IJCM  Vol.5 No.5 , March 2014
Review of Medical Treatment of Stable Ischemic Heart Disease

Medical treatment is the initial treatment strategy and is the cornerstone of management in patients with stable ischemic heart disease (IHD). Many patients are not suitable for percutaneous or surgical revascularization because of unfavourable anatomy, or the presence of co-morbidities. In addition, many patients have recurrence of angina following revascularization due to restenosis or incomplete revascularization. Furthermore, randomized clinical trials comparing optimal medical treatment to revascularization have not clearly shown that myocardial revascularization is superior to optimal medical treatment. Traditional drugs for angina treatment include b-blockers, calcium channel blockers and nitrates. Newer drugs are available with different mechanisms of action and with equal efficacy that do not cause significant hemodynamic deterioration. The availability of these newer drugs expands the therapeutic potential of medical treatment to even a wider population with stable IHD. Revascularization in patients with stable ischemic heart disease has never been shown to reduce hard endpoints (death or myocardial infarction) in randomized clinical trials.

Cite this paper
Mobeirek, A. , Albackr, H. , Shamiri, M. and Albacker, T. (2014) Review of Medical Treatment of Stable Ischemic Heart Disease. International Journal of Clinical Medicine, 5, 249-259. doi: 10.4236/ijcm.2014.55039.
[1]   Hemingway, H., Langenberg, C., Damant, J., Frost, C., Pyörälä, K. and Barrett-Connor, E. (2008) Prevalence of Angina in Women versus Men: A Systematic Review and Meta-Analysis of International Variation across 31 Countries. Circulation, 117, 1526-1536. http://dx.doi.org/10.1161/CIRCULATIONAHA.107.720953

[2]   Finn, S.D., Gardin, J., Abrams, J., Berra, K., Blankenship, J.C., Dallas, A.P., et al. (2012) ACCF/AHA/ACP/AATS/ PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients with Stable Ischemic Ischemic Heart Disease: Executive Summary. A Report of the American College 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 of Thoracic Surgeons. Journal of the American College of Cardiology, 60, 2564-2603.

[3]   Montalescot, G., Sechtem, U., Achenbach, S., Andreotti, F., Arden, C., Budaj, A., 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. European Heart Journal, 34, 2949-3003.

[4]   Izzo, P., Macchi, A., De Gennaro, L., Gaglione, A., Di Baise, M. and Brunetti, N.D. (2012) Reccurent Angina after Coronary Angioplasty: Mechanisms, Diagnostic and Therapeutic Options. European Herat Journal: Acute Cardiovascular Care, 1, 158-169.

[5]   Abbate, A., Biondi-Zoccai, G., Agostani, P., Lipinski, M. and Vetrovec, G. (2006) Recurrent Angina after Revascularization: A Clinical Challenge. European Herat Journal, 28, 1057-1065. http://dx.doi.org/10.1093/eurheartj/ehl562

[6]   Wright, R., Flapan, A., McMurry, J., Slattery, J., White, H., Spaulding, C., et al. (1994) Scandinavian Simvastatin Study (4S). Lancet, 344, 1765-1768. http://dx.doi.org/10.1016/S0140-6736(94)92906-8

[7]   Sacks, F.M., Pfeffer, M.A., Moye, L.A., Rouleau, J.L., Rutherford, J.D., Cole, T.G. and Cholesterol and Recurrent Events Trial Investigators (1996) The Effect of Pravastatin on Coronary Events after Myocardial Infarction in Patients with Average Cholestrol Levels. New England Journal of Medicine, 335, 1001-1009.

[8]   The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group (1998) Prevention of Cardiovascular Events and Death with Pavastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol Levels. New England Journal of Medicine, 339, 1349-1357.

[9]   Heart Protection Study Collaborative Group (2003) MRC/BHF Heart Protection Study of Cholestrol Lowering with Simvastatin in 5963 with Diabetes: A Randomized Placebo-Controlled Trial. Lancet, 361, 2005-2016.

[10]   Cannon, C.P., Braunwald, E., McCabe, C.H., et al. (2004) Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes. New England Journal of Medicine, 350, 1495-1504.

[11]   LaRosa, J.C., Grundy, S.M., Waters, D.D., et al. (2005) Treating to New Targets (TNT). Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease. New England Journal of Medicine, 352, 1425-1435.

[12]   Stone, N., Robinson, J., Lichtenstein, A.H., Merz, C.N.B., Blum, C.B., Eckel, R.H., Goldberg, A.C., et al. (2013) 2013 ACC/AHA Guideline on Treatment of Blood Cholestrol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, Published Online.

[13]   Antithrombotic Trialists’ Collaboration (2002) Collaborative Meta-Analysis of Randomized Trials of Antiplatelet Therapy for Prevention of Death, Myocardial Infarction, and Stroke in High Risk Patients. BMJ, 324, 71-86.

