Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.
A majority of patients with hypertension fail to achieve blood pressure ( The overall incidence of adverse events was comparable between the groups.Compared with continued olmesartan, sacubitril/valsartan was more effective and generally safe in patients with hypertension uncontrolled with olmesartan 20 mg.
6This 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 treatmentrelated 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. J Clin Hypertens (Greenwich). 2012;14:206-215. Ó2012 Wiley Periodicals, Inc.Based on evidence from a number of large antihypertensive trials, 1-9 most guidelines acknowledge that combination therapy is needed to reduce blood pressure (BP) successfully to goal in the majority of patients; only a minority of patients achieve their BP goal with a single agent.10-14 Also, the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) study showed a significant reduction of cardiovascular (CV) events and death in hypertensive patients at high CV risk treated with a combination of an angiotensin-converting enzyme (ACE) inhibitor and a calcium channel blocker (CCB).15 Nevertheless, despite rigorous and comprehensive guidelines, and a trend towards an increase in the use of combination therapy in treatment practice, 16 several studies have demonstrated the persistence of poor BP goal rates in treated patients. [17][18][19] The impact of poor BP control is compounded by the often high prevalence of other CV risk factors in hypertensive patients (eg, hypercholesterolemia, obesity, type 2 diabetes mellitus [T2DM], and smoking).13 Therefore, an urgent need still remains to improve the management of hypertension. One logical approach would be to use 2 drugs from different classes and complementary mechanisms of action in combination. Such combinations may result in additional BP decreases and improved goal rates, compared with either agent used alone.
20-23Furthermore, single-pill combinations (SPCs) are known to increase treatment adherence and reduce health care costs. [24][25][26][27] A combination of a CCB and an angiotensin II receptor blocker (ARB) is a rational approach for managing hypertension and there is increasing evidence that this combination is effective. 11,13,28,29 The aim of the current study was to compare the efficacy and tolerability of the SPC of telmisartan 80 mg ⁄ amlodipine 10 mg (T80 ⁄ A10) with that of...
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