Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

World Congress of Cardiology

Barcelona, Spain / September 2-6, 2006

Risk assessment has been integrated into management strategies in many areas of cardiovascular care, including acute coronary syndromes and coronary artery disease (CAD). As suggested by Dr. Christopher Granger, Assistant Professor of Medicine, Duke University Medical Center, Durham, North Carolina, the same approach should be used in patients with chronic heart failure (CHF). Such a strategy, he noted, would help physicians decide on both the choice and intensity of treatment and ensure the absolute benefit of an intervention is worth the risk. Key drivers of risk in CHF can be divided into five broad categories, including patient demographics, clinical variables such as New York Heart Association (NYHA) class, electrocardiographic variables, functional status, blood markers and hemodynamic parameters, notably ejection fraction (EF).

More specifically, the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) database revealed that the presence of diabetes in the setting of CHF was of “critical importance” in determining patient prognosis, Dr. Granger observed. Declining renal function is a major risk factor for worse outcomes in both CAD and CHF, as is the presence of anemia, he added. Patients over 60 years of age were also at higher risk of reaching the primary end point of CHARM. Secondary end points included cardiovascular death and hospitalization for heart failure; EF <45%; NYHA class; and a low body weight (<71 kg for men, <59 kg for women).

As pointed out by Dr. Piotr Ponikowski, Military Hospital, Wroclaw, Poland, both cardiovascular and non-cardiovascular comorbidities are extremely common in CHF and these comorbidities need to be factored into treatment decisions as they can dramatically influence prognosis. In his own large CHF outpatient department, for example, over one-third of patients have diabetes and 27% have chronic obstructive pulmonary disease.

Large databases also suggest that up to 40% of CHF patients have five or more comorbidities and these affect outcome and interact with treatment. However, not all traditional cardiovascular disease risk factors negatively influence outcome in CHF patients. For example, mild obesity in CHF is actually related to a better survival, whereas losing weight is “an ominous sign,” Dr. Ponikowski noted. Low cholesterol levels in CHF patients are also related to a poor outcome.

Intuitively, recognition and potential reversal of risk factors for worse outcomes should improve the poor prognosis of CHF patients. In the CHARM trial, for example, treatment with the angiotensin receptor blocker (ARB) candesartan reduced the risk of new-onset diabetes by 22% compared with placebo. Both ACE inhibitors and other ARBs have similarly been associated with a lower risk of new-onset diabetes, as well as atrial fibrillation, in a variety of patient populations.

Patients at highest risk of adverse outcomes also derive the greatest benefit from medical therapies; consequently, speakers here agreed, for these patients in particular, a special effort should be made to put them and keep them on what are known to be highly effective therapies.

Approaches to CHF Management

Does evidence support a cornerstone approach to basic CHF management? This was addressed by Dr. Marc Pfeffer, Professor of Medicine, Harvard Medical School, Boston, Massachusetts, who argued that first and foremost, the ACE inhibitors have proven results in the management of CHF if patients are able to tolerate them. However, there is also good evidence from the literature supporting the use of the ARBs both on top of an ACE inhibitor and on top of a beta blocker. In Val-HeFT (Valsartan Heart Failure Trial), for example, the addition of the ARB valsartan to background ACE inhibitor-based therapy did not improve survival but it did decrease morbidity compared to placebo controls. Moreover, in the small subgroup in Val-HeFT who could not tolerate an ACE inhibitor, the ARB significantly reduced morbidity and mortality in the absence of ACE inhibition.

The same clinical benefit was observed in the CHARM-Alternative trial, where over 2000 patients who could not tolerate an ACE inhibitor were given candesartan in addition to other standard CHF medications. Results in this large group of patients showed that the ARB reduced the risk of reaching the primary end point of the trial—namely, cardiovascular death and hospitalization for heart failure—compared with placebo. Dr. Pfeffer observed, “If a patient is not on an ACE inhibitor, it’s a clear yes to use an ARB in this patient group.”

CHARM-Added also demonstrated that additional candesartan given to patients already on an ACE inhibitor led to a 15% relative risk reduction in the primary end point compared with placebo. A reduction in hospitalization for heart failure was again observed in Val-HeFT in patients receiving both an ACE inhibitor and an ARB, “so adding an ARB on top of an ACE inhibitor produces a benefit,” Dr. Pfeffer noted.

In Val-HeFT, there was a suggestion that the addition of the study ARB might be associated with a worse outcome in patients who were on both an ACE inhibitor and a beta blocker. In contrast, findings from the much larger cohort enrolled in the CHARM-Added study did not support this association. Indeed, in CHARM-Added, “the favourable influence of adding candesartan was not altered by the presence or absence of beta blocker therapy, which is a very important interpretation of the data,” Dr. Pfeffer stated. CHARM investigators were also asked by regulatory officials if the same clinical benefit seen when the ARB was added to an ACE inhibitor and a beta blocker could not have been achieved by simply giving patients a higher dose of an ACE inhibitor. As Dr. Pfeffer indicated, evidence-based doses of the ACE inhibitors were used in CHARM, and patients were started on and remained on good doses of ACE inhibitors. However, there was no modification of the 15% benefit seen in CHARM-Added based on the ACE inhibitor dose, Dr. Pfeffer emphasized.

