Antihypertensive Efficacy of Chronopharmacotherapeutical Approach to Arterial Hypertension in Post Transient Ischemic Attack Patients

Aim. To assess antihypertensive efficacy of various 24-hour regimens of antihypertensive drugs prescription and the influence on 24-hour profile of blood pressure (BP) and aortic pressure, in systemic hypertension patients post transient ischemic attack. Material and methods. Totally, 174 patients were included, with grade 1-2 hypertension and previous non-effective treatment; who during the previous 4 weeks had transient ischemic attack. All patients were randomized to 3 groups according to the treatment variant: group 1 (n=59) — valsartan 160 mg and thiazide-like diuretic in the morning, group 2 (n=58) — thiazide-like diuretic in the morning and valsartan 160 mg at bedtime, group 3 (n=57) — thiazide-like diuretic in the morning and valsartan 80 mg b.i.d. (morning and bedtime). At baseline and in 12 months of therapy all patients underwent BP monitoring (ABPM) with assessment of mean 24 hour, daytime, nocturnal systolic BP (SBP) and diastolic BP (DBP), mean pulse pressure, time index of hypertension, SBP and DBP variability at daytime and at night, prominence and velocity of morning SBP and DBP raise, heart rate, central aortic pressure (CAP): SBP and DBP in aorta, variability of SBP and DBP in aorta, pulse BP in aorta, augmentation index in aorta, pulse pressure amplification, ejection period duration, efficacy index of subendocardial blood flow. Valsacor (KRKA, Slovenia) was included in the study as valsartan. Results. In 12 weeks of fixed combination therapy, the target levels of BP were registered: in group 1 — 43 patients (72,9%), group 2 — 48 (82,7%), group 3 — 55 (96,4%). Reached target BP was more common in b.i.d. intake of valsartan (group 3) comparing to group 1 (p=0,001) and group 2 (p=0,03). Statistically significant positive shifts of ABPM and CAP values were registered in all three regimens. However, in group 2 there was significantly more prominent decrease of the main parameters of ABPM and CAP, than in group 1. Valsartan two times daily (group 3) led to more prominent (p<0,05) improvement of ABPM and CAP value comparing to any variant of its once per day usage (group 1 and 2). In 12 months of treatment, there was a significant (p<0,05) increase in all groups of patients with normalized 24 hour BP profile (“dipper”): in group 1 — 28 (65%), group 2 — 37 (77%), group 3 — 48 (87%). Normalized 24 hour BP trend was registered more commonly in the group 3 patients comparing to those of groups 1 and 2. The differences in the number of “dipper” patients were significant between groups 3 and 1 (p=0,01). Conclusion. The study showed that b.i.d. or bedtime valsartan intake in combination with diuretic leads to more prominent improvement of the main ABPM and CAP parametes in comparison with the drug intake in the morning, in patients with transient ischemic attack. Two times daily intake of valsartan leads significantly (p<0,05) to normalization of 24 hour BP profile in most patients (87%) and more prominent improvement of the main ABPM, CAP values comparing to once per day morning or evening intake of the drug.