Stable angina: drugs, angioplasty or surgery?

Transcription

1 Euopean Heat Jounal (997) 8 {Supplement B), B2-B Stable angina: dugs, angioplasty o sugey? G.Jackson Guy's Hospital, London, U.K. Stable angina is a common condition with a good oveall pognosis and annual motality is 2-4%, whateve teatment is employed. Medical theapy with nitates, /?- blockes, calcium antagonists and lipid-loweing agents is appopiate as fist-line theapy in those patients not specifically identified as being at isk by execise testing and/o angiogaphy. Dosage should be optimized. Coonay atey bypass gafting appeas to impove pognosis in those at isk when compaed with medical theapy but the tials ae old and do not take into account majo advances in medical theapy no the use of ateial conduits in coonay atey bypass gafting (CABG). Pecutaneous tansluminal coonay angioplasty (PTCA) elieves symptoms when medical theapy is ineffective but its ole as an initial theapy has not been established, no does it compae favouably with CABG with egad to the degee of evasculaization and subsequent e-intevention o need fo additional anti-anginal dugs. Thee ae little substantial data on pognostic effects. PTCA is, howeve, less taumatic, less expensive and associated with a quicke ecovey than CABG, poviding a viable altenative fo symptomatic (not pognostic) benefit in appopiately selected and infomed patients. Medical theapy, PTCA and CABG should not be seen as competitive but complementay stategies. Optimal utilization of all thee teatment modalities, eithe alone o in combination, can povide substantial symptomatic elief fo the angina patient. (Eu Heat J 997; 8 (Suppl B): B2-B) Key Wods: Angina, coonay atey bypass gafting, pecutaneous tansluminal coonay angioplasty, ^-blockes, nitates, calcium channel blockes. Intoduction The goals of teatment fo patients with stable angina pectois, achieved by both identifying those at isk and intevening to modify the isk, ae to impove symptoms and theeby quality of life, to polong suvival and, ideally, a combination of the two. Patients with symptoms that ae efactoy to medical theapy should undego angiogaphy, with a view to intevention by PTCA o CABG. This statement assumes that 'failed' medical teatment equates with 'failed optimal' medical teatment, which may not be the case, as dugs ae fequently not titated to thei established maximally effective doses, e.g. atenolol 5 mg daily is fequently not inceased to mg daily. Independently of symptoms, howeve, patients may need angiogaphy to identify thei isk status. Pognosis is influenced by the natue, location and extent of coonay atey disease (CAD), as well as the quality of left venticula function' '. Evidence fo a beneficial effect on motality is only available fo CABG and elates to specific anatomical subsets, compised of left main stem disease, thee-vessel disease, with o Coespondence: D Gaham Jackson, Guy's Hospital, St Thomas' Steet, London SE 9RT, U.K X/97/OB2+9 $8./ without educed left venticula function, and two- o thee-vessel disease involving the poximal left anteio descending (LAD) atey. The thee majo tials of sugey vs medical theapy which established these findings ae now ove 2 yeas old' " 3. Since these data wee published, significant advances in medical theapy, and to a lesse extent, CABG (the use of ateial conduits such as the intenal mammay atey), have been made. Thus, it cannot be claimed that medical theapy at the time of these tials was optimal. Fo example, thee was no standadized dose of /J-blockade, aspiin was not outinely in use and lipid-loweing theapy was hadly in existence. Thee ae many poblems with the data available, both old and new, and it is easy to let ou peceptions of the data (based on logic and eason) oveule the scientific facts. Randomized tials become necessay when thee ae easonable doubts as to the meaning of data. The poblem with stable angina is the inceasing, athe than the deceasing, numbe of such doubts. If we look at the diffeent modalities of teatment, compising eithe dugs, PTCA o CABG, we should expect to be able to eview tials of dugs vs CABG, dugs vs PTCA, dugs vs PTCA o CABG and PTCA vs CABG. The fact that a complete set of data is 997 The Euopean Society of Cadiology

