Claudio Borghi, Francesca Santi

Hypertension is one of the most important and widespread risk factors for the development of cardiovascular disease. Once, combination therapy was traditionally reserved as a third-line or fourth-line approach in the management of hypertension. However, several major intervention trials in high-risk patient populations have shown that an average of 2-4 antihypertensive agents are required to achieve effective blood pressure control. Combination treatment should be considered as a first choice in patients at high cardiovascular risk and in individuals for whom blood pressure is markedly above the hypertension threshold (eg, more than 20 mmHg systolic or 10 mmHg diastolic), or when milder degrees of blood pressure elevation are associated with multiple risk factors, subclinical organ damage, diabetes, renal failure, or associated cardiovascular disease. A number of clinical trials have demonstrated that a fixed combination of lercanidipine and enalapril has better efficacy and tolerability than monotherapy with either agents. The fixed-dose formulation of lercanidipine-enalapril was well tolerated in all clinical trials, with an adverse event rate similar to that of the component drugs as monotherapy. The advantages of combination therapy include improved adherence to therapy and minimization of blood pressure variability. In addition, combining two antihypertensive agents with different mechanisms of action may provide greater protection against major cardiovascular events and the development of end-organ damage.