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Beta-blockers and primary cardioprotection in hypertension.

Theoretical and experimental data coupled with findings from several studies, showing the beneficial effect of beta-blocking therapy in reducing the risk of death and re-infarction among infarct patients (secondary cardioprotection), suggested that beta-blockers could reduce the incidence of coronary events also in hypertensive patients with no clinical evidence of coronary heart disease (CHD) (primary cardioprotection). In order to evaluate the primary cardioprotective potential of beta-blockers as compared to diuretics in the treatment of hypertension, some large-scale, randomized, prospective studies were set up in the middle and late 1970s. The results of three of these trials, the MRC, the IPPPSH and the HAPPHY studies, were negative or non-conclusive and somehow conflicting. None of them showed any difference between beta-blockers and diuretics in reducing the incidence of CHD, but the MRC and the IPPPSH studies suggested that beta-blockers were better than diuretics in male non-smokers. However, the HAPPHY study did not confirm such a hypothesis. More recently, two studies, the Clatterbridge study (retrospective, non-controlled) and the MAPHY study (prospective, controlled) gave positive results about the primary cardioprotective effect of beta-blockers. In particular, the MAPHY study demonstrated that starting antihypertensive treatment with the beta1-selective beta-blocker metoprolol instead of a thiazide diuretic led to lower total and cardiovascular mortality, mainly by reducing fatal CHD and fatal stroke. Although more evidence is needed, the primary cardioprotective effect demonstrated with metoprolol in the MAPHY study might have important implications for clinical practice and public health.