ISCHEMIA - the Largest Ever Randomized Study in Stable Coronary Artery Disease. Baseline Characteristics of Enrolled Patients in One Russian Site

Indications for coronary revascularization in patients with stable coronary heart disease (CHD), presented in the current international guidelines are largely based on the clinical trials conducted sometimes more than 30 years ago. ISCHEMIA is the major multicenter international randomized trial intended to answer the question about the optimal treatment strategy in stable coronary artery disease at the present time. Purpose. To analyze the most important baseline characteristics of patients enrolled in the ISCHEMIA study in one Russian site. Methods. The principal inclusion criteria are a positive stress test (in our center, exercise stress echocardiography) of at least moderate risk and obstructive coronary heart disease confirmed by coronary computed tomography angiography (CCTA). Main exclusion criteria are a significant stenosis of the left main coronary artery by CCTA, clinical progression/destabilization of the ischemic heart disease, angina of IV CCS class, left ventricular ejection fraction (EF) <35%. Enrolled patients are randomized into the conservative or invasive treatment groups. Results. We analyzed the data of 28 randomized patients who completed at least 6 months of follow-up. Mean pts age is 62.6±5.5 years, 75% are males. ^e prevalence of risk factors (RFs) is the following: arterial hypertension - 93%, diabetes mellitus -29%, history of smoking - 64%, family history of CHD - 36%. 36% of pts have the history of myocardial infarction; the median duration of clinical CHD is 24 months. Mean EF is 65%. 100% of patients are taking aspirin, >80% -beta blockers, >80% - ACE inhibitors/ARBs. ^ey are at well controlled resting heart rate (<70 bpm in 82%) and blood pressure (<140/90 mm Hg in 82%). The level of depression by the PHQ-8 scale is 5.35±4.11 (average for chronic diseases). The lipids control and lipid-lowering therapy are inadequate: low density lipoprotein cholesterol (LDL C) is 2.55 (2.04-4.08) mmol/l, LDL C is below 1.8 mmol/l in 18%, only 33% of pts are taking a high-intensity statin. At the end of the 6-month follow-up, LDL C was 2.07 (1.79-2.53), a decrease of 19 (0.58-43.5) %, p=0.003. LDL C was <1.8 mmol/l in 28% of patients and 63% were taking a high-intensity statin. Mean angina CCS class at baseline was 1.8±0.6, 79% of patients having the 2nd CCS class. At the stress test, 78% completed the load of >5 METs, the median ischemic area was 4.0 (3.5-5.5) segments, in 71% the ischemia in the left anterior descendent artery region was provoked. The ratio of interventional to surgical revascularization in the invasive group was 1.2, indicating anatomically diffuse CHD in 45% of these patients. Conclusion. In ISCHEMIA pts enrolled in our center, the main RFs, except the lipid-related, were well controlled at baseline; the lipid-related RFs improved after 6 months. Ischemic symptoms were mild or moderate, but the variables of the stress test and low PCI:CABG ratio indicate the study pts are moderate or high risk pts.

стабильная ишемическая болезнь сердца , рандомизированное исследование , российский медицинский центр, stable ischemic heart disease , randomized study , Russian medical center

1. Patel M.R., Dehmer G.J., Hirshfield J.W. et al. ACCF/SCAI/STS/ AATS/AHA/ASNC 2009 Appropriateness criteria for coronary revascularization. J Am Coll Cardiol 2009;53(6):530-553. doi: 10.1016/j.jacc.2008.10.005

2. Hlatky M.A., Boothroyd D.B., Bravata D.M. et al. Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials. Lancet 2009;373:1190-1197. doi: 10.1016/S0140-6736(09)60552-3

3. Kappetein A.P., Mohr F.W., Feldman T.E. et al. Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial. Eur Heart J 2011;17:2125-134. doi:10.1093/eurheartj/ehr213

4. Qadir I., Salick M. M., Perveen S., Sharif H. Mortality from isolated coronary bypass surgery: a comparison of the Society of Thoracic Surgeons and the EuroSCORE risk prediction algorithms. Interactive CardioVasc Thoracic Surg 2012;14:258-262. doi:10.1093/icvts/ivr072

5. Reynolds H.R., Picard M.H., Hochman J.S. Does ischemia burden in stable coronary artery disease effectively identify revascularization candidates? Ischemia burden in stable coronary artery disease does not effectively identify revascularization candi6. Hachamovitch R. Does Ischemia burden in stable coronary artery disease effectively identify revascularization candidates? Ischemia burden in stable coronary artery disease effectively identifies revascularization candidates. Circ Cardiovasc Imaging 2015;8:e000352. doi: 10.1161/CIRCIMAGING.113.000352

