Differences in ischemic threshold and nitrate efficacy between normotensive and hypertensive patients with stable angina pectoris.
The coexistence of ischemic heart disease with hypertension makes antihypertensive therapy essential, since relief of hypertension may ameliorate the coronary disease. On the other hand, the effect of antianginal nitrate therapy in patients with stable angina pectoris and systemic arterial hypertension is not fully understood. This study assessed the effects of hypertension on the ischemic threshold and the time to moderate angina, measured as parameters of nitrate efficacy. In this double-blind, parallel-group study, 141 patients with stable angina pectoris were randomly assigned to receive 5 mg, 10 mg or 20 mg isosorbide-5-mononitrate or matching placebo bid for 21 days. Ninety-three normotensive and 48 hypertensive patients were compared with regard to the time to moderate anginal pain and the ischemic threshold before and after nitrate treatment on the first day of the study. The acute nitrate effect 2 h after drug administration was substantially attenuated in hypertensives at both 10 and 20 mg of isosorbide-5-mononitrate, with the time to moderate anginal pain being significantly shortened. Impaired vasodilatator response of the arterial vasculature to organic nitrates, probably due to impaired biotransformation of organic nitrates to nitric oxide in hypertensive patients, is suggested as a possible mechanism for the diminished nitrate effect. Thus, oral nitrate therapy does not have the same beneficial antianginal effect in hypertensive patients as it does in normotensives. Dose adjustment based on the pretreatment blood pressure, and the administration of higher doses of oral nitrates should therefore be considered in hypertensive patients suffering from stable angina pectoris.
Marmor
A
A
Division of Cardiology, Rebecca Sieff Hospital, Safed, Israel.
Reizin
L
L
Caspi
A
A
Botvin
S
S
Schneeweiss
A
A
D000368:Aged; D000787:Angina Pectoris / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate