В данном клиническом семинаре (лекции) обоснована необходимость оптимизации медикаментозного лечения больных со стабильной стенокардией. Качество терапии этой группы больных не соответствует современным возможностям. В большинстве случаев проводимое медикаментозное лечение не обеспечивает достижения целевого уровня контроля имеющихся факторов риска плохого прогноза жизни больных. В определенной степени неоптимальное лечение в целом способствует сохранению показателя смертности от сердечно-сосудистых заболеваний на уровне, который является одним из самых высоких в мире. Кроме неоптимального использования препаратов, имеющих доказательства положительного влияния на выживаемость больных, очень часто рекомендуются вещества, которые не получили таких доказательств. Большинство из них составляют группу так называемых метаболических препаратов. Их широкое назначение больным с разнообразными формами патологии, не только с сердечно-сосудистыми заболеваниями, стало своеобразной модой в медицине нашей страны, несмотря на отсутствие фармакоэкономического обоснования их пользы.
In this clinical seminar (lecture) we argue the urgency to optimize the drug therapy in patients with stable angina pectoris. Today the quality of their treatment remains lower than it could be. In majority of cases the applied drug therapy does not allow to control the risk factors of inappropriate prognosis. Inadequate treatment of angina pectoris contributes to very high mortality rate due to cardiac diseases in Russian Federation. Prescription of drugs with proven positive effect is often based on non-optimal schemes. Moreover, there is a wide-spread tendency to prescribe metabolic drugs to patients with cardiovascular pathology and other diseases notwithstanding the fact that the pharmacoeconomic validity оf such drugs remains to be demonstrated.
2. The Academic Research Organization Consortium for Continuing Evaluation of Scientific Studies – Cardiovascular (ACCESS CV). Sharing Data from Cardiovascular Clinical Trials – A Proposal. N Engl J Med 2016; 375: 407–9.
3. Саютина Е.В., Чигинева В.В., Золозова Е.А. и др. Контроль ишемии миокарда у больных стенокардией напряжения с многососудистым атеросклеротическим поражением. Кардиология. 2012; 8: 15–9. / Saiutina E.V., Chigineva V.V., Zolozova E.A. i dr. Kontrol' ishemii miokarda u bol'nykh stenokardiei napriazheniia s mnogososudistym ateroskleroticheskim porazheniem. Kardiologiia. 2012; 8: 15–9. [in Russian]
4. Карлова Н.А., Золозова Е.А., Пшеницин А.И. и др. Оценка терапевтической эффективности и безопасности оригинального препарата бисопролола и его дженерика бипрола у больных стабильной стенокардией. Кардиология. 2015; 1: 23–8. / Karlova N.A., Zolozova E.A., Pshenitsin A.I. i dr. Otsenka terapevticheskoi effektivnosti i bezopasnosti original'nogo preparata bisoprolola i ego dzhenerika biprola u bol'nykh stabil'noi stenokardiei. Kardiologiia. 2015; 1: 23–8. [in Russian]
5. Euro Heart Survey of stable angina: prospective observational study. Eur Heart J 2005; 26: 1011–22.
6. ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. 2013.
7. ESC guidelines stable coronary artery disease. Eur Heart J 2013; 34 (38): 2927–8.
8. PEGASUS-TIMI 54 Steering Committee and Investigators. Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction. N Engl J Med 2015; 372: 1791–800.
9. Serebruany VL. The TRITON versus PLATO trials: differences beyond platelet inhibition. Thromb Haemost 2010; 103 (2): 259–61.
10. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348 (9038): 1329–39.
11. Lee M, Wu YL, Saver JL et al. Is clopidogrel better than aspirin following breakthrough strokes. A retrospective cohort study. BMJ Open 2014; 4 (12): e006672.