6. Hachamovitch R. Does Ischemia burden in stable coronary artery disease effectively identify revascularization candidates? Ischemia burden in stable coronary artery disease effectively identifies revascularization candidates. Circ Cardiovasc Imaging 2015;8:e000352. doi: 10.1161/CIRCIMAGING.113.000352

7. Stone G.W., Hochman J.S., Williams D.O. et al. Medical therapy with versus without revascularization in stable patients with moderate and severe ischemia. The case for community equipoise. J. Am Coll Cardiol 2016;67:81-99. doi:10.1016/ j.jacc.2015.09.056.

8. Boden W.E., O'Rourke R.A., Teo K.K. et al.; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N. Engl J. Med 2007;356: 1503-16. doi:10.1056/NEJMoa070829.

9. Pijls N.H., Fearon W.F., Tonino P.A. et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study. J. Am Coll Cardiol 2010;56:177-184. doi: 10.1016/j.jacc.2010.04.012

10. Bangalore S., Kumar S., Fusaro M. et al. Short- and long-term outcomes with drug-eluting and bare-metal coronary stents: a mixed-treatment comparison analysis of 117 762 patient-years of follow-up from randomized trials. Circulation 2012;125:2873-2891. doi: 10.1161/CIRCULATIONAHA.112.097014

11. Мовсесянц М.Ю., Покатилов А.А., Прямиков А.Д. и др. Измерение фракционного резерва кровотока при поражении коронарных артерий. Сердце 2012;9(3):145-149

12. The BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N. Engl J. Med 2009;360:2503-2515. doi: 10.1056/NEJMoa0805796.

13. Hueb W., Lopes N., Gersh B.J. et al. Ten-year follow-up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease. Circulation 2010;122:949-957. doi :10.1161/CIRCULATIONAHA.109.911669

14. Шальнова С.А., Оганов Р.Г., Стэг Ф.Г., Форд Й. от имени участников регистра CLARIFY. Ишемическая болезнь сердца. Современная реальность по данным всемирного регистра CLARIFY Кардиология 2013; 8:28-33

15. Карпов Ю. А., Глезер М. Г., Васюк Ю. А. и др. Антиангинальная эффективность и переносимость ивабрадина в терапии пациентов со стабильной стенокардией: результаты исследования КОНТРОЛЬ-2. Кардиоваскулярная терапия и профилактика 2011;10(8):83-89

16. Tendera M., Chassany O., Ferrari R. et al.; SIGNIFY Investigators. Quality of Life With Ivabradine in Patients With Angina Pectoris: Ue Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease Quality of Life Substudy. Circ Cardiovasc Qual Outcomes 2016;9(1):31-8. doi: 10.1161/CIRCOUTCOMES.115.002091

17. Tardif J.C., Ponikowski P., Kahan T.; ASSOCIATE Investigators. Effects of ivabradine in patients with stable angina receiving ß-blockers according to baseline heart rate: an analysis of the ASSOCIATE study. Int J. Cardiol 2013;168(2):789-794. doi: 10.1016/j.ijcard.2012.10.011

18. Mangiacapra F., Colaiori I., Ricottini E. et al. Heart Rate reduction by IVabradine for improvement of ENDothELial function in patients with coronary artery disease: the RIVENDEL study. Clin Res Cardiol 2017;106:69. doi:10.1007/s00392-016-1024-7

19. Gloekler S., Traupe T., Stoller M. et al. The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease. Heart 2014;100(2):160-166. doi: 10.1136/heartjnl-2013-304880

20. Kroenke K., Strine T.W., Spitzer R.L. et al. The PHQ-8 as a measure of current depression in the general population. J. Affect Disord 2009;114(1-3):163-173. doi: 10.1016/j.jad.2008.06.026.

21. Sicari R., Nihoyannopoulos С., Evangelista A. et al. Stress echocardiography expert consensus statement European Association of Echocardiography (EAE) (a registered branch of the ESC). Eur J. Echocardiography 2008;9:415-437. doi:10.1093/ejechocard/jen175

22. Fihn S.D., Gardin J.M., Abrams J. et al. 2012 ACCF/AHA/ACP/ AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J. Am Coll Cardiol 2012;60(24):1-121.