LEFT MAIN CORONARY ARTERY DISEASE- MANAGEMENT STRATEGY

Review Article

Since the 1st clinical description of Left main coronaryartery (LMCA) disease in 1912, its management hasremained more or less constant [1]. A left main stenosisgreater than 50% is considered angiographicallysignificant and needs revascularization. Isolated Left maininvolvement is seen in 7% of Coronary artery disease(CAD) and in 13%, 17% and 27% cases it is associatedwith single, double and triple vessel disease respectively[2]. As the left main disease involves a large myocardiumat risk, the management option possess a greater challenge.Serial published literature has consistently shown poorlong term survival in medically managed group andsupported the usefulness of CABG and established it’srole. Coronary artery bypass surgery (CABG) isconsidered the gold standard for the treatment of anysignificant left main coronary artery disease. Howevertreatment option has evolved dramatically in last threedecades since the performance of 1st angioplasty in 1977by Gruentiz, et al. [3]. Since then a lot of trials, registrieshave come up regarding usefulness of PCI in managing leftmain disease. Still we do not have enough clinicalevidence to recommend PCI in all cases of left maindisease.

MEDICAL VS SURGERY

Various trials have compared the outcome of medicalVs surgical treatment in LMCA disease. In the CASSregistry done between 1974-1979 about 1484 patients hadsignificant LMCA disease (>50% stenosis) (331 medical,1133 surgical) [2]. The long term data of >16 years offollow up was published in 1995. The 15 years survivalwas 37% in surgical group compared to 27% in medicalgroup, besides 25% in medical group.

Subsequently underwent CABG also. The mediansurvival was 13.3 year (12.8-13.8 year) in CABG arm

LEFT MAIN CORONARY ARTERY DISEASE- MANAGEMENT STRATEGY

P C Rath and B V PurohitCath Lab & Interventional Cardiology Department, Apollo Health City, Jubilee Hills,

Hyderabad 500 033, India.Correspondence to: Dr P C Rath, Director, Cath Lab & Interventional Cardiology, Apollo Health City, Jubilee Hills,

Hyderabad 500 033, India.E-mail: drpcrath@hotmail.com

Key words: Left main coronay artery disease.

compared to only 6.6. year (5.4-7.9 year) in medical arm.In another landmark study the VA cooperative study the 3year survival in medically managed group was only 60%.The 11 year cumulative surgical survival was 59% insurgical group. The outcome of medical treatment couldnot be concluded as almost 50% of medical group patientunderwent CABG while another 44% had died and only 4patients were still medically treated by 7 years [4].

PCI IN LEFT MAIN DISEASE

Gruentiz did the 1st PCI in a left main stenosis.Gruentiz’s 3rd patient a 43 years old man with severeangina, had significant left main disease but unfortunatelythe patient expired suddenly 4 months after the procedure[3]. This dampened the enthusiasm of LMCAintervention. However In mid 80’s a study of about 20patients with left main disease treated by PCI waspublished which showed that about 5% requiredemergency CABG and at a mean follow up of about 2½year 37% required CABG5. In another large series of 127procedures by O’Keefe, et al. the initial success rate was94%, but there was a 9.1% procedural mortality and only35% survived up to 3 years [6]. Subsequently with thedevelopment of stents periprocedural complications werereduced significantly however the rate of rest enosis wasstill very high with these bare metal stents (BMS).

In a large series of almost 140 patient reported bySilvestri, et al in 2000 ( includes 47 patients documentedhigh risk for CABG) with palmatz schatz stent 30 daymortality was 6% (9% in high risk and 0% in low riskgroup) and 1 year TLR was 18% [7]. In the large ULTIMAregistry the in hospital mortality was 12% and a further17% mortality within 12 months [8]. Initial encouragingdata came from study of Park, et al. On 42 patients treatedwith stents in LMCA disease there was no in-hospital

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mortality, 1 year mortality was 2.5% and angiographyrestenosis was 22% [9].

The development of drug eluting stent (DES) whichreduced the Restenosis to single digit further encouragedthe interventionist to use PCI as an alternate to CABG.With this the question came whether DES is superior toBMS, are all DES equally effective and what is role ofDES Vs CABG in cases of LMCA diseases?

