European guidelines onthe management ofstable coronary artery diseaseKey points&new position for Ivabradine and TrimetazidineESC 2013Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.

Definisi dan PatofisiologiPenyakit arteri koroner stabil (coronary artery disease ) ditandai dengan episode reversible miokard dimana terjadi mismatch antara kebutuhan dan suplai oksigen yang biasanya diinduksi oleh aktivitas, emosi, stres, namun dapat juga terjadi secara spontan

Epidemiologi5-7 % pada wanita berusia 45-64 tahun 10-12 % pada wanita berusia 65-84 tahun4-7 % pada pria berusia 45-64 tahun12-14 % pada pria berusia 65-84 tahun

manifestasi awal dari CAD adalah disfungsi endotel dan penyakit mikrovaskuler . Keduanya terkait dengan peningkatan risiko komplikasi dari CAD

Diagnosis dan penilaian Digunakan untuk mengkonfirmasi diagnosis iskemia pada pasien SCAD Untuk mengidentifikasi atau mengecualikan kondisi terkait atau faktor pencetus, Membantu dalam menemukan risiko yang terkait dengan penyakit dan Untuk mengevaluasi efektivitas pengobatan.

Gejala dan tanda Karakteristik ketidaknyamanan yang berhubungan dengan iskemia miokard (angina pektoris) dapat dibagi menjadi empat kategori :LokasiKarakterDurasiFaktor yang meringankan

LokasiKetidaknyaman yang disebabkan oleh iskemia miokard biasanya terletak di dada, dan dapat dirasakan sampai ke rahang bawah atau gigi, antara tulang belikat, lengan, pergelangan tangan, dan jari.

KarakterKetidaknyamanan sering digambarkan sebagai tekanan, sesak, kadang-kadang terasa seperti tercekik, rasa terbakar.Ketidaknyamanan dada juga dapat disertai dengan gejala kurang spesifik seperti kelelahan, pingsan, mual, gelisah.

DurasiDurasi ketidaknyamanan ini singkat. Tidak lebih dari 10 menit dalam sebagian kasus bahkan menit atau kurang.

Faktor yang meringankan dan memperberatFaktor yang memperberat :Peningkatan aktifitas fisik (berjalan)Makan beratSetelah bangun di pagi hari

Faktor yang meringankan :Latihan lebih lanjut (berjalan)Pemberian bucal atau nitrat sublingual dengan cepat dapat meredakan angina

Tes BiokimiaHitung darah lengkapHemoglobin sebagai bagian dari hitung darah lengkapHormon tiroid memberikan informasi yang berkaitan dengan kemungkinan penyebab iskemiaGlukosa plasma puasa dan Hb terglikosilasi (HbA1c) harus diukur pada setiap pasien dengan dugaan CAD

To obtain relief of angina symptoms the guidelines advise:Short-acting nitrates to provide immediate relief of angina symptoms.Anti-ischemic drugs like -blockers, CCBs, Trimetazidine, IvabradineLifestyle changes, regular exercise training and patient education.

To prevent the occurrence of cardiovascular events the guidelines advise:To reduce the incidence of acute thrombotic events and the development of ventricular dysfunction by pharmacological or lifestyle interventions.A combined pharmacological and revascularization strategy in patients with severe lesions in coronary arteries.Aims to focus onMontalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.

Medical management of SCAD patientsWe recommend the old drugs as first line treatment because they are cheap, effective and available everywhere.We have roughly the same level of evidence for all of the second line drugs and we recommend that physicians also choose according to what is available in their country.Chairmen opinion:*Angina reliefEvent prevention -blockers and/or CCBIvabradineLong-acting nitratesNicorandilRanolazineTrimetazidine Lifestyle management Control of risk factors Aspirin (if intolerance, consider clopidogrel) Statins Consider ACE inhibitors or ARBs+ consider angio PCI-stenting or CABGShort-acting nitrates, plus1st line2nd lineMontalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.*New ESC Guidelines published on stable coronary artery disease. Eur Heart J. 2013;34:2927-2930.

