By: Dr. Geoffrey Modest
Two drug-company sponsored papers were published in New England Journal of Medicine comparing percutaneous coronary intervention (PCI) with coronary-artery bypass grafting (CABG), looking specifically at how the newer drug-eluting stents compare with surgery.
- a large East Asian non-inferiority study with 27 centers randomly assigned patients with multi-vessel coronary artery disease (CAD) to PCI with everolimus-eluting stent vs CABG (see DOI: 10.1056/NEJMoa1415447).
–880 patients were enrolled (only 1/2 of the anticipated). Mean age 64, 70% male, BMI 25, 41% diabetic, 67% hypertensive, 20% current smoker, 53% hyperlipidemia. 47% with stable angina, 43% unstable angina, 9% acute MI in past 90 days; ejection fraction 59%; 77% with 3 vessel disease and 23% with 2 vessel disease (they excluded those with clinically significant left main disease)
–primary endpoint: composite of death, MI, or target-vessel revascularization at 2 years
–at 2 years: primary endpoint in 11% in PCI group and 7.9% in CABG (absolute risk diff of 3.1%, non-significant p=0.32 for noninferiority)
–at 4.6 years: primary endpoint in 15.3% in the PCI group and 10.6% in CABG (abs diff of 4.7%, with HR 1.47 and p=0.04). No significant difference in composite of death, MI, stroke; but there was increase in PCI group for repeat revascularization in 11.0% vs 5.4%, p=0.003, and spontaneous MI (ie non-periprocedural MI) in 4.3% vs 1.6%, p=0.02.
–on secondary subgroup analysis, comparing diabetic vs non-diabetic: in diabetics, the rate of primary endpoint was much higher in PCI group (19.2% vs 9.1%, p=0.007) and in non-diabetics was a nonsignificant 12.6% vs 11.7%. But on further scrutiny:
–if look at all primary endpoints, diabetics having PCI vs CABG had HR=2.29 (1.35-3.89) and non-diabetics was nonsignificant (HR=1.16)
–if look at deaths: non-significant difference in PCI vs CABG independent of diabetes status. Similarly if look at “death, MI, or stroke”
–if look only at revascularizations, diabetics had HR of 4.31 (1.76-10.6), and nonsignificant for non-diabetics
- an observational New York State registry study looked at long-term mortality after CABG vs PCI with everolimus-eluting stents in patients with multi-vessel CAD in the time period 2008-2011 (see DOI: 10.1056/NEJMoa1412168).
–9223 patients had PCI and 9223 had CABG, mean age 65, 72% male, 80% white/9% black/10% Hispanic, 70% with EF>50%, 35% with prior MI, 45% with 2-vessel dz and the rest with 3. They excluded those with >50% left main lesions.They performed propensity scoring, since more of those with 3-vessel disease got CABG.
–after 2.9 years, those with PCI vs CABG had:
–similar risk of death [3.1% vs 2.9% per year, HR 1.04 (0.93-1.17)]
–higher risk of MI [1.9% vs 1.1% per year, HR 1.51 (1.29-1.77)], but was only significant in the group who had incomplete revascularization by PCI [ie, raising the untested assumption that one could try PCI and consider CABG in the group who cannot be completely revascularized]
–higher risk of repeat revascularization [7.2% vs 3.1%/year, HR 2.35 (2.14-2.58)]
—lower risk of stroke [0.7% vs 1.0%/year, HR 0.62 (0.50-0.76)], especially evident in the first 30 days post-procedure. Though review of the stroke curve shows that even after 4 years, the curves are splaying apart (ie, seems to be increasing strokes over time in the CABG group)
–no difference in outcome in those who had diabetes
So, there are several reasons I am posting about this:
–These drug-eluting stent studies are much more impressive than the earlier stent studies in finding that, for many important endpoints, the stents are pretty much as good as CABG (which is clearly more invasive). The first study found no real difference in nondiabetics, and for diabetics really only for revascularizations. It was notable that all of the data on diabetics above was buried in the supplemental appendix, which requires going onto the New England Journal webpage to access and scrolling down to the middle of the 27 pages…..the second study found higher risk of MI and repeat vascularizations in those with PCI, but no difference in death and a significantly lower risk of stroke. So, this PCI intervention does provide a viable option to the much more aggressive CABG
–I think the first study highlights an increasingly frequent issue in study design: the use of composite endpoints. I believe the rationale is that by grouping several outcomes as the primary outcome, the chance to achieve statistical significance increases. But there may be very different inherent values to these different endpoints, and those are personal values and may be different for the provider and the particular patient. So, for example, I would consider the need for revascularization to be a much less significant outcome, and would be happier with 2 revascularizations than to have a CABG. On the other hand, a stroke would be a much worse outcome for me. And a heart attack in the middle, but closer to the stroke. Another issue obscured by the composite endpoint in this case is the timing of the event. In both studies there is greater immediate mortality with CABG, which, within the first 30 days, in the large second study was 1.1% vs 0.6% with PCI, and an individual patient may well consider it much more important to survive the first month than having long-term benefit years hence. So just looking at the “primary outcome” obscures the fact that embedded in that outcome are really bad outcomes and some not-so-bad, and therefore the primary outcome of the study may not be very useful in making clinical decisions. It then behooves us guys in primary care to evaluate the risks/benefits of the specific clinical outcomes in the context of the values of the individual patient we are treating.