Benefits of Fixed Dose Combination of Ramipril/Amlodipine in Hypertensive Diabetic Patients: A Subgroup Analysis of RAMONA Trial

Background: Combination of angiotensin-converting enzyme inhibitors and calcium channel blockers has been successfully used in the antihypertensive therapy for many years. Fixed dose combinations of ramipril/amlodipine have a benefit effect for patients to achieve target blood pressure (BP). This study aimed to assess the efficacy and safety of fixed dose combinations of ramipril and amlodipine (Egiramlon (R)) in hypertensive diabetic patients. Methods: Hypertensive diabetic patients who were enrolled into the RAMONA trial were included in this open, prospective, Phase IV observational clinical study. Patients had mild-to-moderate hypertension and failed to reach target BP levels through their previous therapy. During the four months of observation, patients took part in three visits (1st day = visit 1, 1st month = visit 2, and 4th month = visit 3) where they received a fixed dose combination of 5/5, 5110, 10/5, or 10/10 mg ramipril/amlodipine, respectively, with the possibly required dose titrations, based on the decision of their attending physician. Target BP for diabetic patients was < 140/85 mmHg. BP levels were measured in all visits, by taking two readings at 2-min interval. Laboratory tests including full blood count, renal function test, electrolytes, blood glucose, serum cholesterol, uric acid, triglycerides, liver function test, creatinine kinase, and midstream urinalysis were performed at visit 1 and visit 3. Results: The 6423 patients completed the study. Among these patients, 1276 (19.9%) patients suffered from type 2 diabetes mellitus. The mean age of these diabetic patients was 64.2 +/- 10.0 years; 707 (55.4%) patients were males. Target BP was achieved by 891 (69.8%) of diabetic patients at visit 3 (primary endpoint). BP decreased from 157.5/91.3 +/- 9.6/7.6 mmHg (visit 1) to 130.9/79.6 +/- 7.4/5.8 mmHg (visit 3). As for the secondary endpoint of the study, total cholesterol decreased from 5.50 +/- 1.13 mmol/L (visit 1) to 5.20 +/- 0.95 mmol/L (P = 0.000), low-density lipoprotein cholesterol decreased from 3.20 +/- 0.93 mmol/L to 3.00 +/- 0.77 mmol/L (P = 0.000), triglyceride decreased from 2.20 +/- 1.14 mmol/L to 2.00 +/- 1.97 mmol/L (P = 0.000), while high-density lipoprotein cholesterol increased from 1.30 +/- 0.42 to 1.35 +/- 0.30 mmol/L (P = 0.001) until the end of the 4th month (visit 3). Fasting blood glucose of the hypertensive diabetic patients decreased from 7.20 +/- 1.88 mmol/L to 6.70 +/- 1.38 mmol/L (P = 0.000), while HbA1c decreased from 7.90 +/- 1.78% to 7.60 +/- 1.83% (P = 0.000). Various fixed dose combinations of ramipril/amlodipine were well tolerated and no adverse event related to the use of the medicine has appeared. Conclusions: The fixed dose combination of ramipril/amlodipine was effective in hypertensive diabetic patients who failed to reach target BP previously.