Thomas W. Littlejohn

Results of Treatment With Telmisartan-Amlodipine in Hypertensive Patients

This randomized 4×4 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).

Telmisartan plus amlodipine in patients with moderate or severe hypertension: results from a subgroup analysis of a randomized, placebo-controlled, parallel-group, 4 x 4 factorial study.

Abstract Background: Patients with moderate-to-severe hypertension frequently require ≥ 2 antihypertensives to achieve blood pressure (BP) control. An angiotensin receptor blocker (ARB) plus a calcium channel blocker (CCB) seems particularly attractive for these difficult-to-control patients. Methods: Patients with Stage 1 or 2 hypertension were randomized to telmisartan 0, 20, 40, or 80 mg plus amlodipine 0, 2.5, 5, or 10 mg for 8 weeks. Only those with a diastolic BP (DBP) ≥ 100 mm Hg at baseline were included in this subgroup analysis. The primary endpoint was the change in the in-clinic seated trough cuff DBP from baseline to study end for combination versus respective monotherapies. Secondary endpoints included the change in the in-clinic seated trough systolic BP (SBP), BP response, and control rates. Results: A total of 1078 patients (mean [standard deviation] baseline in-clinic BP: 154.7 ± 11.7/103.5 ± 3.5 mm Hg) were analyzed. In-clinic DBP and SBP reductions were significantly greater with combination therapies than respective monotherapies. The greatest least-square mean (standard error) SBP/DBP reductions (−26.5 ± 1.2/−21 ± 0.8 mm Hg) were observed with telmisartan 80 mg plus amlodipine 10 mg; 77% and 85% of patients in this treatment group achieved BP control (< 140/90 mm Hg) and DBP control (< 90 mm Hg), respectively. Peripheral edema was reported in 17.2% of patients in the amlodipine 10 mg group; however, this was substantially lower when telmisartan was used in combination: 7% (telmisartan 40 mg/amlodipine 10 mg) and 9.5% (telmisartan 80 mg/ amlodipine 10 mg). Conclusions: Telmisartan plus amlodipine provides effective BP lowering at all clinically relevant doses (up to −26.5 mm Hg SBP), and almost 9 out of 10 patients may achieve DBP control. Peripheral edema is up to 59% less when telmisartan 40 mg is used in combination with amlodipine 10 mg compared with amlodipine 10 mg monotherapy alone.

24‐Hour Efficacy and Safety of Triple‐Combination Therapy With Olmesartan, Amlodipine, and Hydrochlorothiazide: The TRINITY Ambulatory Blood Pressure Substudy

J Clin Hypertens (Greenwich). 2011;13:873–880. ©2011 Wiley Periodicals, Inc.

Cefdinir Versus Cephalexin for the Treatment of Skin and Skin-Structure Infections

Because of increasing resistance to older antimicrobial agents, newer drugs need to be evaluated for the treatment of skin and skin-structure infections (SSSIs). This double-masked, randomized, comparative, multicenter study enrolled patients aged 13 years or older with SSSIs to receive either cefdinir 300 mg BID or cephalexin 500 mg QID for 10 days. Nine hundred fifty-two patients (474 in the cefdinir group and 478 in the cephalexin group) took part, primarily white males between 18 and 65 years of age. There were two follow-up visits, with efficacy determined at the test-of-cure visit, 7 to 16 days posttherapy. Many patients were not microbiologically assessable, primarily because of negative cultures at study admission. Patients who required surgical intervention (e.g., incision and drainage) at the site of infection more than 24 hours after the initiation of drug therapy were defined as treatment failures. Significantly more isolated pathogens were resistant to cephalexin than to cefdinir. In the 178 efficacy-assessable cefdinir-treated patients, the rate of pathogen eradication was 93% (200/215), and the rate of successful clinical response was 88% (157/178), compared with 89% (221/247) and 87% (177/204), respectively, in the 204 efficacy-assessable cephalexin-treated patients. Using confidence-interval analysis, the microbiologic and clinical response rates of the cefdinir-treated patients were statistically equivalent to those of the cephalexin-treated patients. At the follow-up visits, patients were questioned about any adverse events occurring since their previous visit. Any untoward symptom occurring during or within 2 days after completion of drug treatment was considered an adverse reaction if the investigator judged it to be definitely, probably, or possibly related to the study drug. One hundred twenty-three (26%) cefdinir-treated patients and 77 (16%) cephalexin-treated patients experienced at least one adverse reaction, a statistically significant difference. Study drug was discontinued for adverse reactions in 20 (4%) cefdinir-treated patients and 13 (3%) cephalexin-treated patients; in the two groups, 10 and 7 patients, respectively, were discontinued for diarrhea. Cefdinir taken BID was as effective as cephalexin taken QID in the treatment of mild-to-moderate SSSIs and was well tolerated by most patients. The increased antibacterial activity of cefdinir must be balanced against the higher rate of diarrhea seen in patients treated with this drug.

