JOURNAL REVIEW PRIMARY PCI : Part 1 Speaker: Dr Sandeep Mohanan Senior Resident Department of Cardiology Government Medical College Calicut

TOPIC OVERVIEW COMPARISON OF PRIMARY PCI TO THROMBOLYSIS ASPIRATION THROMBECTOMY IN PRIMARY PCI DISTAL PROTECTION DEVICES IN PRIMARY PCI STENT USAGE IN PRIMARY PCI

PRIMARY PCI vs THROMBOLYSIS Efficacy Subgroups - Diabetics and Elderly Pre-hospital fibrinolysis(Pharmacoinvasive) : TRANSFER AMI, STREAM Facilitated PCI : CARESS in AMI, FINESSE-2, ASSENT-4 -- Inferior to PPCI -- IIa B in AHA 2013

Efficacy of primary PCI vs thrombolysis Keeley et al. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials . :Lancet. 2003;361:13–20. 23 RCT trials ever since advent of PPCI for AMI till 2003. Well matched for heterogeneity and accepted as the reference for recommendations in the AHA and ESC guidlines.

Keeley et al. Lancet 2003

Keeley et al. Lancet 2003

Keeley et al. Lancet 2003

Andersen HR et al. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med. 2003;349:733– 42. 1572 patients with AMI—PPCI vs iv alteplase RESULTS: Primary end point was reached in 8.5% for PPCI vs 14.2% of the patients for TT (P=0.002) (30 days) The better outcome after angioplasty was driven primarily by a reduction in the rate of reinfarction (1.6% vs. 6.3%, P<0.001); No significant differences in the rate of death (6.6% vs 7.8%, P=0.35) or the rate of stroke (1.1% vs 2%, P=0.15). 96% were transferred from referral hospitals to an invasive-treatment center within 2 hours. CONCLUSIONS: A strategy for reperfusion involving the transfer of patients to an invasive-treatment center for primary angioplasty is superior to fibrinolysis, provided that the transfer takes two hours or less.  Strong basis for present AHA/ESC guideline recommendation on timing of PPCI

Death / MI / Stroke at 30 Days DANAMI 2 study (Danish trial in acute MI)- (AHJ2003, EHJ 2008, Circulation 2010) High-risk ST elevation MI patients (>4 mm elevation), Sx < 12 hrs 5 PCI centers (n=443) and 22 referral hospitals (n=1,129), transfer criteria < 3 hrs Lytic therapy Front-loaded tPA 100 mg (n=782) Primary PCI with transfer (n=567) Primary PCI without transfer (n=223) Death / MI / Stroke at 30 Days

DANAMI-2: Primary Results Combined Transfer Sites Non-Transfer Sites P=0.0003 P=0.002 P=0.048 RRR 40% RRR 45% RRR 45% Death / MI / Stroke (%) Lecture Notes Shown here are the primary results of the trial. At both sites where patients were transferred as well as in those sites that did not require transfer, there was a reduction in the composite endpoint of death/recurrent MI and stroke. Lytic Primary PCI Lytic Primary PCI Lytic Primary PCI

DANAMI-2: Primary outcomes Death Recurrent MI Stroke P=0.35 P<0.0001 P=0.15 Lecture Notes Examination of the individual components of the primary endpoint demonstrates that the primary endpoint is driven predominantly by a reduction in the risk of recurrent MI among those patients treated with PCI. Lytic Primary PCI Lytic Primary PCI Lytic Primary PCI

DANAMI conclusion Median D2B time was 114 mins. For such patients, the incidence of the composite endpoint of death, recurrent MI, and stroke is reduced compared with the administration of tPA and heparin

DANAMI2 Long term follow up

DANAMI2 subgroup analysis (Circ 2010)

PPCI in DIABETICS Timmer JR. Primary percutaneous coronary intervention compared with fibrinolysis for myocardial infarction in diabetes mellitus: Arch Intern Med. 2007 Jul 9;167(13):1353-9. A pooled 19 trials comparing primary PCI with fibrinolysis for treatment of STEMI. RESULTS: Of 6315 patients, 877 (14%) had diabetes. 30 day mortality (9.4% vs 5.9%; P < .001) --higher in diabetes. Mortality was lower after PPCI compared to TT in both groups -- with diabetes(OR- 0.49, 95% CI, 0.31-0.79; P = .004) and -- without diabetes (OR- 0.69; 95% CI 0.54-0.86, P = .001),

PPCI in the Elderly GUSTO IIB trial was one of the first to report that PCI is superior to fibrinolysis. De Boer et al. JACC 2002 : -- 87 patients , >75yrs PPCI vs SK.  RR of the primary composite end point of death, reinfarction, or stroke at 30 days of 4.3 (95% CI 1.2-20) for SK vs PCI.   SENIOR PAMI -largest RCT for elderly undergoing PPCI vs TT by Grines et al(2005) -- 481 patients >70 yrs 55% reduction in the combined end point of death, stroke, or reinfarction (P = 0.0093) associated with PCI. However, no advantage of one strategy over the other was found among those older than 80 years.  Meta-analysis of 22 randomized trials comparing primary PCI with fibrinolysis, de Boer et al. showed a mortality/stroke reduction favoring primary PCI in all age strata. 1) de Boer, M. J. et al. for the Myocardial Infarction Study Group. Reperfusion therapy in elderly patients with acute myocardial infarction: a randomized comparison of primary angioplasty and thrombolytic therapy. J. Am. Coll. Cardiol. 39, 1723-1728 (2002). 2) Grines, C. L. SENIOR PAMI: a prospective randomized trial of primary angioplasty and thrombolytic therapy in elderly patients with acute myocardial infarction. Presented at the 17th Annual Transcatheter Cardiovascular Therapeutics Symposium, October 16-21, 2005. 3) de Boer, S. P et al. for the PCAT-2 Trialists Collaborators Group. Mortality and morbidity reduction by primary percutaneous coronary intervention is independent of the patient's age. JACC Cardiovasc. Interv. 3, 324-331 (2010).

PPCI in the very elderly (>85yrs) Omar Rana et al. Percutaneous Coronary Intervention in the Very Elderly (≥85 Years) Trends and Outcomes. Br J Cardiol. 2013;20(1):27-31 Single centre retrospective analysis. B/w 2006 and 2010, 294 patients PCI (mean age 88 ± 2 years, 56% male) 62% underwent PPCI and 38% elective PCI 30-day mortality (5.6% vs. 3.4%, p=0.24) and 1 year mortality (20.0% vs. 14.0%, p=0.19) Male sex, previous PCI and shock – independent predictors PCI is a safe option for the very elderly with ACS. RCTs further required.

Guideline statement on PPCI vs Thrombolysis AHA 2013 : I A “ In the absence of contraindications, fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previous 12 hours when it is anticipated that primary PCI cannot be performed within 120 minutes of FMC”

THROMBECTOMY in PPCI Evidence on efficacy Thrombosuction devices *Mechanical thrombectomy (Angiojet, Rescue, Xsizer) * Manual aspiration thrombectomy (TVAC, Diver, Export, Pronto)

