INTRODUCTION

A heart attack (also known as a myocardial infarction) is the death of heart muscle from the sudden blocka e of a coronary artery by a blood clot! Coronary arteries are blood "essels that su##ly the heart muscle with blood and o$y en! %locka e of a coronary artery de#ri"es the heart muscle of blood and o$y en& causin in'ury to the heart muscle! In'ury to the heart muscle causes chest #ain and #ressure! If blood flow is not restored within () to *) minutes& irre"ersible death of the heart muscle will be in to occur! +uscle continues to die for ,-. hours at which time the heart attack usually is /com#lete!/ The dead heart muscle is re#laced by scar tissue! 0A##ro$imately one million Americans suffer a heart attack each year! 1our hundred thousand of them die as a result of their heart attack!2 (American 3eart Institute)

CONT4NT5
Treatment of heart attacks include anti-#latelet medications to #re"ent formation of blood clots in the arteries& anti-coa ulant medications to #re"ent rowth of blood clots in the arteries& coronary an io ra#hy with either #ercutaneous transluminal coronary an io#lasty (6TCA) with or without stentin to o#en blocked coronary arteries& clotdissol"in medications to o#en blocked arteries& su##lemental o$y en to increase the su##ly of o$y en to the heart7s muscle& medications to decrease the need for o$y en by the heart7s muscle& and medications to #re"ent abnormal heart rhythms! The #rimary oal of treatment is to 8uickly o#en the blocked artery and restore blood flow to the heart muscle& a #rocess called re#erfusion! Once the artery is o#en& dama e to heart muscle ceases& and the #atient becomes #ain free! %y minimi9in the e$tent of heart muscle dama e& early re#erfusion #reser"es the #um#in function of the heart! O#timal benefit is obtained if re#erfusion can be established within the first *-, hours of a heart attack! Delay in establishin re#erfusion can result in more wides#read dama e to heart muscle and a reater reduction in the ability of the heart to #um# blood! 6atients with hearts that are unable to #um# sufficient blood de"elo# heart failure& decreased ability to e$ercise& and abnormal heart rhythms! Thus& the amount of healthy heart muscle remainin after a heart attack is the most im#ortant determinant of the future 8uality of life and lon e"ity!

Anti-#latelet a ents

Anti-#latelet a ents are medications that #re"ent blood clots from formin by inhibitin the a re ation of #latelets! 6latelets are fra ments of cells that circulate in the blood! 6latelets be in the formation of blood clots by clum#in to ether (a #rocess called a re ation)! 6latelet clum#s are then stren thened and e$#anded by the action of clottin factors (coa ulants) that result in the de#osition of #rotein (fibrin) amon the #latelets! A re ation of #latelets occurs at the site of any in'ury or laceration& but it also occurs at the site of ru#ture of cholesterol #la8ues in the walls of coronary arteries! 1ormation of clots at the site of an in'ury or laceration is desirable because it #re"ents e$cessi"e loss of blood& but formation of clots inside coronary arteries blocks the arteries and causes heart attacks! There are three ty#es of anti-#latelet a ents -- as#irin& thieno#yridines& and the lyco#rotein IIb:IIIa inhibitors! These a ents differ in their mode of action& anti-#latelet #otency& s#eed of onset of action& and cost!

