Updates 20 June 2016
Association of Urinary Sodium Excretion with Cardiovascular Events in Individuals with and without Hypertension.
Restriction of salt intake is commonly advised as part of primary prevention against adverse cardiovascular events. There is however a “U shaped curve” in the relation between daily urinary sodium excretion and adverse events, which raises the question of whether or not dietary sodium restriction is warranted for all people.
A pooled analysis of four large studies by Mente et al has now been reported in the Lancet and provides some clarity to this question. Among 63,559 patients with hypertension and 63,559 without, daily urinary sodium excretion was related to composite outcome of death and/or major cardiovascular event over 4 years.
Higher sodium intake was associated with a greater rise in systolic blood pressure in hypertensive patients (2.08 mmHg increase per g increase in sodium intake) than in normotensive patients (1.22 mmHg, p<0.0001). In hypertensive patient both high daily sodium excretion (≥7 g/day) and low sodium excretion (<3 g/day) were associated with increased risk of adverse events.
In contrast, among normotensive patients, only low sodium excretion was associated with increased risk of adverse cardiovascular events. The authors conclude that efforts at lowering daily sodium intake are best targeted at individuals with hypertension and high sodium intake.
Liraglutide and Improved Cardiovascular Outcomes in Type 2 Diabetes
Until recently, excellence in blood sugar control has been associated with improvements in micro-vascular, but not macro-vascular, complications for individuals with Type 2 diabetes. There are now emerging clinical trials of newer agents, such as glucagon-like peptide (GLP-1) analogues, which suggest that improvements in macro-vascular outcomes may also be achieve.
In the NEJM, Marso et al report the results of the LEADER trial, which examined the effect of adding liraglutide (a GLP-1 analogue) to usual therapy in patients with Type 2 diabetes. A total of 9340 patients who were at high risk of adverse cardiovascular outcomes were randomized 1:1 to liraglutide or placebo in addition to usual therapy and followed for a mean 3.8 years. The primary composite outcome was first occurrence of death from cardiovascular causes, nonfatal MI or nonfatal stroke.
The patients receiving liraglutide had lower HbA1c (-0.4%), greater weight loss and lower systolic blood pressure than the placebo group. The primary outcome occurred in 13% of the liraglutide group and 14.9% of the placebo group (p<0.001 for non-inferiority and p=0.01 for superiority). Death from cardiovascular causes was significantly less in the liraglutide group (HR = 0.78, CI 0.66 – 0.93, p=0.007), but occurrence of non-fatal MI and non-fatal stroke did not significantly differ between liraglutide and placebo groups.
The authors concluded that addition of liraglutide reduced the rates of cardiovascular events and death compared to placebo, with the caveat that the study population was high-risk and these benefits may not be observed in lower risk populations.
This study adds to the emerging body of evidence that newer treatments for control of blood sugar in Type 2 diabetes may confer prognostic benefit for adverse cardiovascular events.
Pulseless Electrical Activity and Cardiac Arrest
Out of hospital cardiac arrest (OHA) continues to have poor outcomes, despite slowly increasing community awareness of CPR techniques, increased availability of automated defibrillator devices and strategies of immediate defibrillation.
The demographics appear to be changing with and increasing proportion of pulseless electrical activity (PEA) arrests, which have less favourable outcomes. The demographics of current OHA are described by Wolbinski et al in the recent issue of Heart Lung and Circulation.
This review of 749 consecutive OHA in the Wellington region over a five years period found that the presenting rhythm was VT/VF in 46% cases, asystole in 37% and PEA in 17%. Patients with PEA were older than those with VT/VF and were more likely to be female and more likely to have underlying chronic respiratory disease, but were less likely to have known prior cardiovascular disease.
The increasing incidence of PEA may well reflect better management of patients with chronic heart disease and use of implantable defibrillators, as well as an ageing population with multiple co-morbidities. The adverse outcomes observed with OHA and PEA will require new management strategies, which must be informed by better understanding of the pathogenesis of PEA and knowledge of the time course and key stages of its evolution.
New Guidelines for Pharmacological Treatment of Heart Failure
A new Article in Press from the ACC presents updated Guidelines for the Pharmacological Treatment of Heart Failure. Two principal areas of recommendation are addressed.
The first series of recommendations address the use of angiotensin-receptor blockers (ARB) and neprilysin inhibitors in patients with heart failure with reduced ejection fraction (HFrEF).
These can be summarised as:
1. The clinical strategy of inhibition of the rennin-angiotensin system with ACE inhibitors OR ARB or an ARB with a neprilysin inhibitor (ARNI), in conjunction with evidence-based beta-blockers and aldosterone antagonists in selected patients is recommended for patients with chronic HFrEF to reduce morbidity and mortality.
2. The use of ACE inhibitors is beneficial for patients with prior or current symptoms of HFrEF to reduce morbidity and mortality.
3. The use of ARBs to reduce morbidity and mortality is recommended in patients with prior or current symptoms of chronic HFrEF who are intolerant to ACE inhibitors because of cough or angioedema.
4. In patients with chronic symptomatic HFrEF NYHA Class II or III who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality.
5. ARNI should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor.
6. ARNI should not be administered to patients with a history of angioedema.
At this time, although Entresto (Novartis) Sacubritil + Valsartan is approved for inclusion in Schedule 4 by the TGA, it was not recommended for inclusion in the PBS at review in March 2016, with the cited reason as “The PBAC did not recommend the listing of sacubitril with valsartan on the basis of uncertain cost-effectiveness and high predicted financial impact”.
The second series of recommendations address the use of Ivabradine in patients with heart failure.
These can be summarised as:
1. Ivabradine can be beneficial to reduce heart failure hospitalization for patients with symptomatic (NYHA Class II-III) stable chronic HFrEF (LVEF<35%) who are receiving guideline directed medical management, including a beta-blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest.