Treatment of elderly patients with isolated systolic hypertension with isosorbide dinitrate in an asymmetric dosing schedule

Abstract

Nitrates decrease pulse pressure more than mean arterial pressure (MAP) and are advocated for the treatment of isolated systolic hypertension (ISH). Nitrates show drug tolerance during chronic treatment so an asymmetric dosing regimen may prevent loss of effect of nitrates. This study investigates the anti-hypertensive effect of isosorbide dinitrate (ISDN) given in a twice daily asymmetric dosing regimen in elderly patients with ISH. After a 6-week placebo run-in period, patients entered the double-blind study. Ten patients received placebo and 11 patients ISDN 20 mg b.i.d. for 8 weeks. This dose could be doubled once. Office systolic and diastolic blood pressures (SBP/DBP) and ambulatory BP were measured. Pulse pressure was calculated as SBP-DBP. Office pulse pressure was more reduced during ISDN (17.9%) than with placebo (5%; P < 0.05). SBP and MAP decreased compared to baseline, but the changes were not statistically significant between the two groups. DBP tended to increase with ISDN compared to placebo. Mean 24-h, mean daytime and mean night-time pulse pressure decreased after treatment with ISDN (10.7%, 12.1%, 7.9%, respectively). Pulse pressure tended to decrease more during the day than during the night with ISDN. No changes could be demonstrated with placebo. In conclusion, pulse pressure decreased with ISDN, resulting in a lower SBP without a decrease in DBP. The latter may preserve coronary perfusion in ISH. With the asymmetric dosing regimen the decrease in pulse pressure was not clear at night. Whether a decrease in nocturnal BP, in addition to the spontaneous decrease, is advisable in ISH remains a matter of debate.