Effect of delapril–manidipine combination vs irbesartan–hydrochlorothiazide combination on fibrinolytic function in hypertensive patients with type II diabetes mellitus

Abstract

The aim of this double-blind, double-dummy, parallel group study was to compare the effects of delaprilmanidipine combination vs a irbesartan-hydrochlorothiazide combination on plasma tissue plasminogen activator (t-PA) and plasmogen activator inhibitor type I (PAI-l) activities in hypertensive patients with type II diabetes mellitus. After a 4-week run-in placebo period, 80 patients (37 male and 43 female), aged 41-65 years, were randomly allocated to an 8-week treatment with delapril 30 mg once daily or irbesartan 150 mg once daily. Thereafter, manidipine l0 mg once daily was added to delapril treatment and hydrochlorothiazide 12.5 mg to irbesartan treatment for a further 8 weeks. Blood pressure (BP), plasma t-PA and PAI-l activities were evaluated at the end of the run-in period, after 4-week monotherapy treatments, and at the end of the combination treatment periods. Both combination treatments, delapril-manidipine and irbesartan-hydrochlorothiazide, produced a greater reduction in systolic BP/diastolic BP (SBP/DBP) values (À27.6/21.8 mmHg and À26.4/20.2 mmHg, respectively) than the respective monotherapies (À15.2/ 11.7 mmHg with delapril and À16.3/11.3 mmHg with irbesartan). Delapril monotherapy significantly decreased plasma PAI-l activity (À10.4 IU/mI; Po0.05). The addition of manidipine produced a significant increase in t-PA activity ( þ 0.27 IU/mI); Po0.05). Irbesartan monotherapy did not significantly affect the fibrinolytic balance, whereas the addition of hydrochlorothiazide worsened it, producing a significant increase in PAI-l activity ( þ 9.5 IU/ml; Po0.05). In hypertensive patients with type II diabetes mellitus, the combination delapril-manidipine may determine a greater improvement of the fibrinolytic function than the respective monotherapy, while the association irbesartan-hydrochlorothiazide may worsen it.

Effects of Manidipine/Delapril versus Olmesartan/Hydrochlorothiazide Combination Therapy in Elderly Hypertensive Patients with Type 2 Diabetes Mellitus

“…Although the clinical relevance of diuretic-induced metabolic side effects is still debated, the choice of antihypertensive drugs, particularly in high-risk patients such as those with diabetes, should favor agents that do not worsen the global cardiovascular risk profile. No significant changes in metabolic parameters were observed in the patients treated with manidipine/delapril, which confirms previous observations (54,55).…”

Are we content with lowering blood pressure alone, or should we be asking something more from the antihypertensive drugs we use?: effects of antihypertensive agents on fibrinolytic function

“…25,26 Finally, the unfavourable effect of hydrochlorothiazide on fibrinolysis has previously been observed. 23 In the study by Mugellini et al, 18 it is of note that there were no statistical differences in blood pressure-lowering efficacy between both combinations of antihypertensive drugs with no changes in the whole study period. This feature is especially important in diabetic patients where the treatment of cardiovascular risk factors needs to be more intensive.…”

“…17 In this issue of Journal of Human Hypertension, Mugellini et al, 18 report on the different effect of two combinations of recognised antihypertensive agents on the fibrinolytic system. Based on this well-conducted, double-blind, parallel group study, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a calcium antagonist (delapril and manidipine) resulted in a greater improvement of the fibrinolytic function than the combination of an angiotensin receptor antagonist (ARB) and a diuretic (ibersartan and hydrochlorothiazide).…”

“…33,34 The present (and previous) work suggests that the ACE inhibitors have a better effect on fibrinolytic function than ARB. 18,21,23 Thus, the question is not should we treat (where the answer is clear) but how to treat hypertension, and importantly, are we content with lowering blood pressure alone, or should we be asking something more from the antihypertensive drugs we use.…”

Fixed-dose manidipine/delapril versus losartan/hydrochlorothiazide in hypertensive patients with type 2 diabetes and microalbuminuria

“…14 Other randomized clinical trials have demonstrated similar efficacy with regard to BP reduction with a manidipine/delapril combination compared with enalapril/HCTZ 15 or with irbesartan/HCTZ. 16 In addition to control of BP, inhibitors of the renin-angiotensin system appear to have independent effects on microalbuminuria. 17 The present data with the manidipine/delapril combination on microalbuminuria are consistent with previous studies of combination regimens that included an inhibitor of the renin-angiotensin system and a calcium channel blocker.…”