The prevalence of diabetes mellitus has grown to staggering numbers, and its incidence is expected to rise in the next 2 decades. The need for novel approaches to treat hyperglycemia cannot be ignored. Current agents have been shown to modestly improve glycemia and in some cases prevent complications of diabetes, but they become less effective over time and are often accompanied by undesirable adverse effects. Dapagliflozin is the lead agent in a new class of oral antidiabetic agents known as sodium-glucose cotransporter type 2 (SGLT2) inhibitors, which represent a novel approach to the management of type 2 diabetes mellitus. By selectively and reversibly blocking the SGLT2 receptor, dapagliflozin prevents the reabsorption of glucose at the renal proximal tubule. Phase II and III clinical trials have demonstrated that dapagliflozin is a safe and effective method for treating type 2 diabetes. Dapagliflozin produces a sustained, dose-dependent reduction in plasma glucose levels while simultaneously improving insulin secretion and sensitivity. Over 12-24 weeks, reductions in hemoglobin A(1c) ranged from 0.54-0.89% when dapagliflozin was administered once/day (either as monotherapy or add-on therapy to oral antidiabetic drugs with or without insulin) to patients with type 2 diabetes. Therapy with dapagliflozin also results in a mild osmotic-diuretic effect that may account for decreases in total body weight (~2-3 kg) and blood pressure (systolic 2-5 mm Hg, diastolic 1.5-3 mm Hg), and increases in hematocrit (1-2%). Dapagliflozin has a favorable safety profile, with the rates of hypoglycemia similar to those of placebo. Genital and urinary tract infections were more commonly reported in patients taking dapagliflozin (2-13%) than those taking placebo (0-8%). Dapagliflozin does not appear to cause electrolyte disturbances, hepatotoxicity, or nephrotoxicity. Results from clinical trials have been promising, and well-designed clinical programs that address the long-term safety and efficacy of dapagliflozin are under way.

Ticagrelor's improved pharmacokinetic and pharmacodynamic profile builds upon the limitations of currently available P2Y12 receptor antagonists. Ticagrelor represents a promising approach for the prevention of cardiovascular events in patients with ACS.

Blood pressure (BP) characteristics, such as central aortic pressure and arterial stiffness, independently predict cardiovascular events. The effects of pharmacologically dissimilar b-blockers on these properties have not been fully elucidated. Patients with essential hypertension and without significant concomitant cardiovascular disease were randomly assigned to controlled-release carvedilol, forcetitrated to 80 mg (n=22), or atenolol, force-titrated to 100 mg (n=19); each was given once daily for 4 weeks. Baseline characteristics were similar. At the end of week 4, atenolol and carvedilol reduced central and brachial systolic and diastolic BP to a similar extent. Central augmentation index was increased in atenolol-treated patients but not carvedilol-treated patients (atenolol 4.47% vs carvedilol )0.68%; P=.04). Mean augmented central aortic pressure increased slightly during atenolol treatment (+1.1 mm Hg) but decreased slightly during carvedilol treatment ()1.1 mm Hg), although the difference in these changes was not statistically significant (P=.23). Pulse pressure amplification was reduced more with atenolol at week 4 (atenolol )10.7% vs carvedilol )1.8%; P=.02). Therefore, we conclude that carvedilol results in more favorable pulse pressure amplification and augmentation index by increasing arterial compliance and reducing the magnitude of wave reflection, respectively, compared with atenolol. J Clin Hypertens (Greenwich). 2011;13:917-924. Ó2011 Wiley Periodicals, Inc.For many years, b-blockers were advocated as first-line therapy for most patients with hypertension. This class flourished during the past 50 years as the mainstay for the prevention and treatment of various cardiovascular disorders such as cardiac arrhythmias, myocardial infarction, and hypertension. Recently, the role of bblockers in uncomplicated hypertension has been questioned. Indeed, several recently updated guidelines have deemphasized their place in therapy.2,3 The reasons for this evolution are multifactorial, including publication of several clinical trials and meta-analyses which concluded that b-blockers are less effective than contemporary antihypertensives. [4][5][6][7] These observations could be ascribed to multiple factors including the fact that b-blockers exhibit an adverse metabolic profile, are poorly tolerated relative to newer antihypertensives, and have mismatched mechanisms of action with the pathophysiology of hypertension in elderly hypertensive patients. [8][9][10][11] Multiple recent studies suggest that blood pressure (BP) characteristics beyond the brachial cuff, such as central aortic pressure, wave reflection, and arterial stiffness, independently predict cardiovascular events, including all-cause and cardiovascular mortality, fatal and nonfatal coronary events, and fatal strokes in uncomplicated essential hypertension.12-15 These characteristics cannot be appreciated with conventional clinic BP measurements at the brachial artery. Radial artery tonometry and synthesis of the central aortic pressure wavefor...

The objective of this review is to evaluate the role of fixed-dose triple-combination therapy for the management of hypertension. An assessment of clinical trials showed that half the patients with hypertension have uncontrolled blood pressure (BP), with underlying factors including therapeutic inertia and poor patient adherence. Many patients will require three antihypertensive agents to achieve BP goals, and current guidelines recommend combining drugs with complementary mechanisms of action. Three single-pill triple-combination treatments are available and each includes an agent affecting the renin-angiotensin-aldosterone pathway (either a direct renin inhibitor or an angiotensin II receptor blocker) in combination with a calcium channel blocker and diuretic. These triple-combination therapies consistently demonstrated significantly greater BP reduction relative to the component dual combinations, with BP reductions documented across a range of patient populations. Triple-combination treatments were well tolerated in all clinical trials reviewed. The use of single-pill, triple-combination antihypertensive therapy has been shown to be an effective, well-tolerated, and convenient treatment strategy that can help patients achieve BP control.

Background Elevated central systolic blood pressure (BP) increases the risk of cardiovascular events and appears superior to peripheral BP for long term risk prediction. The objective of this study was to identify demographic and clinical factors associated with central pressures in patients with uncomplicated hypertension. Methods and Results We prospectively examined peripheral BP, central aortic BP, and arterial wall properties and wave reflection in 57 subjects with uncomplicated essential hypertension in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study. Significant predictors of central SBP included height, smoking status, HR, and peripheral SBP, while central DBP was explained by peripheral DBP and HR. These variables accounted for nearly all of the variability in central SBP and central DBP (R2= 0.94 and R2= 0.98, respectively). Central pulse pressure variability was largely explained by gender, ex-smoking status, HR, peripheral SBP, and peripheral DBP (R2=0.94). Central augmented pressure had a direct relationship with smoking status, peripheral SBP, and duration of hypertension, whereas it was indirectly related to height, HR, peripheral DBP. Conclusions Easily obtainable demographic and clinical factors are associated with central pressures in essential hypertensive persons. These relationships should be considered in future studies to improve assessment of BP to reduce cardiovascular risk and mortality.