Skip to main content
NCBI home page
Clinical Cardiology logoLink to Clinical Cardiology
. 2009 Feb 3;22(4):303–308. doi: 10.1002/clc.4960220410

Attenuated severity of new acute ischemic events in patients with previous coronary heart disease receiving long‐acting nitratesa

David Garc ía‐Dorado 1,✉, GaietÀ Permanyer‐Miralda 1, Carles Brotons 1, Francisco Calvo 1, Marta Campreci ós 1, Juan Oliveras 1, M Teresa Santos 1, Irene Moral 1, J Soler‐Soler 1
PMCID: PMC6655313  PMID: 10198741

Abstract

Background: Platelet aggregation and secondary vasoconstriction are key events in the genesis of acute coronary syndromes.

Hypothesis: Since nitrates have vasodilatory and antiaggregant effects, treatment with long‐acting nitrates at the time of onset of acute coronary syndromes could be associated with attenuation of their severity.

Methods: A consecutive series of 533 patients with acute coronary syndrome and past history of coronary artery disease admitted to the Cardiology Service of a general hospital was studied. A specific questionnaire assessed the use of nitrates and other relevant drugs, as well as other clinical variables. The diagnosis of unstable angina or acute myocardial infarction (MI) was established according to clinical, electrocardiographic, and enzymatic criteria.

Results: In the whole cohort, 169 patients had MI and 364 had unstable angina. Previous use of long‐acting nitrates was significantly more common in patients with unstable angina (56%) than in those with MI (37%) (p<0.0001). Multivariate analysis identified being a nonsmoker [odds ratio: 95%, confidence limits (CL) 0.37, 0.23–0.59], previous unstable angina (CL 0.62, 0.41–0.92), use of aspirin (CL 0.58, 0.41–0.92), and use of long‐acting nitrates (CL 0.61, 0.40–0.93) as the independent predictors of the development of unstable angina rather than MI; of these the combination of nitrates and aspirin was the strongest predictor.

Conclusions: Long‐acting nitrates as well as aspirin are suggested to have a protective or modifying effect on the development of acute coronary syndromes, favoring unstable angina rather than acute MI.

Keywords: long‐acting nitrates, unstable angina, myocardial infarction, aspirin

Full Text

The Full Text of this article is available as a PDF (725.9 KB).

References

  • 1. Davies MJ: Acute coronary thrombosis: The role of plaque disruption and its initiation and prevention. Eur Heart J 1995; 16: L3–7 [DOI] [PubMed] [Google Scholar]
  • 2. Giri S, Waters DD: Pathophysiology and initial management of the acute coronary syndromes. Curr Opin Cardiol 1996; 11: 351–360 [DOI] [PubMed] [Google Scholar]
  • 3. Fuster V: Elucidation of the role of plaque instability and rupture in acute coronary events. Am J Cardiol 1995; 76: 24C–33C [DOI] [PubMed] [Google Scholar]
  • 4. Badimon L, Chesebro JH, Badimon JJ: Thrombus formation on ruptured atherosclerotic plaques and rethrombosis on evolving thrombi. Circulation 1992; 86 (suppl 6): III74–III85 [PubMed] [Google Scholar]
  • 5. Lacoste LL, Théroux P, Lidón RM, Colucci R, Lam JYT: Antithrombotic properties of transdermal nitroglycerin in stable angina pectoris. Am J Cardiol 1994; 73: 1058–1062 [DOI] [PubMed] [Google Scholar]
  • 6. Torfgard KE, Ahlner J: Mechanism of actions of nitrates. Cardiovasc Drugs Ther 1994; 8: 701–717 [DOI] [PubMed] [Google Scholar]
  • 7. Weber AA, Strobach H, Schror K: Direct inhibition of platelet function by organic nitrates via oxide nitric formation. Eur J Pharmacol 1993; 247 (1): 29–37 [DOI] [PubMed] [Google Scholar]
  • 8. Chirkov YY, Naujalis JI, Sage RE, Horowitz JD: Antiplatelets effects of nitroglycerin in healthy subjects and in patients with stable angina pectoris. J Cardiovasc Pharmacol 1993; 21: 384–389 [DOI] [PubMed] [Google Scholar]
  • 9. Loscalzo J: Antiplatelet and antithrombotic effects of organic nitrates. Am J Cardiol 1992; 70: 18B–22B [DOI] [PubMed] [Google Scholar]
  • 10. Stamler JS, Loscalzo J: The antiplatelet effects of organic nitrates and related compounds in vitro and in vivo and their relevance to cardiovascular disorders. J Am Coll Cardiol 1991; 18: 1529–1536 [DOI] [PubMed] [Google Scholar]
  • 11. Anggard EE: Endogenous nitrates: Implications for treatment and prevention. Eur Heart J 1991; 12 (suppl A): 5–8 [PubMed] [Google Scholar]
  • 12. García‐Dorado D, Théroux P, Tornos P, Sambola A, Oliveras J, Santos M, Soler‐Soler J: Previous aspirin use may attenuate the severity of the manifestations of acute ischaemia syndromes. Circulation 1995; 92: 1743–1748 [DOI] [PubMed] [Google Scholar]
  • 13. GISSI‐3 (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico) : GISSI‐3: Effect of lisinopril and transdermal glyceril‐trinitrate singly and together on 6‐week mortality and ventricular function after acute myocardial infarction. Lancet 1994; 343: 1115–1122 [PubMed] [Google Scholar]
  • 14. ISIS‐4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS‐4 : A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. Lancet 1995; 345: 669–685 [PubMed] [Google Scholar]
  • 15. Ardissino D, Merlini PA, Savonitto S, Demicheli G, Zanini P, Bertocchi F, Falcone C, Ghio S, Marinoni G, Montemartini C, Mussini A: Effect of transdermal nitroglycerin or N‐acetylcysteine, or both, in the long‐term treatment of unstable angina pectoris. J Am Coll Cardiol 1997; 29: 941–947 [DOI] [PubMed] [Google Scholar]
  • 16. Thadani U: Oral nitrates: More than symptomatic therapy in coronary artery disease. Cardiovasc Drugs Ther 1997; 11 (suppl 1): 213–218 [DOI] [PubMed] [Google Scholar]
  • 17. Gerzer R, Drummer C, Karrenbrock B, Heim JM: Inhibition of platelet activating factor‐induced platelet aggregation by molsidomine, SIN‐1, and nitrates in vivo and ex vivo. J Cardiovasc Pharmacol 1989; 14 (suppl 11): S115–S119 [PubMed] [Google Scholar]
  • 18. Watanabe H, Kakihana M, Ohtsuka S, Enomoto T, Yasui K, Sugishita Y: Platelet cyclic GMP: A potentially useful indicator to evaluate the effects of nitroglycerin and nitrate tolerance. Circulation 1993; 88: 29–36 [DOI] [PubMed] [Google Scholar]
  • 19. Théroux P, Lidón RM: Unstable angina: Pathogenesis, diagnosis and treatment. Curr Probl Cardiol 1993; 18: 157–231 [DOI] [PubMed] [Google Scholar]
  • 20. Folts JD, Stamler J, Loscalzo J: Intravenous nitroglycerin infusion inhibits cyclic blood flow responses caused by periodic platelet thrombus formation in stenosed canine coronary arteries. Circulation 1991; 83 (6): 2122–2127 [DOI] [PubMed] [Google Scholar]
  • 21. Yao SK, Akhtar S, Scott‐Burden T, Ober JC, Golino P, Buja LM, Cassecells W, Willerson JT: Endogenous and exogenous nitric oxide protects against intracoronary thrombosis and re‐occlusion after thrombolysis. Circulation 1995; 92: 1005–1010 [DOI] [PubMed] [Google Scholar]
  • 22. Hinte TH, Vatner SF: Comparison of effects of nifedipine and nitroglycerin on large and small coronary arteries and cardiac function in conscious dogs. Circ Res 1983; 52 (suppl I): 139 [PubMed] [Google Scholar]
  • 23. Fuster V, Dyken ML, Vokonas PS, Hennekens C: Aspirin as a therapeutic agent in cardiovascular disease. Circulation 1993; 87: 659–675 [DOI] [PubMed] [Google Scholar]
  • 24. De Belder AJ, MacAllister R, Radomsky MW, Moncada S, Vallance PJ: Effects of S‐nitroso‐glutathione in the human forearm circulation: Evidence for selective inhibition of platelet activation. Cardiovasc Res 1994; 28: 691–694 [DOI] [PubMed] [Google Scholar]
  • 25. Negrescu EV, Grünberg B, Kratzer MAA, Lorenz R, Siess W: Interaction of antiplatelet drugs in vitro: Aspirin, iloprost, and the nitric oxide donors SIN‐I and sodium nitroprusside. Cardiovasc Drugs Ther 1995; 9: 619–629 [DOI] [PubMed] [Google Scholar]
  • 26. Langford EJ, Wainwright RJ, Jewitt DE, Martin JF: Nitric oxide donors inhibit platelet activation in acute coronary syndromes. Eur J Cardiol 1995; 16 (suppl): 1184 [Google Scholar]
  • 27. Langford EJ, Brown AS, Wainwright RJ, de Belder AJ, Thomas MR, Smith RE, Radomski MW, Martin JF, Moncada S: Inhibition of platelet activity by S‐nitrosoglutathione during coronary angioplasty. Lancet 1994; 344 (8935): 1458–1460 [DOI] [PubMed] [Google Scholar]
  • 28. Fernández Avilés F, García Morón F: The effect of a reduction in plasma cholesterol on the evolution of coronary disease. Rev Esp Cardiol 1995; 48 (suppl 5): 43–51 [PubMed] [Google Scholar]
  • 29. Shah PK: New insights into the pathogenesis and prevention of acute coronary syndromes. Am J Cardiol 1997; 79: 17–23 [DOI] [PubMed] [Google Scholar]
  • 30. Ambrose JA: Plaque disruption and the acute coronary syndromes of unstable angina and myocardial infarction: If the substrate is similar, why is the clinical presentation different? J Am Coll Cardiol 1992; 19: 1653–1658 [DOI] [PubMed] [Google Scholar]

Articles from Clinical Cardiology are provided here courtesy of Wiley

RESOURCES