There is also evidence from RALES (Randomized Aldactone Evaluation Study) that the addition of spironolactone to an ACE inhibitor and a beta blocker could lead to a further reduction in cardiovascular risk in patients with systolic dysfunction CHF.

“Adding a proven ARB at a proven dose or spironolactone is your choice, but either choice requires monitoring, as done in CHARM,” Dr. Pfeffer stressed; two weeks after initiating therapy, patients need to be monitored for hyperkalemia. As safety data from the CHARM program showed, the incidence of hyperkalemia remains very low in patients receiving the ARB, provided they are carefully monitored.

Comorbidities

Optimized medical therapy should improve clinical outcomes in CHF patients but as discussed by Dr. Graham Jackson, Guy’s and St. Thomas’ National Health Service Foundation Trust, London, UK, there is more to CHF management than neurohormonal manipulation. As he pointed out, CHF causes more severe impairment of physical and social functioning and energy levels than chronic lung disease, arthritis and other cardiac conditions, including angina. As severity of the disease increases, “overall quality of life markedly declines,” he added, and CHF is often accompanied by depression in a substantial proportion of patients. Because the symptoms of depression—apathy, fatigue, anergia—are often associated with CHF, “depression is often overlooked,” Dr. Jackson noted.

Accompanying the depression are frequent feelings of hopelessness, worthlessness and low self-esteem, all of which may contribute to erectile dysfunction in men and sexual dysfunction in women. Very little research has been carried out on the treatment of erectile dysfunction and sexual dysfunction in CHF patients but it is a major problem for many patients and it can lead to serious emotional distress, as Dr. Jackson observed. Thus, physicians need to start asking about erectile dysfunction and sexual dysfunction in their CHF patients and, when present, give patients hope that it can often be corrected with medical and non-medical strategies. “Begin with non-threatening questions,” Dr. Jackson advised. For example, physicians may suggest that some of the compounds used to treat CHF cause difficulties with achieving or maintaining an erection and if that is happening to them, there may be ways to manipulate treatment to lessen its effect on erectile dysfunction. Many patients with an implantable cardioverter defibrillator report either abstaining from sex or having decreased sexual activity following defibrillator implantation out of concerns that the device will be triggered during sex. Patients also tend to overestimate the exertion required for sex, and they need to understand that if they can complete a six-minute walk test or go up and down two flights of stairs, they should not be concerned about over-exerting themselves during sex.

“There is also no contraindication for the use of erectile dysfunction drugs in CHF patients, provided they are not on nitrates,” Dr. Jackson noted. If they are, there are alternatives to erectile dysfunction agents, including intracavernosal alprostadil (if the latter is used, Dr. Jackson reminded the audience that patients should use the device only twice a week and inject it into different sites each time).

Female sexual dysfunction may require something as simple as a lubricant but intravaginal estrogen can also help reverse vaginal atrophy and stimulate lubrication to allow women to have non-painful sex as well.

“It’s not always easy to treat these patients and it’s not always successful, but most of the time it is and quality of life will often improve, and depression and anxiety will lift [with enhanced sexual activity], so people should be encouraged to report any persistent sexual problem,” Dr. Jackson concluded.

Guidelines Assist Decision-Making

As in many other areas of medicine, there are a number of different guidelines developed by associations and societies in order to help practitioners in their decision-making concerning the management of CHF. At present, the four main sets of guidelines available to practitioners in Western societies come from the Canadian Cardiovascular Society (CCS), the European Society of Cardiology, the American College of Cardiology/American Heart Association and the Heart Failure Society of America.

As noted by Dr. Karl Swedberg, Sahlgrenska Academy of Medicine, Göteborg University, Sweden, “The four documents show only minor differences as regards initial therapy,” the common denominator being a combination of an ACE inhibitor and a beta blocker. The main divergence in the guidelines concerns recommendations for the use of ARBs and the strength of evidence accorded to each of the recommendations.

As Dr. Swedberg told the audience, the CCS guidelines committee believed that the ARBs have clearly been shown to reduce hospital admissions for patients with CHF, and consequently they accorded their recommendation for ARB use with the highest level of evidence.

The European Society of Cardiology in turn recommended ARB use in patients who are ACE inhibitor-intolerant, those who remain symptomatic on an ACE inhibitor or who are deteriorating, or those with preserved or low ejection fractions.

“New pharmacological treatments have reduced mortality and improved morbidity and quality of life in CHF, but treatment has become more complicated and requires a combination of several neurohormonal antagonists,” Dr. Swedberg stated. “Thus, the role of guidelines in this context becomes important.”

Canadian practitioners who plan to attend the Canadian Congress of Cardiology this year in October can also look forward to new guidelines on heart failure management, which will be presented during the meeting, scheduled to take place October 21 to 26 in Vancouver, British Columbia.

Summary

Both medical therapy and device-based strategies, including cardiac resynchronization and ICDs, have steadily improved outcomes for CHF patients. Improvements may well continue as many new compounds and devices are currently in development. In the meantime, optimizing treatment of CHF itself with cornerstone therapies, including proven ACE inhibitors, beta blockers and ARBs—most importantly, at a proven dose—has been shown to reduce CHF-related morbidity and mortality and improve quality of life. At the same time, treating comorbidities where possible may well enhance clinical outcomes for these patients as well.