Coronary Interventions Indications, Treatment Options and Outcomes

A talk should be like a woman s skirt long enough to cover the subject, but short enough to keep it interesting.

Coronary anatomy Physiology Pathology Clinical Presentation Outline of the talk Complications and Prognosis Indications for intervention Interventional treatment options Outcomes associated with different interventions (built into talk)

Anatomy of the Heart

Coronary Anatomy

Coronary Physiology Normal coronaries Supply myocardium with oxygenated blood Allow for normal myocardial contractility Directly related to myocardial function : Ejection Fraction

Coronary Pathology STENOSED:

Myocardial Ischemia due to Coronary Artery Disease (CAD) increased myocardial metabolic demand decreased delivery of oxygen and nutrients to the myocardium via the coronary circulation An interruption in the supply of myocardial oxygen and nutrients occurs when a thrombus is superimposed on an ulcerated or unstable atherosclerotic plaque and results in coronary occlusion. A high-grade (>75%) fixed coronary artery stenosis caused by atherosclerosis dynamic stenosis associated with coronary vasospasm

Definition of Myocardial Infarction (MI) Myocardial infarction occurs when myocardial ischemia, a diminished blood supply to the heart, exceeds a critical threshold and overwhelms myocardial cellular repair mechanisms designed to maintain normal operating function and homeostasis. Ischemia at this critical threshold level for an extended period results in irreversible myocardial cell damage or death. Acute myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide.

Coronary Physiology OCCLUDED :

AMI: Pathophysiology Ruptured plaque with occlusive thrombus

Histology of Coronary Artery Stenosis

Clinical Presentation Angina Pectoris Sudden Death Arrythmias Heart Failure

Complications and Prognosis

Indications: Why Intervene? Prevention Of Sudden Cardiac Death (SCD) Acute Pump Failure Arrhythmias Prevention of Subacute Complications Arrhythmias Mechanical complications (mitral valve regurgitation, VSD) Heart Failure (Ischemic Cardiomyopathy) Long-term Survival

Fig 2 Kaplan-Meier cardiovascular mortality in 28 day survivors of acute myocardial infarction: Perth MONICA cohort 1984-93. Tom Briffa et al. BMJ 2009;338:bmj.b36 2009 by British Medical Journal Publishing Group

Variables associated with 30d mortality in AMI patients

The 95% CI for the OR of variables found to be significantly associated with five-year survival after discharge from hospital following an acute myocardial infarction (MI)

Deaths per 100,000 population Decline in Deaths from Cardiovascular Disease in Relation to Scientific Advances 600 500 400 300 200 100 1958 Coronary arteriography Developed (Sones) 1954 First Open-heart procedure (Gibbon) 1962 First betablocker developed (Black) 1961 Risk factors defined 1961 Coronary care unit developed (Julian) 1969 First description of CABG (Favaloro) 1972 NHBPEP 1976 First HMG CoA reductase inhibitor described (Endo) 1979 Coronary angioplasty developed (Grüntzig) 1980 First implantable cardioverter-defibrillator developed (Mirowski) 1983 CASS 1985 TIMI 1 1985 NCEP 1986 GISSI and ISIS-2 0 1950 1960 1970 1980 1990 2000 2010 2020 Year 1992 SAVE 1993 Superiority of primary PCI vs. fibrinolysis in acute MI noted 2007 Benefit of cardiac resynchronization therapy in heart failure demonstrated 2002 Efficacy of drug-eluting vs. baremetal stents determined 2002 ALLHAT 2009 Left-ventricular assist device as destination therapy in advanced heart failure shown to be effective 2009 Genome wide association in early-onset MI described 2009 Deep gene sequencing for responsiveness to cardiovascular drugs performed Nabel EG and Braunwald E. NEJM 2012;366:54-63

Interventional Options for CAD AMI Thrombolysis Primary PCI Non-AMI ( stable CAD ) PCI CABG

PCI (percutaneous coronary intervention) Balloon Angioplasty / PTCA Stent procedure

AMI Mortality and TIME to reperfusion The importance of time to thrombolysis in acute myocardial infarction and the absolute reduction in 35-day mortality. The benefit from thrombolytic therapy is greatest when it is administered within two hours of symptom onset. The survival benefit is progressively reduced as the delay in therapy increases After two hours, the benefit from thrombolytic therapy fits a linear function (black line) in which the benefit falls by approximately 1.6 lives per 1000 patients per hour of treatment delay.

AMI - thrombolysis 51% mortality reduction at 21days if administered within 1hr of pain onset Mortality among fibrinolytic-treated and control patients according to treatment delay. 18% mortality reduction if administered 4-6 hours of pain onset 1.6 additional deaths per 1hour delay in treatment D-N-T 30 minutes Contra-indicated > 75 years (10% ICH) Harvey D. White, and Frans J. J. Van de Werf Circulation. 1998;97:1632-1646

Fibrinolytic therapy Did save lives compared to placebo, BUT - At best, restored TIMI 3 flow in 55% (rt-pa), + - Incidence of recurrent ischemia and reinfarction + ICH 0.5-1.0% of pts 2 hours after t-pa 6 hours after t-pa

AMI Primary PCI (percutaneous coronary intervention)

POBA in AMI

AMI- POBA vs Thrombolysis 44% mortality reduction at 30d

AMI Primary PCI impact of time on outcome D2B < 60 minutes

Do whatever it takes to reduce time from symptom onset to ER arrival and time from ER arrival to PCI! Public awareness of MI Sx Chest pain centers of excellence with lower DBTs and excellent outcomes Regional coordination Ambulance ECG telemetry Ambulance/ER CCL activation ICs sleep in hospital Continual QI

The Greatest Limitation of Primary PCI in STEMI: Poor recovery of LV function 49 yo man presents with crushing chest pain for 90 mins Baseline

Primary PCI POBA vs Stenting Stenting vs POBA 48% RR in vessel reocclusion 2 nd Gen. DES > 1 st Gen. > BMS at 1 year (mortality, ST and TVR) Thrombus Apiration Initial trials positive Latest trials failed Possible benefit in heavy thrombus burden Direct stenting better than PTCA + stent

CV Death, MI, Shock or Class IV Heart Failure (%) TOTAL: 1 Endpoint (n=10,063) CV death, MI, shock or class IV heart failure at 6 months 8% PCI alone 7.0% 6.9% 6% Thrombectomy 4% 2% HR 0.99 (95% CI 0.85-1.15) P=0.86 No. at risk Thrombectomy PCI alone 0% 0 5033 5030 1 4734 4727 2 4696 4688 3 Months 4678 4666 4 4662 4653 5 4647 4642 6 4628 4618 Jolly SS et al. NEJM 2015:on-line

Non-AMI ( stable CAD ): PCI vs CABG

Non-AMI ( stable CAD ) Low immediate risk (< 1%) Dependent on operator skill (>50 PCIs pa) Worse long-term outcome: Repeat-revascularisation Angina Mortality benefit (none??) 2nd Generation DES PCI (stenting)

Coronary Bypass Surgery

Non-AMI ( stable CAD ) Indication: (greatest mortality benefit) Triple Vessel Disease (TVD) Left Main Stem Proximal LAD Higher perioperative mortality and stroke 3-5% Operator skill and experience CABG

CABG Improved long-term outcome LIMA to LAD drives mortality benefit 98% 10-year LIMA patency rate Repeat revascularisation Vein graft failure

CABG Complete revascularisation Preserves myocardium Greater mortality benefit Arterial grafts Improved long-term outcome Technically challenging Longer procedure time ~ operative mortality

PCI vs CABG: LM ORIGINAL ARTICLE Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease Gregg W. Stone, M.D., Joseph F. Sabik, M.D., Patrick W. Serruys, M.D., Ph.D., Charles A. Simonton, M.D., Philippe CONCLUSIONS In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776.)

PCI vs CABG

Stable CAD: Medical Therapy

Criticism on COURAGE "The COURAGE investigators have interpreted the results saying that since there were no differences in death or MI, why start with angioplasty? I interpret it the other way," Stone told heart wire. "I interpret it as there was no increased death or MI with angioplasty and in fact there was a 10% to 15% trend toward reduction in death and MI, and in the patients who had symptoms, symptoms were significantly improved.... So I look at COURAGE as a supportive trial for angioplasty as a safe and effective first-line approach if you want to provide your optimal care to patients and especially those who have symptoms. For the ones who don't have symptoms, there the trial is more equivocal, and I think that, depending on the coronary anatomy, probably either approach is acceptable." As a final point, the Viewpoint authors point out that symptoms were significantly reduced throughout three years of follow-up, and need for antianginal medications was reduced for five years, despite the fact that 32% of the patients in the OMTalone arm crossed over at a mean of 10.8 months and required angioplasty.

Thank You!