DRUG ELUTING STENT IN LMCA

A lot of studies are available regarding role of DES inLMCA. The DELFT registry (Drug eluting stent for leftmain) published its 3 year outcome data in 2008 [10]. Inthis registry DES was implanted in 358 consecutivepatients from 2002-2009 and after 3 years follow up theMACE free survival was 73.5%. The rate of reinfarction,TLR and TVR was 8.6%, 5.8% and 14.2% respectively.

DES VS BMS

There are a lot of studies comparing DES vs BMS inLMCA disease. The large multicentre LEMANs registrywhich included 257 patients between 1997 to 2008 (DES94, BMS - 158) and the first 30 days rate of death, MI were1.6% and 3.6% respectively [11]. Incidence of acute andsub acute stent thrombosis was 0.8% & 0.4% in DES andBMS group respectively. The overall restenosis was12.1% at 1 year whereas in vessel with >3.8 mm diameterthe restenosis was only 6.1%. The 5 and 10 year survivalrate was 78.1% and 68.9%. At 4 year follow up the overallMACE rate was significantly lower in DES compared toBMS 14.9% Vs 25.9% (P = 0.039) despite the fact that theDES group had higher diabetic patients, more NSTEACSpatients, higher distal LMCA lesion, higher surgical riskscore, smaller vessel diameter. There was nonsignificantly lower mortality in DES compared to BMS(9.6% Vs 13.5%). The TLR rate was significantly lower inDES group compared to BMS (3.2% Vs 10.1%). Similarresults were also seen in the meta analysis of DES VsBMS by Pandya, et al [12]. In his meta analysis 44 studieswere included with 10342 patients. At 3 year follow up theover all MACE rate was significantly lower in DES groupcompared to BMS (21.43% Vs 31.6%), which was mainlydue to lower TVR/TLR in DES group (8.03% Vs 16.4%).The mortality rate was also found to be lower in DESgroup compared to BMS (8.8% Vs 12.71%).

With regards to various stent types, we do not haveenough data to support any particular stent. Majority ofstudies are with sirolimus eluting stents and some withPaclitaxel. The ISAR LEFT MAIN study comparedPaclitaxel Vs Sirolimus eluting stent [13]. In this trial theincidence of stent thrombosis was 0.3% in PES and 0.7%

in SES group (p=0.57). There was no significantdifference between the two in terms of death, MI & strokerate. At 1 year the cumulative incidence of death, MI andstroke was 9.6% in PES and 10.2% in SES group (p=0.83)which was maintained even after 2 years follow up. At 2year the cumulative incidence of death, MI and stroke was15.9% PES and 12.3% in SES (p=0.31). The TLR rate was9.2% in PES and 10.7% in SES group (p-0.47). Theincidence of binary angiographic restenosis also did notdiffer in the 2 group (16% in PES and 19.4% in SESgroup). In other prospective study from Asia, 628 Leftmain lesion were treated with various drug eluting stents(248 sirolimus (SES), 172 Paclitaxel (PES), 104Zotarolimus(ZES), 60 Biolimus A 9 (BES), 42 EPCcapture (EPC), 50 Everolimus (EES) [14]. It showedstatistically lower restenosis in patient treated with SES/BES/EES compared to ZES/ECS. The restenosis at 9months was 7.3% (SES) 6.7% (BES), 6.0% (EES),compared to 9.9% (PES), 16.3% (ZES) 16.7% (EES).Similarly overall MACE at 2 year was also statisticallylower in the sub group where SES/BES/EES wasimplanted [14].

DES VS SURGERY

Based on the results of various large studies and metaanalysis surgery is considered mainstay of treatment in leftmain stenosis [2,4,15]. Encouraging results from variousdrug eluting stents studies in left main disease promptedlarger randomized studies, registries and meta analysiswhich showed the safety and efficacy of DES compared tosurgery in LMCA disease.

The randomized PRECOMBAT study comparedsirolimus eluting stent Vs surgery [16]. Out of 1454patients enrolled in this trial 600, were randomized to thestudy (300 CABG, 300 stent) [16]. There was nodifference between the event rate in two group except inrate of TVR. Two year MACE rate was 12.2% in PCI and8.1% in CABG group (p-0.12). Mortality was 2.4% in PCIand 3.4% in CABG group (p=0.75). Incidence of stentthrombosis or graft occlusion was 0.3% Vs 1.4%respectively. However Ischemia driven TVR at end of 2years was significantly more in PCI group 9% Vs 4.2%(p=0.02). Similar results were also found in the SYNTAXtrial which compared paclitaxel eluting stent with CABGin LMCA disease [17]. At 3 year there was no significantdifference in combined end point of death/MI/CVAbetween 2 groups (14.3% in CABG Vs 13.0% in DES).The stroke rate was significantly high in CABG group(4.0% Vs 1.2% p=0.02), however it was mainly due tohigher stroke rate seen in first year only (2.7% Vs 0.3%p=0.009). The stroke rate was almost similar in secondand third year in both group. The only difference was in

