Additivity of nebivolol/valsartan single-pill combinations versus other single-pill combinations for hypertension.

The single-pill combination (SPC) comprising nebivolol (5 mg), a vasodilatory β -selective antagonist/β -agonist, and valsartan (80 mg), a renin-angiotensin-aldosterone system inhibitor, is the only Food and Drug Administration-approved β-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-β-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.

The Elusive Search for Optimal Blood Pressure Targets.

BP treatment thresholds/targets determine when to initiate treatment and to what level BP should be reduced. The Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) recommended a target of <140/90 for most patients and a target <130/80 mmHg for patients with diabetes or chronic kidney disease. Subsequently, meta-analyses, retrospective studies relating on-treatment BP to clinical outcomes and two large, randomized clinical trials (RCTs) have re-evaluated BP targets.

A Call for Appropriate Evidence and Outcomes-Based Use and Measurement of Anticoagulation for Atrial Fibrillation: Moving the Population Towards Improved Health Via Multiple Stakeholders.

A multidimensional approach involving consideration of available resources, individual patient characteristics, patient preferences, and cost of treatment is often required to optimize clinical decision making in the management of atrial fibrillation (AF). In order to bring together varying perspectives on effective tactics and to formulate innovative strategies to improve the management of AF, a think tank consortium of advisors was assembled from across the spectrum of health care stakeholders. Focus groups were conducted and facilitated by a moderator and a notetaker.

LCZ696: the next step in improving RAS inhibition?

LCZ696 is a single molecule which combines the angiotensin receptor blocker valsartan with the neprilysn inhibitor sacubitril (AHU377). In the recently published PARADIGM-HF trial, LCZ696 proved superior to enalapril in reducing overall mortality, heart failure hospitalizations, and other endpoints in patients with systolic dysfunction heart failure. Increases in counter-regulatory natriuretic peptides which oppose sodium retention, vasoconstriction, and the deleterious structural changes which follow neurohormonal activation are thought to account for these improved outcomes.

Is addition of vasodilators to loop diuretics of value in the care of hospitalized acute heart failure patients? Real-world evidence from a retrospective analysis of a large United States hospital database.

Background: Current guidelines recommend the use of intravenous (IV) vasodilators in addition to IV loop diuretics for the treatment of acute heart failure (AHF) patients without hypotension. The evidence basis for these recommendations is limited.

Methods And Results: Hospital billing records for 82,808 AHF patients in the United States were analyzed.

Efficacy and safety of nebivolol and valsartan as fixed-dose combination in hypertension: a randomised, multicentre study.

Background: The fixed-dose combination of any two antihypertensive drugs from different drug classes is typically more effective in reducing blood pressure than a dose increase of component monotherapy. We assessed the efficacy and safety of a fixed-dose combination of a vasodilating β blocker (nebivolol) and an angiotensin II receptor blocker (valsartan) in adults with hypertension.

Methods: We did an 8-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group trial at 401 US sites.

Initial combination therapy reduces the risk of cardiovascular events in hypertensive patients: a matched cohort study.

This study evaluated the effects of initial versus delayed treatment with a drug combination on blood pressure (BP) control and the risk of cardiovascular (CV) events in hypertensive patients. Clinical trials suggest that the time to BP control is an important determinant of long-term outcomes, but real-world evidence is scarce. Using electronic medical charts (2005-2009), we retrospectively analyzed 1762 adult patients with BP elevation initiating combination therapy matched 1:1 with similar patients initiating monotherapy and later switched to combination therapy.

Strategies for combination therapy in hypertension.

Purpose Of Review: To achieve the target blood pressure (BP) mandated by current guidelines, a large majority of patients require simultaneous administration of multiple antihypertensive agents. The purpose of this review is to focus attention on the rational selection of effective drug combinations, and upon ways to use them efficiently to achieve therapeutic objectives. The topic is widely relevant given that more than 46  million ambulatory care visits are conducted in the United States annually for hypertension management.

Long-term safety and tolerability of the oral direct renin inhibitor aliskiren with optional add-on hydrochlorothiazide in patients with hypertension: a randomized, open-label, parallel-group, multicentre, dose-escalation study with an extension phase.

Background: Most patients with hypertension will require combination therapy with at least two agents from different antihypertensive classes to achieve blood pressure (BP) control. Thiazide diuretics, such as hydrochlorothiazide (HCTZ), are widely used in combination therapy. The volume reduction with these agents stimulates the renin-angiotensin system (RAS), making RAS inhibitors such as the direct renin inhibitor aliskiren a logical choice for combination therapy with HCTZ.

Difficult-to-Treat or Resistant Hypertension: Etiology, Pathophysiology, and Innovative Therapies.

Despite the many therapeutic options available today for the treatment of hypertension, a sizable number of patients still remain resistant to treatment. The prevalence of resistant hypertension in the general population under optimal conditions is about 3-5%. Although several factors and conditions can be identified and corrected a percentage of hypertensive patients remain with unacceptably high blood pressure levels.

Combination therapy in hypertension.

The goal of antihypertensive therapy is to abolish the risks associated with blood pressure (BP) elevation without adversely affecting quality of life. Drug selection is based on efficacy in lowering BP and in reducing cardiovascular (CV) end points, including stroke, myocardial infarction, and heart failure. Although the choice of initial drug therapy exerts some effect on long-term outcomes, it is evident that BP reduction per se is the primary determinant of CV risk reduction.

Rationale for triple-combination therapy for management of high blood pressure.

The goals of antihypertensive therapy include optimal reduction in blood pressure (BP) while providing a favorable tolerability profile that promotes long-term adherence to treatment. For most patients with hypertension, these treatment goals cannot be achieved with monotherapy. When instituted early, however, combination therapy results in more rapid control of BP.

Combination therapy in hypertension.

The goal of antihypertensive therapy is to abolish the risks associated with blood pressure (BP) elevation without adversely affecting quality of life. Drug selection is based on efficacy in lowering BP and in reducing cardiovascular (CV) end points including stroke, myocardial infarction, and heart failure. Although the choice of initial drug therapy exerts some effect on long-term outcomes, it is evident that BP reduction per se is the primary determinant of CV risk reduction.

Combination therapy in hypertension.

The goal of antihypertensive therapy is to abolish the risks associated with blood pressure (BP) elevation without adversely affecting quality of life. Drug selection is based on efficacy in lowering BP and in reducing cardiovascular (CV) end points including stroke, myocardial infarction, and heart failure. Although the choice of initial drug therapy exerts some effect on long-term outcomes, it is evident that BP reduction per se is the primary determinant of CV risk reduction.

Efficacy, safety and tolerability of aliskiren, a direct renin inhibitor, in women with hypertension: a pooled analysis of eight studies.

Hypertension is a major risk factor for cardiovascular disease, which is the leading cause of mortality in women in developed countries. This pooled analysis assessed the antihypertensive efficacy, safety and tolerability of monotherapy with the direct renin inhibitor aliskiren (150 mg and 300 mg) over 8-12 weeks in women with mild-to-moderate hypertension (mean sitting diastolic blood pressure (msDBP) ≥95 and <110 mm Hg) across eight randomized and double-blind trials. Safety and tolerability were assessed in the five placebo-controlled trials in the analysis.