Efficacy of Telmisartan Plus Amlodipine in Nonresponders to CCB Monotherapy.
ABSTRACT: Hypertensive patients unable to reach blood pressure (BP) targets with antihypertensive monotherapy may be switched to a combination of two medications with complementary modes of action for improved treatment response. This post hoc analysis pools data from 2812 patients, 1891 of whom were not at goal (diastolic BP [DBP] <90?mm?Hg) with amlodipine 5?mg (A5) monotherapy who subsequently switched to telmisartan 40 or 80?mg (T80)/A5 single-pill combination (SPC) or amlodipine 10?mg (A10) monotherapy, and considers an additional 921 patients, 616 of whom were not at goal with A10 monotherapy who switched to telmisartan/amlodipine SPC. Patients switched to telmisartan/amlodipine SPC achieved significantly greater BP reductions compared with continued monotherapy (P < 0.0001) with reductions of -15.2/-10.9?mm?Hg seen with T80/A5 after 8 weeks in patients switched from A5. BP goal (<140/90?mm?Hg), systolic BP goal (<140?mm?Hg), and DBP goal (<90?mm?Hg) were reached by significantly more patients with telmisartan/amlodipine than with monotherapy (P < 0.0001 for all comparisons; 56.1%, 69.7%, and 66.9%, resp., in patients who switched from A5 to T80/A5). Early use of such combination therapy should be considered to quickly reach BP targets, particularly in patients with added risk.
Project description:An 8-week, randomized, double-blind, controlled study with single-pill combinations of telmisartan 40 mg or 80 mg/amlodipine 5 mg (T40/A5 or T80/A5) vs monotherapy with amlodipine 5 mg or 10 mg (A10) in 1097 patients with uncontrolled hypertension (diastolic blood pressure [BP] ≥ 90 mm Hg). T40/A5 and T80/A5 resulted in significantly greater (P<.0001) reductions in seated trough systolic/diastolic BP vs A5 (-7.4 mm Hg/-3.6 mm Hg; -8.8 mm Hg/-4.9 mm Hg) and a significantly greater (P<.001) proportion of patients achieving systolic/diastolic BP goal rate (60.0%/56.7%; 65.7%/63.8%) vs A5 (39.2%/42.0%). Superior BP reductions were also seen with T40-T80/A5 vs A10, with BP goal rates at least as high as with A10; however, there was significantly more peripheral edema with A10 (27.2% vs 4.3% for pooled T40-T80/A5; P<.0001). Switching patients with uncontrolled BP to a single-pill combination of T40/A5 or T80/A5 is a better treatment option than up-titration to full-dose monotherapy with A10.
Project description:Objective. To evaluate the efficacy and safety of the telmisartan plus amlodipine (T/A) single-pill combination (SPC) in Asian patients with hypertension whose blood pressure (BP) was not adequately controlled on either monotherapy or on low-dose combination therapy. Patients and Methods. Data are presented from five Boehringer Ingelheim-sponsored phase 3, double-blind, 8-week, studies: two studies in nonresponders to amlodipine (data pooled for amlodipine), two studies on nonresponders to telmisartan (pooled data), and one on nonresponders to low-dose T/A SPC. Results. After 8 weeks' treatment, mean reductions from the reference baseline in diastolic BP (DBP; primary endpoint), systolic BP (SBP), and SBP, DBP goal, and response rates were higher with the T/A SPC than respective monotherapies. The T80/A5 SPC resulted in greater reductions in DBP and SBP, and higher DBP goal and response rate than the low-dose T40/A5 SPC. Peripheral edema incidence was low (amlodipine 0.5%, telmisartan 0.0%, and T/A SPC 0.7%). Discussion and Conclusion. In Asian patients whose BP is not adequately controlled with telmisartan or amlodipine monotherapy, T/A SPC treatment results in greater BP reduction, and higher DBP and SBP goal and response rates. The safety and tolerability of the T/A SPC are comparable to those of the respective monotherapies and consistent with those reported in previous studies.
Project description: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).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.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%).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).