As#irin
As#irin inhibits the acti"ity of the en9yme cyclo-o$y enase inside #latelets! Cycloo$y enase is an en9yme whose acti"ity is necessary for the formation of a chemical& thrombo$ane A(& that causes #latelets to a re ate! As#irin& by inhibitin the formation of thrombo$ane A(& #re"ents #latelets from a re atin and thereby #re"ents the formation of blood clots! As#irin alone has its reatest im#act on im#ro"in sur"i"al amon #atients with heart attacks! Numerous studies ha"e shown that as#irin reduces mortality (by (;<) when i"en to #atients with heart attacks! As#irin is easy to use& safe at the low doses used for anti-#latelet action& fast actin (with an onset of action within =) minutes)& and chea#! As#irin is i"en at a dose of >,) m to =(; m immediately to almost all #atients as soon as a heart attack is reco ni9ed! It also is continued on a daily basis indefinitely after the heart attack! The only reason for not usin as#irin is a history of intolerance or aller y to as#irin! As#irin is taken daily followin a heart attack to reduce the risk of another heart attack! (6re"entin further heart attacks is called secondary #re"ention& while #re"entin the first heart attack is called #rimary #re"ention)! The ideal daily dose of as#irin for secondary #re"ention has not been established! 5ome doctors recommend >,) m ? others recommend .> m ! The reason for this difference has to do with as#irin7s occasional lon -term side effect of bleedin (for e$am#le from stomach ulcers)! 4"en thou h the risk of ma'or bleedin with lon -term& moderate dose as#irin (=(; m :day) is low (less than ><)& this risk can be lowered sli htly by usin an e"en lower dose (>,) or .> m :day)! As#irin also benefits #atients with forms of coronary heart disease other than an acute heart attack! As#irin has been shown to reduce heart attacks and im#ro"e sur"i"al! As#irin im#ro"es sur"i"al amon #atients with unstable an ina! 6atients with unstable an ina e$#erience chest #ains at rest or with minimal e$ertion! These #atients ha"e

critically narrowed coronary arteries and are at imminent risk of ha"in a heart attack! As#irin im#ro"es sur"i"al amon #atients with stable e$ertional an ina! These are #atients who e$#erience chest #ain only with e$ertion! It #re"ents formation of blood clots at the site of the 6TCA! As#irin #re"ents the formation of blood clots that can occlude sur ical by#ass rafts! (Occlusion of by#ass rafts can lead to heart attacks!) As#irin in low doses (.> m :day) has been shown to #re"ent first heart attacks (#rimary #re"ention)

The Thieno#yridines
The thieno#yridines such as ticlo#idine (Ticlid) and clo#ido rel (6la"i$) inhibit the AD6 rece#tor on the surface of #latelets! Inhibitin the AD6 rece#tors on the #latelets #re"ent the #latelets from a re atin and causin blood clots to form! The theino#yridines are more #otent anti-#latelet a ents than as#irin! Clo#ido rel (6la"i$) is used far more commonly than ticlo#idine (Ticlid) because ticlo#idine can& in rare instances& cause low #latelet and:or white blood cell counts! Clo#ido rel #lays an im#ortant role in the treatment of heart attacks and is used in the followin situations@ Clo#ido rel is used instead of as#irin in #atients who ha"e an aller y to as#irin! Clo#ido rel often is i"en to ether with as#irin in treatin heart attacks! 5tudies ha"e shown that the combination of as#irin and clo#ido rel is more effecti"e than as#irin alone in im#ro"in sur"i"al and limitin dama e to heart muscle amon #atients with heart attacks! Clo#ido rel is i"en to ether with as#irin to #atients under oin 6TCA with or without coronary stentin (see later discussion)! 5tudies ha"e shown that the combination of as#irin and clo#ido rel is more effecti"e than as#irin alone in #re"entin formation of blood clots that can reocclude the coronary artery unblocked by 6TCA and in #re"entin blood clots within recently #laced stents! After a heart attack or after 6TCA& as#irin is i"en indefinitely! The o#timal duration of clo#ido rel has not been established& and duration of use by #hysicians "aries from weeks to months! 6atients who recei"e the combination of clo#ido rel and as#irin are more likely than #atients who recei"e as#irin alone to de"elo# com#lications of ma'or bleedin followin coronary artery by#ass sur ery! Therefore& ideally clo#ido rel should be sto##ed =-A days before sur ery!

Blyco#rotein IIb:IIIa inhibitors

The lyco#rotein IIb:IIIa inhibitors such as abci$imab (Reo#ro) and e#tifibatide (Inte rilin) #re"ent a re ation of #latelets by inhibitin the lyco#rotein rece#tors on the #latelets! They are the most #otent anti-#latelet a ents& a##ro$imately C times more #otent than as#irin& and three times more #otent than the thieno#yridines! The lyco#rotein IIb:IIIa inhibitors are also the most e$#ensi"e anti-#latelet a ents! The currently 1DA-a##ro"ed lyco#rotein IIb:IIIa inhibitors ha"e to be i"en intra"enously! They usually are i"en alon with as#irin and he#arin! They are 8uick actin ? their ma$imal anti-#latelet effects are achie"ed within minutes of infusion! These inhibitors ha"e become im#ortant in the treatment of #atients with heart attacks& #atients with unstable an ina& and #atients under oin 6TCA with or without stentin ! Numerous

