DES Associated with Less Downstream Lesion Development than BMS

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Patients who receive drug-eluting stents (DES) for a first coronary intervention are significantly less likely to develop new lesions in the downstream target vessel requiring a second intervention within 1 year than patients who receive bare-metal stents (BMS), researchers report in the October 2011 issue of the American Heart Journal.

While some studies have suggested that use of DES may result in endothelial dysfunction manifested through impaired vascular responsiveness in the downstream vessel as well as contributing to late stent thrombosis, few data exist on the effect of an eluted drug on downstream plaque formation.

In light of this, researchers led by Richard A. Krasuski, MD, of The Cleveland Clinic (Cleveland, OH), collected angiographic images and procedural information from 463 patients who underwent implantation of a single DES or BMS in a proximal coronary artery at their institution between January 1992 and June 2009. The DES cohort consisted of sirolimus-eluting (n = 81) and paclitaxel-eluting stents (n = 40).

All patients had an appropriate control vessel for comparison, and returned for a second intervention within 1 year. In addition to the analysis performed on the entire cohort, propensity matching also was performed.

Compared with BMS, DES were associated with reduced risk of new lesion development in the vessel downstream from the stent for both the entire cohort and the propensity-matched cohort (table 1).

Table 1. Risk of New Lesion Development at 1 Year in Downstream Vessels

^aFor comparison of DES vs. BMS

In control vessels, there was no difference in the development of new lesions in patients receiving BMS or DES in the overall cohort or in the propensity-matched cohort (table 2).

Table 2. Risk of New Lesion Development in Control Vessels

^aFor comparison of DES vs. BMS 

Stent Type Sole Predictor

In multivariable regression analysis of the target vessel, there was a significantly reduced hazard for the development of new downstream lesions in patients receiving DES, which was the only significant predictor in the model (HR 0.39; 95% CI 0.19-0.75; P < 0.01). In addition, when need for downstream interventions was analyzed in the target and control vessels, there was significantly reduced risk in the DES-treated target vessel compared with the BMS-treated target vessel for both the entire cohort (RR 0.45; 95% CI 0.21-0.85; P = 0.01) and the propensity-matched cohort (RR 0.41; 95% CI 0.16-0.97; P = 0.04).

There was no difference in the need for downstream interventions in the control vessels of DES patients compared with BMS patients in the overall cohort (RR 0.99; 95% CI 0.35-2.45; P = 0.98) or in the propensity-matched cohort (RR 2.1; 95% CI 0.44-14.8; P = 0.36). 

Dearth of Downstream Investigations Surprising

The study authors say it is “most surprising that the downstream consequences of DES on angiographic lesion development have not been previously directly examined,” despite a significant amount of data on other aspects of stents, such as clinical outcomes and mechanism of action.

“A variety of studies investigating coronary artery disease in heart transplant patients, who have baseline endothelial dysfunction, have shown that antiproliferatives such as sirolimus attenuate the rate of atherosclerotic progression,” they write. “In addition, paclitaxel is a well-known immunomodulatory agent and has also been associated with atherosclerotic regression in animal models, as well as reduced inflammation in stented porcine arteries.”

They add that one would expect long-term effects of these drugs on the downstream vascular bed, especially since the product labeling and pharmacokinetic data indicate that antiproliferative agents are detectable in serum for over 2.5 weeks, and the estimated elution period post implantation is 3 months, depending on stent type.  

In an e-mail communication with TCTMD, Dr. Krasuski said he also believes the results are generalizable to other DES types, not only those that elute paclitaxel and sirolimus.

“Obviously there are a number of different antiproliferative agents and each of them may have different effects on atherosclerotic progression/inhibition, but they likely do have a similar
general effect,” he said.

Dr. Krasuski added that he hopes the results of the study encourage further investigation of the effects of downstream drug delivery on distal coronary arteries. Specifically, he said the next step should be a clinical trial utilizing IVUS and examining the coronaries more thoroughly for atherosclerotic progression.

“I think the study should avoid encompassing too many drug-eluting stents, but ideally should include the ones we believe to have the most potent clinical effects,” he said.

Study Details

Risk factors for atherosclerotic disease, including age, mean systolic blood pressure, prior smoking history, BMI, hyperlipidemia, diabetes, and premature family history of CAD were similar between the BMS and DES groups. While patients receiving DES were just as likely as those receiving BMS to be treated for hypertension, they were more likely to be on lipid-lowering medications.

 

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Source:
Krasuski RA, Cater GM, Devendra GP, et al. Downstream coronary effects of drug-eluting stents. Am Heart J. 2011;162:764-771.

 

 

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