Project description:The aim of this study was to compare 80 mg telmisartan/5 mg amlodipine/12.5 mg hydrochlorothiazide (T80/A5/H12.5) with 80 mg telmisartan/12.5 mg hydrochlorothiazide (T80/H12.5) to determine their relative blood pressure (BP) lowering effects in essential hypertensive patients with inadequate control and to evaluate the long-term safety of T80/A5/H12.5 in a 52-week extension period. Patients (n=132) were randomly assigned to receive double-blind treatment with T80/A5/H12.5 or T80/H12.5 for 8 weeks after a 6-week run-in-period of T80/H12.5. All 126 patients who completed the double-blind period entered the 52-week open-label extension and received T80/A5/H12.5. The adjusted mean changes from the reference baseline of the trough-seated systolic and diastolic BP (SBP/DBP) at week 8 were significantly larger in the T80/A5/H12.5 group (-10.6/-8.8 mm Hg) than in the T80/H12.5 group (-2.3/-1.3 mm Hg) (P<0.0001). The BP-lowering effect of T80/A5/H12.5 was maintained over the 52-week extension period. The adverse events (AEs) during both treatment periods were generally mild. Drug-related AEs were reported in one patient in each group in the double-blind period and in five patients exposed to T80/A5/H12.5 in the double-blind and/or open-label extension period. T80/A5/H12.5 therapy was clinically and statistically superior to T80/H12.5 therapy for the reduction of BP in patients with essential hypertension uncontrolled with T80/H12.5, and its BP-lowering effect was maintained in the long term. T80/A5/H12.5 was generally well-tolerated.
Project description:The efficacy and safety of telmisartan 80?mg/amlodipine 5?mg plus hydrochlorothiazide 12.5?mg (T80/A5/H12.5) was examined for its ability to treat hypertension in Japanese patients whose hypertension is uncontrolled with telmisartan 80?mg/amlodipine 5?mg (T80/A5). Patients aged ?20 years who had essential hypertension despite taking two or three antihypertensive drugs entered a 6-week run-in period on T80/A5. Patients whose hypertension remained uncontrolled were randomly assigned to either the T80/A5/H12.5 group (n=149) or the T80/A5 group (n=160), once daily for 8 weeks. After 8 weeks, patients in the T80/A5/H12.5 group showed a significantly greater adjusted mean reduction in both seated diastolic blood pressure and seated systolic blood pressure than those in the T80/A5 group. Furthermore, more patients achieved a diastolic/systolic blood pressure of <90/140?mm?Hg in the T80/A5/H12.5 group compared with the T80/A5 group. The most common adverse events were nasopharyngitis, elevated blood uric acid levels and hyperuricemia, and the latter two events were more frequent in the T80/A5/H12.5 group than in the T80/A5 group. Overall, T80/A5/H12.5 administered for 8 weeks significantly reduced systolic and diastolic blood pressure and was well tolerated by patients with hypertension uncontrolled with T80/A5.
Project description:Objective. Report of prespecified and post hoc subgroup analyses of a randomized, controlled trial comparing telmisartan 80?mg/hydrochlorothiazide 25?mg (T80/H25) combination therapy with T80 monotherapy, according to the presence of cardiovascular disease (CVD) risk factors. Methods. Hypertensive patients were randomized (2?:?1) to receive T80/H25 or T80 for 6 weeks, following a 1-week, low-dose, and run-in period. Systolic blood pressure (SBP) and diastolic BP reductions and BP goal achievement were evaluated in patients with CVD risk factors: presence of diabetes mellitus (DM), renal impairment, increased body mass index (BMI), and 10-year estimated risk for coronary heart disease (CHD). Results. In total, 888 patients received treatment. Overall, T80/H25 therapy significantly reduced SBP more than T80 monotherapy, irrespective of patient subgroup. In patients with DM, renal impairment, high BMI, and high CHD risk, BP goal achievement rates (<140/90?mm?Hg) at Week 7, among those treated with T80/H25, were 52.8%, 52.8%, 50.6%, and 38.5%, respectively. More patients with DM reached a guideline-based BP goal (<130/80?mm?Hg) at 7 weeks with T80/H25 than with T80 monotherapy (16.7% versus 8.8%). Rates of treatment-related adverse events were low and comparable across patient subgroups. Conclusions. Antihypertensive treatment with T80/H25 single-pill combination is effective and generally well tolerated, irrespective of the presence of CVD risk factors.
