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Editorial
Álvaro Nagib Atallah
Sao Paulo Med J/Rev Paul Med 1999; 117(2):47-8.
Coronary he art dise ase and e stroge n plus
proge stin tre atme nt: the “burde n” of the e vide nce
Hea lth pro fessio na ls’ enthusia sm fo r the prescribing o f estro g ens to g ether with pro g estin in po stmeno pa usa l wo men rec eived a ma jo r setback recently. The publicatio n o f a rando mized trial o f estro g en plus pro g estin fo r seco ndary p re ve ntio n o f c o ro na ry he a rt d ise a se in po stmeno pausal wo men1 has bro ug ht to lig ht so me new evidence in the subject that is co ntrary to the previo us “ co nsensus” . G ro wing evidence fro m o b se rva tio na l stud ie s a mo ng w o me n receiving estro g ens had been indicating so me benefits o f estro gens in the preventio n o f co ro nary heart disease in po stmeno pausal wo men. But this la rg e ra nd o miz e d d o ub le b lind p la c e b o -c o ntro lle d tria l, w hi-c h a ime d to d e te rmine whether estro g en/ pro g estin therapy decreased the risk o f c o ro na ry he a rt dise a se e ve nts in w o me n w ith e sta b lishe d c o ro na ry d ise a se , sho wed that estro g ens to g ether with pro g estin have neg ative effects.
The study was do ne o n 2 .7 6 3 wo men with co ro nary disease. The treated g ro up received 0 .6 2 5 mg o f co njug ated equine estro g ens plus 2 .5 mg o f medro xypro g estero ne acetate daily. The fo llo w -up a ve ra g e d 4 . 1 ye a rs a nd the a dherenc e wa s g o o d. The prima ry o utc o mes were no n-fatal myo cardial infarctio n o r co ro nary heart disease death. 1 7 2 wo men in the ho rmo ne
g ro up and 1 7 6 in the placebo g ro up had these primary events. This lack o f o verall effect o ccurred in spite o f an 1 1 % less lo w density lipo pro tein cho lestero l (LDL-c) level and a 1 0 % g reater hig h density lipo pro tein cho lestero l (HDL-c) level in the ho rmo ne g ro up than in the placebo g ro up (P< 0 .0 0 1 ). Furthermo re, there wa s a sig nific a nt trend o f mo re co ro nary heart disease events in the first year in the ho rmo ne g ro up and fewer in the 3 rd a nd 4 th y e a r. The re w e re 3 4 thro mbo embo lic events in the ho rmo ne gro up and 1 2 events in the pla c eb o g ro up (rela tive risk 2 .8 9 ; 9 5 % C .I. 1 .5 0 to 5 .5 8 ). G a llb la dde r disease was sig nificantly mo re frequent in the ho rmo ne g ro up than in placebo , with 8 4 versus 6 2 cases (P= 0 .0 5 ).
The autho rs co ncluded that the treatment w ith o ra l c o njug a te e q uine e stro g e ns p lus medro xypro g estero ne acetate did no t reduce the o verall rate o f co ro nary heart disease events in the studied patients and did no t reco mmend the use this treatment fo r the purpo se o f seco ndary preventio n o f co ro nary heart disease.1
This trial is a well-perfo rmed study, was suppo rted by the pharmaceutical industry and was published in spite o f the neg ative results.
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Sao Paulo Med J/Rev Paul Med 1999; 117(1):47-8.
that a treatment causes mo re g o o d than harm befo re putting it into g eneral practice. The initial e nthusia sm fo r this tre a tme nt w a s b a se d o n o bservatio nal studies, which are quo ted as level o f e vide nc e IV o r V fo r the ra pe utic de c isio n making .2
Be sid e s tha t a syste ma tic re vie w3 o f o b se rva tio na l stud ie s o n 1 5 0 , 0 0 0 p a tie nts, sho wed a sig nificant increase in breast cancer fo llo wing ho rmo na l repla cement thera py wa s sho wn.
O ne c ritic ism tha t c a n b e ma de o f the estro g en/ pro g estin trial is that it o nly included patients with previo us co ro nary heart disease, with a mean ag e o f 6 6 .7 years, leaving o pen the hyp o the sis tha t tre a tme nt fo r p rima ry p re ve ntio n in y o ung e r w o me n c o uld b e b enefic ia l. It is, ho wever, no t g o o d dec isio n-ma king pra c tic e to g ive tre a tme nt b a se d o n hypo theses and therefo re we need to wait fo r a stud y a ime d a t a nsw e ring suc h a q ue stio n,
because o f its clinical implicatio ns. A larg er study within the N atio nal W o men Initiative, aiming to rando miz e 6 8 ,0 0 0 wo men, is underway and its publicatio n is expected fo r the year 2 0 0 7 . The best existing evidence do es no t justify the use o f estro g en to g ether with pro g estin fo r the p re ve ntio n o f c o ro na ry he a rt d ise a se in po stmeno pausal wo men.
REFERENCES
1. Hulle y S, Grad y D, Bush T, Furb e rg C, He rringto n D, Riggs B, Vittingho ff E. Rando mized trial o f estro gen plus pro gestin fo r sec-o ndary preventisec-o n sec-o f csec-o rsec-o nary heart disease in psec-o stmensec-o pausal wo men. Heart and Estro gen/pro gestin Replacement Study (HERS) Research Gro up. JAMA 1998;280(7):605-13.
2. Ec c le s M, Fre e m antle N, Maso n J. No rth o f England e vid e nc e b ase d guide line s de ve lo pm e nt pro je ct: m e tho ds o f de ve lo ping g uid e line s fo r e ffic ie nt d rug us e in p rim ary c are . Br Me d J 1998;316(7139):1232-5.