Early trials on Aspiration thrombectemy Primary outcome TA / MT Result 1. AJC 2004 100 Early STR Rheolytic MT 90% vs 72% (P=0.02) 2. JACC 2005 Jul 19;46(2):246-52. X AMINE ST trial 201 RCT STR after 1 hour MT (X-Sizer catheter system) STR>50% (68% vs. 53%; p = 0.037). 3. JACC2005 Jul 19;46(2):371-6 REMEDIA trial Combined MBG>/=2+ STR>70% TA[ Diver CE (Invatec)] 46% vs 24.5%, OR 2.6 (p = 0.025) 4. JACC 2006Oct 17;48(8):1552-9. DEAR-MI trial 148 STR>70%, MBG=3 TA[Pronto extraction catheter (Vasc.solutions)] STR>70: 68% versus 50% (p < 0.05); MBG-3 88% versus 44% (p<0.0001) 5. JACC 2006. Jul 18;48(2):244-52. AIMI trial 480 Infarct size by SPECT (30 day MACE) [5-F LF140 RT catheter (Possis Medical)] –no DP -Infarct size larger for RT (P=.03) -MACE & mortality higher for RT (P=0.01/ 0.02) 6. Circulation. 2006 Jul 4;114(1):40-7 215 TA(Rescue catheter (Boston Scientific) Infarct size larger for TA(15%vs 8%)P=0.006 1. Circulation. 2006 Jul 4;114(1):40-7. Epub 2006 Jun 26. Routine thrombectomy in percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction: a randomized, controlled trial. 2. J Am Coll Cardiol. 2006 Jul 18;48(2):244-52. Epub 2006 Jun 23. Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study.Ali A, 3. J Am Coll Cardiol. 2006 Oct 17;48(8):1552-9. Epub 2006 Sep 26. Thrombus aspiration before primary angioplasty improves myocardial reperfusion in acute myocardial infarction: the DEAR-MI (Dethrombosis to Enhance Acute Reperfusion in Myocardial Infarction) study. 4. J Am Coll Cardiol. 2005 Jul 19;46(2):371-6. Manual thrombus-aspiration improves myocardial reperfusion: the randomized evaluation of the effect of mechanical reduction of distal embolization by thrombus-aspiration in primary and rescue angioplasty (REMEDIA) trial.Burzotta F 5. X AMINE ST trial 6. Am J Cardiol. 2004 Apr 15;93(8):1033-5. Comparison of rheolytic thrombectomy before direct infarct artery stenting versus direct stenting alone in patients undergoing percutaneous coronary intervention for acute myocardial infarction.

TAPAS trial (NEJM 2008) -Thrombus Aspiration during Percutaneous coronary intervention in AMI Study Single centre RCT 1071 patients: 535 Manual thrombus aspiration(6-French Export Aspiration Catheter) + PCI vs 536 PCI Aspiration success by histopathological assessment Angiographic (myocardial blush score) and ECG STE resolution assessment The primary end point was a myocardial blush grade of 0 or 1 (defined as absent or minimal myocardial reperfusion, respectively). Results Histopathological examination confirmed successful aspiration in 72.9% of patients. Predilatation was done in 207 of 502 (41·2%) of the patients randomly assigned aspiration.

TAPAS primary endpoint Patients (%) Thrombus aspiration Conventional PCI

TAPAS- ST resolution P < 0.001 Patients (%) Thrombus aspiration Conventional PCI

Myocardial blush grade TAPAS 30-day outcomes P = 0.001 Myocardial blush grade Conclusion: TA results in better reperfusion and clinical outcomes than conventional PCI

Pieter et al. Cardiac death and reinfarction after 1 year in the TAPAS trial: a 1-year follow-up study. (Lancet 2008) Cardiac death at 1 year was 3·6% (19 of 535 patients) in TA group and 6·7% (36 of 536) in the conventional PCI group ( [HR] 1·93; 95% CI 1·11—3·37; p=0·020). 1-year cardiac death or non-fatal reinfarction occurred in 5·6% (30 of 535) in TA group and 9·9% (53 of 536) in conventional PCI group (HR 1·81; 95% CI 1·16—2·84; p=0·009).  Compared with conventional PCI, thrombus aspiration before stenting of the infarcted artery seems to improve the 1-year clinical outcome after PCI for ST-elevation myocardial infarction.

Performance of the TVAC(Nipro) during PPCI Ikari et al. Upfront thrombus aspiration in primary coronary intervention for patients with ST-segment elevation acute myocardial infarction: : VAMPIRE trial (JACC Cardiovasc interventions 2008) Performance of the TVAC(Nipro) during PPCI  The study showed a trend toward improved myocardial perfusion and lower clinical events in patients treated with aspiration. Patients presenting late after STEMI appear to benefit the most from thrombectomy.