[14]   Becker, R.C., Meade, T.W., Berger, P.B. and American College of Chest Physicians (2008) The Primary and Secondary Prevention of Coronary Artery Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 133, 776s-814s. http://dx.doi.org/10.1136/bmj.324.7329.71

[15]   Bhatt, D.L., Fox, K.A., Hacke, W. and CHARISMA Investigators (2006) Clopidogrel and Aspirin versus Aspirin Alone for the Prevention of Atherothrombotic Events. New England Journal of Medicine, 354, 1706-1717.

[16]   Freemantle, N., Cleland, J., Young, P., Mason, J. and Harrison, J. (1999) Beta Blockade after Myocardial Infarction: Systematic Review and Meta Regression Analysis. BMJ, 318, 1730-1737.

[17]   Law, M.R., Morris, J.K. and Wald, N.J. (2009) Use of Blood Pressure Drugs in the Prevention of Cardiovascular Disease: Meta-Analysis of 147 Randomized Trials in the Context of Expectations from Prospective Epidemiological Studies.BMJ, 338, B1665. http://dx.doi.org/10.1136/bmj.b1665

[18]   Poole-Wilson, P.A., Lubsen, J., Kirwan, B.A., van Dalen, F.J., Wagener, G., Danchin, N., et al. (2004) A Coronary disease Trial Investigating Outcome with Nifedipine Gastrointestinal Therapeutic System Investigators. Effects of Long-Acting Nifedipine on Mortality and Cardiovascular Morbidity in Patients with Stable Angina Requiring Treatment (ACTION Trial): Randomized Controlled Trial. Lancet, 364, 849-857.

[19]   Fox, K.M. (2003) European Trial on Reduction of Cardiac Events among Patients with Stable Coronary Artery Disease: Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial (the EUROPA Study). Lancet, 362, 782-788.

[20]   Yusuf, S., Sleight, P., Pogue, J., Bosch, J., Davies, J. and Dagenais, G. (2000) The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an Angiotensin-Converting-Enzyme Inhibitor, Ramipril, on Cardiovascular Events in High-Risk Patients. New England Journal of Medicine, 342, 145-153.

[21]   The IONA Study Group (2002) Effect of Nicorandil on Coronary Events in Patients with Stable Angina: The Impact of Nicorandil in Angina (IONA) Randomized Trial. Lancet, 359, 1269-1275.

[22]   Vicari, R.M., Chaitman, B., Keefe, D., Smith, W.B., Chrysant, S.G., Tonkon, M.J., et al. (2005) Efficacy and Safety of Fasudil in Patients with Stable Angina. A Double Blind Placebo-Controlled, Phase 2 Trial. Journal of the American College of Cardiology, 46, 1803-1811. http://dx.doi.org/10.1016/j.jacc.2005.07.047

[23]   Chazov, E.I., Lepakchin, V.K., Zharova, E.A., Fitilev, S.B., Levin, A.M., Rumiantzeva, E.G. and Fitileva, T.B. (2005) Trimetazidine in Angina Combination Therapy—The TACT Study: Trimetazidine versus Conventional Treatment in Patients with Stable Angina Pectoris in a Randomized, Placebo Controlled, Multicenter Study. American Journal of Therapeutics, 12, 35-42. http://dx.doi.org/10.1097/00045391-200501000-00006

[24]   Tardif, J.C., Ford, I., Tendera, M., Bourassa, M.G. and Fox, K., for the INITIATIVE Investigators (2005) Efficacy of Ivabradine, a New Selective If Inhibitor, Compared with Atenolol in Patients with Chronic Stable Angina. European Heart Journal, 26, 2529-2536. http://dx.doi.org/10.1093/eurheartj/ehi586

[25]   Ruzyllo, W.R., Tendera, M., Ford, I. and Fox, K.M. (2007) Antianginal Efficacy and Safety of Ivabridine Compared with Amlopidine in Patients with Stable Effort Angina Pectoris: A 3-Month Randomised, Double-Blind, Multicenter, Noninferiority Trial. Drugs, 67, 393-405. http://dx.doi.org/10.2165/00003495-200767030-00005

[26]   Tardif, J.C., Ponikowski, P. and Kahan, T., for the ASSOCIATE Study Investigators (2009) Efficacy of the If Current Inhibitor Ivabradine in Patients with Chronic Stable Angina Receiving Beta-Blocker Therapy: A 4-Month, Randomized, Placebo-Controlled Trial. European Heart Journal, 30, 540-548. http://dx.doi.org/10.1093/eurheartj/ehn571

[27]   Fox, K., Ford, I., Steg, P.G., Tendera, M., Ferrari, R., on Behalf of BEAUTIFUL Investigators (2008) Ivabradine for Patients with Stable Coronary Artery Disease and Left-Ventricular Systolic Dysfunction (BEAUTIFUL): A Randomized, Double-Blind, Placebo-Controlled Trial. Lancet, 372, 807-816.

