Antianginal effect of transdermal nitroglycerin and oral nitrates given for 24 hours a day in 2,456 patients with stable angina pectoris. The Italian Multicenter Study.

The effect of transdermal and oral nitrates on anginal symptoms were compared in a randomized trial of 2,456 out-patients with stable angina pectoris recruited in 206 cardiological centers in Italy. Half of the patients had effort-induced angina, 12% rest angina and 38% "mixed angina". Before enrollment, all of the patients were on stable treatment with oral nitrates either as monotherapy or in combination with other antianginal agents. After a 2-week run-in period on the previous oral nitrate regimen, two thirds of the patients were randomized to receive a nitroglycerin patch 5 mg/24 hours for 2 weeks, the remaining one third continued their previous treatment. The patients subsequently reporting > or = 1 anginal attack/2 weeks were titrated to transdermal nitroglycerin 10 mg/24 hours or to the maximum dose of oral nitrates suggested by the manufacturer for the following 4 weeks; asymptomatic patients continued on the initial dosages. The 2-week anginal attack rate was reduced from 4.9 +/- 5.3 to 1.4 +/- 2.5 in the transdermal nitroglycerin group (-71%), and from 4.5 +/- 4.7 to 1.5 +/- 2.7 (-67%) in the oral nitrate group. The proportion of patients free of angina increased from 12% to 54% (+343%) with transdermal nitroglycerin and from 15% to 49% with oral nitrates (+218%) (p < 0.05). The reduction in angina frequency was similar during the day and during the night. Nocturnal angina was rare in patients with effort angina. However, about half of the patients with rest and "mixed" angina had had nocturnal episodes, the number of which was significantly reduced by both regimens: nighttime asymptomatic patients increased from 45% to 82% in the rest angina group, and from 50% to 83% in the "mixed" angina group, with no differences between treatments. Withdrawals due to side-effects were rare: 1.5% with transdermal nitroglycerin and 1.3% with oral nitrates. Headache was the most common side-effect and was more frequently reported with oral nitrates. Although the lack of a placebo control precludes an absolute evaluation of efficacy, the results of the present study suggest that both transdermal nitroglycerin and oral nitrates may provide relief of anginal symptoms over 24 hours in the majority of stable angina patients. Nocturnal angina, reported by 50% of the patients with rest and mixed angina, is effectively reduced by the administration of nitrates over 24 hours.