Thrombectomy with export catheter in infarct-related artery during primary percutaneous coronary intervention – a prospective, randomized trial. EXPIRA trial -- JACC 2009 Impact of TA on myocardial perfusion and infarct size as by CE-MRI analysis  Thrombectomy prevents thrombus embolization and preserves microvascular integrity reducing infarct size, and it therefore represents an useful adjunctive therapy in PPCI.

postprocedural TIMI 3 flow (87.1 vs. 81.2%, P < 0.0001), De Luca G et al. Adjunctive manual thrombectomy improves myocardial perfusion and mortality in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction : a meta-analysis of randomized trials. Eur Heart J.2008 9 RCTs with 2417 patients Adjunctive manual aspiration thrombectomy was associated with significantly improved postprocedural TIMI 3 flow (87.1 vs. 81.2%, P < 0.0001), postprocedural MBG 3 (52.1 vs. 31.7%, P < 0.0001), less distal embolization (7.9 vs. 19.5%, P < 0.0001), significant benefits in terms of 30-day mortality (1.7 vs. 3.1%, P = 0.04).

Tamhane et al. Safety and efficacy of thrombectomy in patients undergoing primary percutaneous coronary intervention for Acute ST elevation MI : A Meta-Analysis (BMC Cardiovascular Disorders 2010) 17 RCTs (3909 patients) Aspiration/Thrombectomy PCI vs conventional PCI No difference in risk of 30-day mortality (OR 0.84, 95% CI 0.54-1.29, P = 0.42) Thrombectomy was associated with a significantly greater likelihood of TIMI 3 flow (OR 1.41, P = 0.007), MBG 3 (OR 2.42, P < 0.001), STR (OR 2.30, P < 0.001), and with a higher risk of stroke (OR 2.88, 95% CI 1.06-7.85, P = 0.04). Outcomes differed significantly between different device classes with a trend towards lower mortality with manual aspiration thrombectomy (MAT) (OR 0.59, 95% CI 0.35-1.01, P = 0.05), whereas mechanical devices showed a trend towards higher mortality (OR 2.07, 95% CI 0.95-4.48, P = 0.07).

Angiojet rheolytic thrombectomy for PPCI VeGAS 1 & 2 trials (AJC 2002) : - RT vs intracoronary UK Encouraging results for Angiojet AIMI (JACC 2006):  Negative results

Comparison of AngioJet Rheolytic Thrombectomy Before Direct Infarct Artery Stenting With Direct Stenting Alone in Patients With Acute Myocardial Infarction  : The JETSTENT Trial (JACC 2010) Multicenter international RCT (December 2005 to September 2009) Coprimary endpoints : STR and Tc-SPECT infarct size Clinical endpoints: MACE at 1,6 and 12m 501 patients with angio evidence of thrombus (BMS) Results: STR was 85.8% vs 78.8% (p = 0.043), 6m MACE was 11.2% vs 19.4% (p = 0.011). The 1-year event-free survival rates were 85.2 ± 2.3% for the RT arm, and 75.0 ± 3.1% for the DS alone arm (p = 0.009). The results of the study support the use of RT before infarct artery stenting in patients with acute myocardial infarction and evidence of coronary thrombus.

Major features of the 2 largest trials on Angiojet RT

JACC 2010 editorial on the JETSTENT trial In light of the often superior thrombus extraction efficiency with mechanical thrombectomy, what explains the disappointing outcomes with mechanical devices in general? JACC 2010 editorial on the JETSTENT trial Rheolytic MT: - Bulkier, complicated use, bigger learning curve, - requires favourable coronary anatomy, longer procedure times, propensity to initially impair distal microcirculation, high incidence of symptomatic bradycardia and need for TPI. MAT: User friendly, quick and easier to learn.

Current guidelines on thrombectomy AHA STEMI 2013: ESC STEMI 2012:

Frobert et al. Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction TASTE trial -(NEJM September 2013) Prospective multicentre RCT from the Swedish registry(SCAAR) 7244 patients –PCI+TA vs conventional PCI Primary endpoint—mortality at 30 days Secondary endpoints – Stent thrombosis, hospitalization, reinfarction Conclusion: Routine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. -There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87).

TASTE - Endpoints P=0.63 P=0.09 --Rates of stent thrombosis were 0.2% and 0.5%, respectively (HR, 0.47 (0.20 to 1.02); P=0.06). 

Consistency of the findings among all subgroups A REVISION OF CURRENT GUIDELINES ?? Awaiting: 1 year f/u results 2) TOTAL trial in the late stages

EMBOLIC PROTECTION DEVICES in PPCI Guard wire occlusion-aspiration system Filter wire sytem Proxis catheter system

Proven role of EPDs in SVGs and carotid interventions Carotid : CABERNET SVG: BLAZE, BLAZE II, FIRE (Filter wire), SAFER (Guard wire), PROXIMAL (Proxis)

Early trials with EPDs - Balloon occlusion devices Primary outcome Particluars Result 2. Am J Cardiol. 2003 Dec 1;92(11):1331-5 - TIMI flow, MBG, 30 day MACE vs adjunctive tirofiban Benefit in all outcomes 1. Catheter Cardiovasc Interv.2004 Apr;61(4):503-11. 42 Vs 101 -TIMI 3 flow - Combined 30-day MACE+ distal thrombemb events+ vasc compli Radial vs Femoral control at separate periods Large IRAs + HBTF 95% vs 79% (P=0.005) P <0.05 for 20 endpoints 3. Catheter Cardiovasc Interv. 2005 Jan;64(1):35-42. 74 (48 vs 26) RCT TIMI flow 6 month angiographic results -Improved immediate TIMI flow. Favourable 6 month results * Late stenosis at site of balloon 1. Catheter Cardiovasc Interv. 2004 Apr;61(4):503-11. Transradial application of PercuSurge GuardWire device during primary percutaneous intervention of infarct-related artery with high-burden thrombus formation. Yip HK, 2. Am J Cardiol. 2003 Dec 1;92(11):1331-5. Effect of the PercuSurge GuardWire device on the integrity of microvasculature and clinical outcomes during primary transradial coronary intervention in acute myocardial infarction. 3. Catheter Cardiovasc Interv. 2005 Jan;64(1):35-42. Six-month angiographic results of primary angioplasty with adjunctive PercuSurge GuardWire device support: evaluation of the restenotic rate of the target lesion and the fate of the distal balloon occlusion site. Wu CJ,

Stone GW et al. Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial. EMERALD trial (JAMA 2005 Mar 2;293(9):1063-72.) . Prospective RCT on 501 patients of STEMI for PCI PCI with a balloon occlusion and aspiration distal microcirculatory protection system (GUARD WIRE) vs angioplasty without distal protection. OUTCOME MEASURES: STR 30 minutes after PCI by continuous Holter monitoring and Infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events. RESULTS: Visible debris was retrieved from 73% (182/250). Complete STR 63.3% vs 61.9% , P = .78, Left ventricular infarct size was similar in both groups (12.0% vs 9.5% ; P = .15). MACE at 6m were 10.0% vs 11.0%, P = .66 CONCLUSIONS: Distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival. The use of GuardWire device increased procedural time by 14 min on average and, due to the occlusive nature of the device, such an increase almost completely translated into a reperfusion delay ----- likely additive muscle loss

Multicenter prospective RCT of 341 AMI +/- Guard wire system Results: Muramatsu T et al. Comparison of myocardial perfusion by distal protection before and after primary stenting for acute myocardial infarction: angiographic and clinical results of a randomized controlled trial. : ASPARAGUS trial (Catheter Cardiovasc Interv 2007) Multicenter prospective RCT of  341 AMI +/- Guard wire system Results: The rates of slow flow and no-reflow immediately after PCI were 5.3 and 11.4% in the GuardWire Plus and control groups, respectively (P = 0.05).

First major trial on Filter devices 200 patients – RCT Gick M at al. Randomized evaluation of the effects of FILTER-BASED DISTAL PROTECTION on myocardial perfusion and infarct size after primary percutaneous catheter intervention in myocardial infarction with and without ST-segment elevation. PROMISE trial Circulation. 2005 First major trial on Filter devices 200 patients – RCT The primary end point was the maximal adenosine-induced Doppler flow velocity in the recanalized infarct artery; The secondary end point was infarct size estimated by the volume of delayed enhancement on nuclear MRI. Thirty-day mortality was 2% in filter-wire group and 3% in the control group.

+/- Filter device system Results: Rate of STR 61% vs 60% (0.85) Cura FA et al. Protection of Distal Embolization in High-Risk Patients with Acute ST-Segment Elevation Myocardial Infarction (PREMIAR). : PREMIAR trial (Am J Cardiol 2007) 140 patients with AMI +/- Filter device system Results: Rate of STR 61% vs 60% (0.85) MBG 67 vs 70% (0.73) In-hospital LVEF 47% vs 45% (0.29) MACE at 6 m 14% vs 15% (0.8) “The use of filter-based distal protection is safe and effectively retrieves debris; however, such use does not translate into an improvement of myocardial reperfusion, left ventricular performance, or clinical outcomes.”

Primary objective was to assess clinical outcomes Role of adjunctive thrombectomy and embolic protection devices in acute myocardial infarction: a comprehensive meta-analysis of randomized trials :European Heart Journal (2008) Primary objective was to assess clinical outcomes 30 trials -6415 patients Mean follow-up of 5.0 months, Overall Mortality was 3.2% for the adjunctive device group vs. 3.7% for PCI alone (rr-0.87; 95% confidence interval, 0.67– 1.13). Thrombus aspiration- 2.7% vs 4.4% (0.018) [ NNT = 59 ] Mechanical thrombectomy - 5.3 vs 2.8% (0.05) [ NNH = 38 ] Embolic protection devices - 3.1% vs 3.4% (0.69) – Neutral effect

Role of Proximal embolic protection-aspiration system (PROXIS) Proven role for SVG graft interventions in the PROXIMAL trial PREPARE trial (JACC cardiovasc interv 2009, Heart 2010)  284 patients , PROXIS system vs conventional PCI STR at 60 min -- 80% vs 72% (0.14) MACCE at 30 days and 6m (8% vs 10%) were similar No difference in finnal infarct size/ LVEF on CMR  No definite benefit

Kelbæk H et al. Randomized Comparison of Distal Protection Versus Conventional Treatment in Primary Percutaneous Coronary Intervention: The Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction : (DEDICATION) Trial. J Am Coll Cardiol. 2008 626 patients Filter wire system vs conventional 50% underwent DES implantation Endpoints --STR, MACCE at 30 days, WMI, Trop I, CK-MB All endpoints were similar. (MACCE) 1 month –5.4% vs 3.2% (p = 0.17).  Routine use of a filterwire system during primary PCI does not seem to improve microvascular perfusion, limit infarct size, or reduce the occurrence of MACCE.

Guideline statement on EPDs in STEMI ESC 2012- : Routine use of distal protection devices is not recommended. (III C) Int J Cardiol 2013:Effect on MVO of DPDs after PPCI 126 patients , prospective RCT Evaluation of MVO by cMRI after PCI for STEMI MVO ratio was larger when DPDs were used. DPDs should not be used for PPCI.