2 Stable angina: dugs, angioplasty o sugey B3 missing has not deteed investigatos fom compaing PTCA with stents [4) without including a dugs goup in the compaison. One assumes that this is on the gounds that estenosis, as the majo poblem associated with PTCA, needs to be addessed befoe the exact ole of PTCA can be defined. This not uneasonable objective should not exclude, howeve, a diect tial of stents vs medical theapy unless the data on PTCA ae ovewhelmingly positive vs medical theapy o CABG. It theefoe becomes impeative to ask, what infomation do we have and how good is it? Medical theapy It is an inescapable fact that in all clinical tials of anti-anginal dugs thee is a significant benefit both subjectively, upon anginal attack ates and glyceyl tinitate consumption, and objectively, upon execise time o time to mm ST depession on a teadmill o bicycle execise ECG. This applies to /?-blockes, calcium antagonists, isosobide mbnonitate and the new potassium channel activato nicoandil. Combination theapy of two dugs, one fom each class, may povide additional impovement but adding a thid agent may povide little exta benefit and may in some instances cause deteioation' 5. Clinical tials use caefully selected cases and usually employ optimal doses of the dugs unde study. Howeve, in clinical pactice, optimal doses may not be employed, paticulaly with /?-blockes, lagely because of unnecessay anxieties about inceasing the dose in the pesence of a esting badycadia' 6. In Fig. an algoithm fo combination theapy is outlined, which is both pactical and safe. Altenatives would include diltiazem 6-2 mg thee times daily o veapamil 4-6 mg thee times daily plus isosobide mononitate. Veapamil should not be combined with ^-blockade because of unpedictable advese inteactions on the conducting system. Diltiazem can be used in combination with /?-blockes but caution is advised because of an additive effect on the sinus node, occasionally leading to a significant symptomatic badycadia. The long-acting dihydopyidines, such as amlodipine, avoid conduction system inteactions with ^-blockes, ae less negatively inotopic and should be pefeed in combination. Medical theapy of angina must also include aspiin, which can educe the isk of vascula death, stoke and myocadial infaction (MI) by 25% [7). Aspiin was not used outinely in the ealie CABG vs medical theapy tials. Lipid-loweing theapy has also been shown to have a significant impact on subsequent cadiovascula events, as well as slowing the pogession and inducing egession of CAD' 8. Fo example, the Scandinavian Simvastatin Suvival Study (4S) Goup tials' 9 epoted a 3% eduction in death and MI associated with the use of the lipid-loweing agent simvastation (Fig. 2). Medical theapy, in addition to lifestyle change (eduction o cessation of smoking, weight loss, educed Amlodipine 5- mg daily i Add atenolol 5- mg daily Anginal patient Atenolol 5- mg daily ' Switch amlodipine to. isosobide mononitate 4 mg twice daily i Combine all thee Figue Combination theapy algoithm. Add amlodipine 5- mg daily intake of satuated fat), has pogessed significantly ove the last 25 yeas and it seems uneasonable to assume that all the data fom 'old' tials ae applicable now. Nonetheless, we have no convincing evidence that conventional medical theapy impoves suvival in stable angina patients. /?-blockes, howeve, impove suvival post infaction and thee is evidence that infacts occuing in patients taking ^-blockes ae smalle 5. Medical theapy vs coonay atey bypass gafting CABG undoubtedly elieves anginal pain when compaed with medical theapy and when symptoms pesist in spite of optimal medical teatment. The opeative isk of death is of the ode of 2% but may ise to 5% in the eldely and fo complex and/o epeat pocedues. Peiopeative infaction occus in 8-% of cases but is usually mino and well toleated. Mobidity includes stenal and back pain, which usually esolves ove 2-3 months, and neuological poblems, which ae tansient in 5-6% but pemanent in -2% of patients. Although 8% of patients ae fee of symptoms up to 5 yeas afte sugey, some will still be taking

