Research Article | Volume 20 Issue 1 (Jan-Dec, 2015) | Pages 1 - 5
Innovations in coronary artery disease: a bench-to-bedside approach
1
Lady Davis Carmel Medical Center and the Ruth and Bruce Rappaport School of Medicine, Technion-IIT, Haifa, Israel Address for correspondence: Basil S. Lewis, Cardiovascular Clinical Research Institute, Lady Davis Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel
Under a Creative Commons license
Open Access
Received
Jan. 1, 2017
Revised
May 5, 2017
Accepted
July 8, 2017
Published
Dec. 31, 2017
Abstract

The 2017 Innovations in Coronary Artery Disease(ICCAD) meeting in Venice, Italy brought together scientists, physicians, and surgeons from 55 countries around the world, who were able to interact and expound on a broad range of new advances and new directions in the field of coronary artery disease. This bench-to-bedside approach allowed for a comprehensive overview of innovations in coronary artery disease.

BASIC SCIENCE ANDMOLECULARBIOLOGY

The basic science sessions focused on three main areas: (i) advances in stem cell science; (ii) studies on cell death, mitochondria, and autophagy; and (iii) novel strategies for protection against ischemia-reperfusion injury. Discussions included stem cell exosomes, iPS-derived extracellular vesicles, and bone marrow cell therapy to repair the failing heart. In the field of ischemia and reperfusion, mTOR signaling and cardioprotection may be important for patients with diabetes, while the role of microRNA, nitric oxide and nitrite pathways, and mitochondrial redox function need further evaluation.

ANGINA PECTORIS: THE ANGINA AWARENESS INITIATIVE

A global angina awareness program was launched at ICCAD 2017 to refocus attention on angina pectoris. Angina pectoris, once a central theme in patient management, has been largely neglected in the era of reperfusion and revascularization. However, angina remains a frequent and disabling condition, affecting 20 000 to 40 000 cases per million European inhabitants, has increasing prevalence in the aging population, and is the initial presentation in approximately 50% of patients with angiographically proven coronary artery disease. Angina is costly, with an estimate that it accounts for 2.6% of overall healthcare expenditures in the European Union, with a staggering annual bill of more than €40 000 million.

The REACH registry highlighted the risk of cardiovascular events in patients with stable coronary artery disease. The 1-year cardiovascular event rates (cardiovascular death, nonfatal myocardial infarction, stroke, and/or hospitalization) increased as a
function of the number of symptomatic disease locations. More than 25% of patients with disease in ≥3 locations had a cardiovascular event at 1 year. The REACH registry also showed that, in the long term, patients with angina at baseline had higher rates of future cardiovascular events, including later heart failure, cardiovascular hospitalization, and coronary revascularization. One-third of patients with chronic stable angina remain symptomatic.4 Moreover, the under-recognition of angina is common in routine clinical practice. The APPEAR study, which involved 155 cardiologists and 1 257 outpatients with coronary artery disease, showed that, in 43% of cases, angina was under-recognized by the treating physician.5 Under-recognition of angina was associated with a lower chance of treatment optimization, resulting in poorer angina control. In addition, angina is an important predictor of events in patients with stable coronary artery disease.

OPTIMAL MEDICAL THERAPY FOR ANGINA

What, then, should be the medical management in patients with stable coronary artery disease? The ESC stable angina guidelines divide angina management into two clear areas: management of anginal symptoms and management of outcome
events using appropriate therapy according to measures of event prediction. The management of angina symptoms is based mainly on short-acting nitrates, β-blockers, and calcium antagonists, while second-line therapy includes ivabradine, long-acting nitrates, ranolazine, and trimetazidine. Second-line drugs may be switched to first-line in certain patients (eg, ivabradine in patients for whom β-blockers are contraindicated).7 Importantly, angiography and revascularization by PCI or bypass surgery should always be considered, depending on the age and clinical state of the patient.

Medical therapy for angina should be optimized on an individual basis for proper symptom control. In a contemporary, multicenter study of US outpatients, 44% of patients were on suboptimal antianginal pharmacologic therapy and there was a wide variability across the sites.8 The CADENCE study in Australia4 found that only 54% of angina patients were treated with either a β-blocker or a nitrate. A cross-sectional, multicenter study in Spain reported that nearly half (49.7%) of the patients reported frequent angina symptoms.

