Determination of the optimal dose of glyceryl trinitrate in the treatment of stable angina

There has been recent controversy over the efficacy of transdermalglyceryl trinitrate (GTN) preparations in the treatment of anginaand their effects on exercise tolerance. To determine the doseof GTN that produces significant anti-anginal effects, symptomlimited exercise testing has been undertaken in seven patientswith stable angina. Doses of 10, 20, 40 and 80 µg min^-1of GTN or placebo were infused during treadmill exercise untilsymptom limiting chest pain or 3 mm ST segment depression occurred.Compared with placebo, total exercise time increased by 47%at 20 µg min^-1 (P<0.05) with no further change at thehigher doses. Duration of exercise before the onset of significantST segment depression increased by 51% at 20 µg min^-1(P<0.05) with no further increase at the higher doses. Thesechanges were accompanied by a 21% increase double product (heartrate x systolic blood pressure) at 20 µg min^-1 (P<0.05)reflecting a higher heart rate achieved as a result of the increasedduration of exercise. These results suggest that 20 µgmin ^-1 may be the optimal dose of GTN to achieve significantantianginal effects as demonstrated by the improved exercisetolerance and reduction of myocardial ischaemia. This impliesthat the dose of GTN delivered by transdermal preparations maybe below the therapeutic level.     

Comparison Between Flecainide and Atenolol in the Suppression of Complex Ventricular Ectopic Activity After Myocardial Infarction: Results of a Double-Blind, Randomized Trial

The efficacy of flecainide (100–150 mg bd) in comparison with atenolol (50–100 mg bd) in suppressing frequent (5/hour) ventricular ectopic activity and nonsustained ventricular tachycardia on ambulatory monitoring was assessed in 26 patients one month after myocardial infarction in a randomized, double-blind trial. Blood drug levels were monitored and monthly follow-up ambulatory monitoring and exercise testing were performed for three months, A successful response (70% suppression of ectopic activity or elimination of ventricular tachycardia) was seen in 100% of patients randomized to flecainide compared with 50% randomized to atenolol (p<.05). Three patients developed serious adverse reactions to treatment, one of whom was receiving flecainide and the other two atenolol. The patient on flecainide suffered an exacerbation of heart failure; one on atenolol experienced bronchospasm and the other a proarrhythmic effect. Flecainide is superior to atenolol in the suppression of ventricular ectopics and nonsustained ventricular tachycardia in patients with recent myocardial infarction, though should be used with care in patients with critically impaired left ventricular function.