New Developments in Anti-Anginal Therapy: Roles of Ivabradine, Allopurinol and of Agents Modifying Myocardial Metabolism
Read full paper at:
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=47096#.VGGcE2fHRK0
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=47096#.VGGcE2fHRK0
Author(s)
Department of Cardiology, The Queen Elizabeth Hospital, Woodville South, Australia.
Department of Cardiology, The Queen Elizabeth Hospital, Woodville South, Australia.
Department of Cardiology, The Queen Elizabeth Hospital, Woodville South, Australia.
Department of Cardiology, The Queen Elizabeth Hospital, Woodville South, Australia.
Department of Cardiology, The Queen Elizabeth Hospital, Woodville South, Australia.
Department of Cardiology, The Queen Elizabeth Hospital, Woodville South, Australia.
Department of Cardiology, The Queen Elizabeth Hospital, Woodville South, Australia.
Over the last 20 years, it has emerged that, while
surgical revascularisation of extensive ischaemic heart disease may have
prognostic advantages, the main issues considered regarding individual
management are usually those of symptomatic improvement only. The major
impetus towards invasive intervention is therefore failure of
prophylactic anti-anginal therapy. On the other hand, many patients,
especially the elderly, now present the clinical problem of ongoing
angina without residual invasive options. There is an ongoing need for
more effective anti-anginal therapies. Of the currently available major
classes of prophylactic anti-anginal agents, neither nitrates, β-blockers
nor calcium antagonists generally produce marked improvements in
exercise duration. Three areas of new therapeutic development in
anti-anginal therapy are worthy of note. These involve the sinus node
inhibitor ivabradine, high dose allopurinol (xanthine oxidase inhibitor)
and a new class of “metabolic modulators” represented by perhexiline,
trimetazidine and probably ranolazine. The current review addresses the
therapeutic potential of these agents. Notably, all of these “new” drugs
are potentially suitable for management of angina in the setting of
impaired left ventricular systolic function, and they may also be
utilized in patients with angina independent of the presence of coronary
disease (for example in hypertrophic cardiomyopathy). The current
evidence for efficacy and potential future development in this area are
reviewed.
KEYWORDS
Cite this paper
Nguyen, T. , Chong, C. , Chan, W. and Horowitz, J.
(2014) New Developments in Anti-Anginal Therapy: Roles of Ivabradine,
Allopurinol and of Agents Modifying Myocardial Metabolism. World Journal of Cardiovascular Diseases, 4, 368-376. doi: 10.4236/wjcd.2014.47046.
| [1] |
Alderman, E.L., Bourassa, M.G.,
Cohen, L.S., Davis, K.B., Kaiser, G.G., Killip, T., Mock, M.B.,
Pettinger, M. and Robertson, T.L. (1990) Ten-Year Follow-Up of Survival
and Myocardial Infarction in the Randomized Coronary Artery Surgery
Study. Circulation, 82, 1629-1646. http://dx.doi.org/10.1161/01.CIR.82.5.1629 |
| [2] |
Boden, W.E., O’Rourke, R.A.,
Teo, K.K., Hartigan, P.M., Maron, D.J., Kostuk, W.J., Knudtson, M.,
Dada, M., Casperson, P., Harris, C.L., Chaitman, B.R., Shaw, L.,
Gosselin, G., Nawaz, S., Title, L.M., Gau, G., Blaustein, A.S., Booth,
D.C., Bates, E.R., Spertus, J.A., Berman, D.S., Mancini, G.B.,
Weintraub, W.S. and COURAGE Trial Research 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 |
| [3] |
Munzel, T., Daiber, A. and
Mulsch, A. (2005) Explaining the Phenomenon of Nitrate Tolerance.
Circulation Research, 97, 618-628. http://dx.doi.org/10.1161/01.RES.0000184694.03262.6d |
| [4] |
Kleschyov, A.L., Oelze, M.,
Daiber, A., Huang, Y., Mollnau, H., Schulz, E., Sydow, K.,
Fichtlscherer, B., Mulsch, A. and Munzel, T. (2003) Does Nitric Oxide
Mediate the Vasodilator Activity of Nitroglycerin? Circulation Research,
93, e104-112. http://dx.doi.org/10.1161/01.RES.0000100067.62876.50 |
| [5] |
Walker, A., McMurray, J.,
Stewart, S., Berger, W., McMahon, A.D., Dargie, H., Fox, K., Hillis, S.,
Henderson, N.J. and Ford, I. (2006) Economic Evaluation of the Impact
of Nicorandil in Angina (IONA) Trial. Heart, 92, 619-624. http://dx.doi.org/10.1136/hrt.2003.026385 |
| [6] |
Fihn, S.D., Gardin, J.M.,
Abrams, J., Berra, K., Blankenship, J.C., Dallas, A.P., Douglas, P.S.,
Foody, J.M., Gerber, T.C., Hinderliter, A.L., King 3rd, S.B., Kligfield,
P.D., Krumholz, H.M., Kwong, R.Y., Lim, M.J., Linderbaum, J.A., Mack,
M.J., Munger, M.A., Prager, R.L., Sabik, J.F., Shaw, L.J., Sikkema,
J.D., Smith Jr., C.R., Smith Jr., S.C., Spertus, J.A., Williams, S.V.,
F. American College of Cardiology, G. American Heart Association Task
Force on Practice, P. American College of, S. American Association for
Thoracic, A. Preventive Cardiovascular Nurses, A. Society for
Cardiovascular, Interventions and S. Society of Thoracic (2012) 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. Journal
of the American College of Cardiology, 60, e44-e164. http://dx.doi.org/10.1016/j.jacc.2012.07.013 |
| [7] | Opie, L.H. and Horowitz, J.D. (2012) Nitrates and Newer Antianginals. In: Opie, L.H. and Gersh, B.J., Eds., Drugs for the Heart, Elsevier, Amsterdam, 38-64. |
| [8] |
Fox, K., Ford, I., Steg, P.G.,
Tendera, M., Ferrari, R. and BEAUTIFUL Investigators (2008) Ivabradine
for Patients with Stable Coronary Artery Disease and Left-Ventricular
Systolic Dysfunction (BEAUTIFUL): A Randomised, Double-Blind,
Placebo-Controlled Trial. Lancet, 372, 807-816. http://dx.doi.org/10.1016/S0140-6736(08)61170-8 |
| [9] |
George, J., Carr, E., Davies,
J., Belch, J.J. and Struthers, A. (2006) High-Dose Allopurinol Improves
Endothelial Function by Profoundly Reducing Vascular Oxidative Stress
and Not by Lowering Uric Acid. Circulation, 114, 2508-2516. http://dx.doi.org/10.1161/CIRCULATIONAHA.106.651117 |
| [10] |
Ekelund, U.E., Harrison, R.W.,
Shokek, O., Thakkar, R.N., Tunin, R.S., Senzaki, H., Kass, D.A., Marban,
E. and Hare, J.M. (1999) Intravenous Allopurinol Decreases Myocardial
Oxygen Consumption and Increases Mechanical Efficiency in Dogs with
Pacing-Induced Heart Failure. Circulation Research, 85, 437-445. http://dx.doi.org/10.1161/01.RES.85.5.437 |
| [11] |
Stull, L.B., Leppo, M.K.,
Szweda, L., Gao, W.D. and Marban, E. (2004) Chronic Treatment with
Allopurinol Boosts Survival and Cardiac Contractility in Murine
Postischemic Cardiomyopathy. Circulation Research, 95, 1005-1011. http://dx.doi.org/10.1161/01.RES.0000148635.73331.c5 |
| [12] |
Noman, A., Ang, D.S., Ogston,
S., Lang, C.C. and Struthers, A.D. (2010) Effect of High-Dose
Allopurinol on Exercise in Patients with Chronic Stable Angina: A
Randomised, Placebo Controlled Crossover Trial. Lancet, 375, 2161-2167. http://dx.doi.org/10.1016/S0140-6736(10)60391-1 |
| [13] |
Rajendra, N.S., Ireland, S.,
George, J., Belch, J.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 |
| [14] |
George, J. and Struthers, A.
(2009) The OPT-CHF (Oxypurinol Therapy for Congestive Heart Failure)
Trial: A Question of Dose. Journal of the American College of
Cardiology, 53, 2405. http://dx.doi.org/10.1016/j.jacc.2008.07.076 |
| [15] |
Kloner, R.A. and Nesto, R.W.
(2008) Glucose-Insulin-Potassium for Acute Myocardial Infarction:
Continuing Controversy over Cardioprotection. Circulation, 117,
2523-2533. http://dx.doi.org/10.1161/CIRCULATIONAHA.107.697979 |
| [16] |
Howell, N.J., Ashrafian, H.,
Drury, N.E., Ranasinghe, A.M., Contractor, H., Isackson, H., Calvert,
M., Williams, L.K., Freemantle, N., Quinn, D.W., Green, D., Frenneaux,
M., Bonser, R.S., Mascaro, J.G., Graham, T.R., Rooney, S.J., Wilson,
I.C. and Pagano, D. (2011) Glucose-Insulin-Potassium Reduces the
Incidence of Low Cardiac Output Episodes after Aortic Valve Replacement
for Aortic Stenosis in Patients with Left Ventricular Hypertrophy:
Results from the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE)
Trial. Circulation, 123, 170-177. http://dx.doi.org/10.1161/CIRCULATIONAHA.110.945170 |
| [17] | Randle, P.J., Sugden, P.H., Kerbey, A.L., Radcliffe, P.M. and Hutson, N.J. (1978) Regulation of Pyruvate Oxidation and the Conservation of Glucose. Biochemical Society Symposium, 43, 47-67. |
| [18] |
Horowitz, J.D., Chirkov, Y.Y.,
Kennedy, J.A. and Sverdlov, A.L. (2010) Modulation of Myocardial
Metabolism: An Emerging Therapeutic Principle. Current Opinion in
Cardiology, 25, 329-334. http://dx.doi.org/10.1097/HCO.0b013e328339f191 |
| [19] |
Kennedy, J.A., Unger, S.A. and
Horowitz, J.D. (1996) Inhibition of Carnitine Palmitoyltransferase-1 in
Rat Heart and Liver by Perhexiline and Amiodarone. Biochemical
Pharmacology, 52, 273-280. http://dx.doi.org/10.1016/0006-2952(96)00204-3 |
| [20] |
Lyon, L.J., Nevins, M.A., Risch,
S. and Henry, S. (1971) Perhexilene Maleate in Treatment of Angina
Pectoris. Lancet, 297, 1272-1274. http://dx.doi.org/10.1016/S0140-6736(71)91783-1 |
| [21] |
White, H.D. and Lowe, J.B.
(1983) Antianginal Efficacy of Perhexiline Maleate in Patients
Refractory to Beta-Adreno-receptor Blockade. International Journal of
Cardiology, 3, 145-155. http://dx.doi.org/10.1016/0167-5273(83)90030-X |
| [22] |
Cole, P.L., Beamer, A.D.,
McGowan, N., Cantillon, C.O., Benfell, K., Kelly, R.A., Hartley, L.H.,
Smith, T.W. and Antman, E.M. (1990) Efficacy and Safety of Perhexiline
Maleate in Refractory Angina. A Double-Blind Placebo-Controlled Clinical
Trial of a Novel Antianginal Agent. Circulation, 81, 1260-1270. http://dx.doi.org/10.1161/01.CIR.81.4.1260 |
| [23] |
Horowitz, J.D., Sia, S.T.,
Macdonald, P.S., Goble, A.J. and Louis, W.J. (1986) Perhexiline Maleate
Treatment for Severe Angina Pectoris—Correlations with Pharmacokinetics.
International Journal of Cardiology, 13, 219-229. http://dx.doi.org/10.1016/0167-5273(86)90146-4 |
| [24] |
Kennedy, J.A. and Horowitz, J.D.
(1998) Effect of Trimetazidine on Carnitine Palmitoyltransferase-1 in
the Rat Heart. Cardiovascular Drugs and Therapy, 12, 359-363. http://dx.doi.org/10.1023/A:1007768716934 |
| [25] |
Unger, S.A., Kennedy, J.A.,
McFadden-Lewis, K., Minerds, K., Murphy, G.A. and Horowitz, J.D. (2005)
Dissociation between Metabolic and Efficiency Effects of Perhexiline in
Normoxic Rat Myocardium. Journal of Cardiovascular Pharmacology, 46,
849-855. http://dx.doi.org/10.1097/01.fjc.0000190488.77434.f1 |
| [26] |
Willoughby, S.R., Stewart, S.,
Chirkov, Y.Y., Kennedy, J.A., Holmes, A.S. and Horowitz, J.D. (2002)
Beneficial Clinical Effects of Perhexiline in Patients with Stable
Angina Pectoris and Acute Coronary Syndromes Are Associated with
Potentiation of Platelet Responsiveness to Nitric Oxide. European Heart
Journal, 23, 1946-1954. http://dx.doi.org/10.1053/euhj.2002.3296 |
| [27] |
Gatto Jr., G.J., Ao, Z., Kearse,
M.G., Zhou, M., Morales, C.R., Daniels, E., Bradley, B.T., Goserud,
M.T., Goodman, K.B., Douglas, S.A., Harpel, M.R. and Johns, D.G. (2013)
NADPH Oxidase-Dependent and -Independent Mechanisms of Reported
Inhibitors of Reactive Oxygen Generation. Journal of Enzyme Inhibition
and Medicinal Chemistry, 28, 95-104. http://dx.doi.org/10.3109/14756366.2011.636360 |
| [28] |
Kennedy, J.A., Beck-Oldach, K.,
McFadden-Lewis, K., Murphy, G.A., Wong, Y.W., Zhang, Y. and Horowitz,
J.D. (2006) Effect of the Anti-Anginal Agent, Perhexiline, on
Neutrophil, Valvular and Vascular Superoxide Formation. European Journal
of Pharmacology, 531, 13-19. http://dx.doi.org/10.1016/j.ejphar.2005.11.058 |
| [29] | Ngo, D.T., Drury, N.E., Pagano, D., Frenneaux, M.P. and Horowitz, J.D. (2011) How Does Perhexiline Modulate Myocardial Energetics and Ameliorate Redox Stress? Abstract. AHA 2011. Circulation, 124, Article ID: A14461. |
| [30] |
Unger, S.A., Robinson, M.A. and
Horowitz, J.D. (1997) Perhexiline Improves Symptomatic Status in Elderly
Patients with Severe Aortic Stenosis. Australian and New Zealand
Journal of Medicine, 27, 24-28. http://dx.doi.org/10.1111/j.1445-5994.1997.tb00909.x |
| [31] |
Lee, L., Campbell, R.,
Scheuermann-Freestone, M., Taylor, R., Gunaruwan, P., Williams, L.,
Ashrafian, H., Horowitz, J., Fraser, A.G., Clarke, K. and Frenneaux, M.
(2005) Metabolic Modulation with Perhexiline in Chronic Heart Failure: A
Randomized, Controlled Trial of Short-Term Use of a Novel Treatment.
Circulation, 112, 3280-3288. http://dx.doi.org/10.1161/CIRCULATIONAHA.105.551457 |
| [32] |
Abozguia, K., Elliott, P.,
McKenna, W., Phan, T.T., Nallur-Shivu, G., Ahmed, I., Maher, A.R., Kaur,
K., Taylor, J., Henning, A., Ashrafian, H., Watkins, H. and Frenneaux,
M. (2010) Metabolic Modulator Perhexiline Corrects Energy Deficiency and
Improves Exercise Capacity in Symptomatic Hypertrophic Cardiomyopathy.
Circulation, 122, 1562-1569. http://dx.doi.org/10.1161/CIRCULATIONAHA.109.934059 |
| [33] | Brottier, L., Barat, J.L., Combe, C., Boussens, B., Bonnet, J. and Bricaud, H. (1990) Therapeutic Value of a Cardioprotective Agent in patients with Severe Ischaemic Cardiomyopathy. European Heart Journal, 11, 207-212. |
| [34] |
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 |
| [35] |
Szwed, H., Sadowski, Z.,
Elikowski, W., Koronkiewicz, A., Mamcarz, A., Orszulak, W., Skibinska,
E., Szymczak, K., Swiatek, J. and Winter, M. (2001) Combination
Treatment in Stable Effort Angina Using Trimetazidine and Metoprolol:
Results of a Randomized, Double-Blind, Multicentre Study (TRIMPOL II).
European Heart Journal, 22, 2267-2274. http://dx.doi.org/10.1053/euhj.2001.2896 |
| [36] |
Danchin, N., Marzilli, M.,
Parkhomenko, A. and Ribeiro, J.P. (2011) Efficacy Comparison of
Trimetazidine with Therapeutic Alternatives in Stable Angina Pectoris: A
Network Meta-Analysis. Cardiology, 120, 59-72. http://dx.doi.org/10.1159/000332369 |
| [37] |
Chaitman, B.R., Pepine, C.J.,
Parker, J.O., Skopal, J., Chumakova, G., Kuch, J., Wang, W., Skettino,
S.L., Wolff, A.A. for Combination Assessment of Ranolazine in Stable
Angina Investigators (2004) 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, 291, 309-316. http://dx.doi.org/10.1001/jama.291.3.309 |
| [38] |
Zacharowski, K., Blackburn, B.
and Thiemermann, C. (2001) Ranolazine, a Partial Fatty Acid Oxidation
Inhibitor, Reduces Myocardial Infarct Size and Cardiac Troponin T
Release in the Rat. European Journal of Pharmacology, 418, 105-110. http://dx.doi.org/10.1016/S0014-2999(01)00920-7 |
| [39] |
Belardinelli, L., Shryock, J.C.