12. Мазур Н.А. Антиагрегантная терапия у больных ишемической болезнью сердца: нерешенные проблемы. Кардиология. 2016; 1: 66–70. / Mazur N.A. Antiagregantnaia terapiia u bol'nykh ishemicheskoi bolezn'iu serdtsa: nereshennye problemy. Kardiologiia. 2016; 1: 66–70. [in Russian]
13. Everly MJ, Heaton PC, Cluxton RJ. Beta-Blocker Underuse in Secondary Prevention of Myocardial Infarction. Ann Pharmacother 2003; 38: 286–93.
14. Le SJ. Prognostic Significance of Resting Heart Rate and Use of β-Blockers in Atrial Fibrillation and Sinus Rhythm in Patients With Heart Failure and Reduced Ejection Fraction: Findings From the Swedish Heart Failure Registry. Circ Heart Fail 2015; 8 (5): 871–9.
15. Flather MD, Shibata MC, Coats AJ et al; SENIORS Investigators. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005; 26 (3): 215–25.
16. Мазур Н.А. Внезапная смерть больных ишемической болезнью сердца. М.: Медицина, 1985; с. 121–42. / Mazur N.A. Vnezapnaia smert' bol'nykh ishemicheskoi bolezn'iu serdtsa. M.: Meditsina, 1985; s. 121–42. [in Russian]
17. Hansen JF. Treatment with verapamil after an acute myocardial infarction. Review of the Danish studies on verapamil in myocardial infarction (DAVIT I and II). Drugs 1991; 42 (Suppl. 2): 43–53.
18. Rehnqvist N, Hjemdahl P, Billing E et al. Effects of metoprolol vs verapamil in patients with stable angina pectoris. The Angina Prognosis Study in Stockholm (APSIS). Eur Heart J 1996; 17 (1): 76–81.
19. The Multicenter Diltiazem Postinfarction Trial Research Group The effect of diltiazem on mortality and reinfarction after myocardial infarction. N Engl Med 1988; 319 (7): 385–92.
20. Poole-Wilson PA, Lubsen J, Kirwan BA et al; Coronary disease Trial Investigating Outcome with Nifedipine gastrointestinal therapeutic system investigators. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial. Lancet 2004; 364 (9437): 849–57.
21. Мазур Н.А. Практическая кардиология. М.: Медпрактика-М, 2015; с. 109–37. / Mazur N.A. Prakticheskaia kardiologiia. M.: Medpraktika-M, 2015; s. 109–37. [in Russian]
22. Хоринака Ш. Влияние никорандила на частоту сердечно-сосудистых событий у пациентов с коронарной болезнью сердца. Рос. кардиол. журн. 2011; 2 (88): 82–90. / Khorinaka Sh. Vliianie nikorandila na chastotu serdechno-sosudistykh sobytii u patsientov s koronarnoi bolezn'iu serdtsa. Ros. kardiol. zhurn. 2011; 2 (88): 82–90. [in Russian]
23. Sakata Y, Nakatani D, Shimizu M et al. Oral treatment with nicorandil at discharge is associated with reduced mortality after acute myocardial infarction. J Cardiol 2012; 59 (1): 14–21.
24. IONA Study Group. Impact of nicorandil in angina: subgroup analyses. Heart 2004; 90 (12): 1427–30.
25. Stoschitzky K, Rezkalla SH, Klone RA. No evidence of nitrate tolerance with Nicorandil. Eur Heart J 2012; 32 (Abstract Supplement): 470.
26. Sekiya M, Sato M, Funada J et al. Effects of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis. J Cardiovasc Pharmacol 2005; 46 (1): 63–7.
27. Patel DJ, Purcell HJ, Fox KM on behalf of the CESAR 2 investigation. Cardioprotection by opening of the KATP channel in unstable angina. Eur Heart J 1999; 20: 51–7.
28. Eguchi Y, Takahari Y, Higashijima N et al. Nicorandil Attenuates FeCl3-Induced Thrombus Formation Through the Inhibition of Reactive Oxygen Species Production. Circ J 2009; 73 (3): 554–61.
29. Izumiya Y, Kojima S, Araki S et al. Long-term use of oral nicorandil stabilizes coronary plaque in patients with stable angina pectoris. Atherosclerosis 2011; 214 (2): 415–21.
