ANTIHYPERTENSIVE TREATMENT - OUR FUTURE F ROM THE PAST

Future trends in hypertensive treatment have to rely on our past and p resent experience with antihypertensive drugs as well as on emerging c oncepts of blood pressure regulation, on which some new drugs in the ' 'pipeline'' are based. Early detection of hypertension, before organ m anifestations particularly in the heart, the kidney and the vessels oc cur, remain mandatory since in most of the patients with mild and mode rate hypertension the high blood pressure is not diagnosed at all or t reated inadequately. Prevention of cardiac, vascular, renal or metabol ic complications has always been better for the patient and less costl y than their repair or reparation. Our present treatment goals have of ten not reached far enough. Normalisation of blood pressure demonstrat es only surrogate efficacy of our treatment. Our ultimate goal has to be improvement of total or cerebrovascular or cardiovascular and cardi ac mortality. Important steps on that road are the prevention or repar ation of cardiac hypertrophy, of the increased extracellular matrix an d collagen deposition, the conservation of vascular integrity includin g both coronary and systemic microangiopathy and macroangiopathy. For the patient this means integrated care of his associated disorders tha t is of coronary artery disease, diabetes mellitus, lipid disorders, o verweight and the metabolic syndrome.True health efficacy (= reduction of total or cerebro- and cardiovascular mortality) has been demonstra ted so far only by blood pressure reduction with diuretics (thiazides) and betablockers in long term studies, whereas sufficient surrogate e fficacy, the lowering of blood pressure, has been demonstrated with al most all the others drugs either in mono- or in combinationtherapy. To gether with ACE-inhibitors, which have demonstrated their prognostic v alue in patients with heart failure of different causes, thiazides (as the most representative diuretic) and betablockade can be considered first line drugs in the treatment of hypertension. Long-term mortality trials for ACE-inhibitors in hypertension are needed, however, to pro ve that the anticipated benefit from the heart failure megatrials can also be taken for granted for hypertensive patients without coronary a rtery disease as well. All other drugs should not or not yet be consid ered first line medication, although treatment behavior in the US and in Europe shows wide-spread use of calcium antagonists in short- and l ong-acting dihydropyridine type hypertensive patients. No peer reviewe d journal has so far published a randomized double-blind trial with th e endpoint of total or cardiovascular mortality in hypertension using calcium antagonists. A recent case control study, as well as the preli minary data from MIDAS and GLANT, for which event rates are available in abstract form, suggest that short acting calcium-antagonists of the dihydropyridine type, though controlling blood pressure well, are not reducing mortality but show a trend to increase cardiovascular events particularly when given in higher doses. In contrast the unpublished data from a Chinese megatrial with dihydropyridines (STONE) demonstrat e effective blood pressure reduction and benefit in mortality in a pop ulation that differs from patients in Europe and in the USA because of the low prevalence of coronary artery disease. No randomized, double blindly aquired data on mortality as the primary end of antihypertensi ve treatment are yet available for verapamil, diltiazem and the new cl ass of longer acting calciumantagonists. Only when speculating from tr ials with calcium antagonists in coronary artery disease e.g. the DAVI T II study, one could imagine so far that prognostic benefit may be ex pected from drugs that do not or very little activate the adrenergic a nd the renin-angiotensin-aldosterone system and the baroreceptors and reduce or at least maintain heart rate. The need for double blind, ran domized trials with the different Ca-antagonists is obvious, before a further widespread use can be recommended. This also applies in part t o ACE-inhibitors and certainly to all the prospectively promising new drugs. In severe hypertension combination therapy is unavoidable in or der to reduce side-effects and have a satisfactory blood pressure. Com bination therapy should take into account the accompanying diseases an d metabolic disorders as well as the complications of hypertension. In mild and moderate hypertension monotherapy should be attempted first, however. New antihypertensive drugs include the angiotensin-II-recept or antagonists, the renin inhibitors, the potassium channel openers, t he therapeutic stimulation of the endothelial NO-liberation by L-Argin in and the inhibition of the endothelin-1-mediated vasoconstriction. A ll those drugs have already demonstrated effective blood pressure redu ction, mortality studies cannot yet be expected. They therefore cannot yet be recommended as standard treatment for clinical practice. But t hey already permit us to make a glimpse into the promising future of a ntihypertensive treatment in the next decade.