[28]   Fox, K., Ford, I., Steg, P.G., Tendera, M., Robertson, M., Ferrari, R., on Behalf of BEAUTIFUL Investigators (2009) Relationship between Ivabridine Treatment and Cardiovascular Outcomes in Patients with Stable Coronary Artery Disease and Left Ventricular Systolic Dysfunction with Limiting Angina: A Subgroup Analysis of the Randomized Controlled BEAUTIFUL Trial. European Heart Journal, 30, 2337-2345. http://dx.doi.org/10.1093/eurheartj/ehp358

[29]   Noman, A., Ang, D.S., Ogston, S., Lang, C.C. and Strthers, A.D. (2010) Effect of High Dose Allopurinol on Exercise Capacity in Patients with Chronic Stable Angina. Lancet, 375, 2126-2127.

[30]   Rajendra, N.S., Ireland, S., George, J., Belch, J., Lang, C.C. and Struthers, A.D. (2011) Mechanistic Insights into the Therapeutic Use of High Dose Allopurinol in Angina Pectoris. Journal of the American College of Cardiology, 58, 820-828. http://dx.doi.org/10.1016/j.jacc.2010.12.052

[31]   Chaitman, B.R., Skettino, S.L., Parker, J.O., Hanley, P., Meluzin, J., Kuch, J., Pepine, C.J., Wang, W., Nelson, J.J., Hebert, D.A. and Wolff, A.A., for the Monotherapy Assessment of Ranolazine in Stable Angina (MARISA) Investigators (2004) Anti-Ischemic Effects and Long-Term Survival during Ranolazine Monotherapy in Patients with Chronic Severe Angina. Journal of the American College of Cardiology, 43, 1375-1382.

[32]   Chaitman, B.R., Pepine, C.J., Parker, J.O., Skopal, J., Chumakova, G., Kuch, J., Wang, W., Skettino, S.L. and Wolff, A.A., for the Combination Assessment of Ranolazine in Stable Angina (CARISA) Investigators (2004) Effects of Ranolazine with Atenolol, Amlopidine, or Diltiazem on Exercise Tolerance and Angina Frequency in Patients with Severe Angina. JAMA, 291, 309-316. http://dx.doi.org/10.1001/jama.291.3.309

[33]   Stone, P.H., Gratsiansky, N.A., Blokhin, A., Huang, I. and Meng, L., on Behalf of the ERICA Investigators (2005) Antianginal Efficacy of Ranolazine When Added to Maximal treaTment with Conventional Therapy: The Efficacy of Ranolazine in Chronic Angina Trial. Circulation, 112, II-748.

[34]   Kosiborod, M., Arnold, S.V., Spertus, J.A., McGuire, D.K., Li, Y., Yue, P., Ben-Yehuda, O., Katz, A., Jones, P.G., Olmsted, A., Belardinelli, L. and Chiatman, B.R. (2013) Evaluation of Ranolazine in Patients with Type 2 Diabetes Mellitus and Chronic Stable Angina: Results from the TERISA Randomized Clinical Trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina). Journal of the American College of Cardiology, 61, 2038-2045. http://dx.doi.org/10.1016/j.jacc.2013.02.011

[35]   Wilson, S., Scirica, B., Murphy, S., Braunwald, E., Karwatowska-Prokopczuk, E., Buros, J., Chaitman, B.R. and Morrow, D. (2009) Efficacy of Ronalizine in Patients with Chronic Angina; Observations from the Randomized Double-Blind, Placebo-Controlled MERLIN-TIMI (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Segment Elevation Acute Coronary Syndromes) 36 Trial. Journal of the American College of Cardiology, 53, 1510-1516.

[36]   Boden, W.E., O’Rouke, R.A., Toe, K.K., Hartigan, P.M., Maron, D.J., Kostuk, W.J., et al., for the COURAGE Study Group (2007) Optimal Medical Therapy with or without PCI for Stable Coronary Disease. The New England Journal of Medicine, 356, 1503-1516. http://dx.doi.org/10.1056/NEJMoa070829

[37]   The BARI 2D Study Group (2009) A Randomized Trial of Therapies for Type 2Diabetes and Coronary Artery Disease. The New England Journal of Medicine, 360, 2503-2515. http://dx.doi.org/10.1056/NEJMoa0805796

[38]   Velazquez, E.J., Lee, K.L., Deja, M.A., Jain, A., Sopko, G., Marchenko, A., et al., for the STITCH Investigators (2011) Coronary-Artery Bypass Surgery in Patients with Left Ventricular Dysfunction. The New England Journal of Medicine, 364, 1607-1616. http://dx.doi.org/10.1056/NEJMoa1100356

[39]   Pursnani, S., Korley, F., Gopaul, R., Kanade, P., Chandra, N., Shaw, R.E. and Bangalore, S. (2012) Percutaneous Coronary Intervention versus Optimal Medical Therapy in Stable Coronary Artery Disease. A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Circulation: Cardiovascular Interventions, 5, 476-490.

[40]   De Bruyne, B., Pijls, N.H., Kalesan, B., Barbato, E., Tonino, P.A., Piroth, Z., et al., for the FAME 2 Trial Investigators (2012) Fractional Flow Reserve-Guided PCI versus Medical Therapy in Stable Coronary Disease. The New England Journal of Medicine, 367, 991-1001. http://dx.doi.org/10.1056/NEJMoa1205361

[41]   International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA Trial) (2014) http://clinicaltrials.gov