Drug-eluting Stents Impede Coronary Collateral Function

BERN, Switzerland, Dec. 27 -- Six months after implantation of coronary stents, patients who received drug-eluting devices had 30% to 40% less collateral function than patients treated with bare metal versions, found researchers here.

The collateral flow index averaged 0.154 +/- 0.097 in drug-eluting stent patients versus 0.224 +/-0.142 among patients treated with bare metal devices ( P=0.0049), reported Christian Seiler, M.D., of University Hospital Bern, and colleagues, in the Jan. 2, issue of the Journal of the American College of Cardiology.

As a result, 50 of 60 patients treated with drug-eluting stents had collaterals that were insufficient to prevent ischemia during occlusion, versus 33 of 60 patients getting bare metal devices (P=0.001).

"Considering the salvaging effect of well-grown collaterals, a potential clinical impact of this finding is that in the presence of stent thrombosis myocardial infarction size and, thus, mortality may be larger in drug-eluting stents than in bare-metal stent-treated patients," Dr. Seiler and colleagues wrote.

Dr. Seiler concluded that the study's findings suggested "a further clinical risk aside from that of more frequent clinical events due to endothelial dysfunction and deficit of endothelial progenitor cells."

Moreover, if stent thrombosis occurs, the lack of adequate collateral function could "render the thrombosis more dangerous (i.e. worsen the consequences of abrupt coronary occlusion by increasing mortality)."

To support this conclusion, Dr. Seiler cited published studies in which the six-month mortality after stent thrombosis in patients with bare-metal stents ranged form 11% to 21%, whereas mortality following drug-eluting stent thrombosis ranged from 29% to 45%.

Dr. Seiler and colleagues studied 120 patients, mean age 60, including 19 women, who had long-term stable coronary artery disease in one to three vessels.

Thirty-seven of the drug-eluting stent patients received Cypher (sirolimus-eluting) stents and 23 were treated with Taxus (palitaxel-eluting) stents.

All patients underwent follow-up angiography because of recurrent chest pain.

Coronary collateral function was assessed using coronary pressure measurements. Additional measurement was done with a unipolar intracoronary ECG from the angioplasty guidewire and three surface leads.

Collateral function was measured following diagnostic angiography. Before hemodynamic and collateral measurements, patients were given 5,000 U of heparin, and two puffs of oral nitroglycerin spray were administered. The pressure guidewire was positioned distal to the site of the angioplasty balloon occlusion and fractional flow reserve was obtained.

If indicated, percutaneous coronary intervention for treatment of restenosis was performed following collateral measurement.

There were no significant differences in arterial blood pressure, left ventricular ejection fraction, left ventricular end-diastolic pressure, central venous pressure immediately before vascular occlusion, or fractional flow reserve between the two stent groups.

"ST-segment elevation of >1 mm on intracoronary ECG (i.e., insufficient collateral flow) was seen significantly less often in the [bare-metal stent] group than in the [drug-eluting stent] group," they wrote.

Moreover, the collateral flow index "was significantly higher in the [bare-metal stent] group than in the [drug-eluting stent] group," they said.

And the difference in collateral flow index was greatest for patients with Taxus stents compared with bare-metal stents.

The authors said that evidence from animal studies suggests that sirolimus (Rapamycin) has anti-angiogenic properties, which would explain the apparent suppression of collateral growth.

The authors also cited published studies that found a higher rate of exercise or acetylcholine-induced endothelial dysfunction in 18 of 21 patients with drug-eluting stents versus three of 16 patients who received bare-metal stents.

Because endothelial dysfunction "can be regarded as the earliest stage of atherosclerosis, and its presence foretells adverse cardiovascular events, an unfavorable clinical impact related to [drug-eluting stents] can be imagined," they wrote.

The authors said their study adds two important findings to these earlier observations: both Cypher and Taxus stents have a negative effect on collateral function and this negative effect is more pronounced with Taxus.

But they pointed out that the study was limited by its cross-sectional rather than longitudinal design, and the quality of matching, while very high, was not absolute.

In an editorial that accompanied the study, Morton J. Kern, M.D., of the University of California-Irvine, said that while the findings from the Swiss group should be considered theoretical until confirmed in a larger study, the study nonetheless "highlights a previously unappreciated downside of [drug-eluting stents]."

Anthony N. DeMaria, M.D, editor-in-chief of the JACC, released a statement urging caution in interpreting the Swiss study.

Noting that acute stent thrombosis is an infrequent occurrence, he said the study did not "establish any link between the effects upon collateral formation and stent thrombosis."

Finally, Dr. DeMaria said the "effect of impaired collateral formation upon the outcome of acute stent thrombosis is speculative."