Prognostic importance of pretreatment and on-treatment blood pressure: Further analysis of the ACTION database and the effect of nifedipine gastrointestinal therapeutic system.

This retrospective further analysis of the ACTION database evaluated the relationships between baseline blood pressure (BP), on-treatment BP (after 6 weeks) and subsequent cardiovascular outcomes. Analyses were performed using multivariate Cox proportional hazard models. Statistically significant (p < 0.

Importance of sustained and "tight" blood pressure control in patients with high cardiovascular risk.

A retrospective further analysis of the ACTION database evaluated the relationship between cardiovascular outcomes and the "quality" of the control of blood pressure (BP). The study population (n = 6287) comprised those patients with four BP measurements during year 1 subdivided according to the proportion of visits in which BP was controlled in relation to two BP targets: < 140/90mmHg and < 130/80 mmHg. Differences between the BP control groups for the major prespecified ACTION outcomes were investigated with Cox proportional hazards models.

Acetaminophen use and risk of myocardial infarction and stroke in a hypertensive cohort.

Recent data suggest that self-reported acetaminophen use is associated with increased risk of cardiovascular events and that acetaminophen causes a modest blood pressure rise. There are no randomized trials or studies using verified prescription data of this relationship. We aimed to assess the relationship between verified acetaminophen prescription data and risk of myocardial infarction or stroke in patients with hypertension.

Thrapeutic equivalence in the treatment of hypertension: Can lercanidipine and nifedipine GITS be considered to be interchangeable?

Aim: To undertake a review of the evidence that nifedipine GITS and lercanidipine are therapeutically equivalent in the management of essential hypertension.

Methods: A systematic review of the published literature was prompted by the findings of two meta-analyses which indicated that there was a lower incidence of peripheral (ankle) oedema with lercanidipine. However, neither meta-analysis gave detailed attention to comparative antihypertensive efficacy or cardiovascular protection.

A review of the gastrointestinal therapeutic system (GITS) formulation and its effectiveness in the delivery of antihypertensive drug treatment (focus on nifedipine GITS).

Hypertension treatment guidelines do not discriminate within drug classes and, furthermore, do not consider whether or not all of the formulations of any given drug licensed for once-daily administration can be considered to be therapeutically interchangeable. This article focuses on this issue with respect to nifedipine and the development of the gastrointestinal therapeutic system (GITS) formulation. Nifedipine GITS is regarded as the gold standard once-daily formulation of nifedipine and, as such, it is anticipated that alternative formulations will be therapeutically equivalent to nifedipine GITS.

Are fixed-dose combination antihypertensives suitable as first-line therapy?

Objective: To contemplate how initial antihypertensive therapy with fixed-dose combinations (FDC) might be incorporated into clinical practice, based on a compilation of evidence comparing FDCs with monotherapy and loose-dose combinations in varying patient populations.

Methods: A non-systematic search of PubMed (from 2007 to 2012) was performed for randomized, controlled trials in order to capture the evidence on FDC versus monotherapy and loose-dose combinations as first-line therapy. The literature search focused on calcium channel blocker (CCB)-renin angiotensin system (RAS) blocker combinations.

Long-acting dihydropyridine calcium-channel blockers and sympathetic nervous system activity in hypertension: a literature review comparing amlodipine and nifedipine GITS.

Calcium-channel blockers (CCBs) constitute a diverse group of compounds but are often referred to as a single homogeneous class of drug and the clinical responses indiscriminately summarized. Even within the dihydropyridine subgroup, there are significant differences in formulations, pharmacokinetics, durations of action and their effects on blood pressure, heart rate, end organs and the sympathetic nervous system. Amlodipine and nifedipine in the gastrointestinal therapeutic system (GITS) formulation are the most studied of the once-daily CCBs.

Once daily nifedipine: the formulation dictates the pharmacokinetic characteristics and the therapeutic responses.

Nifedipine as a pharmacologic agent for treating hypertension and angina pectoris has been available worldwide since the early 1980's. However, the formulation of nifedipine has undergone a number of modifications over time to improve the pharmacokinetic profile and administration regimen from 3 times daily to once daily. Nifedipine Gastrointestinal Therapeutic System (GITS) is the most widely studied of the once daily formulations from both a pharmacokinetic and clinical perspective.

Improving blood pressure control in patients with diabetes mellitus and high cardiovascular risk.

Patients with diabetes mellitus and symptomatic coronary artery disease are also likely to be hypertensive and, overall, are at very high cardiovascular (CV) risk. This paper reports the findings of a posthoc analysis of the 1113 patients with diabetes mellitus in the ACTION trial: ACTION itself showed that outcomes in patients with stable angina and hypertension were significantly improved when a long-acting calcium channel blocking drug (nifedipine GITS) was added to their treatment regimens. This further analysis of the ACTION database in those patients with diabetes has identified a number of practical therapeutic issues which are still relevant because of potential outcome benefits, particularly in relation to BP control.

Benefits of nifedipine GITS in stable coronary artery disease: Further analysis of the "ACTION" database.

Introduction: Retrospective analyses of specific subgroups of patients from the database of the ACTION study have evaluated the effectiveness of a nifedipine gastrointestinal therapeutic system (GITS) on clinical outcomes. These subgroups included those patients receiving: 1) full "optimal" therapy at baseline; 2) full "optimal" therapy at baseline but excluding renin angiotensin system (RAS)-blocking drugs; 3) treatment with nifedipine GITS who were not treated with RAS blockers versus those treated with RAS blockers but not nifedipine GITS.

Methods: Analyses were performed on an intention-to-treat basis.

Potential concerns about generic substitution: bioequivalence versus therapeutic equivalence of different amlodipine salt forms.

Background And Scope: Whether generic drug products are truly therapeutically identical and interchangeable with their innovator counterparts is still a matter of debate. This review discusses the controversies related to the criteria for bioequivalence and therapeutic equivalence. These concerns are illustrated by using the calcium antagonist amlodipine besylate (innovator drug) versus amlodipine maleate (generic), indicated for the treatment of hypertension and angina pectoris, as an example.

Clinical outcomes according to baseline blood pressure in patients with a low ejection fraction in the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) Program.

Objectives: This study sought to investigate the efficacy and tolerability of candesartan, according to baseline blood pressure (BP), in the 4,576 patients with a low ejection fraction (EF) (
Background: Hypotension is a predictor of poor prognosis in heart failure, yet many treatments shown to reduce morbidity and mortality lower blood pressure.

Candesartan cilexetil--a review of effects on cardiovascular complications in hypertension and chronic heart failure.

Unlabelled: Therapeutic interventions that block the renin-angiotensin-aldosterone system (RAAS) have an important role in slowing the progression of cardiovascular risk actors to established cardiovascular diseases. In recent years, angiotensin receptor blockers (ARBs) have emerged as effective and well-tolerated alternatives to an angiotensin-converting enzyme inhibitor (ACEi) for RAAS blockade. The ARB candesartan was initially established as an effective once-daily antihypertensive treatment, providing 24-h blood pressure (BP) control with a trough:peak ratio close to 100%.

From hypertension to heart failure -- are there better primary prevention strategies?

Although in the developed world the incidence of and mortality from coronary heart disease (CHD) and stroke have been declining over the last 15 years, heart failure is increasing in incidence, prevalence and overall mortality, despite advances in the diagnosis and management of the condition. Hypertension, alone or in combination with CHD, precedes the development of heart failure in the majority of both men and women. Whilst there have been improvements in the overall management of hypertension, as reflected in rates of diagnosis, awareness, treatment and control of blood pressure (BP), there are still many patients with hypertension who remain undiagnosed or untreated and of those who do receive treatment many fail to achieve current targets for BP control.

Angiotensin II receptor antagonists alone and combined with hydrochlorothiazide: potential benefits beyond the antihypertensive effect.

Angiotensin II receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics have an accepted place in the management of hypertension. Most patients require combination therapy with two or more drugs to adequately control blood pressure to targets recommended by European and international guidelines. ARBs and the thiazide diuretic hydrochlorothiazide have complementary modes of action.

Dihydropyridine calcium channel blockers: basic pharmacological similarities but fundamental therapeutic differences.

Recent trials indicate that treatment with calcium channel blockers (CCBs) reduces cardiovascular morbidity and mortality in hypertensive patients (including those with significant coronary artery disease). Since the fundamental mechanism of action of all CCBs is the same, it might be assumed that the findings of these outcome studies can be generalized to all types of CCB. However, in the light of the well-recognized clinical pharmacological differences between the 'rate-limiting' agents, verapamil and diltiazem, and the dihydropyridine group of CCBs, this must be considered to be a misconception.

A putative placebo comparison of the SCOPE and LIFE trials.

The Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial and the Study on Cognition and Prognosis in the Elderly (SCOPE) superficially produced comparable outcomes, with effects on stroke greater than those anticipated from blood pressure (BP) lowering alone. This, however, ignores important features of both studies. It ignores firstly the disparate comparator agents - atenolol in LIFE and predominantly hydrochlorthiazide in SCOPE, secondly the small, but potentially important BP differential between the treatment arms in SCOPE and finally the small, statistically non-significant increase in coronary heart disease (CHD) in both trials.

Efficacy and tolerability of long-term rilmenidine treatment in hypertensive diabetic patients. A retrospective analysis of a general practice study.

Introduction: Rilmenidine is a centrally acting antihypertensive which differs from the other representatives of this class by its very high specificity for the imidazoline I1 receptors and its good tolerability. Recent studies have shown rilmenidine improves glucose tolerance and reduces micro-albuminuria in patients with diabetes mellitus.

Methodology: The evidence of these potentially favorable characteristics encouraged a secondary retrospective analysis of a subgroup of 2738 diabetic patients included in a previous long-term open study of rilmenidine alone, or in combination with other classes of antihypertensives.

A chronotherapeutic approach to effective blood pressure management.

The major randomized trials in hypertension have unequivocally demonstrated the benefits of treatment. None of these trials have sought to address the issue of the potential superiority of 24-hour blood pressure control. However, there is a volume of epidemiologic evidence to suggest that prevention of target organ damage requires the sustained reduction of blood pressure throughout the full 24-hour period between doses.