Primary Care Corner with Geoffrey Modest MD: CABG for Ischemic Cardiomyopathy?

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By Dr. Geoffrey Modest

The NEJM just printed the recent study of patients with ischemic cardiomyopathy and the utility of CABG (see DOI: 10.1056/NEJMoa1602001), the STICHES trial (Surgical Treatment for Ischemic Heart Failure Extension Study).

Details:

  • 1212 patients from 22 countries who had coronary artery disease (CAD), ejection fraction (EF) <35% and with coronary arteries amenable to bypass, were randomly assigned to CABG plus optimal medical therapy vs medical therapy alone. Patients recruited from 2002-2007
  • Mean age 60, 12% female, 36% Latino or nonwhite/64% white, BMI 27, 76% with MI, 59% hyperlipidemia, 59% hypertension, 39% diabetes, 86% NYHA class 2 or 3, mean systolic BP 120 mmHg. EF 27%, left main disease in 3%, proximal LAD 67%. 1 vessel disease 22%/2-vessel 38%/3-vessel 37%. No comment on QRS interval.
  • Median follow-up 9.8 years

Results:

  • Primary outcome (death from any cause):
    • 359 (58.9%) in the CABG group and 398 patients (66.1%) in the medical therapy group, a 16% reduction [HR 0.84 (0.73-0.97), p=0.02]
  • Secondary outcomes:
    • Death from cardiovasc cause: 247 patients (40.5%) in CABG group and 297 (49.3%) in med therapy group, a 21% reduction [HR 0.79 (0.66-0.93), p=0.006]
    • ​Death from any cause or hospitalization from cardiovasc causes: 467 patients (76.6%) in CABG group and 524 (87.0%) in med therapy group, a 28% reduction [HR 0.72 (0.64-0.82), p<0.001]​
  • The above results translate to an incremental median survival benefit of about 18 months (1.44 years), and prevention of 1 death from any cause in 14 patients getting a CABG, or one death from a cardiovasc cause for every 11 patients.
  • About 18% had automatic implantable cardioverter-defibillators (AICDs), same in both groups
  • Adverse events: for CABG: 6% had to return to OR, 2% mediastinitis, 8% other infection, 3.6% death within 30 days (vs 1.2% in med-group), 5% pacemaker (vs 0.5% med-group), 1.8% stroke (vs 0.2% med-group)

A few points:

  • The current study is an extension of the STICH trial, which evaluated the results at 56 months, finding no significant difference between the CABG and medical-therapy group in the rate of death from all causes at that time, though the rates of death from cardiovasc causes and death from any cause or hospitalization were significant.
  • Looking at the curves of event rates, the death-from-any-cause and the death-from-cardiovascular-causes curves were similar, with diverging lines showing increasing benefit of CABG over the first 5-6 years, then parallel curves over the rest of the study, suggesting lasting benefit
  • Was this medical therapy optimal? Approx 90% were on ACE-I or ARB, 85% on statin, 90% of b-blocker, 70% on loop or thiazide diuretic, 50% on potassium-sparing diuretic, 20% on digoxin, 84% on aspirin. So, one could argue that there was not full utilization of an aldosterone antagonist, now part of the optimal medical management (of note, the RALES trial, published in 1999, showed a 30% mortality reduction and a 35% lower frequency of hospitalization for worsening heart failure)
  • Was the surgical therapy optimal? Seems pretty good to me. 91% received at least one arterial conduit. The 3.6% perioperative mortality seems reasonable (per the editorialists), though they do suggest using the Society of Thoracic Surgeons risk calculator, which shows the rate can be as low as 0.7% in healthy/low risk, to >7% or more if multiple comorbidities. See http://riskcalc.sts.org/stswebriskcalc/#/calculate

So, to me, this study raises several issues for us and our patients:

  • Though overall this study seems pretty well done, patients need to understand and place their own value on the trade-off of CABG-related early mortality and a reasonably high morbidity (return to OR, infection, stroke) pretty much right away, but living an average of 18 months longer. From the above study, one in 23 will have a really bad short-term outcome (death or stroke).
  • As with any study with long-term follow-up, optimal therapy usually changes by the time the study is published. So, though it seems that the surgical component is quite good (though minimally-invasive surgery did not happen back then), medically adding an aldosterone antagonist more aggressively might have changed the results some, as above. Also, back then we did not have meds for more aggressive lipid management
  • The other real issue, I think, is that they did not use AICDs much in either of the groups. There have been a slew of studies, but the MADIT-2 study was done in 2002, at the time of recruitment for the STICHES study, and showed that after only 20 months, the mortality rates with an AICD was 14.2% vs 19.8% in the medical group alone, a 31% mortality benefit. (By contrast, the mortality benefit from the CABG group in STICHES was not statistically significant until about 6 years or more). The current recommendations for AICD in those with ischemic cardiomyopathy are an EF <35% and NYHA class 2-3, basically the same as in the STICHES study
  • So, what is one to do? It seems that the most logical course at this point is to really maximize medical therapy, including, I think, using more potent statins if needed to lower the LDL to <70, or even consider the PCSK9 inhibitors; making sure that all patients, as tolerated, are on ACE/ARB, b-blockers, an aldosterone antagonist, aspirin, loop diuretics, and other risk factor management. And, if this is insufficient in terms of EF and symptoms, consider an AICD and/or surgery to be discussed with patient. Given the lack of direct comparison between AICD and CABG, my bias would be to the less invasive one.
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