3 B4 G. Jackson Yeas since andomization. I Yeas since andomization 3.7 Log-ank P <. I I I I Yeas since andomization 3 o e as.6.5 Log-ank P<. I I I I I Yeas since andomization Figue 2 Kaplan-Meie cuves fo seconday and tetiay endpoints. CHD=coonay heat disease. Shows esults with simvastatin and placebo esults. (Repoduced fom the Scandinavian Simvastatin Suvival Study Goup ', with pemission.) antianginal dugs. Only 5% ae symptom fee at yeas but this may impove with the geate use of ateial conduits and moe attention to lipid-loweing theapy. CABG, theefoe, has an impotant ole in symptomatic elief. How does it compae with medical theapy with egad to pognosis? The Veteans Administation Study took place between 97 and 974 P. Thee was a high opeative motality of 5-8%, eflecting the ealy days of. sugey and the lack of expetise in the technique. Moeove, thee was a poo vein patency ate of 69% at yea, eflecting the technical limitations. In spite of these esevations, sugey impoved suvival fo left main stem disease. Howeve, it is impotant to point out that, at the time of this tial, the options fo medical theapy wee vey limited. As time has moved on and techniques have impoved, this study has little elevance to cuent pactice. The Euopean Coonay Sugey Study ( ) is pehaps the most elevant study to cuent pactice, since it included patients with mild to modeate angina '. Bette medical theapy was available with ^-blockade but it was not standadized. Up to 7% of patients had suffeed fom a pevious MI. Opeative motality was 3-6%, which is simila to cuent levels and which, in tun, eflects a ise in teatment of moe complex o difficult sugical cases compaed with the easie single- and double-vessel lesions, now 'chey picked' by PTCA opeatos. Vein patency was 77% at 8 months. At 5 yeas, 7-6% of those undegoing sugey had died, compaed with 6-2% of those undegoing medical theapy, epesenting a highly significant 53% eduction. The benefit was most impessive fo left main stem disease (Fig. 3), two-vessel disease, if one lesion was in the poximal LAD atey, thee-vessel disease, with o without good left venticula function, and in the pesence of an abnomal esting o execise ECG. At -yea follow-up, sugical benefit pesisted and was simila in those who did o did not continue to smoke (Fig. 4) tl). This indicates that smokes should not be denied opeative intevention and that theapeutic decision making should theefoe be on the basis

4 Stable angina: dugs, angioplasty o sugey B5 Figue 3 Euopean Coonay Sugey Study: impoved suvival 5 yeas afte coonay atey bypass gafting in patients with left main stem disease. (Repoduced fom Vanauskas et al m with pemission.) of clinical need, athe than the physicians' emotional bias. The Coonay Atey Sugey Study (CASS) excluded left main stem disease 3. Patients with no angina o minimal symptoms wee included and, of cases assessed, only 78 wee andomized, theeby identifying a highly selected goup of patients. At 5 yeas, 92% and 95%, espectively, of those undegoing medical and sugical teatment suvived, epesenting a non-significant diffeence between teatments. Opeative motality was -4% and gaft patency at 6 days was 9%. Medical theapy was not standadized and only 43% used /?-blockes. Sugey impoved pognosis at 6 yeas if thee was thee-vessel disease with educed left venticula function. Rationalizing these tials so that they ae elevant to pactice today is not staightfowad, since diffeent patients ae being evaluated, the medical theapy used is at times unclea and cetainly outdated and sugical techniques have impoved. Futhemoe, any theapeutic conclusions dawn would be made on the basis of subset analysis, which would be seveely citicized if one wee, fo example, evaluating dugs alone. In addition, the latte two tials wee weighted against sugey as medical patients who needed sugey fo elief of symptoms (i.e. medical failues) emained classed as 'medical', even though they may have benefited fom sugey, and those andomized to sugey who efused an opeation wee still classified as 'sugical' even though they wee teated medically. The best pactical guidelines fo teatment and pognosis ae: () an abnomal execise ECG may Non smokes Smokes Yeas I 6 f I I 4 6 Yeas Figue 4 Compaative effects on suvival afte sugey and medical teatment in non-smokes and smokes in the Euopean Coonay Sugey Study. Shows esults of sugical goup (22) and esults of medical goup (29). (Repoduced fom Julian' ' with pemission.)