Simplifying the medication regimen improves symptom control and patient treatment satisfaction.9 Optimizing treatment can lead to major improvements in patient satisfaction and the Seattle Angina Questionnaire score. 

RECENT AND ONGOING CLINICAL TRIALS

During the ICCAD session with the ESC Working Group on Cardiovascular Pharmacotherapy, the recent advances and ongoing news from clinical trials were presented. The COMPASS trial data present perhaps more questions than answers regarding when to use combination antiplatelet-anticoagulant therapy for the secondary prevention of coronary artery disease. Treatment individualization seems to be prudent when considering efficacy and safety issues. Importantly, the findings are clearer for patients with peripheral artery disease. We now have a pharmacotherapy that reduces acute limb ischemic events and the need for limb amputations. The antithrombotic management of patients with both atrial fibrillation and acute coronary syndrome or PCI was examined in the REDUAL-PCI trial. This trial showed that dual therapy with dabigatran and a P2Y12 inhibitor was associated with less bleeding than triple therapy using aspirin, a P2Y12 inhibitor, and warfarin. However, caution must be urged regarding the use of the lower dose of dabigatran (110 mg twice a day) in patients undergoing PCI, since there was a numerically greater incidence of stent thrombosis and ischemic events with this dose. In 2018, we expect the results of the AUGUSTUS trial, which is comparing, in a 2 X 2 factorial design, apixaban with warfarin in combination with a P2Y12 inhibitor, with or without the addition of a third antithrombotic drug (aspirin).

Lipidology outcome trials are breaking new ground almost daily. Is an LDL-C value of ≤50 mg/dL the new target or should it be ≤30 mg/dL? We await further analyses from FOURIER and, in 2018, from ODYSSEY to define the population that will benefit the most from PCSK-9 inhibitors. The ORION program is examining the inhibition of PCSK-9 synthesis by inclisiran, a long-acting inhibitor of mRNA that is administered once or twice every six months. Another new strategy is targeting ANGPTL3 (an inhibitor of lipoprotein lipase), and, in preliminary studies, evolocumab significantly reduces LDL in patients with familial hypercholesterolemia. Apolipoprotein-A1 infusions post–MI are the subject of the AEGIS program and we are waitng to see whether this strategy decreases recurrent cardiovascular events. The PROMINENT study is examining the new SPPARM-α drug pemafibrate on triglyceride levels and outcome in diabetic patients with hypertriglyceridemia. BETonMACE is targeting epigenetics and testing whether apabetalone improves outcome in patients with diabetes and recent acute coronary syndrome.

Recent diabetes trials have shown that SGLT2 inhibitors reduce outcome events; further results are expected regarding dapagliflozin in 2018 and ertugliflozin in 2019. The GLP-1 analogs also carry survival benefits, although it is not clear whether this benefit is confined to drugs administered by daily injection. What is clear is that, in patients with cardiovascular disease, diabetes should now be treated by the cardiologist, just as it is the cardiologist who prescribes statins for lipid management.

In the field of heart failure, the most recent clinical trials have been disappointing, probably reflecting our lack of understanding of the pathophysiology. Despite the success of the PARADIGM trial in selected heart failure patients, the clinical applicability of sacubitril is still not clear in the general heart failure population.

INTERVENTIONAL CARDIOLOGY, VALVE INTERVENTIONS, AND CARDIAC SURGERY

The areas of interventional cardiology and surgery are beyond the scope of the present discussion. Many patients undergoing revascularization are elderly; therefore, additional issues regarding valve disease must be addressed. Cost-benefit studies are starting to show the advantage of transcatheter aortic valve replacement over surgical aortic valve replacement in selected populations. 

CONCLUSION

ICCAD 2017 presented new information regarding stem cells and basic cellular mechanisms and discussed how this information may be translated into clinical use in future research. The angina awareness initiative was launched to remind the modern cardiologist about optimizing medical treatment in the clinical arena and about the importance of recognizing patients with angina who are at an increased risk of future cardiac events. Clinical cardiovascular trials have provided compelling new information that has improved outcomes considerably. Finally, the interventional arena now presents a holistic approach to patients with coronary artery disease, including the management of patients with accompanying valve disease and other comorbidities.

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