and Fraser, H. (2006) Inhibition of the Late Sodium Current as a
Potential Cardioprotective Principle: Effects of the Late Sodium Current
Inhibitor Ranolazine. Heart, 92, iv6-iv14. http://dx.doi.org/10.1136/hrt.2005.078790 |
| [40] |
Parker, J.O., Amies, M.H.,
Hawkinson, R.W., Heilman, J.M., Hougham, A.J., Vollmer, M.C., Wilson,
R.R. and Minitran Efficacy Study Group (1995) Intermittent Transdermal
Nitroglycerin Therapy in Angina Pectoris. Clinically Effective without
Tolerance or Rebound. Circulation, 91, 1368-1374. http://dx.doi.org/10.1161/01.CIR.91.5.1368 |
| [41] |
Chrysant, S.G., Glasser, S.P.,
Bittar, N., Shahidi, F.E., Danisa, K., Ibrahim, R., Watts, L.E.,
Garutti, R.J., Ferraresi, R. and Casareto, R. (1993) Efficacy and Safety
of Extended-Release Isosorbide Mononitrate for Stable Effort Angina
Pectoris. American Journal of Cardiology, 72, 1249-1256. http://dx.doi.org/10.1016/0002-9149(93)90292-K |
| [42] |
Jamal, S.M., Freedman, S.B.,
Thomson, A., Carter, G., Harris, P.J. and Kelly, D.T. (1987) Antianginal
Efficacy of Carvedilol, a New Beta-Blocker with Vasodilating Action.
Journal of Cardiovascular Pharmacology, 10, S141-S146. http://dx.doi.org/10.1097/00005344-198710110-00026 |
| [43] |
Schnellbacher, K., Marsovszky,
E. and Roskamm, H. (1986) Effect of Bisoprolol on Exercise Tolerance in
Patients with Coronary Heart Disease: Placebo-Controlled Double-Blind
Crossover Study. Journal of Cardiovascular Pharmacology, 8, S143-S147. http://dx.doi.org/10.1097/00005344-198511001-00026 |
| [44] |
DiBianco, R., Singh, S., Singh,
J.B., Katz, R.J., Bortz, R., Gottdiener, J.S., Spodick, D.H., Laddu,
A.R. and Fletcher, R.D. (1980) Effects of Acebutolol on Chronic Stable
Angina Pectoris. A Placebo-Controlled, Double-Blind, Randomized
Crossover Study. Circulation, 62, 1179-1187. http://dx.doi.org/10.1161/01.CIR.62.6.1179 |
| [45] |
Schwartz, J.B., Jackson, G.,
Kates, R.E. and Harrison, D.C. (1981) Long-Term Benefit of
Cardioselective Beta Blockade with Once-Daily Atenolol Therapy in Angina
Pectoris. American Heart Journal, 101, 380-385. http://dx.doi.org/10.1016/0002-8703(81)90125-3 |
| [46] |
Hung, J., Lamb, I.H., Connolly,
S.J., Jutzy, K.R., Goris, M.L. and Schroeder, J.S. (1983) The Effect of
Diltiazem and Propranolol, Alone and in Combination, on Exercise
Performance and Left Ventricular Function in Patients with Stable Effort
Angina: A Double-Blind, Randomized, And Placebo-Controlled Study.
Circulation, 68, 560-567. http://dx.doi.org/10.1161/01.CIR.68.3.560 |
| [47] |
Pine, M.B., Citron, P.D.,
Bailly, D.J., Butman, S., Plasencia, G.O., Landa, D.W. and Wong, R.K.
(1982) Verapamil versus Placebo in Relieving Stable Angina Pectoris.
Circulation, 65, 17-22. http://dx.doi.org/10.1161/01.CIR.65.1.17 |
| [48] | Andreasen, F., Boye, E., Christoffersen, E., Dalsgaard, P., Henneberg, E., Kallenbach, A., Ladefoged, S., Lillquist, K., Mikkelsen, E., Norder, E., Olsen, J., Pedersen, J.K., Pedersen, V., Petersen, G.B., Schroll, J., Schultz, H. and Seidelin, J. (1975) Assessment of Verapamil in the Treatment of Angina Pectoris. European Journal of Cardiology, 2, 443-452. |
| [49] |
Borer, J.S., Fox, K., Jaillon,
P., Lerebours, G. and Ivabradine Investigators Group (2003) Antianginal
and Antiischemic Effects of Ivabradine, an If Inhibitor, in Stable
Angina: A Randomized, Double-Blind, Multicentered, Placebo-Controlled
Trial. Circulation, 107, 817-823. http://dx.doi.org/10.1161/01.CIR.0000048143.25023.87 |
| [50] |
Tardif, J.C., Ponikowski, P.,
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 eww141111lx |
评论
发表评论