5 B6 G. Jackson Table Angioplasty compaed to medicine (ACME) esults* Dugs PTCA Numbe of patients andomized Numbe of patients with PTCA success Numbe of patients with emegency CABG Numbe of patients with epeat PTCA by 6 months Numbe of patients with CABG Numbe of patients with myocadial infaction Numbe of patients fee of angina (%) Execise incease 7 do 3 47/2 (46%) -5 min 5 8/ /96 (64%t) 2 mintt ( Repoduced fom Paisi et al. ''', with pemission.) Vs medical theapy ^P<Ql; f\p<-ool. JDeath. CABG=coonay atey bypass gafting; PTCA=pecutaneous tansluminal coonay angioplasty. identify a patient at isk; (2) left main stem disease benefits fom CABG; (3) thee-vessel disease, with o without good left venticula function, benefits fom CABG; (4) two-vessel disease, including poximal LAD disease, benefits fom CABG; (5) minimal symptoms with a nomal, o only slightly abnomal, ECG do not identify inceased isk and medical theapy is the pefeed initial option. Medical theapy vs pecutaneous tansluminal coonay angioplasty Thee is only one tial compaing PTCA with medical theapy' ' and it seems extaodinay that such an impotant inteventional technique can be intoduced without fomal study. Thee is no doubt that PTCA elieves anginal symptoms but we lack detailed studies to allow us to position PTCA in a ole othe than that of pain elief. Angioplasty Compaed to Medicine (ACME) was a small andomized study of 22 patients with single-vessel disease, in which PTCA was compaed with conventional medical theapy. PTCA patients wee allowed to take dugs if necessay. The study included patients with ecent MI and those not aleady on optimal medical theapy. While medical theapy was assumed to be optimized afte the tial began, the tial did not addess the question of what to do with patients who have symptoms in spite of medical theapy, which is the most fequent poblem seen in clinical pactice. At 6 months follow-up of the 5 patients allocated to PTCA and the 7 allocated to dugs, feedom fom angina was pesent in 64% of the PTCA and 46% of the medical goups. Thee ae, howeve, seveal caveats egading the data. Fistly, the aveage singlevessel stenosis was 76% fo PTCA and 77% fo dugs with two-thids of the lesions in the ight o cicumflex coonay atey. These ae low-isk lesions, with no advese effect on pognosis, so that symptoms would have to be sevee in spite of optimal medical theapy in ode to justify intevention. Futhemoe, the use of anti-anginal dugs at 6 months was 95% in the medical goup and 9% in the PTCA goup. The use of oal nitates was less afte PTCA (5% vs %, P<) and simila findings occued with calcium antagonists (7% vs 35%,?<-) and y?-blockes (5% vs 3%, P<). Howeve, it is impotant to ealize that the benefit deived fom PTCA was, fo many, associated with additional use of anti-anginal dugs. Moeove, since only 5% of the medical goup wee eceiving /?-blockes, it is doubtful that medical theapy was indeed optimal. Table identifies the significant diffeences in e-intevention between the goups, aising questions not only about the tauma to the patient, but also the cost of the pocedue. The ACME study eally does not signifificantly pogess the agument compaing PTCA with medical theapy. We can deduce that PTCA should be eseved fo those who emain symptomatic in spite of optimal medical theapy, but thee is no mandate fo PTCA as an altenative to medical theapy fo those with minimal symptoms and a modest single stenosis. Pecutaneous tansluminal coonay angioplasty vs coonay atey bypass gafting Data have now been published fom seveal tials compaing PTCA and CABG 2 " 6 but only two included a pedominant numbe of stable angina patients' 2 ' 5 (Table 2). In spite of the diffeences between the tials, a emakably consistent message emeges: () PTCA and CABG ae no diffeent with egad to motality at 2-3 yeas (Fig. 5); (2) CABG povides a consistently bette complete evasculaization ate; (3) CABG povides a consistently bette outcome with egad to the need fo e-intevention (Fig. 6); (4) PTCA patients need moe anti-anginal dugs; (5) PTCA is a less taumatic pocedue. Whilst thee is no doubt that PTCA and CABG ae effective teatments fo angina, it does appea that CABG does not cay an inceased isk and is moe

