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
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.


CONCLUSIONS
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.


BACKGROUND
EUDRACT Number: 2012-002988-10.
Servicio de Medicina Interna, Hospital Universitario de la Princesa, Diego de León 62, Planta 10, 28006, Madrid, Spain. danielabadperez@hotmail.com.
Daniel
D
Abad-Pérez
Blanca
B
Novella-Arribas
Francisco J
FJ
Rodríguez-Salvanés
Luis M
LM
Sánchez-Gómez
Iluminada
I
García-Polo
Carmen
C
Verge-González
Carmen
C
Suárez-Fernández
D000284:Administration, Oral; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D002985:Clinical Protocols; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004548:Elasticity; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D063177:Pulse Wave Analysis; D012107:Research Design; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate