Does the exercise protocol matter when assessing the anti-anginal effects of drug therapy?

Four exercise test protocols (Bruce, Balke, Ellestad and Steep)were compared in 16 patients with proven coronary artery diseasein demonstrating the anti-anginal effects of sublingual glyceryltrinitrate in a randomization double-blind trial. Glyceryl trinitrate significantly improved the time, heart rateand rate pressure product to peak exercise, onset of anginaand 1 mm ST segment depression in all four protocols (P<0.05)(except rate pressure product to angina in the Balke protocol).The increase in exercise time was greatest for the Balke protocolat peak exercise (188.1±187.1) (mean±SD in s),at onset of angina (251.9±247.1) and at 1 mm ST depression(233.6±243.8), followed by the Steep and Bruce protocols,and was lowest for the Ellestad protocol 41.9±42.4, 96.5±65.8,82.6±74.0, respectively. Increase in time to peak exercisewith glyceryl trinitrate was significantly greater for the Balkeprotocol in comparison with the other three protocols and forthe Bruce and Steep protocols when compared to the Ellestadprotocol. Time to 1 mm ST depression with treatment was significantlygreater on the Balke and Bruce protocols than the Ellestad protocol,and to onset of angina for the Balke compared to other threeprotocols. There were no significant differences between theBruce and Steep protocols for any of the endpoints. The magnitudeof treatment effect in the different protocols was accompaniedby correspondingly greater inter-patient variability such thatno protocol was more, or less, sensitive than another in detectingtreatment effect. Changes in heart rate and rate pressure productwith treatment were generally similar between the differentprotocols. In conclusion, a protocol with small and frequent increments(Balke), although able to show greater increase in exerciseduration with glyceryl trinitrate than more aggressive protocols,is no more sensitive at detecting treatment effect.