Combating Inflammation in Cardiovascular Disease.

The role of inflammation in promoting atherosclerosis and subsequent cardiovascular disease is increasingly recognised, particularly after the publication of Anti-inflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS) and Colchicine Cardiovascular Outcomes (COLCOT) trials. It appears that specifically targeting the Nod-like receptor protein 3 (NLRP3) inflammasome-interleukin 1/interleukin 18-interleukin 6 pathway appears to be most beneficial in cardiovascular risk reduction. High sensitivity C-reactive protein (CRP) is a downstream biomarker of inflammation that can be used to monitor treatment. This article will discuss the role of inflammation in cardiovascular disease, the utility of high sensitivity C-reactive protein and treatments that target this inflammation. While further research is needed into the cost effectiveness and safety of newer agents, it remains an evolving approach to manage cardiovascular risk.

The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study.

BACKGROUND: During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. METHODS AND RESULTS: Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. CONCLUSIONS: During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.

Update on the management of atrial fibrillation.

Atrial fibrillation (AF) is a common arrhythmia, with a prevalence that increases markedly with increasing age. Presence of AF has implications for management of future stroke risk. If the patient's pulse is irregular, an electrocardiogram should be ordered. Key management decisions are whether to adopt a rhythm control or a rate control strategy and whether to initiate anticoagulation. The primary aim of a rhythm control strategy is improved symptom control. AF ablation may be considered in younger patients (aged < 65 years) with paroxysmal or early persistent AF. AF increases the risk of stroke, and anticoagulation should be considered on the basis of stroke risk - clearly indicated with a CHADS 2 score (congestive heart failure, hypertension, age ≥ 75 years, diabetes, 1 point each; previous stroke or transient ischaemic attack, 2 points) of ≥ 2 - independent of the type of AF. In most patients with AF, the benefit of stroke reduction with systemic anticoagulation will outweigh its bleeding risks. All anticoagulants and antiplatelet agents increase the risk of bleeding. However, the new oral anticoagulants tend to have an improved safety profile, particularly in regard to intracranial bleeding, and are at least as effective as warfarin for stroke prevention.

Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20 mg daily for patients with normal renal function and 15 mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30 ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF.

Treatment disparities and effect on late mortality in patients with diabetes presenting with acute myocardial infarction: observations from the ACACIA registry.

OBJECTIVES: To compare the use of evidence-based pharmacological and invasive treatments and 12-month mortality rates between patients with and without diabetes who present with acute myocardial infarction (MI), and to explore the relationship between these treatments and late clinical outcomes. DESIGN AND SETTING: Prospective, nationwide multicentre registry: the Acute Coronary Syndrome Prospective Audit (ACACIA). PATIENTS: Patients presenting to 24 metropolitan and 15 non-metropolitan hospitals with acute coronary syndrome (ACS) and a final discharge diagnosis of acute MI between November 2005 and July 2007. MAIN OUTCOME MEASURE: All-cause mortality at 12 months. RESULTS: Nearly a quarter of 1744 patients with a final diagnosis of acute MI had a history of diabetes on presentation. Patients with diabetes were older, with a greater prevalence of comorbidities than non-diabetic patients, and were less likely to be treated at discharge with evidence-based medications (aspirin, clopidogrel, a statin and/or a beta-blocker) or to receive early invasive procedures. After adjusting for baseline characteristics and therapeutic interventions, diabetes at presentation was independently associated with a higher mortality at 12 months after MI (hazard ratio, 1.79; 95% CI, 1.18-2.72; P=0.007). Early invasive management and discharge prescription of guideline-recommended medications were associated with a significantly reduced hazard of mortality at 12 months. CONCLUSION: Patients with diabetes have a higher risk than non-diabetic patients of late mortality following an acute MI, yet receive fewer guideline-recommended medications and early invasive procedures. Increased application of proven pharmacotherapies and an early invasive management strategy in patients with diabetes presenting with ACS might improve their outcomes. STUDY PROTOCOL NUMBER (SANOFI-AVENTIS): PML-0051.

Invasive management and late clinical outcomes in contemporary Australian management of acute coronary syndromes: observations from the ACACIA registry.

OBJECTIVE: To describe the impact of invasive management on 12-month survival among patients with suspected acute coronary syndrome (ACS) in Australia. DESIGN AND SETTING: Prospective nationwide multicentre registry. PATIENTS: Patients presenting to 24 metropolitan and 15 non-metropolitan hospitals with ST-segment-elevation myocardial infarction (STEMI), and high-risk and intermediate-risk non-ST-segment-elevation ACS (NSTEACS) between 1 November 2005 and 31 July 2007. MAIN OUTCOME MEASURES: Death, myocardial infarction (MI) or recurrent MI, revascularisation and stroke at 12 months. RESULTS: Among 3402 patients originally enrolled, vital status at 12 months was available for 3393 (99.7%). Patients from non-metropolitan areas (810) constituted 23.9% of patients. Early invasive management was more commonly undertaken among patients with STEMI (STEMI, 89.7% v non-STEMI, 70.8% v unstable angina, 44.8% v stable angina, 35.8%; P<0.001). Factors most associated with receiving invasive management included admission with suspected STEMI or high-risk NSTEACS, being male and the hospital having an onsite cardiac surgical service. Overall mortality by 12 months among patients with STEMI, non-STEMI, unstable angina and stable angina was 8.0%, 10.5%, 3.3%, and 3.7% (P<0.001), respectively. After adjusting for a propensity model predicting early invasive management and other known confounders, early invasive management was associated with a 12-month mortality hazard ratio of 0.53 (95% CI, 0.34-0.84, P=0.007). CONCLUSIONS: A substantial burden of late morbidity and mortality persists among patients with ACS within contemporary Australian clinical practice. Under-use of invasive management may be associated with an excess in 12-month mortality, suggesting the need for more use of invasive management among these patients.