The insufficient nitrate response: patients' characterization and response to beta and calcium blockade

Little information has been published regarding the nitrate-induced changes of left ventricular volumes at rest and during exercise in relation to the degree of the anti-ischaemic response. Therefore we assessed the electrocardiographically defined nitrate response to a single tablet of 80 mg isosorbide dinitrate s.r. and compared it to the changes in end-diastolic volumes at rest and during exercise, as determined by radionuclide ventriculography. Thirty-four of the 63 patients were classified as good nitrate responders, whereas 29 patients showed insufficient nitrate response with regard to the reduction of exercise-induced ST-segment depression. The baseline characteristics were quite comparable. At rest the ISDN-induced decrease of the end-diastolic count rate was significantly less (-17%) in patients with insufficient ST-segment response when compared to patients with good ST-segment response (-25%). During exercise, in patients with good ST-segment response, ISDN reduced the end-diastolic volume significantly (-19%), whereas in patients with insufficient ST-segment response the end-diastolic volume remained unchanged. In this special subset of patients with insufficient nitrate response we further evaluated the effects of additional beta or/and calcium blockade. The benefits from verapamil were equivalent to propranolol. However, a considerable part of the patients investigated needed the combination of verapamil and propranolol for an optimal anti-ischaemic drug treatment. Thus, our data support the concept that preload reduction plays a major role for the anti-ischaemic effects of ISDN in patients with exercise-dependent ischaemia. Since, a suboptimal therapeutic effect must be considered, objective control of the nitrate therapy (usually by exercise- and Holter-ECG) must be regarded as obligatory for each individual patient if optimal results are to be expected.