Long-Term Tolerability and Efficacy of Single-Pill Combinations of Telmisartan 40-80 mg Plus Amlodipine 5 or 10 mg in Patients Whose Blood Pressure Was Not Initially Controlled by Amlodipine 5-10 mg: Open-Label, Long-Term Follow-Ups of the TEAMSTA-5 and TEAMSTA-10 Studies

Abstract

Background: Two 8-week, randomized, double-blind, controlled studies previously evaluated the efficacy and tolerability of single-pill combinations of telmisartan 40-80 mg/amlodipine 5-10 mg (T40-80/A5-10) in patients with hypertension not at diastolic blood pressure (DBP) goal (DBP <90 mm Hg) after 6 weeks of amlodipine 5 mg monotherapy (A5) (TEAMSTA-5) or amlodipine 10 mg monotherapy (A10) (TEAMSTA-10). The long-term (≥6 months) tolerability and efficacy of single-pill combinations of T40-T80/A5-A10 have now been evaluated in 2 open-label studies in patients who had successfully completed either TEAMSTA-5 or TEAMSTA-10 (TEAMSTA-5 and TEAMSTA-10 Follow-Ups).

Methods: In the TEAMSTA-5 Follow-Up, 976 patients whose blood pressure was not initially controlled by taking A5 received T40/A5 for 4 or 8 weeks, with consecutive uptitration to T80/A5 if DBP was ≥90 mm Hg. In TEAMSTA-10 Follow-Up, 838 patients not initially achieving blood pressure control using A10 received T40/A10 for 4 weeks before randomization to T40/A10 or T80/A10; after 4 weeks, patients randomized to T40/A10 with DBP ≥90 mm Hg were uptitrated to T80/A10. In both studies, add-on antihypertensive medication was allowed if DBP was not at goal.

Results: Treatment compliance in both follow-up studies was ≥98.4%. Single-pill combinations of T40-T80/A5-A10 resulted in additional clinically relevant blood pressure reductions and 67% to 93% of patients achieved DBP goal (<90 mm Hg); only 1% to 19% of patients received additional medication for hypertension, of whom 29% to 76% achieved DBP goal. Long-term treatment with T40-T80/A5-A10 was well tolerated, with comparable adverse event profiles for all telmisartan/amlodipine combinations. The most common drug-related adverse events were peripheral edema (1.9%-3.9%) and dizziness (1.5% in the T80/A5 group only); these were consistent with the known tolerability profiles of telmisartan/amlodipine combinations. Overall treatment discontinuation rates due to adverse events were low (0.7%-1.5%).

Conclusions: In patients not achieving DBP goal with either A5 or A10 monotherapy, the vast majority achieved DBP goal with single-pill combinations of T40-T80/A5-A10. Long-term treatment was well tolerated with high compliance, promoting treatment adherence regardless of telmisartan/amlodipine dose. ClinicalTrials.gov identifiers: NCT00614380 (TEAMSTA-5 Follow-up) and NCT00624052 (TEAMSTA-10 Follow-up).

Keywords: amlodipine; angiotensin II receptor blocker; calcium channel blocker; essential hypertension; single-pill combination; telmisartan.

Figure 1

Design of (A) TEAMSTA-5 and TEAMSTA-5 Follow-Up and (B) TEAMSTA-10 and TEAMSTA-10 Follow-Up studies evaluating the safety and efficacy of telmisartan 40 mg/amlodipine 5 mg (T40/A5), telmisartan 80 mg/amlodipine 5 mg (T80/A5), telmisartan 40 mg/amlodipine 10 mg (T40/A10), and telmisartan 80 mg/amlodipine 10 mg (T80/A10) single-pill combinations with or without additional antihypertensive medication (add-on). E= enrollment; R = randomization; T = treatment. *Patients could only be randomized if diastolic blood pressure (DBP) was not adequately controlled after 6 weeks of A5 or A10 monotherapy (ie, DBP ≥90 mm Hg); ^†At these visits, patients were uptitrated to T80/A5 or T80/A10 if DBP ≥90 mm Hg (ie, response-driven titration); ^‡Add-on therapy could be given if trough DBP ≥90 mm Hg.

Figure 2

Comparison of the duration-adjusted (A) patients per 100 patient years and (B) incidence per 100 patient years of drug-related adverse events, peripheral edema, adverse events leading to premature discontinuation, and serious adverse events in patients receiving long-term, open-label treatment with telmisartan 40 mg/amlodipine 5–10 mg (T40/A5–10) and patients receiving telmisartan 80 mg/amlodipine 5–10 mg (T80/A5–10) (data for TEAMSTA-5 [n = 1814] and −10 [n = 1008] Follow-Up; pooled post-hoc analysis).

Figure 3

Proportions of patients achieving (A and B) diastolic blood pressure (DBP) goal (mean seated trough cuff DBP <90 mm Hg) and (C and D) systolic blood pressure (SBP) goal (mean seated trough cuff SBP/DBP <140/90 mm Hg) after long-term, open-label treatment with telmisartan 40–80 mg/amlodipine 5 mg (T40–T80/A5) single-pill combinations with or without additional antihypertensive medication (add-on), and telmisartan 40–80 mg/amlodipine 10 mg (T40–T80/A10) single-pill combinations with or without add-on.

Figure 4

Changes in mean seated trough cuff blood pressure (BP) in patients receiving long-term, open-label treatment with (A) telmisartan 40–80 mg/amlodipine 5 mg (T40–T80/A5) single–pill combinations with or without additional antihypertensive medication (add-on), and (B) telmisartan 40–80 mg/amlodipine 10 mg (T40–T80/A10) single-pill combinations with or without add-on. DBP = Diastolic blood pressure; SBP = systolic blood pressure.