Achieving Blood Pressure Control with Telmisartan and Fixed Dose Combination of Telmisartan and Hydrochlorothiazide

Introduction

Hypertension is a global health problem affecting about one billion individuals worldwide. It is associated with increased cardiovascular and renal morbidity (1) and also represents the leading risk factor for death in the world, causing an estimated 7.5 million deaths a year (13% of all deaths) (2). Moreover, the total burden of cardiovascular disease (CVD) affects about 128 million people annually, with these figures expected to rise because of aging and a greater number of the population having cardiovascular risk factors (3).

Telmisartan is a potent, long-lasting antagonist of the angiotensin II type-1 receptors and is indicated for the treatment of essential hypertension and cardiovascular prevention (4). The efficacy of telmisartan in controlling blood pressure (BP) has been well documented. Its effect arises three hours after the first dose (with maximum BP reduction attained four to eight weeks after the beginning of the therapy) and persists constantly over 24 hours after dosing. Telmisartan effectively reduces both systolic blood pressure (SBP) and diastolic blood pressure (DBP). In most of the studies in which telmisartan was compared with other medication (with or without addition to hydrochlorothiazide; HCTZ), it showed similar or even higher efficacy, with a better tolerability profile (5). Based on these data, telmisartan represents an important treatment option for hypertension (4).

Patients and Methods

A total number of 1,234 patients with arterial hypertension were included in the non-interventional clinical study TANDEM. The study was designed to determine the safety and efficacy of telmisartan and the fixed-dose combination (FDC) telmisartan/HCTZ in the treatment of arterial hypertension in a real-life outpatient setting. Hypertensive patients were selected throughout Slovenia and enrolled in the study from September 2014 to June 2015. Patients were included in this non-interventional clinical study according to indications in the summary of product characteristics. (6)

At the initial evaluation (visit 1), each patient received a detailed explanation of the objectives and procedures of this study and was asked to sign an informed consent to participate before any procedure was performed. The protocol of this open, prospective phase IV, 16-week active treatment study was submitted to and approved by the Republic of Slovenia National Medical Ethics Committee. (6)

During the 16-week period, the enrolled patients participated in three visits: the first visit upon inclusion in the study, the second after one month of the treatment, and the third after four months of the treatment. At the first visit, a physician prescribed telmisartan or FDC telmisartan/HCTZ, and determined the dosage according to the baseline BP level. The treatment consisted of telmisartan or FDC telmisartan/HCTZ tablets administered in doses of up to 80 mg telmisartan and up to 25 mg HCTZ. If ambulatory BP levels after four weeks of the treatment were still above 140/90 mmHg, the doctor upgraded either the therapy to FDC, or the dosage. (6)

History and physical examinations were used to assess the safety profile. The patients were asked about any signs or symptoms they experienced since their last visit, and physical examinations were carried out to identify any possible pathological signs of adverse events. All noted adverse events were stratified according to the time of occurrence, frequency, severity, therapeutic measures, and outcome. (6)

Results

Of the 1,234 enrolled patients, approximately half of them were women (55.5%). The mean age was 64.9±11.4 years. The statistical analysis included 1,228 patients (6 patients only came for the first visit). (6)

Of the total population of 1,228 patients, 98 (8%) had recently been diagnosed with hypertension and had not received any antihypertensive medicine (treatment-naďve patients), while 1,130 (92%) had already been treated with antihypertensives, switched from other antihypertensive medication, or needed an additional antihypertensive medicine primarily due to not achieving BP levels. (6)

The baseline SBP was 156.96±16.92 mmHg (95% confidence interval 155.74-157.64 mmHg) and DBP 90.18±10.14 (95% confidence interval 89.61-90.75 mmHg). After 16 weeks of treatment with telmisartan and its FDC telmisartan/HCTZ, SBP and DBP levels decreased significantly (p<0.0001). The average absolute decrease in SBP between first and last visits was 21.03±16.72 mmHg and 9.31±9.70 mmHg in DBP (Figure 1). (6)

Figure 1. The average levels of systolic (SBP) and diastolic (DBP) blood pressure (mmHg) upon each visit. (6)

The observed reductions were highly correlated with the baseline BP: higher BP reductions were observed with higher baseline BP levels. In patients with baseline SBP≥180 mmHg, reduction in BP was the highest (SBP decreased by 53.17±20.69 mmHg, and DBP by 25.17±8.74 mmHg), whereas reduction in BP between first and last visits was also significant (p<0.0001) in all other grades of hypertension. Among patients with isolated systolic hypertension, BP significantly decreased (p<0.0001) between the first and last visit. SBP decreased by 19.12±15.34 mmHg, and DBP by 2.98±7.81 mmHg (Figure 2). (6)

Figure 2. Average decreases in systolic (SBP) and diastolic (DBP) blood pressure between first and last visits in patients with different grades of hypertension and in patients with isolated systolic hypertension. (6)

After four months of the treatment, telmisartan or FDC telmisartan/HCTZ was the only antihypertensive treatment in 55% of patients. Other patients were also concomitantly treated with other antihypertensive medication. At the end of the study, 56% of patients achieved target BP with 80 mg of telmisartan or 80 mg/12.5 mg of FDC telmisartan/HCTZ (Figure 3). (6)

Figure 3. Percentage of patients who were treated exclusively with telmisartan and telmisartan/ hydrochlorothiazide (without combining these two medicines). (6)

Concerning the tolerance profile, telmisartan and FDC telmisartan/HCTZ were very well tolerated at all doses. The analysis revealed that adverse event incidence during 16 weeks of treatment was low, as during the course of the study only 2.7% of patients experienced adverse events related to the treatment. The frequency of the observed adverse events was low. Among all the reported adverse events, dizziness, flatulence, and hypotension were most common. Only 1.2% of patients discontinued the treatment because of treatment-related adverse events. (6)

The clinical efficacy of the treatment was very good or excellent in 93.5% of all patients. Their BP was either 139/89 mmHg or lower (diabetic patients 139/84 mmHg or lower) and they reported no adverse effects or only mild ones; or their BP was 149/94 mmHg or lower (diabetic patients 149/89 mmHg or lower) and they reported no adverse effects (Figure 4). (6)

Figure 4. Clinical efficacy of treatment with telmisartan and its fixed-dose combination with hydrochlorothiazide. (6)

The study involved two subgroups of patients: those who had been treated with other antihypertensives but failed to achieve target levels before the treatment with telmisartan or FDC telmisartan/HCTZ, and those who had not been treated previously. Both subgroups showed excellent or very good clinical efficacy in more than 93% of patients after being treated with telmisartan or FDC telmisartan/HCTZ. (6)

The treatment with telmisartan or FDC telmisartan/HCTZ is beneficial in all grades of hypertension and also in patients with isolated systolic hypertension. After four months of treatment with telmisartan and FDC telmisartan/HCTZ, BP was effectively reduced, and almost two thirds of patients achieved target BP values. (6)

Conclusion

The results confirmed that telmisartan and FDC telmisartan/HCTZ effectively decrease BP in patients with all grades of essential hypertension in real-life settings. Most patients achieved optimal BP targets. During the course of the study, the reported adverse events incidence rate was low. Telmisartan (Tolura®) and FDC telmisartan/hydrochlorothiazide (Tolucombi®) seem to be a beneficial option for effective BP control, which is a key factor influencing cardiovascular outcomes. (6)