Abstract
The number of patients with coronary artery disease and its risk factors is increasing in Western nations. New treatments for these patients may soon include a class of agents known as the metabolic modulators. This group of agents consists of the partial fatty acid oxidation inhibitors trimetazidine and ranolazine, as well as dichloroacetate, which promotes carbohydrate utilization. Metabolic modulators also include the nutriceuticals L‐carnitine and D‐ribose. The available evidence regarding the benefits of each of these five agents is reviewed.
Keywords: trimetazidine, ranolazine, dichloroacetate, carnitine, ribose, angina, ischemia, coronary artery disease
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References
- 1. Hutter JD, Piper HM, Spieckerman PG: Effect of fatty acid oxidation on efficiency of energy production in rat heart. Am J Physiol 1985; 249: H723–H728 [DOI] [PubMed] [Google Scholar]
- 2. Detry JM, Sellier P, Pennaforte S, Cokkinos D, Dargie H, Mathes P: Trimetazidine—a new concept in the treatment of angina: Comparison with propranolol in patients with stable angina. Br J Clin Pharmacol 1994; 37: 279–288 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Szwed H, Pachocki R, Domzal‐Bochenska M, Szymczak K, Szydlowski Z, Paradowski A, Gajos G, Kaluza G, Kulon I, Wator‐Brzezinska A, Elikowski W, Kuzniak M: Efficacy and tolerance of trimetazidine, a metabolic antianginal, in combination with a hemodynamic antianginal in stable exertional angina: TRIMPOL I, a multicenter study. Presse Med 2000; 29: 533–538 [PubMed] [Google Scholar]
- 4. Marzilli M, Klein WW: Efficacy and tolerability of trimetazidine in stable angina: A meta‐analysis of randomized, double‐blind, controlled trials. Cor Artery Dis 2003; 14: 171–179 [DOI] [PubMed] [Google Scholar]
- 5. McCormack JG, Stanley WC, Wolff AA: Ranolazine—a novel metabolic modulator for the treatment of angina. Gen Pharmacol 1998; 30: 639–645 [DOI] [PubMed] [Google Scholar]
- 6. Rupp H, Zarain‐Herzberg A, Maisch B: The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Herz 2002; 27: 621–636 [DOI] [PubMed] [Google Scholar]
- 7. Wyatt KM, Skene C, Veitch K, Hue L, McCormack JG: The antianginal agent ranolazine is a weak inhibitor of the respiratory complex I, but with greater potency in broken or uncoupled mitochondria than in coupled mitochondria. Biochem Pharmacol 1995; 50: 1599–1606 [DOI] [PubMed] [Google Scholar]
- 8. Wolff AA: MARISA—Monotherapy Assessment of Ranolazine in Stable Angina (abstr). J Am Coll Cardiol 2000; 35: 408A [Google Scholar]
- 9. Louis AA, Manousos IR, Coletta AP, Clark AL, Cleland JG: Clinical trials update—The Heart Protection Study, IONA, CARISA, ENRICHD, ACUTE, ALIVE, MADIT II, and REMATCH. Eur J Heart Fail 2002; 4: 111–116 [DOI] [PubMed] [Google Scholar]
- 10. Wargovich TJ, MacDonald RG, Hill JA: Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease. Am J Cardiol 1988; 61: 65–70 [DOI] [PubMed] [Google Scholar]
- 11. van der Vusse GJ, Glatz JFC, Stam HCG, Reneman RS: Fatty acid homeostasis in the normoxic and ischemic heart. Physiol Rev 1992; 72: 881–940 [DOI] [PubMed] [Google Scholar]
- 12. Pauly DF, Yoon SB, McMillin JB: Carnitine‐acylcarnitine translocase in ischemia: Evidence for sulfhydryl modification. Am J Physiol (Heart Circ Physiol) 1987; 253: H1557–H1565 [DOI] [PubMed] [Google Scholar]
- 13. Pauly DF, Kirk KA, McMillin JB: Carnitine palmitoyltransferase in cardiac ischemia. Circ Res 1991; 68: 1085–1094 [DOI] [PubMed] [Google Scholar]
- 14. Fritz IB, Arrigoni‐Martelli E: Sites of action of carnitine and its derivatives on the cardiovascular system: Interactions with membranes. Trends Pharmacol Sci 1993; 14: 355–360 [DOI] [PubMed] [Google Scholar]
- 15. Lopaschuk G: Regulation of carbohydrate metabolism in ischemia and reperfusion. Am Heart J 2000; 139: S115–S119 [DOI] [PubMed] [Google Scholar]
- 16. Iliceto S, Scrutinio D, Bruzzi P, D'Ambrosio G, Boni L, DiBiase M, Biasco G, Hugenholtz PG, Rizzon P: Effects of L‐carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: The L‐Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) Trial. J Am Coll Cardiol 1995; 26: 380–387 [DOI] [PubMed] [Google Scholar]
- 17. Pliml W, Von Arnim T, Stablein A, Hofmann H, Zimmer HG, Erdmann E: Effects of ribose on exercise‐induced ischaemia in stable coronary artery disease. Lancet 1992; 340: 507–510 [DOI] [PubMed] [Google Scholar]
- 18. Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, Wang W, Skettino SL, Wolff AA: Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: A randomized controlled trial. J Am Med Assoc 2004; 291: 309–316 [DOI] [PubMed] [Google Scholar]
- 19. Chaitman BR, Skettino SL, Parker JO, Hanley P, Meluzin J, Kuch J, Pepine CJ, Wang W, Nelson JJ, Hebert DA, Wolff AA: Anti‐ischemic effects and long‐term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol 2004; 43: 1375–1382 [DOI] [PubMed] [Google Scholar]