Exercise capacity with transdermal nitroglycerin in patients with stable angina pectoris

Abstract

Transdermally delivered nitroglycerin (TTS-NTG) through a rate-controlling membrane yields stable blood levels for 24 h. We studied the effect of TTS-NTG (25 mg per 10 cm2) on exercise induced angina in 10 patients with stable angina pectoris, all in NYHA class III, who were not under treatment with other cardiac drugs. In a pre-study exercise test, all patients had angina pectoris and more than one mm ST depression. The study was placebo controlled and double blind with a randomized cross-over. Exercise tests were carried out on a treadmill according to the Bruce-protocol, 12 to 16 h after administration of TTS-NTG or of an identical placebo. After a 48 h wash-out period, the procedure was repeated after application of a plaster with the alternative content. A significant improvement was seen on TTS nitroglycerin compared with placebo in the total duration of exercise (7.2 +/- 3.6 min (mean +/- SD) vs 6.2 +/- 3.8 min; P less than 0.002). In 7 patients, the time to onset of angina was extended by TTS nitroglycerin. Maximal ST depression (lead V4 and V6) was significantly lower on TTS nitroglycerin (1.85 +/- 1 mm) compared with placebo (2.2 +/- 1 mm; P less than 0.05). It is concluded that 12 to 16 h after administration, transdermally delivered nitroglycerin improves exercise capacity and reduces maximal ST depression in patients with stable angina.

Influence of Transdermal Nitrates on Exercise Capacity in Patients with Stable Angina

“…Eleven previous studies relating to efficacy in angina pectoris have been published, of which eight have demonstrated variable clinical benefit whilst three have shown no measurable effect whatever. [8][9][10][11][12][13][14][15][16][17][18] The discrepancy between the studies is principally related to the dose regime and the presence or absence of concomitant anti-anginal medication. The three studies showing no demonstrable effect utilized a fixed dose protocol of one nitrate patch delivering 5 mg per 24 .…”

Comparison of transdermal nitrate and isosorbide dinitrate in chronic stable angina.

“…In our study, comparison of the two placebo treatment periods (pretreatment and washout, see Table 3) confirmed that the frequency of angina attacks reduced and exercise tolerance improved with time. In any cross-over study, it is important that patients enter both active treatment periods in the same clinical state, but the effect of these changes was minimized by comparing the differences from base- (Cerri et al, 1984;Hollenberg & Go, 1984;Naafs et al, 1984;James et al, 1985) and repeated administration (Georgopoulos et al, 1982;Letzel et al, 1982;Hollenberg & Go, 1984). In contrast, other studies have failed to demonstrate a therapeutic effect (Crean et al, 1984;Parker & Fung, 1984;Dickstein & Knutsen, 1985).…”

“…New formu-lations of transdermal nitrate (TN) have been described, which control the release of nitroglycerin from a drug reservoir (Shaw & Urquhart, 1981;Muller et al, 1982). Initial studies have suggested that TN is effective at reducing the frequency of anginal attacks (Garnier et al, 1982;Letzel & Johnson, 1984), and some controlled trials have supported this observation (Georgopoulos et al, 1982;Letzel et al, 1982;Thompson, 1983;Cerri et al, 1984;Hollenberg & Go, 1984;Naafs et al, 1984). More recently, several studies have failed to demonstrate a *Present address and correspondence: Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland therapeutic effect of TN (Crean et al, 1984;Parker & Fung, 1984;Reichek et al, 1984;Dickstein & Knutsen, 1985).…”

Tolerance to Organic Nitrates: Evidence, Mechanisms, Clinical Relevance, and Strategies for Prevention

“…These systems continuously release nitroglycerin by matrix diffusion-controlled or membrane permeationcontrolled drug delivery systems and result in an elevated nitroglycerin blood level that persists for at least 24 hours (19,20). The results of reported placebo-controlled studies are contradictory; some show a complete failure of transdermal nitroglycerin to enhance exercise capacity in patients with angina pectoris (21,22), whereas other studies show a beneficial effect (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). In addition, the results of studies about the persistence of the antianginal effect of transdermal nitroglycerin have conflicted.…”