Background:

Despite a growing body of data demonstrating the benefits of multidisciplinary care in heart failure, persistently high rates of readmission, especially within the first month of discharge, continue to be documented.



Aims:

As part of an ongoing randomized study on the value of multidisciplinary care in a high risk (NYHA Class IV), elderly (mean age 69 years) heart failure population, we examined the effects of this intervention on previously high (20%) 1-month readmission rates.



Methods:

Unlike previous studies of this approach, both multidisciplinary (MC) and routine care (RC) populations were cared for by the cardiology service, complied with adherence to clinical stability criteria prior to discharge (100% of patients) and received at least target dose angiotensin-converting enzyme (ACE) inhibition with perindopril prior to discharge (94% of indicated patients). We analysed death and unplanned readmission for heart failure at 1 month.



Results:

This early report from the first 70 patients (67% male, 71% systolic dysfunction with a mean ejection fraction of 31.0 ± 6.7%) enrolled in this study demonstrates elimination of 1-month hospital readmission in both RC and MC groups. This unexpected result represents a dramatic improvement both for this patient cohort (20% 30-day readmission rate prior to enrolment reduced to 0% following the index admission in both care groups) and in comparison with available data.



Conclusions:

Critical contributors to this improvement appear to be specialist cardiology care, adherence to clinical stability criteria prior to discharge and routine use of target or high-dose ACE inhibitor therapy prior to discharge. Widespread application of this approach may have a dramatic improvement in morbidity of CHF while limiting the escalating costs of this condition.

Elimination of early rehospitalization in a randomized, controlled trial of multidisciplinary care in a high-risk, elderly heart failure population: the potential contributions of specialist care, clinical stability and optimal angiotensin-converting enzyme inhibitor dose at discharge.

Perindopril is a long-acting, once-daily lipophilic angiotensin-converting enzyme inhibitor with high tissue angiotensin-converting enzyme affinity, lowering angiotensin II and potentiating bradykinin. Its efficacy, safety and tolerability are well established in the treatment of hypertension and heart failure. Moreover, large morbidity-mortality trials, such as the EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) and Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), have shown that antihypertensive treatment with perindopril reduces and prevents cardiovascular disease in a large range of patients with vascular diseases, whether hypertensive or not. Thus, the outcome of these and other trials support the concept of cardiovascular protective properties of angiotensin-converting enzyme inhibition with perindopril in addition to the obvious blood-pressure-lowering effect. Considering its properties and the gathered clinical evidence on efficacy and tolerability, perindopril fulfils the criteria of the latest guidelines for hypertension and cardiovascular disease management and should therefore be considered as a first-line antihypertensive agent, forming a consistent part of the comprehensive strategy against hypertension and related cardiovascular complications.

Angiotensin-converting enzyme inhibition in cardiovascular disease: evidence with perindopril.

Specific Properties and Effect of Perindopril in Controlling the Renin–Angiotensin System

Ongoing developments in our understanding of cardiovascular disease, together with the introduction of new drugs to treat these conditions, has led to much debate over the optimal management of hypertension. The ALLHAT study showed no major differences in cardiovascular outcome among three major classes of antihypertensive drugs. Indeed, large meta-analyses have substantiated this view, and most experts would agree that BP reduction matters more than the choice of antihypertensive agent. However, recently published data from the ASCOT-BPLA trial for hypertensive patients at moderate risk of cardiac events have caused some experts to re-evaluate this view. The recent Blood Pressure Lowering Treatment Trialists' Collaboration publication confirmed this change. In the ASCOT-BPLA trial, antihypertensive therapy based on amlodipine+perindopril significantly reduced total and cardiovascular mortality as well as other clinically relevant outcomes in comparison with a traditional strategy based on atenolol and a thiazide diuretic, despite both regimens producing nonsignificantly different reductions in brachial BP. These findings suggest that amlodipine/perindopril may exert a beneficial effect by acting on other parameters such as central BP or BP variability. ACE inhibitors have been shown to have antiatherosclerotic and antithrombogenic effects, to improve endothelial dysfunction, and to prevent cardiac remodeling in patients with coronary heart disease. In this regard, perindopril, which has relatively high affinity for ACE and true 24-hour duration of action, is one of the most extensively studied ACE inhibitors. More recent data suggest that ACE inhibitors reduce arterial stiffness, an independent risk factor for cardiovascular events, and have a beneficial effect on central aortic BP, thus providing a possible explanation for the findings of ASCOT-BPLA and confirming that ACE inhibitors are an appropriate first choice for patients with hypertension.

ACE inhibition in hypertension: focus on perindopril.

Despite their proven value in reducing morbidity and mortality in different grades of heart failure, angiotensin converting enzyme (ACE) inhibitors continue to be underused. One reason for this is clinicians' apprehension of first-dose hypotension. We conducted a double-blind, randomised, placebo-controlled parallel group study to investigate the effect of various ACE inhibitors on first-dose hypotension. Eighty unselected patients were randomised into five treatment groups: placebo, captopril 6.25 mg, enalapril 2.5 mg, perindopril 2 mg and lisinopril 2.5 mg. Blood pressure was measured at baseline, half hourly for two hours and hourly for three hours after drug treatment. The maximum drops in mean arterial pressure (in mmHg +/- SD) were placebo 5.89 +/- 2.65, perindopril 5.29 +/- 2.49, enalapril 13.28 +/- 3.31, lisinopril 15.04 +/- 5.74 and captopril 16.76 +/- 5.74 (all p < 0.05 vs placebo except for perindopril). Perindopril, unlike the other ACE inhibitors studied, did not produce first-dose hypotension following its initiation in patients with congestive heart failure.

First-dose response to angiotensin-converting enzyme inhibition in congestive cardiac failure : A Malaysian experience

We previously demonstrated differing blood pressure (BP) responses to the first dose of angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF). We wished to confirm the disparate responses to the first dose of these agents, study the response to repeated dosing, and explore possible explanations (slow, tight binding, and steric hindrance) for the phenomenon. Forty-eight elderly patients (aged 51-85 years) with stable CHF were studied for 48 hours. Groups (n = 12) received one of the following: (a) perindopril 2 mg orally (p.o.) + placebo intravenously (i.v.) (day 1) and perindopril 2 mg p.o. (day 2); (b) enalapril 2.5 mg p.o. + placebo i.v. (day 1) and enalapril 2.5 mg p.o. (day 2); (c) placebo p.o. + perindopril at 0.167 mg i.v. (day 1) and perindopril 2 mg p.o. (day 2); or (d) placebo p.o. + placebo i.v. (day 1) and placebo p.o. (day 2). Supine BP was measured on day 1. On day 2, BP was recorded by ambulatory BP monitor. Blood samples were taken at baseline and at intervals during the 48-h study period for estimation of neurohumoral parameters. Inhibition of the renin-angiotensin system (RAS) was estimated by plasma ACE inhibition and also by the ratio of angiotensin II (Ang II)/Ang I + Ang II. On day I, enalapril 2.5 mg caused a greater decrease in BP than did placebo response between 6 and 9 h postdose. Perindopril 2 mg produced a profile of BP response similar to that of placebo. Ambulatory BP on day 2 was consistently lower with enalapril as compared with perindopril. Profiles of plasma ACE inhibition were similar with each active therapy. Enalapril therapy produced a greater increase in plasma renin activity (PRA) than did other treatments. There was no temporal dissociation between plasma ACE inhibition and profile of Ang peptides for any treatment. We have confirmed the disparate BP responses to perindopril and enalapril in CHF. We noted no evidence of slow, tight binding or steric hindrance to explain these differences.

Differing early blood pressure and renin-angiotensin system responses to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure

BACKGROUND
Breakthrough seizures and status epilepticus require urgent management. Administration of intravenous push (IVP) levetiracetam has been demonstrated to be safe as compared to intravenous piggyback (IVPB). This transition can potentially offer faster time to administration and reduced drug and material cost. The objective of this study was to observe safety of administration in patients receiving levetiracetam via IVP compared to IVPB in acute care settings.


METHODS
This is a multi-center, observational, retrospective cohort study of 1214 adult patients who received levetiracetam pre- and post-implementation of IVP over a 6 month timespan. Primary outcome was time from order verification to administration of urgent first-time doses. Secondary outcomes included time to administration of loading doses and cost. Safety outcome was infusion site related reactions.


RESULTS
Time from order verification to administration of urgent first-time doses pre- and post-implementation of IVP administration was reduced from 61 minutes to 47 minutes (P=0.0002). Infusion site related reactions were observed in 6 out of 5432 doses in the IVPB arm and in 5 out of 4700 doses in the IVP arm (P=1). Total estimated cost was $76,171.96 for the 5449 IVPB total doses and $11,484.33 for the 4721 IVP total doses.


CONCLUSIONS
Transition from IVPB to IVP administration reduced time from order verification to administration of urgent first-time doses with both administrations having similar incidence of infusion site related reactions. Cost savings and improved workflow were observed. Levetiracetam administered via IVP may be considered as a safe alternative method of administration in the acute care setting.

Evaluation of Safety Outcomes of Undiluted Levetiracetam Intravenous Push Compared to Intravenous Piggyback.

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Differing early blood pressure and renin-angiotensin system responses to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure

Evaluation of Safety Outcomes of Undiluted Levetiracetam Intravenous Push Compared to Intravenous Piggyback.