The renin-angiotensin system plays an important role in the regulation of cardiovascular homeostasis. Angiotensin II causes vasoconstriction, decreases sodium and water excretion via stimulation of the secretion of aldosterone and facilitates sympathetic activity. All of these effects increase blood pressure.

Differences between angiotensin receptor blockers (ARBs) are responsible for variations in lipid solubility, distribution, bioavailability, biotransformation, plasma half-life and elimination. All of these factors contribute to differences in their duration of action and, therefore, affect their physiological effects. Telmisartan has s unique pharmacological properties. (1-3) It is highly lipophilic and has rapid membrane permeability kinetics. These properties facilitate easy distribution into tissue. Telmisartan is cleared almost entirely by the liver and it is not metabolized by the cytochrome P450 system and is therefore well tolerated when used in combination with other commonly used medications. No dosage adjustment based on gender, age or in case of renal insufficiency is required. Telmisartan can be taken with or without food. (3, 4)

After the initial rapid absorption telmisartan is slowly eliminated, with a mean terminal elimination half-life of approximately 24 hours. (5) This is the longest half-life of any of the ARB available for the treatment of hypertension. (3) The benefit of the long duration of action of telmisartan is apparent after a missed dose. Early morning blood pressure (BP) surge and 24h-mean BP is linked to target-organ damage and cardiovascular events. Antihypertensive agents should sustain BP control, particularly in the last 6 h of the dosing interval or if dosing is missed. Due to its longer half-life, telmisartan provides consistent and sustained control of blood pressure.The activity of telmisartan is carried over from the previous dose and activity persists beyond the 24 h dosing interval. Moreover, telmisartan provides 48 h protection against loss of BP control following a missed dose, providing extra reassurance for patients who might occasionally forget to take their medication. (6)

The efficacy of telmisartan has been evaluated in many clinical trials in broad spectrum of hypertensive patients. (7) Telmisartan up to 160 mg once daily consistently reduced supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p ≥0.05) to greater extent than placebo at trough or throughout the 24-hour dosage interval. Dosages above 80 mg once daily did not result in further BP reduction in patients with mild to moderate hypertension In addition to placebo controlled trials, telmisartan has been examined with the ACE inhibitors, the ARBs, the beta-blockers and the calcium channel blockers. In these studies, most patients were treated for mild-to-moderate hypertension. The results of clinical studies show that telmisartan typically reduces BP after the first dose, and there is a gradual increase in its antihypertensive effect for up to 12 weeks during continued treatment, with most of the BP reduction occurring during the first 4 weeks. (7)

Like all ARBs telmisartan has no effect on bradykinin metabolism. (8) Comparative clinical trials with ACE inhibitors, for instance lisinopril showed comparable reduction of BP. Although both treatments were generally well tolerated, significantly fewer patients receiving telmisartan experienced treatment-related cough compared with lisinopril (3% vs. 7%; p=0.018). (9)

The impact of switching patients who had previously experienced dry cough with the ACE inhibitor enalapril to telmisartan, also showed reduced risk of cough. (10)

Telmisartan has been compared with ramipril in a broad cross-section of patients at increased cardiovascular risk. In the ONTARGET clinical study it was demonstrated that telmisartan is as effective as ramipril in reducing cardiovascular events in a wide cross-section of at-risk cardiovascular patients, but it was better tolerated. (11)

Telmisartan reduces CV risk not only by reducing the BP, but also by reducing other metabolic parameters which has beneficial effect on CV disease. (12) At the therapeutic doses telmisartan also exerts PPAR (peroxisome proliferator-activated receptor) — activating ability, which cannot be seen with other ARBs. (3, 13) This causes favourable effects on glucose and lipid metabolism, which could be benefitial in patients with hypertension and metabolic disturbances. (3, 14) Telmisartan is so far the only ARB with clinical evidence and indication of cardiovascular event risk reduction. (2, 15)

In September 2013 Krka has complimented its ARBs portfolio in Croatia with a new sartan, telmisartan named Tolura® in dosages of 40 mg and 80mg, providing flexible and effective treatment of hypertension among the Croatian patients. Tolura® is indicated for the treatment of hypertension and cardiovascular prevention — reduction of cardiovascular morbidity in patients with manifest atherothrombotic cardiovascular disease (history of coronary heart disease or peripheral arterial disease) or type 2 diabetes mellitus with documented target organ damage (Figure 1).