This is the first study to evaluate the most recent ESC/EASD recommendations for heart failure therapy in a large contemporary cohort of patients with heart failure. Moreover, no previous paper has studied a comparably high number of diabetic patients with heart failure and normal ejection fraction (HFNEF).
Our study has three major findings:
Around 90% of diabetic patients with SHF are treated with ACEi/ARB and beta-blockers. This therapy pattern is not different from patients without diabetes.
In contrast, diabetic patients with HFNEF are less likely to receive ACEi/ARB and beta-blockers. However, as compared to non-diabetic patients, they are more likely to receive these therapies. Blood pressure control in diabetic HFNEF patients is poorer than in diabetic SHF patients.
Irrespective of renal function, diabetic SHF patients are less likely to receive aldosterone antagonists.
Heart failure therapy in surveys
The percentage of patients with SHF receiving ACEi/ARB and betablockers was close to 90% and, hence, much higher than reported in previous surveys (e. g., the EuroHeart Survey) . The large proportion of university centres and the exclusive recruitment in cardiology clinics may be an explanation . An additional possibility is that slowly but steadily we reach a better implementation of guidelines in Germany.
Heart failure therapy in patients with diabetes
There are very few, if any, clinical trials on heart failure treatment available that specifically address heart failure with the comorbidity diabetes. Therefore, recent recommendations carry a low level of evidence (level C) and are derived from subgroup analyses of patients suffering from diabetes in large heart failure trials . In patients with SHF, the use of ACEi/ARB, beta-blockers and aldosterone antagonists have been shown to reduce morbidity and mortality (for review, see ). Aldosterone antagonists reduce mortality in heart failure patients with reduced ejection fraction and are of benefit in patients with systolic heart failure and recent myocardial infarction, with or without concomitant diabetes [14–16].
For HFNEF, there is yet no evidence-based drug-specific mortality reducing therapy available. Three trials investigated the use of ACEi and ARBs in HFNEF patients and failed to show a reduction in mortality [17–19]. Other treatment strategies, e.g. aldosterone receptor blockade, are currently investigated in clinical trials. Tight blood pressure control is the only recommendation supported by evidence in HFNEF, thus one would expect that this only recommendation would be strictly followed. However, our study shows that blood pressure control in HFNEF was inferior to SHF, the difference of about 15 mmHg in systolic blood pressure is partly explained by less pharmacotherapy.
The lack of evidence for heart failure treatment in HFNEF might explain the lower use of ACEi/ARBs, beta-blockers and aldosterone receptor blockers in patients with HFNEF. In contrast, data from the CHARM trial which was the largest trial to include patients with both SHF and HFNEF, showed that the presence of diabetes was of greater harm in HFNEF than in SHF patients . It is unknown whether a more aggressive antihypertensive therapy develops benefit in patients with HFNEF, but it has been shown that diastolic dysfunction, a relevant pathophysiology in HFNEF, is improved by lowering blood pressure . We were recently able to show that diastolic dysfunction is impaired along the whole diabetic continuum . Furthermore, diastolic dysfunction, which is believed to be the responsible mechanism for the development of heart failure in the majority of patients with HFNEF, is known to be found more frequent in diabetic patients . This increase in frequency of diastolic dysfunction in diabetes mellitus is thereby independent of renal function and can also be found under effective glycaemic control [24, 25]. Given the proposed association of diabetes mellitus and blood pressure control with diastolic dysfunction, we argue for an improvement of antihypertensive therapy and of glycaemic control in patients with HFNEF. However, the hypothesis that strict blood pressure and glycaemic control is beneficial in diabetic HFNEF patients should be tested in a prospective randomised trial.
Role of comorbidities
The use of ACEi/ARB or spironolactone may cause hyperkalemia, especially in patients with impaired renal function. A large population-based study from Ontario showed an increased incidence of hyperkalemia and subsequent mortality after the publication of the RALES trial and the rate of hyperkalemia in real-world is thought to be much higher than in clinical trials for various reasons (e. g. less frequent assessment of electrolytes and renal function, higher dosage of medication) [11, 26, 27]. In heart failure patients, diabetes has been shown to be an independent risk factor for the development of hyperkalemia and severe hyperkalemia (associated with hospitalization or death) [28, 29]. Even with impaired renal function, however, heart failure patients with diabetes will benefit from ARB therapy and aldosterone receptor blockade, similarly to patients without diabetes [28, 29]. Our data from a clinical practice setting suggest that the presence of the heart failure comorbidity diabetes restrains doctors from prescribing evidence-based therapy in heart failure patients - possibly in fear of side-effects, although these side-effects can be easily monitored by simple blood tests. As a consequence, we suggest that diabetic heart failure patients should receive appropriate doses of ACEi/ARB and/or aldosterone receptor blockers under a tight control of potassium and renal function markers, rather than withholding these potentially life-saving drugs. Moreover, future heart failure trials should focus on common comorbidities in heart failure populations (diabetes, impaired renal function, high age).