6 Stable angina: dugs, angioplasty o sugey B7 Table 2 Summay of tials Lausanne 2 RITA" 3 ERACI< U GABI" 5 EAST 6 Numbe of patients Male (%) Unstable angina (%) Extent CAD (%) -vessel 2-vessel 3-vessel Yeas of follow-up Risk of death/mi/evasculaization (%) PTCA CABG Anti-anginal dugs (%) PTCA CABG EAST=Emoy Angioplasty Sugey Tial; ERACI=Estudio Randomizado Agentino de Angioplatia vs CIugia; GABI=Geman Angioplasty Bypass Intevention; RITA=Randomised Intevention Teatment of Angina. bo c ivi c o -B apo P =.73 I. I Months afte andomization Numbe of patients/popotion alive CABG PTCA )7.98 9/.97 87/.96 84/.94 84/.94 94/.97 9/.95 89/.9S 88/.94 86/ /.94 84/.93 Figue 5 Suvival of patients with multivessel coonay disease afte teatment with CABG ( ), o PTCA ( ). The numbe of patients at isk and the estimated pobability of suvival ae shown below the figue fo each 6-month inteval. (Repoduced fom King et a/.' 6 ', with pemission.) effective in elieving symptoms whethe thee is one-, two- o thee-vessel disease. The poblem with PTCA emains the appoximately one-thid estenosis ate at 4-6 months. Thee is no doubt that if this could be esolved o substantially educed, PTCA would assume a fa moe impotant ole fo symptomatic patients, but it would need longe-tem follow-up fo its pognostic ole to be fully defined. The cuent follow-up studies extend to 2-3 yeas. This peiod has the effect of minimizing poblems associated with CABG (vein gaft failue is a late event) and maximizing those linked with PTCA (estenosis is an ealy event). It will be inteesting to see the esults of the compaison ove a 5- yea peiod, although with moden lipid-loweing theapy thee may be fewe poblems with CABG gaft failue. The solution to ou dilemma on teatment selection is to look at the theapeutic egimes as complementay and not mutually exclusive. As PTCA has, as yet, no demonstable pognostic benefit, those in whom CABG has a poven benefit should be teated sugically. Whee thee ae altenatives, the patient must be fully infomed of the options. Those with suitable lesions (efactoy to medical theapy) should be offeed PTCA initially (lowe initial cost, less tauma, quicke ecovey) and CABG if needed subsequently. Whee angina ecus afte CABG, PTCA should be consideed whee possible, with o without continuing medical theapy. Fo the patient, PTCA will usually be seen as the moe attactive pocedue. It should only be pefomed within the confines of ou knowledge (unless subject to clinical tials) and by people expeienced in the technique fom centes whee the esults ae good enough. Just as we demand opeative figues of ou sugeons, so should we povide ou PTCA esults. Pecutaneous tansluminal coonay angioplasty vs stents Given ou limited knowledge of the ole of PTCA fo single-vessel disease in stable angina, it is a little supising that a PTCA vs stent tial was pefomed (Benestent) without a dug compaato goup' 4 '. The ationale of the study elates to the ecognized poblem of estenosis associated with PTCA and its pevention though the use of stents. A total of 52 patients wee andomized to stent (262) o PTCA (258). Afte exclusions, 52 patients (2%) in the stent goup at 7 months follow-up and 76 patients (3%) in the PTCA goup eached a pimay endpoint (,P=2). The pimay endpoints wee death, the occuence of a cadiovascula accident, MI, the need fo CABG o a second pecutaneous intevention involving the peviously teated lesion eithe at the time of the initial pocedue o duing the subsequent 7 months. The diffeence pincipally eflected a educed estenosis ate fom 32% to 22% (.P=2) and a

