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Abstract

Our aim was to determine the relative efficacy of isosorbide mononitrate (ISMN) as an adjunctive therapy for patients with systolic hypertension refractory to conventional antihypertensive agents. This was addressed by two double-blind randomised trials in subgroups from a total of 16 patients with treated systolic blood pressure above 155 mmHg at entry. On each study day, the trial drug was given at 08.00 h; between 08.00 and 16.00 h, repeated measurements were made of office blood pressure, and of pulse-wave contour using percutaneous applanation tonometry to determine aortic systolic blood pressure (ASBP) and aortic pulse wave reflectance (APWR).

The first trial was a single-dose crossover trial between placebo, captopril 25 mg, eprosartan 600 mg and ISMN 60 mg, each given (a week apart) on a single day as an adjunct to ongoing therapy with beta blocker/calcium antagonist/diuretic. ISMN decreased ASBP by 28 ± 4 (SEM) mmHg and APWR by 17 ± 3 mmHg (each P< 0.005) at 16.00 h, whereas the ACE inhibitor and angiotensin II receptor antagonist each had significantly smaller and less sustained effects.

The second trial tested for evidence of tolerance after long-term ISMN. Patients treated for periods of 6-60 months with ISMN 60-120 mg/day as an adjunct to conventional antihypertensive therapy were studied on the day before 2 weeks substitution of ISMN by placebo, and on the first day of re-introduction of active ISMN. Both ASBP and APWR were decreased by ISMN from elevated baseline levels (P< 0.02); these effects were reversible by withdrawing ISMN, and were not significantly greater when ISMN was reinstated.

We conclude that ISMN is a potent adjunctive agent for antihypertensive therapy, reducing ASBP and APWR in patients with refractory systolic hypertension and also exceeding angiotensin inhibitors in these effects. Moreover, with a single daily dose, given early morning, no loss of effect with prolonged use was detected.

pulse wave reflectance, isosorbide mononitrate, systolic hypertension
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© American Journal of Hypertension, Ltd. 2001
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