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.

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.

Aliskiren monotherapy does not cause paradoxical blood pressure rises: meta-analysis of data from 8 clinical trials.

Angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and diuretics all cause reactive rises in plasma renin concentration, but particularly high levels have been reported with aliskiren. This prompted speculation that blockade of plasma renin activity with aliskiren could be overwhelmed, leading to paradoxical increases in blood pressure. This meta-analysis of data from 4877 patients from 8 randomized, double-blind, placebo- and/or active-controlled trials examined this hypothesis.

Combined renin-angiotensin-aldosterone system inhibition in patients with chronic heart failure secondary to left ventricular systolic dysfunction.

The prevalence of heart failure (HF) is high and still on the rise. In 2004, an estimated 5.2 million adults in the United States carried the diagnosis of HF with a mortality rate of >19%.

Direct renin inhibition: an update.

Aliskiren, the first orally effective direct renin inhibitor, is an effective antihypertensive agent with distinctive properties including placebo-like tolerability, pharmacologic effects that persist after drug discontinuation, and a unique mechanism of action. When combined with agents that inhibit the renin-angiotensin-aldosterone system (RAAS), such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers, additional blood pressure reduction reflects more complete RAAS blockade. Concern that marked elevation in plasma renin concentration following aliskiren administration might lead to RAAS-induced paradoxical blood pressure increases appears unfounded, based upon analyses of patients participating in clinical trials.