Cardiovascular risk reduction in hypertension: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers. Where are we up to?

Previously, management of hypertension has concentrated on lowering elevated blood pressure. However, the target has shifted to reducing absolute cardiovascular (CV) risk. It is estimated that two in three Australian adults have three or more CV risk factors at the same time. Moderate reductions in several risk factors can, therefore, be more effective than major reductions in one. When managing hypertension, therapy should be focused on medications with the strongest evidence for CV event reduction, substituting alternatives only when a primary choice is not appropriate. Hypertension management guidelines categorise angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) interchangeably as first-line treatments in uncomplicated hypertension. These medications have different mechanisms of action and quite different evidence bases. They are not interchangeable and their prescription should be based on clinical evidence. Despite this, currently ARB prescriptions are increasing at a higher rate than those for ACEI and other antihypertensive classes. Evidence that ACEI therapy prevents CV events and death, in patients with coronary artery disease or multiple CV risk factors, emerged from the European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA) and Heart Outcomes Prevention Evaluation (HOPE) trials respectively. The consistent benefit has been demonstrated in meta-analyses. The clinical trial data for ARB are less consistent, particularly regarding CV outcomes and mortality benefit. The evidence supports the use of ACEI (Class 1a) compared with ARB despite current prescribing trends.

Is addition of angiotensin receptor blockade superior to increasing ACE inhibitor dose in patients with heart failure?

We conducted a prospective, randomised, open-label, blinded end point (PROBE) study examining the relative efficacy of irbesartan 300 mg/day versus maximising dose of ACE inhibitor, additional to background conventional heart failure therapy. Patients with CHF, NYHA Class II-III and a left ventricular ejection fraction <40% were randomised to one of two treatment arms. All patients were receiving ≤ half target dose of ACE inhibitor as background therapy. 44 patients received an increase in their background ACE inhibitor while 45 patients were given irbesartan (target dose 300 mg/day) in addition to their background ACE inhibitor. The primary end-point was change in brain natriuretic peptide (BNP) from baseline to 6 months. Change in hs-CRP level, 6 min walk distance, and Minnesota living with heart failure quality of life questionnaire (MLWHF) from baseline to 6 months were also evaluated. Patients were well matched at baseline for all end-point parameters as well as for age, gender and baseline systolic ventricular function. There was general improvement in clinical status for all patients but no significant difference between increased ACE inhibitor vs added ARB for change in BNP, hs-CRP, NYHA, 6 min walk or MLWHF (all P>0.05). This PROBE study has demonstrated similar clinical responses with increased dose of ACE inhibitor compared to addition of ARB in patients with systolic CHF. These findings suggest that either approach to increasing renin-angiotensin blockade in patients taking low doses of background ACE inhibitor results in similar clinical outcomes.

Addressing the burden of heart failure in Australia: the scope for home-based interventions.

The growing burden of heart failure (HF) challenges health practitioners to implement and evaluate models of care to facilitate optimal health related outcomes. Australia supports a publicly funded universal health insurance system with a strong emphasis on primary care provided by general practitioners. The burden of chronic HF, and a social and political framework favoring community-based, noninstitutionalized care, represents an ideal environment in which home-based HF programs can be implemented successfully. Cardiovascular nurses are well positioned to champion and mentor implementation of evidence-based, patient-centered programs in Australian communities. This paper describes the facilitators and barriers to implementation of best practice models in the Australian context. These include the challenge of providing care in a diverse, multicultural society and the need for clinical governance structures to ensure equal access to the most effective models of care.

Rapid onset and dissipation of left atrial spontaneous echo contrast during percutaneous balloon mitral valvotomy.

BACKGROUND: Thromboembolism after percutaneous balloon mitral valvotomy (PBMV) has been attributed to dislodement of preexisting thrombus during transseptal puncture and instrumentation of the left atrium. The occurrence of thromboembolic events after PBMV in the absence of demonstrable left atrial thrombus before PBMV suggests that thrombus might form during the procedure. Spontaneous echo contrast (SEC) is a swirling pattern of blood echogenicity that is a marker of blood stasis in the left atrium. Exacerbation of left atrial SEC during PBMV may be indicative of an increased thromboembolic risk. METHODS: Transesophageal echocardiography was performed during PBMV in 20 patients with mitral stenosis. Grades of severity of left atrial SEC [0 (nil) to 4+ (severe)] were allocated before and after each balloon inflation. RESULTS: Before PBMV, SEC was present in 17 patients. New SEC or increased severity of SEC was observed during 49 of 56 balloon inflations. SEC was unchanged after six deflations, decreased after 14 deflations, and disappeared after 36 deflations. The mean times to onset and dissipation of SEC after balloon inflation and deflation were 3.1+/-1.5 and 3.9+/-1.6 seconds, respectively. After successful PBMV, SEC was unchanged in three patients, decreased in one, and resolved in 13. CONCLUSIONS: SEC is a dynamic and acutely reversible phenomenon that is highly sensitive to changes in left atrial hemodynamic conditions. Left atrial blood stasis induced by balloon inflation may promote thrombogenesis during PBMV.

Continuous home ambulatory intravenous inotropic drug therapy in severe heart failure: safety and cost efficacy.

Some patients with dilated cardiomyopathy who are inotrope dependent but remain well by undergoing infusions can be managed by ambulatory infusions at home. We report our results in 20 patients awaiting heart transplantation, unable to be weaned from intravenous inotropic therapy on 2 or more occasions, but who were well while receiving inotropes and received home ambulatory infusions. The patients were treated with ACE inhibitors, digoxin, diuretics, vasodilators, close electrolyte management, and low-dose amiodarone for those with more than four-beat ventricular tachycardia. Infusions were delivered by a tunneled subclavian catheter and syringe driver. Thirteen patients received dopamine, four received dobutamine, and three received both. Mean duration of inotropic therapy was 5 months with 70% of the time spent as an outpatient. Eleven patients received transplants, two remain on the waiting list, and seven died after being removed from the list because of general deterioration or renal dysfunction. There were no sudden deaths. Actuarial survival was 71% at 3 months, which is not less than that expected for an inotrope-dependent population. All patients with idiopathic dilated cardiomyopathy survived to transplantation. In contrast, all three with right heart failure caused by pulmonary vascular disease and four of seven with ischemic cardiomyopathy died. Inpatient days were reduced by 70%, leading to considerable cost savings. Home ambulatory inotropic therapy is safe, cost-effective, best suited to those with idiopathic dilated cardiomyopathy, and dramatically reduces inpatient hospital duration.