STENT USAGE IN PPCI POBA vs Stent BMS vs DES Newer stent designs in PPCI

POBA vs Stent in PPCI No remaining dispute on the superiority of stenting Trial Publication Favouring Stenting STENT PAMI Circulation 1999 √ FRESCO JACC 1998 GRAMI AJC 1998 PASTA Catheter Cardiovasc interv 1999 STENTIM2 JACC 2000 CADILLAC NEJM 2002 - However no conclusive mortality benefit in any study

===> No definite mortality benefit upto 1 year for Stenting vs POBA Clinical Outcomes of Primary Stenting versus Balloon Angioplasty in Patients with Myocardial Infarction : A Meta-analysis of RCTs (Am J Med 2004) 1979-2002, 9 trials ---4433 patients. Stenting vs POBA Mortality: 30 days - 1.17 (95% confidenceinterval [CI]: 0.78 to 1.74) 6m - 1.07 (95% CI: 0.76 to 1.52) 12m - 1.09 (95% CI: 0.80 to 1.50) Reinfarction at 1, 6 and 12 m:  0.52 (95% CI: 0.31 to 0.87), 0.67 (95% CI:0.45 to 1.00) & 0.67 (95% CI: 0.45 to 0.99) Target vessel revascularization 0.46 (0.34 to 0.61) at 30 days, 0.42 (0.35 to 0.51) at 6m & 0.48 (0.39 to 0.59) at 12 m No increased bleeding complications ===> No definite mortality benefit upto 1 year for Stenting vs POBA

Mehta RH et al. Comparison of coronary stenting versus conventional balloon angioplasty on five-year mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. :Am J Cardiol.2005 To study the long term outcome of stenting vs POBA 2,087 patients enrolled from various PAMI trials 692 (33%) underwent stenting. Absolute difference in mortality rates favoured stent usage In-hospital (2.2% vs 3.3%), 1-year (3.3% vs 5.2%), and 5-year (10% vs 13%) Regression model identified significant 5 yr mortality reduction with stenting vs POBA (HR 0.60, 95% confidence interval 0.42 to 0.85). The absolute reduction in mortality was greatest in the highest risk group. ESC 2012 and AHA 2013 --- Primary stenting preferred to balloon angioplasty (Class I A)

BMS vs DES in PPCI PES versus BMS --- PASSION trial, NEJM 2006 SES versus BMS --- TYPHOON trial , NEJM 2006 --- SESAMI trial , JACC 2007 EES versus BMS --- EXAMINATION trial, LANCET 2012 METAANALYSIS --- EHJ 2012

Death, reinfarction, or TLR (%) Laarman et al.Paclitaxel-Eluting versus Uncoated Stents in Primary Percutaneous Coronary Intervention : PASSION (NEJM 2006) 619 patients with STEMI, PES (TAXUS)vs BMS Primary end point-- composite of death from cardiac causes, recurrent myocardial infarction, or target-lesion revascularization at 1 year Included LMCA, bifurcation and high thrombus burden lesions p=0.12 Death, reinfarction, or TLR (%)

PASSION results (contd) 7.4% 6.5% 6.2% % Death/MI and TLR 4.8% Stent thrombosis at 1 year – 1% in PES and DES All individual endpoints revealed a trend for benefit with PES – statistically NS

Target Vessel Failure at one year Spaulding et al, Sirolimus-Eluting versus Uncoated Stents in Acute Myocardial Infarction: TYPHOON, NEJM 2006 712 STEMI at 48 centres, SES (CYPHER) vs BMS Primary EP – Target vessel failure (TVR, Reinfarction, death) Target Vessel Failure at one year p=0.003 TVF

TYPHOON results(contd) Rate of Target Lesion Revascularization (%) p<0.0001 Rate of death - 2.3% and 2.2%, P = 1.00 Reinfarction - 1.1% and 1.4%, P = 1.00 Stent thrombosis -3.4% and 3.6%,P = 1.00 TLR 4 year follow up (JACC Cardiovasc 2011) – 580 patients Freedom from TLR at 4 years 92.4% vs. 85.1%; p = 0.002; Freedom from cardiac death (97.6% and 95.9%; p = 0.37) Freedom from repeat myocardial infarction (94.8% and 95.6%; p = 0.85) Definite/probable stent thrombosis-- SES: 4.4%, BMS: 4.8%, p = 0.83. The all-cause death rate was 5.8% in the SES and 7.0% in the BMS group (p = 0.61).