Project description:Older patients frequently receive angiotensin II receptor blocker/diuretic combinations to control blood pressure (BP), although there have been relatively few trials specifically examining this patient population. A pooled analysis was performed of data from 7 randomized trials of telmisartan/hydrochlorothiazide combinations or telmisartan monotherapy in older (65 years and older) and younger (younger than 65 years) patients to better understand the response of older patients to a telmisartan/hydrochlorothiazide combination. Telmisartan doses were 40 mg and 80 mg (T40 and T80). Hydrochlorothiazide doses were 12.5 mg and 25 mg (H12.5 and H25). A total of 3654 patients were included and the mean treatment duration was approximately 8 weeks. BP reductions with telmisartan/hydrochlorothiazide combinations were broadly similar in older and younger patients. In older patients, mean BP reductions from baseline were -30.1/-19.0 mm Hg with the T80/H25 combination and -21.7/-13.0 mm Hg with T80 monotherapy. Tolerability was similar regardless of age, and the incidence of adverse events in both older and younger patients was similar to placebo. The telmisartan/hydrochlorothiazide combination, particularly high-dose T80/H25, is effective and well tolerated in patients 65 years and older as well as in younger patients.
Project description:This 8-week, randomized, double-blind, controlled study compared efficacy and tolerability of telmisartan/amlodipine (T/A) single-pill combination (SPC) vs the respective monotherapies in 858 patients with severe hypertension (systolic/diastolic blood pressure [SBP/DBP] ≥180/95 mm Hg). At 8 weeks, T/A provided significantly greater reductions from baseline in seated trough cuff SBP/DBP (-47.5 mm Hg/-18.7 mm Hg) vs T (P<.0001) or A (P=.0002) monotherapy; superior reductions were also evident at 1, 2, 4, and 6 weeks. Blood pressure (BP) goal and response rates were consistently higher with T/A vs T or A. T/A was well tolerated, with less frequent treatment-related adverse events vs A (12.6% vs 16.4%) and a numerically lower incidence of peripheral edema and treatment discontinuation. In conclusion, treatment of patients with substantially elevated BP with T/A SPCs resulted in high and significantly greater BP reductions and higher BP goal and response rates than the respective monotherapies. T/A SPCs were well tolerated.
Project description:The single-pill combination (SPC) comprising nebivolol (5 mg), a vasodilatory ?1 -selective antagonist/?3 -agonist, and valsartan (80 mg), a renin-angiotensin-aldosterone system inhibitor, is the only Food and Drug Administration-approved ?-blocker/renin-angiotensin-aldosterone system inhibitor SPC for hypertension. Additive effects of four nebivolol/valsartan SPC doses (5 mg/80 mg, 5/160 mg, 10/160 mg, 10/320 mg nebivolol/valsartan) were compared with five Food and Drug Administration-approved non-?-blocker/renin-angiotensin-aldosterone system inhibitor SPCs (aliskiren/hydrochlorothiazide, aliskiren/amlodipine, valsartan/amlodipine, aliskiren/valsartan, and telmisartan/amlodipine). Additivity is the ratio of placebo-adjusted SPC blood pressure (BP) reduction to the placebo-adjusted monotherapy component BP reduction sums. A weighted average of comparator scores was calculated and compared vs nebivolol/valsartan. Additivity ratio scores for nebivolol/valsartan SPCs (diastolic BP range: 0.735-0.866; systolic BP range: 0.717-0.822) were similar to the comparator weighted average (diastolic BP: 0.837; systolic BP: 0.825). Among the nebivolol/valsartan SPCs, 5/80 mg had the greatest additivity (diastolic BP: 0.866; systolic BP: 0.822). BP reduction contributions with monotherapy were similar for nebivolol/valsartan 5/80 mg SPC. Additivity scores for nebivolol/valsartan and select non-?-blocker/renin-angiotensin-aldosterone system inhibitor SPCs were comparable.
Project description:This randomized 4 x 4 factorial study determined the efficacy and safety of telmisartan (T) plus amlodipine (A) in hypertensive patients. Adults (N=1461) with stage 1 or 2 hypertension (baseline blood pressure [BP]: 153.2[12.1]/101.7[4.3] mm Hg) were randomized to 1 of 16 treatment groups with T 0, 20, 40, 80 mg and A 0, 2.5, 5, 10 mg for 8 weeks. In-clinic BP reductions were greater with combination therapy than respective monotherapies. The greatest least-square mean systolic/diastolic BP reductions were observed with T80 mg plus A10 mg (-26.4/-20.1 mm Hg; P<.05 compared with both monotherapies). BP control was also greatest in the T80-mg plus A10-mg group (76.5% [overall control] and 85.3% [diastolic BP control]), and BP response rates >90% with this combination. Peripheral edema was most common in the A10-mg group (17.8%); however, this rate was notably lower when A was used in combination with T: 11.4% (T20/A10), 6.2% (T40/A10), and 11.3% (T80/A10).