Efficacy and safety of triple-combination therapy with olmesartan, amlodipine, and hydrochlorothiazide in study participants with hypertension and diabetes: a subpopulation analysis of the TRINITY study

BACKGROUND Most patients with hypertension and diabetes require two or more antihypertensive agents to achieve the recommended blood pressure (BP) goal of <130/80 mm Hg. This prespecified subgroup analysis from the TRIple Therapy with Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in HyperteNsIve PatienTs StudY assessed the efficacy and safety of triple-combination treatment (olmesartan medoxomil 40/amlodipine besylate 10/hydrochlorothiazide 25 mg) versus the component dual-combination treatments according to diabetes status (diabetes; non-diabetes). METHODS Participants received dual-combination treatment for 4 weeks or placebo for 2 weeks. Participants receiving placebo switched to dual-combination treatment from week 2 to week 4. At week 4, participants switched to triple-combination treatment or continued on dual-combination treatment until week 12. RESULTS The prespecified changes in BP from baseline for the diabetes subgroup receiving triple-combination treatment were greater than the respective dual-combination treatments (P ≤ .0013). Also, more participants with diabetes receiving triple-combination treatment reached BP goal (<130/80 mm Hg) versus those receiving dual-combination treatments (P ≤ .0092). In a post hoc analysis, significantly greater proportions of study participants with diabetes achieved BP targets with triple-combination treatment compared with each dual-combination treatment. Most treatment-emergent adverse events were mild to moderate in severity. CONCLUSIONS In participants with hypertension and diabetes, triple-combination treatment led to greater BP reductions and enabled greater proportions of participants to reach BP goal versus the dual-combination treatments. Triple-combination treatment was well tolerated in both diabetes and non-diabetes subgroups.

Management of Hypertension in Patients With Diabetes Using an Amlodipine-, Olmesartan Medoxomil-, and Hydrochlorothiazide-Based Titration Regimen

The safety and efficacy of an amlodipine/olmesartan medoxomil (OM)-based titration regimen was assessed in patients with type 2 diabetes mellitus and hypertension. After a 2- to 3-week placebo run-in period, 207 patients received amlodipine 5 mg and were uptitrated to amlodipine/OM 5/20, 5/40, and 10/40 mg and then amlodipine/OM 10/40 mg plus hydrochlorothiazide 12.5 and 25 mg in a step-wise manner at 3-week intervals if the seated blood pressure (BP) remained ≥120/70 mm Hg. The primary end point was the change from baseline in the mean 24-hour ambulatory systolic BP after 12 weeks of treatment. The baseline mean ± SD seated cuff systolic/diastolic BP was 158.8 ± 13.1/89.1 ± 10.1 mm Hg and the mean ± SD 24-hour ambulatory systolic/diastolic BP was 144.4 ± 11.7/81.6 ± 9.8 mm Hg. At week 12, the change from baseline in the mean ± SEM 24-hour ambulatory systolic/diastolic BP was -19.9 ± 0.8/-11.2 ± 0.5 mm Hg (p<0.0001 vs baseline), and 70% of patients had achieved a 24-hour ambulatory BP target of <130/80 mm Hg. At the end of 18 weeks of active treatment in patients uptitrated to amlodipine/OM 10/40 mg plus hydrochlorothiazide 25 mg, the change from baseline in the mean ± SEM seated BP was -28.0 ± 1.5/-13.7 ± 1.0 mm Hg (p<0.0001 vs baseline), with 62% of patients reaching the guideline-recommended seated BP goal of <130/80 mm Hg. Drug-related treatment-emergent adverse events occurred in 19.3% of patients. The most frequent events were peripheral edema (6%), dizziness (3%), and hypotension (2%). In conclusion, this amlodipine/OM-based titration regimen was well tolerated and effectively lowered BP throughout the 24-hour dosing interval in patients with hypertension and type 2 diabetes.