Menichelli et al. Randomized trial of Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute Myocardial Infarction :SESAMI trial (JACC 2007) RCT of 320 STEMI , SES vs BMS Primary end point was binary restenosis (>50% stenosis) at 1yr RESULTS: Binary restenosis was 9.3% vs. 21.3%,; p = 0.032), TLR 4.3% vs. 11.2%; p = 0.02, MACE 6.8% vs. 16.8%; p = 0.005, Definite stent thrombosis was 1.2% vs 0.6% 3 year f/u (JACC 2010) : Similar results

Sabate et al, Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction EXAMINATION trial: Lancet. 2012 Multicentre RCT 1504 patients EES vs BMS ....1 year RESULTS The primary endpoint – 11.9% vs 14.2% (0.19) Rates of TLR was significantly lower in the EES group– 2% vs 5% (0.007) Other endpoints were similar. Stent thrombosis rates EES 0.5% vs BMS 1.9% (0.019) Primary endpoints were significantly better for LAD-plasty (9.5% vs 18.9%) --(Insights from EXAMINATION- AHJ Sept 2013)

Comparison of drug-eluting stents with bare metal stents in patients with ST-segment elevation myocardial infarction : A METAANALYSIS (EHJ 2012) 15 RCTs with 7867 patients  1st gen DES vs BMS in STEMI Stent thrombosis at 5 years was similar for DES and BMS  RR- 1.08, 95% CI 0.82– 1.43]. ST for 1st yr --RR of 0.80 (95% CI 0.58 –1.12) ST after 1st year 2.1(95% CI1.20 –3.69 ) TVR was less for DES (RR 0.51, 95% CI 0.43–0.61) – benefit greater in 1st yr Other endpoints(30D,6m & 1yr) were similar for both NNT to prevent 1 TVR till 5 years = 15 NNH to produce 1 ST till 5 years = 79

Guideline statements on DES vs BMS in PPCI AHA 2013 ESC 2012

M-Guard A novel Co-Cr stent wrapped with ultra thin polymer mesh Excellent Deliverability and Flexibility Built in embolic protection Plaque stabilization Rapid exchange deliverysystem

Multicentre RCT -- 433 patients with STEMI Stone et al. Prospective, Randomized, Multicenter Evaluation of a Polyethylene Terephthalate Micronet Mesh-Covered Stent (MGuard) in STEMI : The MASTER Trial (J Am Coll Cardiol 2012 Sep 28) Multicentre RCT -- 433 patients with STEMI The primary endpoint was the rate of complete (≥70%) STR measured 60 to 90 min post-procedure. RESULTS: Complete STR was (57.8% vs. 44.7%;; p = 0.008). Superior rates of TIMI3 flow (91.7% vs. 82.9%, p = 0.006) MBG 2 or 3 (83.9% vs. 84.7%, p = 0.81). MACE at 30 days were similar  Long term results awaited

MAGICAL trial - unpublished Data of 54 patients who underwent PPCI with M Guard stent Comparison with a matched cohort from TAPAS trial presented at ESC interventional conference.

Closed vs Open cell stent for high-risk PCI in STEMI :COCHISE study (AHJ 2013) Ongoing quest to tackle the no-reflow phenomenon after PPCI. An attempt to assess the effect of free-cell area. Coronary flow patterns by MBG and TFC after PPCI between both stent designs RCT of 223 patients. Significantly higher TFC, lower TIMI 3 flow and lower MBG3 in open stent group. Closed stent design has better angiographic results following PPCI.

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