studies ha"e shown that lyco#rotein IIb:IIIa inhibitors@ Decrease the si9e of the blood clot blockin the coronary arteries& thus im#ro"in blood flow& limitin dama e to heart muscle& and im#ro"in sur"i"al amon #atients with heart attacks? Decrease the incidence of heart attacks and im#ro"e sur"i"al amon #atients with unstable an ina? 6re"ent the formation of blood clots inside coronary stents and in coronary arteries unblocked by 6TCA& thus decreasin the incidence of heart attacks and im#ro"in sur"i"al& s#ecifically& when i"en intra"enously at the time of 6TCA and stentin and followed by oral as#irin and clo#ido rel! The ma'or risk of lyco#rotein IIb:IIIa inhibitors is bleedin ! Therefore& #atients on he#arin& as#irin& and lyco#rotein IIb:IIIa inhibitors ha"e to be monitored closely for bleedin ! Recent studies ha"e demonstrated e8ual efficacy of abci$imab and e#tifibatide! 4#tifibatide is shorter actin than abci$imab! In the e"ent of ma'or bleedin & the anti#latelet effect of e#tifibatide can be re"ersed within hours of sto##in the intra"enous infusion& while the anti-#latelet effect of abci$imab will last much lon er! 5ometimes& transfusions of #latelets are necessary to treat ma'or bleedin due to abci$imab! An uncommon side effect of lyco#rotein IIb:IIIa inhibitors is the de"elo#ment of low #latelet counts (thrombocyto#enia)! Thrombocyto#enia can increase the risk for bleedin and& in rare instances& may actually cause blood to clot! Thus& #atients recei"in lyco#rotein IIb:IIIa inhibitors should ha"e their #latelet counts monitored closely!

Anti-coa ulants
Coa ulants (clottin factors) are #roteins #roduced by the li"er! Clottin factors are res#onsible for /cementin / clum#s of #latelets to ether to form a stron er and lar er clot! Anti-coa ulants such as intra"enous or subcutaneous he#arin& subcutaneous low molecular wei ht he#arin& and oral warfarin (Coumadin)& #re"ent the formation of blood clots either by inhibitin the #roduction of clottin factors or by interferin with the action of the clottin factors!

3e#arin
3e#arin #re"ents the formation and rowth of blood clots by inhibitin the action of clottin factors that cement the clum#s of #latelets to ether! 3e#arin is i"en either intra"enously or as a subcutaneous (under the skin) in'ection! 3e#arin commonly is i"en intra"enously& usually with as#irin& anti-#latelet a ents& or fibrinolytic (clot-dissol"in ) medications for treatin heart attacks! Intra"enous he#arin is i"en (usually with as#irin or an anti-#latelet a ent) to #atients with heart attacks who are under oin 6TCA with or without stentin ! 3e#arin also is i"en to #atients who are at risk of de"elo#in blood clots within the chambers (atria and "entricles) of the heart! (1or e$am#le& #atients with atrial fibrillation can de"elo# blood clots in the atria! 6atients with lar e heart attacks and ma'or dama e to the heart muscle also can de"elo# blood clots in the "entricles!) 3e#arin7s anti-coa ulant effect is fast actin (be innin shortly after the start of the infusion) and dose-related ( reater with hi her doses)! The duration of he#arin

treatment

for

heart

attacks

is

a##ro$imately

*.

hours!

3e#arin7s ma'or side effect is bleedin & and the most serious bleedin com#lication is intracranial hemorrha e (bleedin into the brain)! The risk of bleedin is hi her with hi her doses! Thus& #atients recei"in he#arin will under o fre8uent blood testin to measure A66T le"els! The A66T le"el is a measure of the de ree of anti-coa ulation! The oal is to kee# the #atient7s A66T le"el in a safe ran e and to a"oid abnormally hi h A66T le"els that si nify e$cessi"e anti-coa ulation and a reater risk of bleedin ! If there is bleedin & he#arin has the ad"anta e of ha"in a short duration of action& and its anticoa ulant effects disa##ears ra#idly after sto##in the intra"enous infusion!

