Favourable interaction of calcium antagonist plus ACE inhibitor on cardiac haemodynamics in treating hypertension: Rest and effort evaluation

The aim of the study was to evaluate the effects of verapamil sustained release (SR) 240 mg, enalapril and their combination on blood pressure (BP) and cardiac haemodynamics at rest and during exercise in 20 patients with moderate essential hypertension (seven men and 13 women, mean age ± s.d. 53.7 ± 15.8 years). After a 4 week placebo run-in period, patients were randomly allocated to received verapamil SR 240 mg once daily or enalapril 20 mg once daily for 4 weeks in a double-blind fashion. Patients whose diastolic blood pressure (DBP) was still ≥ 95 mm Hg at the end of this period received verapamil SR plus enalapril for an additional 4 weeks. At the end of the placebo, single and combined treatment periods, resting and exercise (bicycle ergometry) haemodynamics were evaluated by radionuclide ventricular angiography (technetium-99m) and the following parameters were assessed: BP, heart rate, double product, systemic vascular resistances (SVR), cardiac output (CO), stroke volume (SV), ejection fraction (EF) mean ejection rate (mER) and peak filling rate (PFR). Both verapamil SR and enalapril monotherapies significantly reduced resting and exercise BP (P < 0.01), with a BP normalisation (DBP ≤ 95 mm Hg) of five of 10 and 4 of 10 patients respectively. A greater BP fall and a normalisation of 11 of 11 patients was obtained in non-responders to monotherapy, when treated with verapamil SR and enalapril (P < 0.01). Verapamil SR also reduced heart rate at rest and during exercise (-11.8% and -18.4%, respectively, P < 0.05). Double product was significantly reduced at rest and during exercise in the verapamil group (P < 0.01); enalapril alone and verapamil plus enalapril reduced double product only at rest (P < 0.01). Resting and exercise SVR significantly decreased in the verapamil, enalapril and combined treatment groups (rest -16%, -13% and -15%; exercise -19%, -18% and -15%, respectively, P < 0.01). Left ventricular function showed a trend towards improvement after monotherapies; CO, EF and mER significantly improved with the combined regimen. In conclusion, verapamil SR and enalapril in a once a day administration were effective in the treatment of moderate hypertension, their anti-hypertensive effect was associated with a significant reduction of SVR. A further BP reduction was obtained with the combination of the two drugs that induced a reduction of SVR with a good tolerability profile. The better BP reduction obtained with the combination of the two drugs was associated with an improvement of left ventricular function particularly during effort where, for any reduction in DBP, there was more improvement in SV and CO.