The efficacy and safety of the fixed, low-dose verapamil SR and trandolapril combination therapy in mild to severe essential hypertensive patients non-responsive to monotherapy: a multicenter trial

The aim of this study was to evaluate the effects of a fixed, low-dose combination of sustained release (SR) verapamil and trandolapril in patients (pts) with mild to severe essential hypertension uncontrolled by monotherapy. The study material consisted of 138 (77 women, 61 men; mean age 51.6±10.3 years, ranged 21-70) pts. After a placebo wash-out period of one week, all pts had taken a fixed combination of verapamil SR 180 mg and trandolapril 2 mg (Tarka®) once a day for 6 weeks. The sitting systolic and diastolic blood pressures (BPs) were significantly reduced from 168.5±15.6/100.3±8.1 mmHg to 137.6±13.1/85.1±8.1 mmHg at the end of the trial (p<0.001 and p<0.001). The percentage of reduction for systolic and diastolic BPs were 19% and 17%, respectively. The target value of BP (BP<140/90 mm Hg and reduction of diastolic BP>10 mm Hg) was achieved in 70% of the pts at the end of 6 weeks. The heart rate was reduced slightly, but significantly (p<0.01). The left ventricular mass detected by echocardiography was significantly reduced from 124.0±32.09 g to 118.2±25.9 g (p<0.001), and the E/A ratio of mitral inflow was increased from 0.9±0.4 to 1.0±0.4 (p<0.01). Adverse effects developed in 17 (12%) pts (cough in 3 pts, headache in 5 pts, palpitations in 2 pts, constipation in 3 pts, tinnutus in 2 pts, edema in 1 patient and flushing in 1 patient), 2 of them were withdrawn from the trial due to the side effects (1 patient with flushing and 1 patient with cough). No clinically relevant changes in laboratory parameters (glucose, urea, creatinine, uric acid, electrolytes, GOT, GPT, alkaline phosphatase, total cholesterol, HDL-cholesterol, VLDL-cholesterol, triglycerides, protein) have been detected. In conclusion, it was confirmed that a fixed verapamil SR and trandolapril combination has 1. Superior antihypertensive efficacy compared to monotherapy, 2. High efficacy with excellent tolerability and safety, 3. A neutral impact on the metabolic parameters, and 4. Regressive effect on left ventricular hypertrophy.