Dow molecular wei ht he#arin

Dow molecular wei ht he#arins such as eno$a#arin (Do"eno$) and dalte#arin (1ra min)& are sub-fractions of he#arin with lon er-lastin effects than he#arin! They can be i"en e"ery >(-(* hours as subcutaneous in'ections (like insulin)! 5tudies ha"e shown eno$a#arin and dalte#arin to be e8ui"alent to intra"enous he#arin in #atients with many conditions such as heart attacks& unstable an ina& and blood clots in the "eins or arteries of the lun s! The effects of low molecular wei ht he#arins enerally wear off after ,->( hours! They are not used in #lace of intra"enous he#arin in #atients under oin 6TCA or stentin !

Earfarin
Earfarin (Coumadin) #re"ents the formation of blood clots by inhibitin the #roduction of clottin factors by the li"er! Earfarin must be taken orally and is slow actin ? it can take days to achie"e an ade8uate anti-coa ulant effect! Earfarin7s anti-coa ulant effect is dose-related& that is& it7s effect is reater with lar er doses! %ecause of its slow onset of action& Coumadin is not commonly used immediately for the treatment of heart attacks! Instead& it is used orally on a lon -term basis in selected #atients after heart attacks to #re"ent blood clots! 1or e$am#le& #atients with atrial fibrillation or #atients with ma'or dama e to "entricular muscle will take warfarin daily on a lon -term basis to #re"ent blood clots in the atria and "entricles& res#ecti"ely! Earfarin also is commonly used to #re"ent blood clots in "eins of the le s in #atients who are likely to de"elo# them! The risk with warfarin is abnormal bleedin & and the risk of bleedin is hi her with hi her doses! Thus& #atients on warfarin should ha"e their blood tested fre8uently (often weekly) to measure their #rothrombin time and INR! Dike A66T& the #rothrombin time and INR measure the de ree of anti-coa ulation! The oal of treatment is to kee# the #rothrombin time and INR in a safe ran e& a"oidin e$cessi"ely hi h #rothrombin time and INR le"els that indicate too much anti-coa ulation and a reater risk of bleedin ! The effects of warfarin may be increased or decreased reatly by many other medications or foods& and it is crucial to re"iew these medications and foods with the doctor!

Earfarin has a lon duration of action& and it7s anti-coa ulation effect can last se"eral days after it is sto##ed! Therefore& transfusions of clottin factors and:or "itamin F (to stimulate the li"er to #roduce the clottin factors de#leted by treatment with warfarin) must be i"en to re"erse the anti-coa ulation in the e"ent of serious bleedin !

Clot-dissol"in dru s
Ehile anti-#latelet a ents and anti-coa ulants #re"ent the formation of blood clots& they cannot dissol"e e$istin blood clots and hence cannot be relied u#on to o#en blocked arteries ra#idly! Clot-dissol"in dru s (also called fibrinolytic or thrombolytic medications) actually dissol"e blood clots and can ra#idly o#en blocked arteries! Intra"enous administration of clot-dissol"in dru s such as tissue #lasmino en acti"ator (T6A) or TNF can o#en u# to .)< of acutely blocked coronary arteries! The earlier these dru s are administered& the reater the success at o#enin the artery and the more effecti"e the #reser"ation of heart muscle! If clot-dissol"in dru s are i"en too late (more than , hours after the onset of the heart attack)& most of the muscle dama e already may ha"e occurred! If a hos#ital does not ha"e a catheteri9ation laboratory with the ability to #erform 6TCA& or if there are lo istic reasons why 6TCA will be delayed& clot-dissol"in dru s can be #rom#tly administered to achie"e re#erfusion! 6TCA then may be #erformed in #atients who fail to res#ond to the clot-dissol"in dru s! (If #rom#t 6TCA and stentin are a"ailable& it has been demonstrated that they are #referable to clot-dissol"in dru s to o#en arteries!) Clot-dissol"in dru s increase the risk of bleedin enou h so that some #atients cannot be treated with them& for e$am#le& #atients with recent sur ery or ma'or trauma& recent stroke& bleedin ulcer& or other conditions that increases the risk of bleedin !

