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Higher Dose Rapamycin in Diabetics Alleviates Restenosis (HiDRAR) Study

Professor Martin T Rothman and Dr Ajay Jain Bart’s
& The London NHS Trust London Chest Hospital, London, United Kingdom

This prospective randomised double blind controlled trial is designed to assess the clinical event rate and in-stent restenosis (ISR) rates following treatment with a drug eluting stent (DES) that delivers a high dose of rapamycin compared to standard dose rapamycin DES, in diabetic patients with coronary artery disease and angina. The stents will be coated with a tailored dose of rapamycin in-house using the Translumina Stent Coating System™ (Translumina GmbH, Germany ). The difference in clinical event rates and severity of restenosis between the two treatment modalities will be investigated.
The rate of restenosis is higher in diabetics following angioplasty and therefore this group are at particular risk of recurrent events. The benefits of drug elution at conventional dose in ISR in diabetic patients is limited, with diabetic patients continuing to have higher restenosis rates than non-diabetics in the DES era. The role of high dose DES in diabetic patients has not been investigated.

Diabetes and coronary artery disease
Diabetes is a chronic disease with high cardiovascular morbidity and mortality. Although there has been considerable improvement in managing patients with coronary artery disease, adverse events remain heightened among patients with diabetes. Epidemiological studies have reported a two fold increased risk of ischaemic heart disease amongst men and three fold amongst women who are diabetic.

Sirolimus or, as it is more often referred to, Rapamycin will coat the stents to be used. It evolved from a failed macrolide antibiotic that was found to inhibit smooth muscle proliferation by binding an intracellular protein receptor FKBP12, which in turn blocks a signal transduction protein (TOR), preventing cell cycle progression at the G1/S phase transition. In 1999, rapamycin was approved by the US Food and Drug Administration as an agent to prevent acute rejection in renal transplant patients. The implantation of rapamycin-coated stents in de-novo lesions has been shown to safe and effective in inhibiting neo-intimal formation.

Some degree of restenosis may be attributable to insufficient inhibition of tissue reaction and neo-intimal growth by the anti-proliferative action of the specific drug or dose used. This leads to the inference that an individualised approach should be adopted by tailoring the choice and dosing of eluting drugs according to the specific lesion or patient characteristics. The potential benefit in terms of reduction in restenosis by the use of higher dose eluting stents in diabetics has not been investigated.
Links to
British Cardiovascular Intervention Society
The Vascular Society
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