Angiotensin II-receptor antagonist losartan does not prevent nitroglycerin tolerance in patients with coronary artery disease

Cardiovasc Drugs Ther. 2004 Sep;18(5):363-70. doi: 10.1007/s10557-005-5060-1.

Abstract

The study evaluated the effect of Losartan in preventing nitrate tolerance during continuous transdermal nitroglycerin (TD-GTN) therapy in patients with coronary disease. Fifteen subjects with chronic stable ischemia evaluated by exercise test, were randomized to 28 days of TD-GTN 20 mg once a day without free interval plus Losartan 100 mg or Losartan-placebo with a double blind crossover design. Myocardial ischemic parameters during stress test were evaluated after each test period and results of Losartan therapy were compared to those with placebo. Time to onset 1 mm ST-depression was significantly higher after acute TD-GTN 20 mg with respect to placebo run-in, sustained TD-GTN 20 mg plus Losartan 100 mg or Losartan-placebo (p < 0.001). ST-depression at peak exercise and time to recovery of ST segment were markedly lower after acute TD-GTN 20 mg compared to placebo run-in (p < 0.05), sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001) or Losartan-placebo (p < 0.05). At 1 mm-ST depression and at peak exercise, systolic blood pressure and rate-pressure product significantly decreased after sustained TD-GTN 20 mg plus Losartan 100 mg (p < 0.001, p < 0.05 respectively) with respect to placebo run-in, acute and sustained TD-GTN 20 mg plus Losartan-placebo. Moreover at peak exercise, these data were also observed after acute TD-GTN 20 mg compared to placebo run-in and sustained TD-GTN 20 mg plus Losartan-placebo (p < 0.001). The AT(1) antagonist Losartan administration does not prevent the development of nitrate tolerance during continuous TD-GTN therapy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Cutaneous
  • Angina Pectoris / drug therapy*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Tolerance
  • Electrocardiography
  • Female
  • Heart Rate / drug effects
  • Humans
  • Losartan / therapeutic use*
  • Male
  • Middle Aged
  • Nitroglycerin / administration & dosage
  • Nitroglycerin / therapeutic use*
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / therapeutic use*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Vasodilator Agents
  • Nitroglycerin
  • Losartan