-risk characteristics for future adverse cardiac outcomes.
Ischemia, rather than stenosis, is the more appropriate target for coronary revascularization. FAME and FAME II studies demonstrated that physiological evaluation is the clinical standard to guide PCI for intermediate coronary stenosis. Current guidelines recommend the use of fractional flow reserve (FFR) or instantaneous wave-free ratio (an adenosine-free pressure-derived index that circumvents the limitations and discomfort of hyperemic agents) to guide coronary revascularization. Less invasive alternatives, such as computed tomography-derived FFR and quantitative flow ratio, are increasingly used to expand the use of physiological evaluation.
However, it is notable that ischemia is not the only factor predicting cardiovascular outcomes and physiological evaluation is not everything for all CAD patients. For example, high-risk subsets of FFR-negative lesions (FFR >0.80), such as patients with diabetes mellitus or vulnerable stenosis presenting thin-cap fibro-atheroma, have worse outcomes, most likely due to plaque instability or rapid progression of atherosclerotic plaque. COMBINE OCT-FFR study proved that adding OCT plaque morphological evaluation to FFR hemodynamic assessment of intermediate lesions in diabetic patients better predicts MACE and possibly lead to new revascularization strategies. Platforms that combine anatomical and functional evaluation in a single test, such as IVUS-derived FFR and OCT based FFR, are currently under intense development efforts.
Intravascular imaging and physiological evaluation have their own strengths and complementary advantages in lesions with different characteristics and are irreplaceable. The combination or fusion of the two techniques will further optimize the precise medicine of PCI.
Anti-inflammatory Therapy in Progression of Coronary Artery Disease
Cholesterol is important for atherosclerosis development but must be viewed under schematic frameworks that also consider the complex interaction between inflammation and cholesterol. Chronic inflammation plays an important role in the initiation and progression of coronary atherosclerosis. Furthermore, uncontrolled inflammation renders coronary plaques “unstable” and vulnerable to rupture or erosion, and ultimately acute coronary events. Several pro-inflammatory cytokines, including C-reactive protein, tumor necrosis factor-α, and interleukin-6, have been shown to promote coronary atherosclerosis and serve as the independent risk factors for CAD. In the Canakinumab anti-inflammatory Thrombosis Outcome Study (CANTOS), the anti-interleukin-1β antibody canakinumab reduced the rate of recurrent cardiovascular events by 15% in patients with a history of myocardial infarction and an elevated baseline level of C-reactive protein. The encouraging result of CANTOS re-ignited the interest in anti-inflammatory therapy for CAD using re-purposing of the agents already on-market for other indication. However, canakinumab was extremely expensive and associated with a slight but significant increase in fatal infection or sepsis. As an inexpensive and orally administered drug, colchicine can exert its anti-inflammatory effect by reducing the expression of E-selectin, L-selectin, and endothelin, and its safety has been widely verified. In the COLCOT study, 0.5 mg daily colchicine reduced the risk of ischemic cardiovascular events by 23% in patients with recent myocardial infarction. In order to further explore the evidence of such a risk reduction in patients with chronic coronary disease, the recently published LoDoCo2 study showed that colchicine at a dose of 0.5 mg daily significantly reduces the risk of cardiovascular events by 31% in patients with chronic coronary disease. Notably, the benefits were observed early following treatment initiation and continued over time, even in patients receiving other preventive therapies.
Based on the evidence of CANTOS, COLCOT, and LoDoCo2 study, anti-inflammatory therapy, especially low-dose colchicine picked up new support as the secondary prevention in CAD.
Individualized Antiplatelet Strategy after Coronary Intervention
Dual antiplatelet therapy (DAPT) is a cornerstone in preventing stent thrombosis and recurrent ischemic events after PCI, but strategy and duration of DAPT remain controversial.
In the era of 1st generation DES, intensive and prolonged DAPT was the norm due to relatively high rate of late stent thrombosis. Conceivably, bleeding was a major concern. Due to thinner stent struts, more biocompatible polymers, and favorable drug-eluting characteristics, new-generation DES is associated with significantly lower stent thrombosis rate. Accordingly, there has been a trend toward shorter and more balanced DAPT, with a switch to monotherapy at 3 months or even earlier. In addition to DES type, clinical characteristics, complexity of coronary anatomy, and presence of diabetes or renal dysfunction must be considered when assessing the risk of thrombotic events. Clearly, a “one size fits all” approach is inadequate; individualized programs that pinpoint optimal balance between thrombotic and bleeding risks are needed.
Genetic factors inducing interindividual variability must be considered in DAPT strategy. To produce antiplatelet activity, clopidogrel must be activated by CYP2C19. Clinical response to clopidogrel is thus dependent on CYP2C19 gene polymorphism. TAILOR-PCI study is the largest trial to date investigating the use of genetic testing to detect clopidogrel loss-of-function genotype to guide antiplatelet strategy in patients undergoing PCI. The result showed that genotype-guided selection of P2Y12 inhibitor resulted in 34% reduction in cardiovascular events at 1 year, as well as 40% reduction in the total number of events. Although the genotype-guided strategy failed to reach the primary endpoint of a 50% reduction in cardiovascular events at 1 year, a post hoc analysis found 79% reduction in the rate of adverse events in the first 3 months of treatment in genotype-guided group. Considering the high frequency of the loss-of-function CYP2C19 alleles in East Asian populations, an individualized antiplatelet strategy based on genotyping may be particularly important.
In conclusions, our knowledge about CAD has expanded to a critical mass that allows meaningful translation of precision medicine into the real-world use. We believe that the individualized management for CAD is now feasible as well as obligatory.
Financial support and sponsorship
Conflicts of interest
Jun-Bo Ge is the Editorial Board member of the journal.
|1||Ge J, Erbel R, Gerber T, Görge G, Koch L, Haude M, et al. Intravascular ultrasound imaging of angiographically normal coronary arteries: A prospective study in vivo. Br Heart J 1994;71:572-8. doi: 10.1136/hrt. 71.6.572.|
|2||Mintz GS, Guagliumi G. Intravascular imaging in coronary artery disease. Lancet 2017;390:793-809. doi: 10.1016/S0140-6736(17) 31957-8.|
|3||Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213-24. doi: 10.1056/NEJMoa0807611.|
|4||Xaplanteris P, Fournier S, Pijls NHJ, Fearon WF, Barbato E, Tonino PA, et al. Five-Year Outcomes with PCI Guided by Fractional Flow Reserve. N Engl J Med 2018;379:250-9. doi: 10.1056/NEJMoa1803538.|
|5||Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med 2017;377:1119-31. doi: 10.1056/NEJMoa1707914.|
|6||Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med 2019;381:2497-505. doi: 10.1056/NEJMoa1912388.|
|7||Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TS, et al. Colchicine in patients with chronic coronary disease. N Engl J Med 2020;383:1838-47. doi: 10.1056/NEJMoa2021372.|
|8||Pereira NL, Farkouh ME, So D, Lennon R, Geller N, Mathew V, et al. Effect of genotype-guided oral P2Y12 inhibitor selection versus conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: The TAILOR-PCI randomized clinical trial. JAMA 2020;324:761-71. doi: 10.1001/jama. 2020.12443.|