30. Markham A, Plosker GL, Goa KL. Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardio-protective effects. Drugs 2000; 60: 955–74.
31. Kasama S, Toyama T, Sumino H et al. Long-term nicorandil therapy improves cardiac sympathetic nerve activity after reperfusion therapy in patients with first acute myocardial infarction. J Nucl Med 2007; 48 (10): 1676–82.
32. Kasama S, Toyama T, Hatori T et al. Comparative effects of nicorandil with isosorbide mononitrate on cardiac sympathetic nerve activity and left ventricular function in patients with ischemic cardiomyopathy. Am Heart J 2005; 150 (3): 477.e1–477.e8.
33. Evans M, Carrero JJ, Szummer K, Akerblom A. Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Myocardial Infarction Patients With Renal Dysfunction. J Am Coll Cardiol 2016; 67: 1687–97.
34. Sleight P. The HOPE Study (Heart Outcomes Prevention Evaluation). J Renin Angiotensin Aldosterone Syst 2000; 1 (1): 18–20.
35. Campbell DJ. A review of Perindopril in the reduction of cardiovascular events. Vasc Health Risk Manag 2006; 2 (2): 117–24.
36. Tardif JC, Ponikowski P, Kahan T. ASSOCIATE Study Investigators. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J 2009; 30 (5): 540–8.
37. Fox K, Ford I, Steg PG et al; SIGNIFY Investigators. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med 2014; 371 (12): 1091–9.
38. Tanboğa İH, Topçu S, Aksakal E et al. The Risk of Atrial Fibrillation With Ivabradine Treatment: A Meta-analysis With Trial Sequential Analysis of More Than 40 000 Patients. Clin Cardiol 2016; 39 (10): 615–20.
39. Szwed H, Sadowski Z, Elikowski W et al. Combination treatment in stable effort angina using trimetazidine and metoprolol: results of a randomized, double-blind, multicentre study (TRIMPOL II). TRIMetazidine in POLand. Eur Heart J 2001; 2 (24): 2267–74.
40. The EMIP-FR Group. Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy; A double-blind, placebo-controlled, randomized trial European Myocardial Infarction Project – Free Radicals. Eur Heart J 2000; 21 (18): 1537–46.
41. www.EMA/412151/2012 EMEA/H/A-31/130521. 2012
42. Chaitman BR, Pepine CJ, Parker JO et al; Combination Assessment of Ranolazine In Stable Angina (CARISA). Investigators. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA 2004; 291 (3): 309–16.
43. Melloni C, Newby LK. Metabolic efficiency with ranolazine forless ischemia in non-ST elevation acute coronary syndromes (MERLIN TIMI-36) study. Exp Rev Cardiovasc Ther 2008; 6 (1): 9–16.
44. Стаценко М.Е., Туркина С.В. Метаболическая кардиопротекция мельдонием у больных ишемической болезнью сердца: итоги и перспективы. Лечащий врач. 2012; 7: 96–103. / Statsenko M.E., Turkina S.V. Metabolicheskaia kardioprotektsiia mel'doniem u bol'nykh ishemicheskoi bolezn'iu serdtsa: itogi i perspektivy. Lechashchii vrach. 2012; 7: 96–103. [in Russian]
________________________________________________
1. http://www.gks.ru/wps/wcm/connect/rosstatmain/rosstat/ru/statistics/population/demography
2. The Academic Research Organization Consortium for Continuing Evaluation of Scientific Studies – Cardiovascular (ACCESS CV). Sharing Data from Cardiovascular Clinical Trials – A Proposal. N Engl J Med 2016; 375: 407–9.
