Has antihypertensive therapy been oversimplified?

Recent large clinical studies have shown that the pharmacological treatment of mild hypertension does not lower the incidence of myocardial infarction and total mortality. It seems that rt is not sufficient merely to lower BP; the various long term effects of antihypertensive agents on reflex mechanisms and thus central haemodynamrcs must be taken into account. Early hypertension is charactensed by mcreased cardrac output and heart rate. wrth normal total penpheral resistance After 10-20 years wrthout treatment. there rs a decrease rn cardrac output and stroke volume and total perrpheral resrstance rncreases

Thrazide druretrcs mrtrally reduce plasma volume and cardrac output. but do not affect total penpheral resrstance After 1 year of treatment. cardiac output returns to the pretreatment level and total penpheral resrstance decreases. Thrazrde diuretrcs thus induce almost normal haemodynamics at rest and dunng exercrse. but biochemrcal adverse effects have reduced !herr populanty m recent years

Beta-blockers have a slowmg effect on heart rate and thus reduce cardrac output and cause a reflex mcrease m total penpheral resrstance The acute reduclion m cardrac output rs moderated during long term therapy Dunng exercrse. heart rate remams depressed by about 30% or 45 beats/min and cardiac output rs reduced by 15-25% Slowing of the heart rate rs less marked wrth beta-blockers with mtnnsic sympathomrmetrc activrty. However. rn a comparative study between pmdolol and acebutolol maximal oxygen uptake was reduced more by pindolol, although this drug has strong intnnsic sympathomrmetrc acllvrty. Thrs may have been because of the non-selectrve nature of pmdolol: vascular d2-blockade could restrict vasodilatron dunng exercrse

The alpha-blocker doxazosrn. adm1nrstered Intravenously reduces total per1pheral resrstance and thus BP. both at rest and dunng exerc1se Dunng chronrc oral treatment. BP has been reduced by 19% and total penpheral res1stance by 20%. w1th no change in heart rate. Labetalol. an a­d-blocker. appears to have a similar acute effect to that of d-blockers while chronic treatment causes a 20% drop 1n BP with a Similar decrease 1n total penpheral res1stance Card1ac output 1ncreases both at rest and dur1ng exercise

Calc1um antagonists lower BP and total penpheral res1stance w1th vary1ng effects on heart rate and atr1oventrrcular conduction For 1nstance. the d1hydrepyr1d1ne n1sold1p1ne increases heart rate and card1ac output 1n1t1ally but th1s effect d1sappears w1th chron1c adm1n1strat1on

In contrast. verapam1l and drlt1azem do not 1ncrease heart rate Dur1ng exerc1se. HR IS decreased by about 10°o and AV conduct1on IS prolonged however. card1ac output IS not decreased because of a compensatory 1ncrease 1n stroke volume

0156-2703!87 /1212-0003/0$01.00/0 © ADIS Press

ACE 1nh1b1tors reduce total per1pheral res1stance through the ren1n-ang1otens1n system thereby reduc1ng BP but not affect1ng card1ac output

Thus. 1t IS poss1ble to lower BP and total perrpheral res1stance w1th a number of ant1hypertens1ve drugs Cho1ce of drug may then be d1ctated by haemodynam1c effects and d1fferent drugs may be prescr1bed to d1fferent pat1ent groups .i-blockers seem to be the cho1ce 1n ang1na patrents where a decrease 1n card1ac workload IS requrred Pat1ents w1th recent myocardial 1nfarct1on w1ll also benef1t from the protection aga1nst re1nfarct1on or sudden death conferred by d-blockers Pat1ents w1th perrpheral vascular d1sorders wrll benef1t more from treatment wrth a calc1um antagonist or u-receptor blocker than a d-blocker. Heart failure pat1ents w1th hypertenSIOn respond well to ACE 1nh1b1tors Phys1cally act1ve. younger pat1ents w1th hypertension requrre a calc1um antagonist. an o blocker or an ACE 1nh1b1tor to reduce BP w1thout affectrng blood flow. Although thrs method avo1ds the oversrmpl1f1cat1on of reduc1ng BP. 1t IS not yet known if such an approach to the treatment of hypertens1on w1ll result 1n a better long term prognosiS than that seen so far w1th d-blockers and d1uret1cs lund Johansen P Arnencan Heart Jo11rnal 114 958·964 Oct 1987

INPHARMA"' 12 December 1987 3