Different effects of aliskiren and losartan on fibrinolysis and insulin sensitivity in hypertensive patients with metabolic syndrome.
The aim of this study was to compare the effect of aliskiren and losartan on fibrinolysis and insulin sensitivity (IS) in hypertensive patients with metabolic syndrome. After 2-week placebo period, 76 outpatients with mild to moderate hypertension and metabolic syndrome were randomized to aliskiren 300 mg od or losartan 100 mg od for 12 weeks. Clinic blood pressure (BP), plasma PAI-1 antigen, and tPA activity were evaluated after 2, 4, 8, and 12 weeks of treatment. At the end of each treatment period patients performed an euglycemic hyperinsulinemic clamp and IS was assessed by glucose infusion rate (GIR). Both aliskiren and losartan induced a significant and similar SBP/DBP reduction (-15.6/10.7 mmHg and -15.5/10.5 mmHg, p<0.001 vs. baseline, respectively). Both drugs decreased PAI-1 antigen and activity after 2 weeks of treatment; subsequently, only the decreasing effect of aliskiren was sustained throughout the 12 weeks [-7.5 ng/ml (-31%) p<0.05 vs. baseline], while with losartan PAI-1 increased at week 12 [+3.6 ng/ml (+15%), p<0.05 vs. baseline and p<0.01 vs. aliskiren)]. The tPA activity showed no significant change with aliskiren and a decrease with losartan [-0.04 IU/ml (-8%), p<0.05 vs. baseline and p<0.01 vs. aliskiren]. Aliskiren significantly increased GIR [+1.4 mg/min/kg (+28%), p<0.01 vs. baseline] while losartan did not change it [+0.2 mg/min/kg (+4%), NS vs. baseline, p<0.05 vs. aliskiren)]. These results indicated that in this type of patients, despite similar BP reduction, aliskiren improved the fibrinolytic balance as well as IS, while losartan worsened the fibrinolytic balance and did not affect IS. The clinical relevance of these different effects remains to be clarified.
Fogari
R
R
Department of Internal Medicine and Therapeutics, Centro Ipertensione e Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy. r.fogari@unipv.it
Zoppi
A
A
Mugellini
A
A
Lazzari
P
P
Derosa
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000577:Amides / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005650:Fumarates / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008875:Middle Aged; D055815:Young Adult
D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D007328:Insulin; C446481:aliskiren; D019808:Losartan