3. Saiutina E.V., Chigineva V.V., Zolozova E.A. i dr. Kontrol' ishemii miokarda u bol'nykh stenokardiei napriazheniia s mnogososudistym ateroskleroticheskim porazheniem. Kardiologiia. 2012; 8: 15–9. [in Russian]
4. Karlova N.A., Zolozova E.A., Pshenitsin A.I. i dr. Otsenka terapevticheskoi effektivnosti i bezopasnosti original'nogo preparata bisoprolola i ego dzhenerika biprola u bol'nykh stabil'noi stenokardiei. Kardiologiia. 2015; 1: 23–8. [in Russian]
5. Euro Heart Survey of stable angina: prospective observational study. Eur Heart J 2005; 26: 1011–22.
6. ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. 2013.
7. ESC guidelines stable coronary artery disease. Eur Heart J 2013; 34 (38): 2927–8.
8. PEGASUS-TIMI 54 Steering Committee and Investigators. Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction. N Engl J Med 2015; 372: 1791–800.
9. Serebruany VL. The TRITON versus PLATO trials: differences beyond platelet inhibition. Thromb Haemost 2010; 103 (2): 259–61.
10. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348 (9038): 1329–39.
11. Lee M, Wu YL, Saver JL et al. Is clopidogrel better than aspirin following breakthrough strokes. A retrospective cohort study. BMJ Open 2014; 4 (12): e006672.
12. Mazur N.A. Antiagregantnaia terapiia u bol'nykh ishemicheskoi bolezn'iu serdtsa: nereshennye problemy. Kardiologiia. 2016; 1: 66–70. [in Russian]
13. Everly MJ, Heaton PC, Cluxton RJ. Beta-Blocker Underuse in Secondary Prevention of Myocardial Infarction. Ann Pharmacother 2003; 38: 286–93.
14. Le SJ. Prognostic Significance of Resting Heart Rate and Use of β-Blockers in Atrial Fibrillation and Sinus Rhythm in Patients With Heart Failure and Reduced Ejection Fraction: Findings From the Swedish Heart Failure Registry. Circ Heart Fail 2015; 8 (5): 871–9.
15. Flather MD, Shibata MC, Coats AJ et al; SENIORS Investigators. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005; 26 (3): 215–25.
16. Mazur N.A. Vnezapnaia smert' bol'nykh ishemicheskoi bolezn'iu serdtsa. M.: Meditsina, 1985; s. 121–42. [in Russian]
17. Hansen JF. Treatment with verapamil after an acute myocardial infarction. Review of the Danish studies on verapamil in myocardial infarction (DAVIT I and II). Drugs 1991; 42 (Suppl. 2): 43–53.
18. Rehnqvist N, Hjemdahl P, Billing E et al. Effects of metoprolol vs verapamil in patients with stable angina pectoris. The Angina Prognosis Study in Stockholm (APSIS). Eur Heart J 1996; 17 (1): 76–81.
19. The Multicenter Diltiazem Postinfarction Trial Research Group The effect of diltiazem on mortality and reinfarction after myocardial infarction. N Engl Med 1988; 319 (7): 385–92.
20. Poole-Wilson PA, Lubsen J, Kirwan BA et al; Coronary disease Trial Investigating Outcome with Nifedipine gastrointestinal therapeutic system investigators. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial. Lancet 2004; 364 (9437): 849–57.
21. Mazur N.A. Prakticheskaia kardiologiia. M.: Medpraktika-M, 2015; s. 109–37. [in Russian]
22. Khorinaka Sh. Vliianie nikorandila na chastotu serdechno-sosudistykh sobytii u patsientov s koronarnoi bolezn'iu serdtsa. Ros. kardiol. zhurn. 2011; 2 (88): 82–90. [in Russian]
23. Sakata Y, Nakatani D, Shimizu M et al. Oral treatment with nicorandil at discharge is associated with reduced mortality after acute myocardial infarction. J Cardiol 2012; 59 (1): 14–21.
24. IONA Study Group. Impact of nicorandil in angina: subgroup analyses. Heart 2004; 90 (12): 1427–30.
25. Stoschitzky K, Rezkalla SH, Klone RA. No evidence of nitrate tolerance with Nicorandil. Eur Heart J 2012; 32 (Abstract Supplement): 470.
