Results of ESPRIT Study Published in Clinical Nephrology
INGELHEIM AND LONDON -- April 4, 2005 -- The results of the Efficacy and Safety in Patients with Renal Impairment treated with Telmisartan (ESPRIT) study, published today in Clinical Nephrology, show that treatment with the angiotensin receptor blocker (ARB) telmisartan (Micardis®/Pritor®) is effective and well-tolerated in hypertensive patients with chronic kidney disease (CKD).1 The new study demonstrates that telmisartan is a viable treatment option in hypertensive patients with severe CKD, as well as those patients with mild/moderate CKD.
In the open-label, multicentre ESPRIT study, 82 patients with mild-moderate hypertension (diastolic blood pressure 90-109mmHg) and CKD (mild/moderate, severe, or haemodialysis patients) received treatment with once daily telmisartan 40-80 mg to measure the effects on blood pressure and renal function, and assess the tolerability of telmisartan.
After 12 weeks, efficacy of telmisartan was confirmed by the diastolic blood pressure (DBP) and systolic blood pressure (SBP) target responses. Over three quarters (76.8%) of patients achieved the target DBP of <90mmHg or a reduction €10mmHg, the primary endpoint of the study.1 The overall reduction of DBP compared to baseline was 12.3 € 9.4 mmHg.1
Furthermore, 76.8% of patients in the ESPRIT study achieved SBP <140 mmHg or a reduction €10 mmHg.1 Incidence of adverse events was low and no patients were withdrawn due to lack of efficacy.1 Telmisartan showed excellent tolerability, with a treatment compliance of more than 97% observed in the study. These results demonstrate that telmisartan is an effective and well-tolerated anti-hypertensive treatment for patients with CKD.1
Lead study investigator, Dr Arya Sharma, Professor of Medicine, McMaster University, Ontario, Canada, commented, ôHigh blood pressure is both a common cause and consequence of CKD. Rigorous control of blood pressure, with an effective anti-hypertensive agent such as telmisartan, is essential in reducing cardiovascular disease, the most common cause of death in patients with chronic kidney disease.ö
Chronic kidney disease is a worldwide problem, being under-diagnosed and undertreated.2 There are currently an estimated 5.6 million adults in the USA with elevated serum creatinine values, a marker of CKD, and approximately 70% of these are hypertensive.3
Current US and European guidelines advocate first-line use of an ARB or ACE inhibitor to lower blood pressure in CKD patients.3,4 Many studies have demonstrated that anti-hypertensive regimens that include an ARB or an ACE inhibitor are more effective in slowing progression of CKD than other anti-hypertensive regimes.5-9
The ESPRIT study results are consistent with the findings, from 2001, of a double-blind randomised trial that showed telmisartan to be as effective as enalapril in achieving DBP target in moderate CKD patients.10 More recently, the Diabetics Exposed to T elmisartan And enalaprIL (DETAIL) study, published in the New England Journal of Medicine, November 2004, showed that telmisartan was as effective as enalapril in protecting hypertensive patients with type 2 diabetes against the progression of diabetic nephropathy.11
Dr. Sharma concluded, “The benefits of blood pressure lowering in CKD patients to prevent CKD progression and reduce cardiovascular risk are well recognized. The results of ESPRIT show telmisartan offers an ideal combination of both blood pressure lowering and good tolerability making it a valid choice as a first line anti-hypertensive in renal patients independent of CKD severity.”