Coronary an io ra#hy and #ercutaneous transluminal coronary an io#lasty

Coronary an io ra#hy and #ercutaneous transluminal coronary an io#lasty (6TCA) is the most direct method of o#enin a blocked coronary artery! The #rocedures are #erformed in the catheteri9ation laboratory in a hos#ital! Under $-ray uidance& a tiny #lastic catheter with a balloon on its end is ad"anced o"er a uide wire from a "ein in the roin or the arm and into the blocked coronary artery! Once the balloon reaches the blocka e& it is inflated& #ushin the clot and #la8ue out of the way to o#en the artery! 6TCA can be effecti"e in o#enin u# to C;< of arteries! In addition& the an io ram ($ray #ictures taken of the coronary arteries) allows e"aluation of the status of the other coronary arteries so that lon -term treatment #lans may be formulated! 1or o#timal benefits& coronary an io ra#hy and 6TCA should be #erformed as soon as #ossible! +ost cardiolo ists recommend that the time inter"al between the #atient7s arri"al at the hos#ital and the de#loyment of the an io#lasty balloon to o#en the artery should be less than ,)-C) minutes!

1or best results& the coronary an io ram and 6TCA should be #erformed by an e$#erienced cardiolo ist in a well-e8ui##ed cardiac catheteri9ation laboratory! The cardiolo ist is considered e$#erienced if he or she #erforms more than A; such #rocedures a year! The catheteri9ation laboratory #ersonnel are considered e$#erienced if the facility #erforms more than ()) such #rocedures a year! It also is im#ortant that there be a sur ical team to #erform immediate o#en-heart sur ery (coronary artery by#ass raftin ) in the e"ent that 6TCA is unsuccessful in o#enin the blocked artery or if there is a serious com#lication of 6TCA! 1or e$am#le& in a small number of #atients& 6TCA cannot be #erformed because of technical difficulties in #assin the uide wire or the balloon across the narrowed arterial se ment! O#en-heart sur ery also will be necessary if there is a serious com#lication such as coronary artery in'ury durin 6TCA or an abru#t closure of the coronary artery shortly after 6TCA! These com#lications may occur in >-(< of #atients! The most serious com#lication of 6TCA is an abru#t closure of the coronary artery within the first few hours after 6TCA! Abru#t coronary artery closure (that can lead to further heart dama e) occurs in ;< of #atients after sim#le balloon an io#lasty (without stentin )! Abru#t closure is due to a combination of tearin (dissection) of the inner linin of the artery& blood clottin at the site of the balloon& and constriction (s#asm) or elastic recoil of the artery at the site where the balloon is inflated! Indi"iduals at an increased risk for abru#t closure include women& #atients with unstable an ina& and #atients ha"in heart attacks!

Coronary artery stents

Coronary artery stents are small hollow cylinders that can be de#loyed o"er the an io#lasty balloons and left within the coronary arteries to kee# the arteries o#en! 5tents hel# #re"ent abru#t closure of arteries shortly after 6TCA ! They also #re"ent restenosis (recurrent narrowin of the arteries) se"eral months after 6TCA! Coronary stents decrease the risks of arterial dissections& elastic recoil& and artery s#asm that can occur after 6TCA and cause re-occlusion of the artery! 5tudies ha"e shown that the incidence of abru#t coronary artery closure after 6TCA has declined dramatically with the introduction of coronary stents! Coronary stents also hel# to kee# the coronary arteries o#en in the lon er-term! After a successful 6TCA& as many as =)-*)< of #atients will de"elo# recurrent narrowin (restenosis) at the site of inflation of the balloon& usually within , months followin 6TCA! Restenosis may or may not be accom#anied by sym#toms such as an ina! Thus& restenosis often is detected by e$ercise stress tests #erformed * to , months after 6TCA! The wides#read use of coronary stents has reduced this incidence of restenosis by as

much as ;)<! The recent introduction of coated stents (stents that are coated with chemicals to further reduce restenosis) has reduced the incidence of restenosis to well under >)< and has been a ma'or im#ro"ement in treatment! 6atients with coronary artery stents usually are maintained on full doses of daily as#irin! 1or the first *->( weeks after the #lacement of stents& #atients are i"en an additional anti-#latelet dru such as ticlo#idine or clo#ido rel because the metal surface of the stents may #romote the formation of blood clots in the first se"eral weeks after the stent is inserted!