Medical management of SCAD patientsChairmen opinion:*Angina reliefEvent prevention -blockers and/or CCBIvabradineLong-acting nitratesNicorandilRanolazineTrimetazidine Lifestyle management Control of risk factors Aspirin (if intolerance, consider clopidogrel) Statins Consider ACE inhibitors or ARBs+ consider angio PCI-stenting or CABGShort-acting nitrates, plus1st line2nd lineAbout revascularization, chairmen hopes that guidelines will shift physicians practice so that they consider optimal medical treatment as their first course of action in stable CAD patients.Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.*New ESC Guidelines published on stable coronary artery disease. Eur Heart J. 2013;34:2927-2930.

WomenWomen more frequently have CAD with stable angina and no obstructive coronary disease.Women are more likely to have complications from revascularization.

Diabetic patientsNeed different risk factor management.

Older patients High-risk group with higher mortality and higher rates of myocardial infarction. Usually undertreated, receiving less drugs.Difficult diagnosis due to atypical symptoms.Higher risk of complications during and after coronary revascularization.Comorbidities/intoleranceDepending on comorbidities/tolerance, it is indicated to use second-line therapies as first-line treatment in selected patients.Specific patient profilesMontalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.

Therapy to prevent MI and deathAspirinLow-dose aspirin is the drug of choice in most cases and clopidogrel may be considered for some patients.

StatinTarget LDL-C: 50% reduction if the target level cannot be reached.

Renin-angiotensin-aldosterone system blockersACE inhibitors are recommended for the treatment of patients with SCAD, especially with coexisting hypertension, LVEF 40%, diabetes, or chronic kidney disease, unless contra-indicated.ARBs are recommended as an alternative therapy for patients with SCAD when ACE inhibition is indicated but not tolerated.Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.

Adding ivabradine 7.5 mg twice daily to atenolol therapy gave better control of heart rate and anginal symptoms.

In 1507 patients with prior angina enrolled in the Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction (BEAUTIFUL) trial, ivabradine reduced the composite primary end point of CV death, hospitalization with MI and HF, and reduced hospitalization for MI. The effect was predominant in patients with a heart rate 70 bpm.

Ivabradine is thus an effective anti-anginal agent, alone or in combination with -blockers.New ESC guidelines and IvabradineMontalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.

New ESC guidelines and TrimetazidineTrimetazidine is an anti-ischemic metabolic modulator, with similar anti-anginal efficacy to propranolol in doses of 20 mg thrice daily.

Trimetazidine (35 mg twice daily) added to -blockade (atenolol) improved effort-induced myocardial ischemia, as reviewed by the EMA in June 2012.

In diabetic persons, Trimetazidine improved HbA1c and glycemia, while increasing forearm glucose uptake.Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.

ConclusionESC Guidelines highlighted two aims for the pharmacological management of stable CAD patients: obtain relief of symptoms and prevent cardiovascular events.

CAD patients should all receive aspirin and a statin, plus an ACE inhibitor in case of comorbidities.

-blockers or CCBs should be prescribed as first-line treatment to reduce angina.

Ivabradine and Trimetazidine (as well as long-acting nitrates, nicorandil and ranolazine) are recommended second-line, in combination with first-line treatment, in patients remaining symptomatic.

Physicians should consider optimal medical treatment before revascularization procedures.Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.

Abbreviation: ESC, European Society of Cardiology*The two aims of the pharmacological management of stable coronary artery disease (SCAD) patients are to obtain relief of symptoms and to prevent cardiovascular events.*Medical management of patients with stable coronary artery disease.Abbreviations: CABG, coronary artery bypass graft; CCB, calcium channel blockers; PCI, percutaneous coronary intervention; SCAD, stable coronary artery disease*Medical management of patients with stable coronary artery disease.Abbreviations: CABG, coronary artery bypass graft; CCB, calcium channel blockers; PCI, percutaneous coronary intervention.*Abbreviation: CAD, coronary artery disease.*Abbreviations: LDL-C, low density lipoprotein C; LVEF, left ventricular ejection fraction; SCAD, stable coronary artery disease.*Trimetazidine is:

recognized as an anti-ischemic metabolic modulator, as effective as -blockers.

mentioned as especially effective in combination with -blockers to reduce ischemia.

indicated as first-line treatment in selected patients, according to comorbidities/tolerance, (this means trimetazidine could be also used as a first-line therapy in stable CAD patients intolerant of or contraindicated to -blockers or CCBs).

mentioned as particularly beneficial to treat angina patients with diabetes.

(Class IIb.)

**