7 B8 G. Jackson cd ft ;eof Repeated ^ PTCA ^^J* CABG 5 aptca A_ A ' fo A Repeated CABG Hospitalization 3 months 6 months 2 months Figue 6 Rate of futhe inteventions CABG ( ) o PTCA ( ) in the two teatment goups duing the initial hospitalization and 3, 6 and 2 months late. (Repoduced fom Hanun et a/." 5, with pemission.) eduction in elective epeat evasculaization fom 22% following PTCA to 3-5% with stents. The Stess tial' 7, half of whose patient population had unstable disease, epoted simila findings. Both studies epoted significantly inceased vascula complications and a significantly longe hospital stay in the stent goup vs PTCA. Clealy stents incease cost but if the vascula and thombotic poblems with stents ae ovecome (and this looks likely in the nea futue with hepain-bonded stents and modification of anti-coagulation egimens) and the estenosis ate emains educed ove a longe peiod of time, they ae likely to have an inceasing ole electively fo symptomatic angina patients. Howeve, the dange of 'stent mania' is a eality fo, at pesent, thee is no mandate fo elective stent placement based on the data we have fo native coonay vessel disease and stable angina that pesists despite medical theapy. Optimal medical theapy Optimal medical theapy is difficult to define because of the individual natue of the anginal patient. Aspiin should be outinely pescibed unless specifically containdicated. Aside fom sublingual nitates, the agents of pimay inteest ae /?-blockes, calcium antagonists, oal nitates and the new potassium channel activato nicoandil. In clinical tials all these dugs ae effective, because they ae invaiably used at an optimum dosage in caefully selected patients with caeful subjective and objective monitoing. In clinical pactice and in the compaative tials with CABG and PTCA thee is consistent evidence of undedosing. Given that the pimay indication fo PTCA is pain elief not esponsive to medical theapy, it follows that patients may be eceiving intevention eithe inappopiately o too soon. Fo example, while esting heat ate is a simple guide to the impact of ^-blockade, it is the execise heat ate that detemines full effectiveness' 65. A esting heat ate below 6 beats. min ~' is not an indication fo dose eduction o stopping dose titation, unless thee ae symptoms such as excessive lethagy o fatigue. Although advese effects may limit the use o dosage of any dug, the single geatest eason fo failue of efficacy emains the failue to optimize dosage of single agents o agents in combination. Many patients take atenolol 5mg.day~', yet mg is the optimal taget if symptoms pesist. Fom all the eseach tials cuently available we can establish the following dose guidelines' 5. () Atenolol 5-mg. day". Table 3 shows how individual optimal doses can be selected, e.g. popanolol 8 mg twice o thee times daily. Popanolol is used as the efeence dug with a potency of and, theefoe, dosage of othe /?-blockes is compaed with 8 mg popanolol equivalent, not with total daily dose. Popanolol 8 mg can be given twice daily (half-life h). It is equal to atenolol mg (potency :) and atenolol can be given once daily (phamacodynamic half-life h). (2) Diltiazem 6-2 mg thee times daily o Retad 9 mg o 2 mg twice daily. (3) Veapamil 4-6 mg thee times daily. (4) Amlodipine 5- mg daily. (5) Isosobide mononitate 2-4 mg twice daily o a once-daily pepaation (4, 5 o 6 mg). (6) Nicoandil -2 mg twice daily. With egad to combination theapy, we know that /J-blockes plus mononitates, calcium antagonists plus nitates and /?-blockes plus calcium antagonists ae all additive. It is not safe to pescibe veapamil with ^-blockade and diltiazem should be used cautiously. Combination theapy can be used to cicumvent advese effects, fo example, atenolol loomg.day' with side effects may have the same efficacy as atenolol 5 mg. day ~' plus amlodipine 5 mg. day ~' with a significantly educed incidence of advese effects. Tiple theapy emains a poblem. The evidence that it impoves symptoms is not at all clea and one study showed no benefit ove double theapy 8. It is my view that if double theapy using optimal doses of each agent is ineffective in elieving symptoms, angiogaphy should be the next option. While individuals may espond to tiple theapy, at this level of medical theapy with pesistent symptoms othe options should be pusued. Fig. 7 contains an algoithm summaizing a poposed anti-anginal medical stategy.

