Effects of manidipine and its combination with an ACE inhibitor on insulin sensitivity and metabolic, inflammatory and prothrombotic markers in hypertensive patients with metabolic syndrome: the MARCADOR study.

BACKGROUND AND

objectiveMetabolic syndrome is common in patients with hypertension and increases the risk of developing diabetes mellitus. The objective of this study (the MARCADOR study) was to compare the effects of manidipine 20  mg with the extemporary combination of manidipine 10  mg/lisinopril 10  mg, amlodipine 10  mg and telmisartan 80  mg on insulin sensitivity, as well as metabolic, inflammatory and prothrombotic markers, in hypertensive non-diabetic patients with metabolic syndrome.

methodsThis study had a prospective, randomized, open-label, blinded endpoint (PROBE) design. A total of 120 patients aged 35-75 years with stage I-II essential hypertension (systolic blood pressure [BP] 140-179  mmHg, diastolic BP 90-109  mmHg) and metabolic syndrome were recruited from general practitioner clinics in Northern Gran Canaria Island, Spain and randomized to receive amlodipine 10  mg (n = 30), telmisartan 80  mg (n = 30), manidipine 20  mg (n = 30) or (low-dose) manidipine 10  mg/lisinopril 10  mg (n = 30), all administered once daily. At baseline and after 14 weeks of treatment, BP, insulin sensitivity, lipid profile, and albumin and metanephrin excretion as well as several other metabolic, inflammatory, prothrombotic and growth/adhesion markers were measured. The primary endpoint was the change in insulin sensitivity.

resultsA total of 115 patients completed the study. All treatments significantly lowered BP from baseline. Compared with amlodipine, manidipine had significantly superior effects (p < 0.05) on insulin resistance (-26.5% vs -3.0%), albumin/creatinine ratio (-28.2% vs -3.6%), low-density lipoprotein (LDL) cholesterol (-6.8% vs +1.7%), and several other metabolic, inflammatory and prothrombotic markers. Manidipine was associated with a slightly greater increase in insulin sensitivity than manidipine/lisinopril, but manidipine/lisinopril was significantly more effective than manidipine and telmisartan for improving a number of metabolic, inflammatory, prothrombotic and growth/adhesion markers. Amlodipine was associated with a significantly greater incidence of adverse effects compared with telmisartan, manidipine and manidipine/lisinopril (26.7% vs 3.3%, 3.3% and 13.3%, respectively).

conclusionIn patients with hypertension and metabolic syndrome, manidipine, both alone and in combination with the ACE inhibitor lisinopril, is significantly superior to amlodipine for improving insulin sensitivity as well as several metabolic, inflammatory and prothrombotic markers. Furthermore, the combination of manidipine and lisinopril appears to have greater efficacy than manidipine alone and telmisartan with respect to the improvement of metabolic, inflammatory and prothrombotic markers.