Improvements in Revascularization Reduce Cardiac Death, MI and Repeat Revascularization, but not All-Cause Mortality in Japan

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Amid changing practice patterns and improvements in technique and technology, long-term rates of mortality have held steady in Japanese patients undergoing coronary revascularization between the bare-metal stent (BMS) and drug-eluting stent (DES) eras. However, other outcomes including cardiac death, myocardial infarction (MI), and repeat revascularization at 2 years all decreased, reports a registry study published online March 7, 2014, ahead of print in the American Journal of Cardiology.

A team led by Takeshi Kimura, MD, of Kyoto University (Kyoto, Japan), looked at nearly 20,000 patients who were enrolled in the CREDO-Kyoto registry at the time of their first isolated coronary revascularization; those with AMI were excluded. The researchers compared 2 groups:

  • Cohort 1: treated in the BMS era, 2000 to 2002 (n = 8,986)
  • Cohort 2: treated in the DES era, 2005 to 2007 (n = 10,339)

Patients in Cohort 2 tended to be older than those in Cohort 1, and they were more likely to be male and have comorbidities such as diabetes, hypertension, and peripheral vascular disease. They also were less likely to have histories of MI.

Lower Cardiac Death, MI, Repeat Revascularization

Use of PCI over CABG rose from Cohort 1 to Cohort 2 (73% vs 81%), especially in patients with 3-vessel disease (50% vs 61%) and left main disease (18% vs 36%). Evidence-based medications also were more prevalent in the DES vs BMS eras, with use of statins (28% vs 47%), beta-blockers (17% vs 25%), and ACE inhibitors/ARBs (33% vs 47%) each increasing (P < 0.001 for all comparisons).

Among patients receiving PCI, stent use became more common during the DES era compared with the BMS era (94% vs 82%). Patients who underwent CABG in Cohort 2 were more likely than those in Cohort 1 to do so off-pump (65% vs 43%) and with the internal thoracic artery as a bypass graft (98% vs 94%; P < 0.001 for all comparisons).

At 2-year follow-up, the rates of all-cause death, cardiac death, MI, and stroke were similar between the 2 groups, though patients treated in Cohort 2 were less likely to require repeat revascularization. After multivariable adjustment, however, the differences in cardiac death and MI became statistically significant (table 1).

Table 1. Clinical Outcomes at 2 Years

 

 

Cohort 1
(n = 8,986)

Cohort 2
(n = 10,339)

Adjusted HR
(95% CI)

P Value

All-Cause Death

6.2%

6.4%

0.91
(0.81-1.03)

0.15

Cardiac Death

3.3%

3.1%

0.84
(0.71-0.997)

0.047

MI

2.9%

2.5%

0.80
(0.67-0.96)

0.02

Stroke

3.4%

3.6%

0.97
(0.82-1.14)

0.71

Repeat Revascularization

29.7%

24.2%

0.73
(0.69-0.77)

< 0.001


Among those who received PCI, Cohort 2 had a lower risk of MI (adjusted HR 0.80; 95% CI 0.65-0.98; P = 0.03) and repeat revascularization (adjusted HR 0.63; 95% CI 0.60-0.67; P < 0.001). In the CABG group, there were no significant differences in any of the endpoints, though there were positive trends for cardiac death (adjusted HR 0.74; 95% CI 0.54-1.02; P = 0.07) and MI (adjusted HR 0.74; 95% CI 0.48-1.12; P = 0.15) in Cohort 1.

Patients with severe CAD, whether 3-vessel or left main, again had a lower likelihood of needing repeat revascularization during the DES era (adjusted HR 0.85; 95% CI 0.77-0.93; P = 0.001) as well as a trend toward lower risk of cardiac death (adjusted HR 0.81; 95% CI 0.65-1.01; P = 0.07).

Secondary Prevention, Shift to PCI Both Important

“[T]he long-term mortality of CAD patients undergoing coronary revascularization in [real-world] clinical practice has not been significantly changed despite introduction of new treatment modalities and strategies including DES, more common use of arterial graft, and more liberal use of evidence-based medications,” Dr. Kimura and colleagues write.

There are 2 main drivers that could have opposing impacts on total mortality, they suggest. Improved secondary prevention, though “far from being optimal,” would likely lead to better results, the researchers note, while the decrease in CABG may have negatively affected survival in that the overall patient population had high levels of diabetes (40.8%) and multivessel CAD (64.4%).

Given that a substantial proportion of deaths were noncardiac, the rise in comorbid cancer from 7% in Cohort 1 to 10% in Cohort 2 may also have played a role (P < 0.001). Increased use of DES and evidence-based medications including statins could be responsible for the drop in MI, they add.

“[F]urther improvement of long-term outcomes… could be expected in the near future by improved treatment strategies such as the more appropriate selection of revascularization procedures for severe coronary artery disease, revascularization based on evaluation of physiological ischemia, and more stringent adherence to evidence-based medicines,” the investigators conclude.

In a telephone interview, Jeffrey W. Moses, MD, of NewYork-Presbyterian Hospital/Columbia University Medical Center (New York, NY), told TCTMD that there has not been a similarly broad study of revascularization—both PCI and CABG—in the United States, so it is difficult to draw direct comparisons to the Japanese experience.

“What I find interesting here, first of all, is that MI went down in spite of a shift toward much heavier use of PCI, especially in complex disease,” Dr. Moses commented, noting that the stable risk of all-cause death can be attributed to the fact that “sicker patients” were being treated in Cohort 2. “And even though they talk about no change in overall death, cardiac death went down,” he said. “They underplay it for some reason. Obviously, it breaks down in some of the subgroups to not be statistically significant but the trends are clear, even in the face of very low statin use even in the second era.”

Today’s outcomes are likely even better, Dr. Moses suggested. “It’s a different era now.... If they extended this to a contemporary cohort, you’d expect these trends to be even more accentuated,” he said.

 

 


Source:

Shiomi H, Morimoto T, Makiyama T, et al. Evolution in practice patterns and long-term outcome of coronary revascularization from bare-metal stent era to drug-eluting stent era in Japan. Am J Cardiol. 2014;Epub ahead of print.

 

 

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Disclosures
  • The study was funded by the Pharmaceuticals and Medical Devices Agency in Japan.
  • Dr. Kimura reports no relevant conflicts of interest.
  • Dr. Moses reports serving as a consultant to Boston Scientific.

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