8 Stable angina: dugs, angioplasty o sugey B9 Table 3 fy-blockes available Dug Potency Cadioselective Optimum dose phamacodynamic half-life (h) Blood bain baie penetation Dosage adjustment Acebutolol Atenolol Bisopolol Metopolol Nadolol Oxpenolol Pindolol Popanolol Timolol Slow-elease oxpenolol Metopolol SA Popanolol LA -3* -5-5-* 6* 6 * + t < ns ns ns - Renal Renal None Live Renal Live None Live Live * Agents with patial agonist (intinsic sympathomimetic activity). tcadio-selectivity of acebutolol is debated. ns=not significant. Conclusion A eview of the available data eveals significant gaps in ou knowledge of the elative meits of medical and inteventional theapy fo stable angina. Some of these eflect medical pogess, which has to some extent invalidated ealie tials, while othes ae ceated by tials diected at the wong questions. 5 yeas o younge Coonay ateiogaphy to detemine anatomy Significant disease?ptca Patient with angina 5-7 yeas Teadmill Positive Non-significant disease Poo esponse 7 yeas o olde symptoms dictate theapy Negative o weakly positive Medical theapy Good esponse It is difficult to ignoe the sugical benefit fo left main stem disease o the data suppoting CABG fo the teatment of thee-vessel disease, with o without impaied left venticula function, and two-vessel disease involving the poximal LAD coonay atey. Howeve, in those with disease othe than left main stem, thee is a need to evisit the ole of medical theapy, paticulaly with the addition of aspiin and lipid-loweing stategies. Optimal medical theapy needs bette definition but, when medicine fails, both PTCA and sugey can offe significant futhe pain elief. When compaed with sugey, PTCA does not educe o incease motality; evasculaization is less complete, e-intevention moe fequent and additional anti-anginal theapy moe fequently necessay. PTCA is associated with lowe mobidity than CABG and, up to 3 yeas post pocedue, lowe cost 9. Thee is no demonstable advantage fo PTCA ove medical theapy in patients with modest single-vessel, o pehaps even double-vessel, disease in the pesence of no, o minimal, symptoms. Teatments ae not mutually exclusive and medical theapy may fequently povide additional benefit when pescibed fo patients afte PTCA o coonay atey bypass gafting. Statistics hide individuals who have thei own pesonal needs, so medical advice needs to be caefully tailoed. We must, howeve, only pactice the medicine we believe is easonable and logical if it is suppoted by the data and advocate teatment we ouselves would be pesonally willing to undetake. Sugey Medical theapy Consevative appoach Figue 7 Investigative appoach to the clinical evaluation of the patient with angina pectois. Nuclea imaging and stess echocadiogaphy complement this algoithm in selected cases. Addendum Since this pape was pesented, the Bypass Angioplasty Revasculaization Investigation (BARI) tial has epoted (2). Only 3% of 829 patients studied had stable angina. The esults wee not unduly diffeent fom the

9 BIO G. Jackson pevious CABG/PTCA tials with 8% of CABG and 43% of PTCA patients undegoing additional evasculaization pocedues at 5 yeas. Thee was no significant diffeence in 5-yea suvival ate (89-3% coonay atey bypass gafting and 86-3% PTCA). Thee is no mention of pecent eceiving anti-anginal dugs in addition to the evasculaization pocedue, though fom the eintevention ates one can deduce that the PTCA goup would be likely to be eceiving moe additional dugs that the CABG goup. Refeences [] Vanauskas E and the Euopean Coonay Sugey