Effect of oral nitrates on pulse pressure and arterial elasticity in patients aged over 65 years with refractory isolated systolic hypertension: study protocol for a randomized controlled trial

BACKGROUND: Isolated systolic hypertension is a highly prevalent disease among the elderly. The little available evidence on the efficacy of nitrates for treating the disease is based on small experimental studies. METHODS/DESIGN: We performed a multicenter, randomized, double-blind, phase III, placebo-controlled trial in 154 patients aged over 65 years with refractory isolated systolic hypertension. Patients were randomized to placebo or 40 mg/day of extended-release isosorbide mononitrate added to standard therapy and titrated to 60 mg/day at week 6 if blood pressure exceeded 140/90 mmHg. The primary objective was to assess the effect on clinical pulse pressure of extended-release isosorbide mononitrate added to standard therapy in patients aged over 65 years with refractory isolated systolic hypertension after 3 months of treatment. The secondary objectives were as follows: to quantify the effect of adding the study drug on central blood pressure and vascular compliance using the augmentation index and pulse wave velocity; to evaluate the safety profile by recording adverse effects (frequency, type, severity) and the percentage of patients who had to withdraw from the trial because of adverse events; to quantify the percentage of patients who reach a clinical systolic blood pressure <140 mmHg or <130 mmHg measured by ambulatory blood pressure monitoring; and to quantify the change in pulse pressure measured by ambulatory blood pressure monitoring. DISCUSSION: Few clinical trials have been carried out to test the effect of oral nitrates on isolated systolic hypertension, even though these agents seem to be effective. Treatment with extended-release isosorbide mononitrate could improve control of systolic blood pressure without severe side effects, thus helping to reduce the morbidity and mortality of the disease. TRIAL REGISTRATION: EUDRACT Number: 2012-002988-10