Olmesartan/amlodipine/hydrochlorothiazide in participants with hypertension and diabetes, chronic kidney disease, or chronic cardiovascular disease: a subanalysis of the multicenter, randomized, double-blind, parallel-group TRINITY study

BackgroundPatients with hypertension and cardiovascular disease (CVD), diabetes, or chronic kidney disease (CKD) usually require two or more antihypertensive agents to achieve blood pressure (BP) goals.MethodsThe efficacy/safety of olmesartan (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg versus the component dual-combinations (OM 40/AML 10 mg, OM 40/HCTZ 25 mg, and AML 10/HCTZ 25 mg) was evaluated in participants with diabetes, CKD, or chronic CVD in the Triple Therapy with Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study (TRINITY). The primary efficacy end point was least squares (LS) mean reduction from baseline in seated diastolic BP (SeDBP) at week 12. Secondary end points included LS mean reduction in SeSBP and proportion of participants achieving BP goal (<130/80 mm Hg) at week 12 (double-blind randomized period), and LS mean reduction in SeBP and BP goal achievement at week 52/early termination (open-label period).ResultsAt week 12, OM 40/AML 10/HCTZ 25 mg resulted in significantly greater SeBP reductions in participants with diabetes (−37.9/22.0 mm Hg vs −28.0/17.6 mm Hg for OM 40/AML 10 mg, −26.4/14.7 mm Hg for OM 40/HCTZ 25 mg, and −27.6/14.8 mm Hg for AML 10/HCTZ 25 mg), CKD (−44.3/25.5 mm Hg vs −39.5/23.8 mm Hg for OM 40/AML 10 mg, −25.3/17.0 mm Hg for OM 40/HCTZ 25 mg, and −33.4/20.6 mm Hg for AML 10/HCTZ 25 mg), and chronic CVD (−37.8/20.6 mm Hg vs −31.7/18.2 mm Hg for OM 40/AML 10 mg, −30.9/17.1 mm Hg for OM 40/HCTZ 25 mg, and −27.5/16.1 mm Hg for AML 10/HCTZ 25 mg) (P<0.05 for all subgroups vs dual-component treatments). BP goal achievement was greater for participants receiving triple-combination treatment compared with the dual-combination treatments, and was achieved in 41.1%, 55.0%, and 38.9% of participants with diabetes, CKD, and chronic CVD on OM 40/AML 10/HCTZ 25 mg, respectively. At week 52, there was sustained BP lowering with the OM/AML/HCTZ regimen. Overall, the triple combination was well tolerated.ConclusionsIn patients with diabetes, CKD, or chronic CVD, short-term (12 weeks) and long-term treatment with OM 40/AML 10/HCTZ 25 mg was well tolerated, lowered BP more effectively, and enabled more participants to reach BP goal than the corresponding 2-component regimens.Trial Identification NumberNCT00649389

Single-Pill Combination of Telmisartan/Amlodipine Versus Amlodipine Monotherapy in Diabetic Hypertensive Patients: An 8-Week Randomized, Parallel-Group, Double-Blind Trial

BACKGROUND Hypertensive patients with diabetes often require combination therapy to achieve a blood pressure (BP) goal, and evidence suggests that time to BP goal is crucial to decrease cardiovascular risk. OBJECTIVE The aim of the study was to investigate whether the single-pill combination of telmisartan and amlodipine was superior to amlodipine alone as initial antihypertensive therapy in patients with diabetes and hypertension. METHODS An 8-week, randomized, parallel-group, double-blind international trial comparing the once-daily single-pill combination of telmisartan 80 mg and amlodipine 10 mg (T/A; n = 352) with once-daily amlodipine 10 mg (A; n = 354) in patients with type 2 diabetes mellitus and stage 1 or 2 hypertension (systolic BP [SBP] >150 mm Hg). RESULTS Patient demographics were similar between treatment groups, with an mean (SD) age of 60.5 (10.1) years; 51.7% were male, the mean (SD) body mass index was 32.0 (6.1) and the mean (SD) duration of hypertension was 8.8 (7.9) years. After 8 weeks (primary end point) as well as after 1, 2, and 4 weeks (key secondary end points), significantly greater decreases in the in-clinic mean seated trough cuff SBP with T/A versus A were achieved (-29.0 mm Hg vs -22.9 mm Hg at 8 weeks; P < 0.0001). After 8 weeks, 71.4% versus 53.8% of patients achieved the BP goal (<140/90 mm Hg) with T/A versus A, with mean SBPs of 131.9 and 137.9 mm Hg, respectively. Similar results were observed in the obese (metabolic syndrome) subpopulation. The more stringent goal (<130/80 mm Hg) was achieved by 36.4% and 17.9% patients in the T/A and A groups, respectively. The most common adverse events were peripheral edema, headache, and dizziness. CONCLUSIONS In this selected population of patients with diabetes and hypertension, T/A provided prompt and greater BP decreases compared with A monotherapy, with the majority of patients achieving the BP goal (<140/90 mm Hg).