The safety of long-term administration of losartan in current clinical practice: a non-intervention NCT-CZ 14/04/LOZ study

Česká verzia

Authors: J. Krupička ¹; K. Ceypová ²; P. Kristenová ²; T. Hauser ²
Authors place of work: Kardiochirurgické oddělení Nemocnice Na Homolce Praha, přednosta prim. MUDr. Štěpán Černý, CSc. ¹; Korporátní oddělení Klinické studie a vývoj, Zentiva a. s., Praha, vedoucí MUDr. Tomáš Hauser ²
Published in the journal: Vnitř Lék 2008; 54(11): 1031-1038
Category: Original Contributions

Summary

Introduction:
Losartan is the longest used angiotensin II receptor blocker in clinical practice [1]. It is one of the first‑line drugs for the treatment of hypertensive disease and there is enough data available today about its use in the treatment of the disease, including some specific situations (left ventricular hypertrophy, cerebrovascular accidents) and cases when the hypertension disease combines with another disease (e. g. diabetic nephropathy) [2]. The primary objective of the non‑intervention multicentre prospective observational open clinical assessment NCT-CZ 14/04/LOZ was to verify on a large sample of patients the safety of Lozap^® and Lozap H^® in current clinical practice.

Material and method:
The six-month clinical study enrolled patients with recently diagnosed hypertension and/or poorly controlled hypertension [blood pressure ≥ 140/90 mm Hg: 4 432 patients (96%); blood pressure: ≤ 139/89 mm Hg 84 patients (2%); value unspecified: 83 patients (2%)]. A standard form was used for data acquisition. A total of 4,599 patients was enrolled (of which 2,386 women, i.e. 51.9%) with mean age 61 ± 12 years (18–95 years; median 60 years) with additional risk factors (cardiovascular diseases in 48%, diabetes mellitus in 33%, lipid metabolism disorder in 42%, obesity in 45% and smoking in 26% of cases, respectively). 2,631 patients (57%) had previously diagnosed hypertension. The average blood pressure (BP) at enrolment in the study was 159/95 mm Hg (median 160/95 mm Hg), and the average heart rate was 76 strokes/min (median 76).

Results:
The most frequently used dose was 50 mg of losartan (Lozap^® or Lozap H^®) – in 4,006 patients (87%) at enrolment in the study and in 3,982 patients (87%) at the end of the study. Adverse effects related to the treatment during the study were reported in a total of 9 patients (0.2%). The therapy was assessed as well tolerated in 96% of patients (4,409), as fairly tolerated in 3% of patients (131) and as poorly tolerated in 0.1% of patients (4). Systolic and diastolic blood pressure decreased by 23 mm Hg and 14 mm Hg respectively to a mean value of 136/81 mm Hg (median 135/80 mm Hg) (P < 0.001 for both systolic and diastolic BP). Improvement in patient status was recorded in 93% of cases (4,254 patients) and no change was recorded in 6% of cases (294 patients).

Conclusion:
Losartan in the form of Lozap^® or Lozap^® is a safe and effective treatment of patients with hypertensive disease. It is effective and safe beginning with the dose of 50 mg and its combination with a diuretic represents a good and safe therapy in patients with insufficient BP response to a 50 mg dose of losartan alone. In case of poor blood pressure response the dose has to be titrated to 100 mg.

Key words:
losartan – hypertensive disease – non‑interventional study – adverse effects

Zdroje

1. Bultas J. Blokátory receptorů AT1 ve světle medicíny založené na důkazech. JACC-CZ 2002; 4: 247–248.

2. Widimský J jr et al. Arteriální hypertenze – současné klinické trendy. IV. sympozium – sborník přednášek. Praha: Triton 2006.

3. Mancia G, De Backer G, Dominiczak A et al. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2007; 28: 1462–1536.

4. Bouček P. Prevence vzniku diabetu 2. typu při léčbě antihypertenzivy ovlivňujícími systém renin‑angiotensin. Vnitř Lék 2006; 52: 791–796.

5. Law MR, Moris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomized trials. BMJ 2003; 326: 1427–1431.

6. Esposti LD, Di Martino M, Saragoni S et al. Pharmacoeconomics of antihypertensive drug treatment: an analysis of how long patients remain on various antihypertensive therapies. J Clin Hypertens 2004; 6: 76–84.

7. Miller FG, Silverman HJ. The ethical relevance of the standard of care in the design of clinical trials. Am J Respir Crit Care Med 2004; 169: 562–564.

8. Grapow MT, von Wattenwyl R, Guller U. Randomized controlled trials do not reflect reality: real-world analyses are critical for treatment guidelines! J Thorac Cardiovasc Surg 2006; 132: 5–7.

9. The ALLHAT Collaborative Research Group. Major outcomes in high‑risk hypertensive patients randomized to angiotensin‑converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288: 2981–2997.

10. Cífková R, Horký K, Widimský J sr et al. Doporučení diagnostických a léčebných postupů u arteriální hypertenze – verze 2004. Doporučení České společnosti pro hypertenzi. Vnitř Lék 2004; 50: 709–722.

11. Dahlof B, Devereux RB, Kjeldsen SE et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995–1003.

12. Kardas P. The DIACOM study (effect of DosIng frequency of oral Antidiabetic agents on the COMpliance and biochemical control of type 2 diabetes). Diabetes Obes Metab 2005; 7: 722–728.

13. Ross SD, Akhras KS, Zhang S. Discontinuation of Antihypertensive Drugs Due to Adverse Events: A Systematic Review and Meta‑analysis. Pharmacotherapy 2001; 21: 940–953.

14. Holden WL, Scarazzini LJ. Postmarketing surveillance for drug safety. Clin Pharmacol Ther 2004; 75: 491–494.

15. Steg PG, Lopez-Sendon J, Lopez de Sa E et al. External validity of clinical trials in acute myocardial infarction. Arch Intern Med 2007; 167: 68–73.

16. Davis BR, Oberman A, Blaufox MD et al. Effect of antihypertensive therapy on weight loss. The Trial of Antihypertensive Interventions and Management Research Group. Hypertension 1992; 19: 393–399.