Telmisartan/Amlodipine: Single-pill combination in hypertension.. - (Page 662)

662 Frampton for high-risk individuals; follow-up was scheduled for 3.5–5.5 years.[77] The primary outcome was a composite of cardiovascular death, non-fatal MI, non-fatal stroke or hospitalization for heart failure (i.e. the primary outcome in the ONTARGET trial[68]); the main secondary outcome was a composite of cardiovascular death, non-fatal MI or non-fatal stroke (i.e. the primary outcome in the HOPE trial[88]). Other secondary endpoints, including renal outcomes, were similar to those for the ONTARGET trial.[70,71] Efficacy assessments were performed on an ITT basis (all randomized patients).[70,71] Baseline characteristics of participants in the two treatment groups were well matched and generally similar to those of the patients in the telmisartan and ramipril arms of the ONTARGET trial[70] (see table III). Over a median follow-up period of 56 months, telmisartan 80 mg once daily did not significantly reduce the incidence of the primary composite endpoint of cardiovascular death, non-fatal MI, non-fatal stroke or hospitalization for heart failure compared with placebo[70] (table V). The composite endpoint of cardiovascular death, non-fatal MI, or non-fatal stroke (HOPE primary endpoint) was reached by 13.0% of telmisartan recipients compared with 14.8% of placebo recipients; this difference was statistically significant using the unadjusted p-value (p = 0.048; table V), but not the adjusted p-value that took into account the multiplicity of comparisons and 87% overlap between the primary and secondary outcomes (p = 0.068).[70] Results for both composite cardiovascular endpoints were consistent across various prespecified subgroups and were unaltered after adjusting for mean SBP/DBP, which was lower in telmisartan recipients than in placebo recipients throughout the trial (weighted mean difference 4.0/2.2 mmHg).[70] There were no significant between-group differences in the rates of other secondary (non-renal) outcomes, with the exception of cardiovascular hospitalizations and new-onset LVH, which occurred less frequently in the telmisartan group than in the placebo group (table V). Telmisartan ª 2011 Adis Data Information BV. All rights reserved. was also more effective than placebo in reducing pre-existing (baseline) LVH, which was present in 12.7% and 12.8% of telmisartan and placebo recipients, respectively.[79] After 5 years, the prevalence of LVH decreased to 9.8% in the telmisartan group, but was unchanged in the placebo group (OR 0.79; 95% CI 0.68, 0.91; p = 0.0017).[79] The effects of telmisartan on major renal outcomes, specifically the 4-fold composite endpoint of dialysis, renal transplantation, doubling of serum creatinine, or all-cause death, and the 2-fold composite endpoint of dialysis or doubling of serum creatinine, were similar to those of placebo[71] (table V). Of the individual components of the composite endpoints, only doubling of serum creatinine occurred more frequently in telmisartan recipients than in placebo recipients (table V). During follow-up, albuminuria increased less with telmisartan than with placebo, whereas eGFR decreased more with telmisartan than with placebo.[71] Baseline geometric mean values for UACR in the telmisartan and placebo groups were 0.68 and 0.66 mg/mmol; the corresponding mean eGFR values were 71.8 and 71.7 mL/min/ 1.73 m2. From baseline to final visit, the geometric mean of the UACR increased by 32% in the telmisartan group compared with 63% in the placebo group (p < 0.001), while the mean eGFR declined by 3.2 mL/min/1.73 m2 in telmisartan recipients versus 0.26 mL/min/1.73 m2 in placebo recipients (p < 0.001).[71] The composite endpoint of new microalbuminuria and/or proteinuria occurred less frequently with telmisartan than with placebo, as did the composite endpoint of dialysis, doubling of serum creatinine, or new microalbuminuria and/or proteinuria (table V). The risk of progression of microalbuminuria to proteinuria was also lower in the telmisartan group than in the placebo group (table V). 4.3 PRoFESS Briefly, the PRoFESS study investigated the efficacy of four regimens for the prevention of recurrent (secondary) stroke in patients aged ‡50 years who had experienced an ischaemic stroke within 120 days prior to study entry and Drugs 2011; 71 (6)

Table of Contents for the Digital Edition of Telmisartan/Amlodipine: Single-pill combination in hypertension..

Telmisartan/Amlodipine: Single-pill combination in hypertension..
Contents
Abstract
Introduction
Pharmacodynamic Properties
Anti-Inflammatory Effects
Endothelial Effects
Metabolic Effects
Cardiovascular Effects
Renal Effects
Cerebrovascular Effects
Pharmacokinetic Properties
Drug Interactions
Therapeutic Efficacy
ONTARGET
TRANSCEND
PRoFESS
Pooled Analyses of the TRANSCEND and PRoFESS studies
Tolerability
Comparisons with Placebo

Telmisartan/Amlodipine: Single-pill combination in hypertension..