Ointments and transdermal nitroglycerin patches for stable angina pectoris.
Nitroglycerin (NTG) ointment is used for the prophylaxis against angina pectoris, but there are no data to support its effectiveness during long-term therapy. Continuous, once-daily application of isosorbide dinitrate cream produces tolerance with complete loss of efficacy within 1 week. Nitroglycerin patches are very popular and continuous once-daily application is still claimed by some investigators to provide 24 hour antiischemic and antianginal efficacy. This claim is based on data from postmarketing studies in a very large number of patients and placebo-controlled studies in smaller groups of patients from Italy, Yugoslavia, Greece, and Germany. In contrast, studies from the United States, Canada, England, and some centers in Germany have failed to show superiority of patches over placebo during continuous therapy. This controversy was addressed by the NTG cooperative study group, in which a total of 562 patients who were responders to sublingual nitroglycerin were studied. Patients received either placebo or NTG patches delivering low (15-30 mg/24 hr), moderate (45-60 mg/24 hr), or large (75 and 105 mg/24 hr) amounts of NTG. Four hours after the initial application, NTG patches increased exercise duration compared to placebo, but this beneficial effect had disappeared by 24 hours. Furthermore, after 8 weeks of continuous therapy, none of the NTG patches were superior to placebo, whether patients were or were not taking concomitant beta-blockers. Therefore, current opinion is that continuous therapy with NTG patches produces pharmacologic tolerance and is ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73104.
U
U
Thadani
R J
RJ
Lipicky
D000279:Administration, Cutaneous; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D000787:Angina Pectoris / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004361:Drug Tolerance; D015444:Exercise; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009824:Ointments; D011358:Product Surveillance, Postmarketing
D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D009824:Ointments; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate