Oral Sirolimus Appears to Augment Efficacy of BMS

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Short-term use of oral sirolimus after bare-metal stent (BMS) implantation reduces restenosis and repeat revascularization compared with stenting alone and may potentially match the efficacy of drug-eluting stents (DES) at lower cost. The findings, culled from a review of the literature, were published online August 8, 2013, ahead of print in the American Journal of Cardiology.

Tarun W. Dasari, MD, MPH, of the University of Oklahoma Health Sciences Center (Oklahoma City, OK), and colleagues conducted a systematic review of research on combined use of BMS and oral sirolimus, identifying 4 studies (n = 488) conducted between 2006 and 2010. Three of the trials gave a sirolimus loading dose (range, 4-10 mg). Total duration of sirolimus use was 14 days in 2 studies and 30 days in 2 studies, and daily doses varied. Follow-up ranged from 7 months to 5 years.

Three studies assessed BMS use with vs. without oral sirolimus:

  • Rodriguez AE, et al. J Am Coll Cardiol. 2006;47:1522-1529.
  • Cernigliaro C, et al. Cardiology. 2010;115:77-86.
  • Stojkovic S, et al. Catheter Cardiovasc Interv. 2010;75:317-325.

Only 1 trial, ORAR III, directly compared BMS plus oral sirolimus vs. DES. Results were published in 2 papers:

  • Rodriguez AE, et al. Eurointervention. 2009;5:255-264.
  • Rodriguez AE, et al. Catheter Cardiovasc Interv. 2012;80:385-394.

Outcomes Favor Oral Sirolimus

In each of the 3 trials looking at BMS with or without oral sirolimus, the adjunctive medication was associated with lower rates of TLR at 6 to 12 months. Two trials found reduced in-stent restenosis at follow-up (table 1).

Table 1. Outcomes After BMS With vs. Without Oral Sirolimus

 

BMS + Sirolimus

BMS Alone

In-Stent Restenosis
Rodriguez AE, et al
Stojkovic S, et al

 
12%
9%

 
36%
49%

TLR
Rodriguez AE, et al
Cernigliaro C, et al
Stojkovic S, et al

 
8%
26%
7%

 
37%
44%
23%


In ORAR III, BMS plus oral sirolimus showed a trend toward lower TLR compared with DES. The treatment also was more affordable than DES use (table 2).

Table 2. Outcomes After BMS/Oral Sirolimus vs. DES

 

BMS + Sirolimus

DES

TLR

10%

14%

Mean per Patient Cost
1 Year
3 Years

 
$5,365.50
$6998.10

 
$6,921.50
$11,201.50


Up to one-quarter of patients receiving oral sirolimus suffered minor side effects including rash (2-3%), angioedema (0-2%), fever (0-5%), and assorted GI issues (diarrhea, 2.5-12%; enteritis, 0-2%; gastritis, 1-9%; constipation, 0-4%; mouth ulceration, 2.5-16%).

Ideal Dosing, Duration Still Unknown

“The studies discussed in this systematic review address a very relevant clinical problem and are hypothesis generating, providing useful insights into the design and conduct of future large-scale randomized trials to assess the efficacy and safety of this strategy not only in coronary disease but also peripheral artery disease,” the researchers note, referring to the data as “encouraging.” In particular, future studies must address dosing and duration of oral sirolimus, they advise.

Dr. Dasari told TCTMD in an e-mail communication that he is unaware of any clinical practice currently employing the strategy of oral sirolimus in conjunction with BMS. “No clinical trials are currently underway testing this strategy in larger patient population,” he added, noting that he is hoping to evaluate the idea not only in a larger US-based study but also specifically in patients who are unlikely to comply with or cannot remain on dual antiplatelet therapy for longer than 1 month due to upcoming surgery, bleeding risk, or concomitant anticoagulant use.

Importantly, Dr. Dasari said, “[t]here are no additional safety concerns with this strategy, other than minor side effects. . . . As the administration of this drug is only for the first 2 to 4 weeks post PCI, long-term side effects are unlikely. It is an orally administered drug so easy to comply with.” Moreover, the potential to save money “could be an important issue here especially in the current state of health care/economy where cost effectiveness is widely welcomed,” he added.

Therapy in Competition with Drug-Eluting Balloons

In a telephone interview, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), confirmed to TCTMD that European practices occasionally use oral sirolimus with BMS and that the drug is approved both in Europe and the United States.

“The problem with all these studies is that there is no standardized dose,” he commented. “The other thing is that those studies are fairly old and so the BMS are fairly clunky. The newer ones are better.”

Though there was much interest in oral sirolimus 8 to 10 years ago, drug-eluting balloons have since become available, Dr. Brener pointed out. Balloons “make more sense” than oral sirolimus, he suggested, because drug delivery is more localized.

 


Source:
Dasari TW, Patel B, Saucedo JF. Systematic review of effectiveness of oral sirolimus after bare-metal stenting of coronary arteries for prevention of in-stent restenosis. Am J Cardiol. 2013;Epub ahead of print.

 

 

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Disclosures
  • Drs. Dasari and Brener report no relevant conflicts of interest.

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