Fosinopril Versus Amlodipine Comparative Treatments Study

Abstract

Background-ACE inhibitors and calcium antagonists may modulate fibrinolysis. We conducted a randomized controlled trial to assess the effects of these drugs on plasminogen activator inhibitor-1 (PAI-1) antigen, an inhibitor of fibrinolysis. Methods and Results-Participants with hypertension and type 2 diabetes mellitus (nϭ96, 51% black) were randomized after an initial 4 weeks of placebo to double-blind 20 or 40 mg fosinopril or 5 or 10 mg amlodipine daily for 4 weeks in a fixed-dose regimen. After 4 weeks of placebo washout, the patients received 4 weeks of crossover treatments. After treatment with placebo, systolic and diastolic blood pressure were 143Ϯ2 and 86Ϯ1 mm Hg and plasma PAI-1 was 43.4Ϯ2.3 ng/mL. Amlodipine achieved a greater systolic and diastolic blood pressure reduction than fosinopril (10 mm Hg versus 8 mm Hg, Pϭ0.029, and 5 mm Hg versus 3 mm Hg, Pϭ0.040, respectively) but tended to increase PAI-1, whereas fosinopril tended to decrease PAI-1 (5.4Ϯ3.6 versus Ϫ3.8Ϯ2.5 ng/mL, Pϭ0.045). The PAI-1 changes depended on drug dose (6.5Ϯ6.1 and 3.4Ϯ3.9 ng/mL with amlodipine 10 and 5 mg, respectively, and Ϫ0.4Ϯ3.1 and Ϫ7.4Ϯ4.0 ng/mL with fosinopril 20 and 40 mg, respectively, P for trend 0.024). No significant differences between fosinopril and amlodipine were found for short-term changes in tissue plasminogen activator antigen, fibrinogen, C-reactive protein, and interleukin-6. The findings were similar in black and white participants. Conclusions-Short-term treatment with fosinopril significantly reduced PAI-1 compared with amlodipine in a dosedependent fashion. This effect, which was independent of blood pressure reduction, may account for the improved clinical outcomes achieved with ACE inhibitors compared with calcium antagonists. (Circulation. 2002;105:457-461.)

Angiotensin-Converting Enzyme Inhibition Alters the Fibrinolytic Response to Cardiopulmonary Bypass

“…When patients who received lisinopril were analyzed by dose level, postoperative PAI-1 antigen concentrations were suppressed in patients taking 20 to 40 mg/d lisinopril but not in patients taking Յ10 mg/d. This finding is in agreement with the findings of Pahor et al, 13 who demonstrated that fosinopril reduces PAI-1 in a dose-dependent fashion.…”

“…Nevertheless, all but 3 patients were taking lisinopril. Moreover, previously published reports that enalapril, 33 quinapril, 8 and ramipril 9 (carboxyl-containing ACEIs like lisinopril), fosinopril 13 (a phosphinyl-containing ACEI), and captopril 34 (a sulfhydryl-containing ACEI) all decrease PAI-1 concentrations suggest that the effect of ACE inhibition on PAI-1 is a class effect. The finding that lisinopril decreased postoperative PAI-1 in the present study confirms a study by Shinosaki et al, 35 who reported that lisinopril suppressed PAI-1 expression in an animal model of mesangioproliferative nephritis but conflicts with a study by Zehetgruber et al, 36 who reported no effect of lisinopril on fibrinolysis.…”

“…There were no significant differences between the 2 groups with regard to CPB time, cross-clamp time, number of grafts, chest tube output at 4 and and the increase in PAI-1 antigen from baseline to POD1 (Pϭ0.009) were higher in the No-ACEI group than in the ACEI group. Because ACE inhibition has been shown to reduce PAI-1 in a dose-dependent manner, 13 we analyzed the effect of lisinopril on PAI-1 separately in individuals who were treated with low doses versus those treated with usual to high doses (Table 3). ACE activity was significantly higher in the low-dose lisinopril versus the usual-to high-dose patients (Pϭ0.028).…”

Comparative study of amlodipine versus ramipril and their effects on markers of renal disease in type 2 diabetes mellitus

“…Falls in SBP (-6.02 mmHg, 4.19 % at 12 weeks) is less while falls in DBP (-8.07 mmHg, 9.05 %) is more as reported by Pahor M, et al (10 mmHg and 5 mm of Hg respectively, at 8 weeks in patients of T2DM with hypertension). 12 While, at 24 weeks both SBP and DBP fall is more in this study as compared to Zaman ZA, et al (14 mm Hg (8.43%) and 8 mm Hg (8.16%) in patients of hypertension with or without T2DM at 24 weeks). 13 In comparison to Agodoa LY, et al both SBP and DBP fall is less at 12 weeks (6.02 mmHg and 8.07 mmHg) while more fall is seen in both these BP at 24 weeks (20.76 mmHg and 10 mmHg respectively at 12 and 24 weeks) in this study.…”

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

“…23 The effects of calcium antagonists on fibrinolysis have been poorly studied and conflicting data have been reported with some studies demonstrating that calcium antagonists improve 24 and others showing impairment of 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.…”