Notes
a) As a result of the ESPRIT study, the European Commission approved the removal of the contraindication for patients with severe renal impairment from the Micardis® / Pritor® European label.
b) The ESPRIT study was funded by Boehringer Ingelheim.
c) Chronic kidney disease is defined by the presence of a marker of kidney damage, such as proteinuria, or a decreased glomerular filtration rate (GFR) for three or more months. Cardiovascular disease is the most common cause of death in individuals with chronic kidney disease.3 Additionally, chronic kidney disease is an independent risk factor for cardiovascular disease.3
d) ESPRIT is one of a number of studies of telmisartan in patients with renal impairment which have already delivered encouraging results.10,12-16 The efficacy of telmisartan in these patients continues to be investigated as part of the ongoing PROTECTION™ (Programme of Research tO show Telmisartan End-organ proteCTION) study programme (co-sponsored by Boehringer Ingelheim and GlaxoSmithKline) involving more than 5,500 patients from 32 countries worldwide.17
e) Telmisartan (Micardis®/ Pritor®) was discovered and developed by Boehringer Ingelheim, Germany. Boehringer Ingelheim markets telmisartan under the trademark Micardis® in 84 countries around the world, including the USA, Japan and major European countries. In Canada and Australia GlaxoSmithKline (GSK) and Boehringer Ingelheim co-promote telmisartan under the Micardis® trademark. GSK currently promotes telmisartan as Pritor® under a co-marketing agreement with Boehringer Ingelheim in 30 countries excluding the USA. Telmisartan was licensed to GSK from Boehringer Ingelheim in March 1998. The European, centralised marketing authorisation for telmisartan 40 mg & 80 mg tablets was granted to GSK (Pritor®) and Boehringer Ingelheim (Micardis®) in December 1998. Furthermore, Boehringer Ingelheim markets telmisartan in cooperation with Bayer AG in some European countries, Yamanouchi in Japan and Abbott Laboratories in the USA.
References
1. Sharma A, et al. Telmisartan in patients with mild/moderate hypertension and chronic kidney disease. Clin Nephrol 2005;63:250-257.
2. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Accessed at http://www.kidney.org/kls//professionals/aboutckd.cfm on 11 Jan 2005.
3. Chobanian AV, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA 2003;289(19):2560-2572.
4. Guidelines Committee. 2003 European Society of Hypertension -- European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003;21(6):1011-1053.
5. Lewis EJ, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993;329:1456-62.
6. Brenner BM, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-9.
7. Lewis EJ, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-60.
8. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997;349:1857-63.
9. Wright JT, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: Results from the AASK trial. JAMA 2002;288:2421-31.
10. Hannedouche T, et al. Evaluation of the safety and efficacy of telmisartan and enalapril, with the potential addition of frusemide, in moderate-renal failure patients with mild-to-moderate hypertension. J Renin Angiotensin Aldosterone Syst 2001;2:246--254.
11. Barnett A, et al. Comparison of Angiotensin-II receptor blocker and angiotensin-converting enzyme inhibition in subjects with type 2 diabetes and nephropathy. N Engl J Med 2004;351:1952-61.
12. Vogt L, et al. Effects of telmisartan versus hydrochlorothiazide on albumin excretion in isolated systolic hypertension. A sub-study from the ARAMIS study. American Society of Nephrology, 2002, abs.
13. Redón J, et al. Renin-angiotensin system gene polymorphisms: relationship with blood pressure and microalbuminuria in telmisartan-treated hypertensive patients. Phamacogenomics J 2004.
14. Cupisti A, et al. Effect of telmisartan on the proteinuria and circadian blood pressure profile in chronic renal patients. Biomed Pharmacother 2003;57(3-4):169-172.
15. Ryšavá R, et al. Influence of telmisartan on blood pressure and proteinuria in the patients with renal insufficiency and proteinuria. In: Timio M, Wizemann V, Venanzi S, editors. Cardionephrology 8. Italy: Editoriale Bios, 2004.
16. Ucak S, et al. Combination of telmisartan and ACE-I significantly reduces urinary albumin excretion in hypertensive patients with type 2 diabetes. 38th Annual Meeting of the European Association for the Study of Diabetes Budapest, Hungary, September 1-5, 2002, abs.
17. Weber M. The telmisartan Programme of Research tO show Telmisartan End-organ proteCTION (PROTECTION). J Hypertens 2003;21(Suppl 6):S37-S46.
SOURCE: Boehringer Ingelheim and GlaxoSmithKline