Study Goup. Twelve yea follow up of suvival in the andomized Euopean Coonay Sugey Study. N Engl J Med 988; 39: [2] Muphy ML, Hultgen HN, Dete K et al. Teatment of chonic stable angina: a peliminay epot of suvival data of the andomized Veteans Administation Coopeative Study. N Engl J Med 977; 297: [3] CASS pincipal investigatos and thei associates. Coonay Atey Sugey Study (CASS): a andomized tial of coonay atey bypass sugey suvival data. Ciculation 983; 68: [4] Seuys PW, De Jaegee P, Kiemeneij F et al. fo the Benestent Study Goup. A compaison of balloon-expandable-stent implantation with balloon angioplasty in patients with coonav atey disease. N Engl J Med 994; 33: [5] Keane D, Jackson G. Dug theapy fo patients with angina pectois: In: Jackson G, ed. Difficult Concepts in Cadiology. London: Dunitz, 994: -42. [6] Jackson G, Atkinson L, Oam S. Reassessment of failed beta blocke teatment in angina pectois by peak execise heat ate measuements. B Med J 975; 3: [7] Juul-Molle S, Eduadsson N, Jahnmatz B et al. Double-blind tial of aspiin in pimay pevention of myocadial infaction in patients with stable chonic angina pectois. Lancet 992; 34: [8] MAAS Investigatos. Effect of simvastatin on coonay atheoma: the Multicente Anti-Atheoma Study (MAAS). Lancet 994; 344: [9] Scandinavian Simvastatin Suvival Study Goup. Randomised tial of cholesteol loweing in 4444 patients with coonay heat disease: the Scandinavian Simvastatin Suvival Study (4S). Lancet 994; 344: [] Julian DG. Smoking and coonay atey bypass sugey. B Heat J 994; 72: 9-. [] Paisi AF, Folland ED, Hatigan P on behalf of the Veteans Affais ACME Investigatos. A compaison of angioplasty with medical theapy in the teatment of single-vessel coonay atey disease. N Engl J Med 992; 326: -6. [2] Goy JJ, Eeckhout E, Bunand B et al. Coonay angioplasty vesus left intenal mammay atey gafting fo isolated poximal left anteio descending atey stenosis. Lancet 994; 343: [3] RITA paticipants. Coonay angioplasty vesus coonay atey bypass sugey: the Randomised Intevention Teatment of Angina (RITA) tial. Lancet 993; 34: [4] Rodiguez A, Boullon F, Peez-Balino N et al. Agentine Randomised Tial of Pecutaneous Tansluminal Coonay Angioplasty vesus Coonay Atey Bypass Sugey in Multivessel Disease (ERACI): in-hospital esults and yea follow up. J Am Coll Cadiol 993; 22: 6-7. [5] Hamm CW, Reimes J, Ischinge T, Ruppecht HJ, Bege J, Bleifeld W. A andomized study of coonay angioplasty compaed with bypass sugey in patients with symptomatic multivessel coonay disease. Geman Angioplasty Bypass Sugey Investigation (GABI). N Engl J Med 994; 33: [6] King SB, Lembo NJ, Weintaub WS et al. fo the Emoy Angioplasty vesus Sugey Tial (EAST). A andomized tial compaing coonay angioplasty with coonay bypass sugey. N Engl J Med 994; 33: [7] Fischman DL, Leon MB, Balm DS et al. fo the Stent Restenosis Investigatos. A andomized compaison of coonay-stent placement and balloon angioplasty in the teatment of coonay atey disease. N Engl J Med 994; 33: [8] Akhas F, Jackson G. Efficacy of nifedipine and isosobide mononitate in combination with atenolol in stable angina. Lancet 99; 338: [9] Sculphe MJ, Seed P, Hendeson RA et al. fo RITA tial paticipants. Health sevice costs of coonay angioplasty and coonay atey bypass sugey: the Randomised Intevention Teatment of Angina (RITA) tial. Lancet 994; 344: [2] The Bypass Angioplasty Revasculaization Investigation (BARI) Investigatos. Compaison of coonay bypass sugey with angioplasty in patients with multivessel disease. N Engl J Med 996; 335: