Reconsidering the Treatment of Patients with Coronary Artery Disease

A New Possibility from CAMELOT
Point of View and Perspectives


Treatment of hypertensive patients with coronary artery disease is still a debated issue. In particular, relatively few controlled clinical trials have prospectively assessed the impact of specific drug classes on adverse outcomes in patients with coronary artery disease and, moreover, it is not clear if a more aggressive therapeutic approach aimed to reduce blood pressure values well below 140/90mm Hg might achieve an adjunctive beneficial effect.

There is a general consensus that hypertensive patients with coronary artery disease should receive treatment with an ACE inhibitor. This consensus is based on the results of the HOPE (Heart Outcomes Prevention Evaluation) and EUROPA (EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease) studies (testing ramipril and perindopril, respectively) and does not take into account that these trials compared an active treatment with placebo, which basically produced a further decrease in blood pressure values, thereby making it difficult to establish whether the beneficial outcome was related to a specific effect of drugs or to the blood pressure reduction. These positive results were not confirmed by the PEACE (Prevention of Events with Angiotensin Converting Enzyme inhibition) study, which demonstrated that adding trandolapril to the treatment of patients with stable coronary artery disease did not produce a further beneficial effect compared with placebo, therefore demonstrating that the addition of an ACE inhibitor in patients with coronary artery disease does not universally produce a beneficial effect.

More recently, two clinical trials have clearly demonstrated that dihydropyridine calcium channel blockers can determine a beneficial outcome in high-risk patients with coronary artery disease. The ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) trial demonstrated that long-acting nifedipine was effective in reducing cardiovascular events in patients with stable symptomatic angina and in patients with high blood pressure values, whereas in normotensive patients there was no difference from placebo. The CAMELOT (Comparison of Amlodipine vs Enalapril to Limit Occurrence of Thrombosis) trial demonstrated that amlodipine produced a statistical 31% reduction in cardiovascular events, while enalapril, despite a blood pressure reduction similar to that achieved with the calcium channel blocker, produced a 15.3% reduction in cardiovascular events, which was not statistically significant. It is worth noting that the effect of amlodipine was still evident in patients with blood pressure values within the normal range.

At least part of the beneficial effect of calcium channel blockers on coronary events can be related to the well documented effect of this class of drugs in preventing atherosclerosis. It is well documented that calcium channel blockers can improve endothelial function by an antioxidant effect and several clinical trials have demonstrated that these drugs can inhibit the progression of atherosclerotic plaque. In CAMELOT, this beneficial effect was confirmed in a sub-study indicating that amlodipine, but not enalapril or placebo, was able to completely block the progression of coronary atherosclerosis, as assessed by intravascular ultrasound.

In conclusion, the CAMELOT study supports the possibility that blood pressure reduction to values much lower than those indicated by current guidelines might achieve a further beneficial effect in patients with coronary artery disease.


  1. 1.
    European Society of Hypertension — European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011–53Google Scholar
  2. 2.
    Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–72PubMedCrossRefGoogle Scholar
  3. 3.
    Rosamond WD, Chambless LE, Folsom AR, et al. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med 1998 Sep 24; 339(13): 861–7PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson KM, Wilson PW, Odell PM, et al. Updated coronary risk profile. Circulation 1991; 83: 357–63Google Scholar
  5. 5.
    Kannel WB. Blood pressure as a cardiovascular risk factor: prevention and treatment. JAMA 1996; 275: 1571–6PubMedCrossRefGoogle Scholar
  6. 6.
    Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 145–53PubMedCrossRefGoogle Scholar
  7. 7.
    Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study): EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Lancet 2003; 362: 782–8PubMedCrossRefGoogle Scholar
  8. 8.
    Braunwald E, Domanski MJ, Fowler SE, et al. Angiotensin-converting-enzyme inhibition in stable coronary artery disease: PEACE Trial Investigators. N Engl J Med 2004; 351: 2058–68PubMedCrossRefGoogle Scholar
  9. 9.
    Poole-Wilson PA, Lubsen J, Kirwan BA, et al. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomized controlled trial. A Coronary disease Trial Investigating Outcome with Nifedipine gastrointestinal therapeutic system investigators. Lancet 2004; 364: 849–57PubMedCrossRefGoogle Scholar
  10. 10.
    Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. CAMELOT investigators. JAMA 2004; 292: 2217–25PubMedCrossRefGoogle Scholar
  11. 11.
    Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA 2003; 290: 2805–16PubMedCrossRefGoogle Scholar
  12. 12.
    Furberg CD, Psaty BM, Meyer JV. Nifedipine: dose-related increase in mortality in patients with coronary heart disease. Circulation 1995; 92 (5): 1326–31CrossRefGoogle Scholar
  13. 13.
    Neal B, MacMahon S, Chapman N. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000; 356: 1955–64PubMedCrossRefGoogle Scholar
  14. 14.
    Staessen JA, Wang JG, Thijs L. Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet 2001; 358(9290): 1305–15PubMedCrossRefGoogle Scholar
  15. 15.
    Staessen JA, Wang JG, Thijs L. Calcium-channel blockade and cardiovascular prognosis: recent evidence from clinical outcome trials. Am J Hypertens 2002; 15(7 Pt 2): 85S–93SPubMedCrossRefGoogle Scholar
  16. 16.
    Opie LH, Schall R. Evidence-based evaluation of calcium channel blockers for hypertension: equality of mortality and cardiovascular risk relative to conventional therapy. J Am Coll Cardiol 2002; 39(2): 315–22PubMedCrossRefGoogle Scholar
  17. 17.
    Lubsen J, Wagener G, Kirwan BA, et al. Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with symptomatic stable angina and hypertension: the ACTION trial (A Coronary disease Trial Investigating Outcome with Nifedipine GITS investigators). J Hypertens 2005; 23: 641–8PubMedCrossRefGoogle Scholar
  18. 18.
    Suwaidi JA, Hamasaki S, Higano ST, et al. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000; 101(9): 948–54PubMedCrossRefGoogle Scholar
  19. 19.
    Heitzer T, Schlinzig T, Krohn K, et al. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001; 104(22): 2673–8PubMedCrossRefGoogle Scholar
  20. 20.
    Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105(9): 1135–43PubMedCrossRefGoogle Scholar
  21. 21.
    Taddei S, Salvetti A. Endothelial dysfunction in essential hypertension: clinical implications. J Hypertens 2002; 20: 1671–4PubMedCrossRefGoogle Scholar
  22. 22.
    Taddei S, Virdis A, Ghiadoni L, et al. Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. Drugs 2002; 62(2): 265–84PubMedCrossRefGoogle Scholar
  23. 23.
    Kiowski W, Linder L, Erne P. Vascular effects of endothelin-1 in humans and influence of calcium channel blockade. J Hypertens Suppl 1994 Jan; 12(1): S21–6PubMedGoogle Scholar
  24. 24.
    Borhani NO, Mercuri M, Borhani PA, et al. Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS): a randomized controlled trial. JAMA 1996; 276(10): 785–91PubMedCrossRefGoogle Scholar
  25. 25.
    Zanchetti A, Rosei EA, Dal Palu C, et al. The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness. J Hypertens 1998; 16(11): 1667–76PubMedCrossRefGoogle Scholar
  26. 26.
    Simon A, Gariepy J, Moyse D, et al. Differential effects of nifedipine and coamilozide on the progression of early carotid wall changes. Circulation 2001; 103: 2949–54PubMedCrossRefGoogle Scholar
  27. 27.
    Zanchetti A, Bond MG, Hennig M, et al. Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis: principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, doubleblind, long-term trial. European Lacidipine Study on Atherosclerosis investigators. Circulation 2002; 106: 2422–7PubMedCrossRefGoogle Scholar
  28. 28.
    Lichtlen PR, Hugenholtz PG, Rafflenbeul W, et al. Retardation of angiographic progression of coronary artery disease by nifedipine: results of the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT). INTACT group investigators. Lancet 1990; 335: 1109–13PubMedCrossRefGoogle Scholar
  29. 29.
    Pitt B, Byington RP, Furberg CD, et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events: PREVENT investigators. Circulation 2000; 102(13): 1503–10PubMedCrossRefGoogle Scholar
  30. 30.
    Jorgensen B, Simonsen S, Endresen K, et al. Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES). J Am Coll Cardiol 2000; 35: 592–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Department of Internal MedicineUniversity of PisaPisaItaly
  2. 2.Clinica Medica, Dipartimento di Medicina Clinica, Prevenzione e Biotecnologie SanitarieUniversity Milano BicoccaMilanItaly

Personalised recommendations