Coronary Artery Revascularization in Diabetes Trial - CARDia

Jan 25, 2010
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Trial Sponsor:
Unrestricted research grants from Eli Lilly, Cordis Johnson & Johnson, Bristol-Myers Squibb, Sanofi-Aventis, and the Hammersmith Hospitals Special Trustees. Further support from Boston Scientific, Medtronic, Guidant, and Jomed.
Date Presented:
01/01/2008
Date Published:
01/01/2009
Date Updated:
01/25/2010
Original Posted Date:
01/25/2010
References

Description:

Given the recent advances in the fields of both coronary artery bypass grafting (CABG) as well as percutaneous coronary intervention (PCI) (especially drug-eluting stent PCI), the goal of this trial was to compare the relative efficacy of CABG versus PCI in diabetic patients with multivessel disease, who were deemed eligible for either CABG or PCI.

Hypothesis:

PCI would be noninferior to CABG in the management of diabetic patients with multi-vessel disease or complex single-vessel disease.

Study Design

Study Design:

Patients Enrolled: 510
Mean Follow Up: 12 months
Mean Patient Age: 64 years
Female: 26
Mean Ejection Fraction: 59.5%

Patient Populations:

  • Multi-vessel disease or complex single-vessel disease (ostial or proximal left anterior descending artery)
  • Diabetes mellitus
  • Anatomy suitable for both PCI and CABG

Exclusions:

  • Previous PCI or CABG
  • Age >80 years
  • Left main disease
  • Cardiogenic shock
  • Recent ST-elevation MI (within 6 weeks)
  • Ejection fraction
  • Contraindications to abciximab, aspirin, and clopidogrel

Primary Endpoints:

Composite of death, nonfatal MI, and nonfatal stroke at 12 months.

Secondary Endpoints:

  • Repeat revascularization within 12 months
  • Severe bleeding complications at 30 days
  • New requirement for permanent dialysis
  • Neurological morbidity
  • Quality of life
  • Cost differences between treatments
  • Change in left ventricular function

Drug/Procedures Used:

All patients in the PCI arm received either bare-metal stents (BMS) (29%) or drug-eluting stents (DES) (71%, all sirolimus-eluting), whereas all patients in the CABG arm underwent on- or off-pump bypass.

Concomitant Medications:

All patients in the PCI arm received aspirin, clopidogrel, and abciximab.

Principal Findings:

A total of 510 patients were randomized, 254 to CABG and 256 to PCI. Fourteen patients in the CABG arm, and one patient in the PCI arm crossed over to the opposite arm. About 38% of the patients were on insulin, and the mean duration of diabetes was about 9.6 years, with a mean glycated hemoglobin of about 7.9%. About 29% of the patients were smokers, 4.8% had evidence of renal disease, and about 90% of the patients also had hyperlipidemia. Three-vessel disease was noted in about 65% of the patients; only about 57% of the patients had normal left ventricular function.

The median time from randomization to procedure was very high in both the CABG and PCI arms (38 vs. 64 days); only 22.6% of the procedures were done acutely. The average length of stay was much higher in the CABG arms (7 vs. 1 day).

Of the patients undergoing PCI, the mean number of stents implanted was 3.6, with an average stent length of 71 mm. About 31% of the patients in the CABG arm underwent off-pump CABG; the left internal mammary artery was used in 94% of the patients. The mean number of grafts per patient was 2.9.

The incidence of the primary endpoint of death, myocardial infarction (MI), or stroke at 12 months was similar in the CABG and PCI arms (10.5% vs. 13.0%, p = 0.39). This, however, crossed the noninferiority margin, and hence could not demonstrate noninferiority of PCI compared with CABG. There was no difference in the incidence of death (3.2% vs. 3.2%, p = 0.97), nonfatal MI (5.7% vs. 9.8%, p = 0.09), or nonfatal stroke (2.8% vs. 0.4%, p = 0.07) between the two arms. There was a significant reduction in the incidence of repeat revascularization in the CABG arm compared with PCI (2.0% vs. 11.8%, p

On subgroup analysis of the DES-PCI patients, the overall 12-month primary outcome rate was again similar with CABG and PCI (12.9% vs. 18.0%, p = 0.13). The incidence of repeat revascularization was again lower in the CABG arm compared with PCI (2.0% vs. 7.3%, p = 0.013), whereas the incidence of nonfatal stroke was higher in the CABG arm (2.5% vs. 0%, p = 0.04).

Interpretation:

The results of the CARDia trial indicate that in diabetic patients with multi-vessel disease or complex single-vessel disease, but not left main disease, PCI is not noninferior to CABG for the composite endpoint of death, MI, or stroke at 12 months. Moreover, there is a higher incidence of repeat revascularization with PCI in these patients, even with DES. There is also a higher incidence of stroke in the CABG arm compared with PCI.

One of the limitations of this trial is that it may be underpowered to study differences between the two arms, since the event rates used for sample size calculations were significantly different from those observed in the study. Even so, the results of this trial are similar to the recently presented SYNTAX trial, which demonstrated better outcomes in diabetic patients with left main and/or three-vessel disease, primarily due to a reduction in the incidence of repeat revascularization.

Long-term follow-up data of the CARDia trial are awaited to assess the durability of these results. Moreover, data from other larger ongoing trials on this topic, such as FREEDOM, are eagerly awaited.

References:

Kapur A, Hall RJ, Malik IS, et al. Randomized Comparison of Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting in Diabetic Patients: 1-Year Results of the CARDia (Coronary Artery Revascularization in Diabetes) Trial. J Am Coll Cardiol 2010;55:432-440.

Coronary Artery Revascularization in Diabetics: The CARDia Trial. Presented by Dr. Akhil Kapur at the European Society of Cardiology, Munich, Germany, August/September 2008.

Keywords: Coronary Artery Disease, Stroke, Insulin, Myocardial Infarction, Ventricular Function, Left, Hyperlipidemias, Drug-Eluting Stents, Sirolimus, Percutaneous Coronary Intervention, Length of Stay, Glycated Hemoglobin A, Metals, Mammary Arteries, Coronary Artery Bypass, Diabetes Mellitus


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