RAS blockade and cardioprotection Finally, combined therapy was characterized by a good safety profile and it was also supported by main- tained renal function, left ventricular function and by in- consistent change in potassium at the end of the treat- ment. However, our study has some possible limitations. First, it did not have a placebo group; such group was not approved by the ethics committee because of the known cardioprotection of ACEi and ARB. This limita- tion is unlikely to affect our data because both mono- therapies significantly reduced LVM. Secondly, we have not assessed the most appropriate dose of each drug in combination treatment. We do not know if a combina- tion of reduced doses of both drugs could offer the same cardioprotection as did the dose we used. In view of this, Peters et al (38) reported that submaximal doses of ACEi and ARB, like we used, are able to induce in combination maximal inhibition of angiotensin II and provide maximal therapeutic efficacy. In addition another study showed that addition of an ARB to an ACEi is more effective than doubling ACEi dose (39). Neverthe- less dual RAS blockade is a relatively new concept and some questions remained unanswered. The duration of action of different ACEi and ARB might influence the ef- fect of different combinations. Moreover complete RAS suppression and thus a higher dose or a shorter dose interval might be needed to obtain organ protection where lower doses are sufficient to treat hypertension (40). Finally, it is possible that reduction in LVM/h2.7 af- REFERENCES 1. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hy- pertension. Ann Intern Med 1991; 114: 345-52. 2. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically deter- mined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561-6. 3. Verdecchia P, Schillaci G, Borgioni C, et al. Prognostic significance of serial changes in left ventricular mass in essential hypertension. Circulation 1998; 97: 48-54. 46 ter combined therapy might be underestimated since not only hypertensive patients recruited by us had left ventricular hypertrophy. Some clinical implications arise from the results of our study. First, combination treatment was well tolerat- ed without evidence of hyperkaliemia after 24 weeks. This provided further evidence to suggest that the pre- sent practice of avoiding use of ACEi and ARB or both, to prevent renal impairment and hyperkaliemia, is no longer justified. However, careful observation is still rec- ommended. In conclusion our data suggest that hyper- tensive patients with higher LVM may be considered a particular subset of hypertensives who may particularly benefit from complete RAS blockade. This indication might also improve the therapeutic strategy for cardio- protection in hypertensive subjects. ACKNOWLEDGEMENTS This study was supported in part by a project grant (60%) from the University of Palermo, Italy. Address for correspondence: Rosario Scaglione, MD Associate Professor of Medical Therapy Via Lombardia, 9 90144 Palermo - Italy rosarioscaglione@yahoo.it 4. Muiesan Ml, Salvetti M, Rizzoni D, et al. Association of change in left ventricular mass with prognosis during long term antihypertensive treatment. J Hypertens 1995; 13: 1091-5. 5. Weber KT. Fibrosis and hypertensive heart disease. Curr Opin Cardiol 2000; 15: 264-72. 6. Weber KT, Eghbali M. Collagen matrix synthesis and degradation in the development and regression of left ventricular hypertrophy. Cardiovasc Rev Rep 1991; 12: 61-9. 7. Diez J, Lopez B, Gonzalez A, Querejeta R. Clinical as- pects of hypertensive myocardial fibrosis. Curr Opin Car- diol 2001; 16: 328-35.