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incidence of repeat revascularization which wassignificantly higher in PCI group (20% Vs 11.7%) (p=0.004). Again this was mainly due to higherrevascularization seen in first year only (11.8% Vs6.5%).In second and third year the incidence of repeatrevascularization was almost similar in both groups. It was8.2% Vs 5.0% in 2nd year (p-0.1) and 3.9% Vs 2.6% in3rd year (P-0.36) in the PCI & CABG arm respectively.The incidence of symptomatic graft occlusion and stentthrombosis at 3 year was similar in 2 groups (3.7% inCABG Vs 4.1% in PCI p-0.8). When sub analysis wasdone in patients with different syntax score, it was seenthat overall MACE rate did not differ in the two arm ofCABG & PCI whether it was low score (syntax score 0-22) (11% CABG Vs 6.9% PCI p-0.26). Intermediate score(syntax score 23-32) (15.6% CABG Vs 10.8% PCIp=0.29) or high score (syntax score > 33) (15.7% CABG,vs 20.1% PCI). The only difference which was observedwas statistically higher repeat revascularization seen inpatient with high syntax score (>33) (9.2% CABG Vs27.7% PCI). Interestingly the incidence of repeatrevascularization did not achieve statistical significance inlow score (13.4% CABG Vs 15.4% PCI p-0.69) andintermediate score (14.07% CABG Vs PCI 15.9%).

Another study which compared sirolimus eluting stentVs CABG (mainly with arterial grafts) showed similarresults [18]. The combined rate of death and MI was 5.0%in stent Vs 7.9% in surgery. Perioperative complicationincluding stroke were higher in surgery then PCI (4% Vs30% p<0.001). However repeat revascularization wassignificantly higher in PCI group than CABG (5.9% Vs14.0%).

The meta analysis by Naik, et al which included 10trials comparing PCI Vs surgery showed no difference inmortality or MACE up to 3 year between CABG or PCIgroup [19]. The only difference seen was higher repeatrevascularization in PCI group in the 1st and 2nd year.This difference again was not seen in the 3rd year (OR3.3(0.96 to 11.33).

When subanalysis were made regarding outcome ofPCI in different anatomic location of left maininvolvement, it was seen that ostial and shaft involvementhad much favorable outcome than distal bifurcation. In theRESEARCH and T-SEARCH registries it was seen thatinitial 30 day outcome in patient with Distal left maindisease (DMLD) was similar to patient without DMLD[20]. However at median follow up of 587 days compositedeath/MI was 17% in the DLMD group and 8% in patientswithout DLMD (HR 2.11, 95% CI 0.45 to 10; p-0.34),whereas the cumulative incidence of TVR was 13% versus3% in patients with and without DLMD (HR 6, 95% CI 1.2

to 29; p-0.02). In the SYNTAX 1 year data sub analysis itwas seen that in patient with isolated left main or Left mainwith single vessel disease (LM+ 1VD), overall MACErate (Death /MI/CVA/TVR) was higher in CABG armthan PCI arm (8.5 Vs 7.1% and 13.2 vs 7.5% respectively).In subset with Left main with two or three vessel (LM +2VD and LM + 3VD) the overall MACE rate was higherin PCI arm than CABG arm 14.4 vs 19.8% and 15.4 vs19.3% respectively) [21].

Due to the publication of these favorable results forPCI in LMCA the recently published guidelines onmyocardial revascularization by ESC/EACTS have givenClass IIa recommendation to Left main PCI in subset ofpatient with Left main disease of Ostium//Shaft if it isIsolated or with Single Vessel disease [22].

CONCLUSION

Treatment of Left main disease is still evolving.CABG is still to be considered the mainstay of thetreatment. However when we decide the treatment inindividual patient, lot of factors should be considered likerisk score, LV function, location of the lesion in Left main,associated involvement of other vessels. In select group ofpatient especially with the involvement of ostium, shaftlocation in isolation or in associated with single vesseldisease, PCI can be an effective alternative option.

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