Nitrates
Nitro lycerin is the most common nitrate used in the treatment of heart attacks! It can be i"en sublin ually (under the ton ue)& as a s#ray& as a #aste a##lied o"er skin& and intra"enously! Intra"enous nitro lycerine has a ra#id onset of action and is commonly used in the initial (first *. hours) treatment of heart attacks! Nitro lycerine is a "asodilator (blood "essel dilator)& which o#ens arteries by rela$in the muscular wall of the artery! Nitro lycerine dilates coronary arteries as well as other blood "essels throu hout the body! %y dilatin blood "essels& nitro lycerine lowers blood #ressure& decreases the work that the heart must do& lowers the demand by the heart for o$y en& #re"ents coronary artery s#asm& im#ro"es blood flow to the heart muscle& and #otentially minimi9es the si9e of the heart attack! Nitro lycerine is es#ecially hel#ful in #atients with heart attacks who also ha"e heart failure or hi h blood #ressure! The common side effects of nitrates are headaches and low blood #ressure! Dow blood #ressure can cause weakness& di99iness& and& sometimes& e"en faintin ! Nitrates should not be i"en in #atients who ha"e taken medicines for erectile dysfunction such as sildenafil (Gia ra) and "ardenafil (De"itra) in the #recedin (* hours& since se"ere low blood #ressure may result! Nitrates should not be i"en in #atients who ha"e taken tadalafil (Cialis) in the #recedin =,-*. hours because the effects of Cialis last lon er than either sildenafil or "ardenafil !

An iotensin con"ertin en9yme inhibitors

An iotensin con"ertin en9yme (AC4) inhibitors& another class of blood "essel dilators& often are i"en orally after a lar e heart attack to im#ro"e the healin of heart muscle! 4$am#les of AC4 inhibitors include ca#to#ril (Ca#oten)& enala#ril (Gasotec)& lisino#ril (Hestril and 6rini"il)& and rami#ril (Altace)! These medications lower the blood #ressure and reduce the workload of the heart& thereby hel#in the dama ed heart muscle to reco"er! They are es#ecially hel#ful in #atients who ha"e reco"ered from heart attacks but ha"e hi h blood #ressure& heart failure& ma'or dama e to the left "entricle& and diabetes mellitus!

%eta-blockers
%eta-blockers such as #ro#ranolol (Inderal)& meto#rolol (Do#ressor& To#rol ID)& and

atenolol (Tenormin) usually are i"en early durin a heart attack and are continued lon term! %eta blockers anta oni9e the action of adrenaline and relie"e stress on the muscles of the heart! %eta-blockers decrease the workload of the heart by slowin the heart rate and decreasin the force of contraction of heart muscle! Decreasin the workload decreases the demand for o$y en by the heart and limits the amount of dama e to the heart muscle! Don -term administration of beta-blockers followin a heart attack has been shown to im#ro"e sur"i"al and reduce the risk of future heart attacks! %eta-blockers also im#ro"e sur"i"al amon #atients with heart attacks by decreasin the incidence of life-threatenin abnormal heart rhythms& for e$am#le& "entricular fibrillation! %etablockers can be i"en intra"enously in the hos#ital and then can be taken orally for lon term treatment! The side effects of beta-blockers are whee9in (worsenin of breathin in #atients with asthma)& abnormally slow heart rate& and e$acerbation of heart failure (es#ecially in #atients with si nificant dama e to their heart muscle)? howe"er& in #atients with chronic heart failure& beta blockers ha"e recently been demonstrated to be hel#ful in decreasin sym#toms and #rolon in life!

O$y en
O$y en also is commonly administered durin the acute #hase of a heart attack as are narcotics such as mor#hine? these a ents aid in the reduction of discomfort and actually hel# minimi9e the amount of heart dama e!

Coronary artery by#ass

In some #atients& 6TCA can be technically difficult or dan erous to #erform! In others& 6TCA and clot-dissol"in medications may fail to achie"e re#erfusion or maintain o#en arteries! These #atients may be considered for coronary artery by#ass raftin sur ery!