26. Sekiya M, Sato M, Funada J et al. Effects of the long-term administration of nicorandil on vascular endothelial function and the progression of arteriosclerosis. J Cardiovasc Pharmacol 2005; 46 (1): 63–7.
27. Patel DJ, Purcell HJ, Fox KM on behalf of the CESAR 2 investigation. Cardioprotection by opening of the KATP channel in unstable angina. Eur Heart J 1999; 20: 51–7.
28. Eguchi Y, Takahari Y, Higashijima N et al. Nicorandil Attenuates FeCl3-Induced Thrombus Formation Through the Inhibition of Reactive Oxygen Species Production. Circ J 2009; 73 (3): 554–61.
29. Izumiya Y, Kojima S, Araki S et al. Long-term use of oral nicorandil stabilizes coronary plaque in patients with stable angina pectoris. Atherosclerosis 2011; 214 (2): 415–21.
30. Markham A, Plosker GL, Goa KL. Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardio-protective effects. Drugs 2000; 60: 955–74.
31. Kasama S, Toyama T, Sumino H et al. Long-term nicorandil therapy improves cardiac sympathetic nerve activity after reperfusion therapy in patients with first acute myocardial infarction. J Nucl Med 2007; 48 (10): 1676–82.
32. Kasama S, Toyama T, Hatori T et al. Comparative effects of nicorandil with isosorbide mononitrate on cardiac sympathetic nerve activity and left ventricular function in patients with ischemic cardiomyopathy. Am Heart J 2005; 150 (3): 477.e1–477.e8.
33. Evans M, Carrero JJ, Szummer K, Akerblom A. Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Myocardial Infarction Patients With Renal Dysfunction. J Am Coll Cardiol 2016; 67: 1687–97.
34. Sleight P. The HOPE Study (Heart Outcomes Prevention Evaluation). J Renin Angiotensin Aldosterone Syst 2000; 1 (1): 18–20.
35. Campbell DJ. A review of Perindopril in the reduction of cardiovascular events. Vasc Health Risk Manag 2006; 2 (2): 117–24.
36. Tardif JC, Ponikowski P, Kahan T. ASSOCIATE Study Investigators. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur Heart J 2009; 30 (5): 540–8.
37. Fox K, Ford I, Steg PG et al; SIGNIFY Investigators. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med 2014; 371 (12): 1091–9.
38. Tanboğa İH, Topçu S, Aksakal E et al. The Risk of Atrial Fibrillation With Ivabradine Treatment: A Meta-analysis With Trial Sequential Analysis of More Than 40 000 Patients. Clin Cardiol 2016; 39 (10): 615–20.
39. Szwed H, Sadowski Z, Elikowski W et al. Combination treatment in stable effort angina using trimetazidine and metoprolol: results of a randomized, double-blind, multicentre study (TRIMPOL II). TRIMetazidine in POLand. Eur Heart J 2001; 2 (24): 2267–74.
40. The EMIP-FR Group. Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy; A double-blind, placebo-controlled, randomized trial European Myocardial Infarction Project – Free Radicals. Eur Heart J 2000; 21 (18): 1537–46.
41. www.EMA/412151/2012 EMEA/H/A-31/130521. 2012
42. Chaitman BR, Pepine CJ, Parker JO et al; Combination Assessment of Ranolazine In Stable Angina (CARISA). Investigators. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA 2004; 291 (3): 309–16.
43. Melloni C, Newby LK. Metabolic efficiency with ranolazine forless ischemia in non-ST elevation acute coronary syndromes (MERLIN TIMI-36) study. Exp Rev Cardiovasc Ther 2008; 6 (1): 9–16.
44. Statsenko M.E., Turkina S.V. Metabolicheskaia kardioprotektsiia mel'doniem u bol'nykh ishemicheskoi bolezn'iu serdtsa: itogi i perspektivy. Lechashchii vrach. 2012; 7: 96–103. [in Russian]
Авторы
Н.А.Мазур
ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1 mazur@land.ru
________________________________________________
N.A.Mazur
Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation. 125993, Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1 mazur@land.ru