By Chris Berrie
HAMBURG, GERMANY -- June 15, 2007 -- Patients with chronic heart failure who are not compliant with their angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARBs), beta blocker or statin therapy increase their risk of dying, according to a population-based study.
Principal investigator Gunnar Hilmar Gislason, MD, senior resident in cardiology, department of cardiology, Gentofte University Hospital, Hellerup, Denmark, presented the findings here on June 11th at the Heart Failure Association of the European Society of Cardiology Heart Failure (ESC-HF) congress.
While there have been great improvements in the treatment of heart failure, researchers have been looking at the potential effects of treatment initiation, underdosing and early termination of treatment.
Dr. Gislason and colleagues designed their study to investigate the association between compliance with pharmacological treatment and mortality in patients with chronic heart failure, as related to initiation and persistence with treatment.
The study population was derived from the Danish nationwide hospitalisations registry and comprised all patients who survived first-time hospitalisation for heart failure in Denmark between 1995 and 2004. In the cohort of 107,092 subjects, mean age was 74.8 years and 51.7% were male.
Similarly, patient compliance with treatment, in terms of initiation and long-term persistence, was based on details in the Danish nationwide drug dispensing registry from pharmacies, and included the use of ACE inhibitors/ ARBs (46,191 patients), beta-blockers (29,084 patients), statins (13,084 patients) and spironolactone (20,166 patients).
For the statistical analysis, poor compliance was defined as a break in therapy of at least 90 days.
The initial analysis included cumulative frequency of treatment initiation during the first year from the patient's discharge from hospital. "The majority of patients claimed their first prescription within the first 90 days after discharge," Dr. Gislason said.
Similarly, patient persistence with pharmacotherapy over the first 5 years from discharge saw an initial rapid decline within the first 6 months from initiation. After 5 years, 79% were still taking their ACE inhibitors/ ARBs, 65% beta blockers, 82% statins and 56% spironolactone.
From the analysis of predictors of persistence, persistence with beta blocker and spironolactone therapy improved during the analysis period even though more patients were initiating treatment. ACE inhibitors/ ARBs and statins showed no such relationship.
Conversely, ACE inhibitors/ ARBs and spironolactone showed decreased persistence with increasing patient age, but no such systematic changes were seen for beta blockers and statins. Of note, men were seen to have a poorer compliance than women for both beta blockers and spironolactone.
For persistence according to the number of concomitant drugs, only spironolactone showed no change, with the other agents all showing improved persistence with increasing concomitant drug use. However, as Dr. Gislason detailed, "In a separate analysis, we found that it was only the combination of spironolactone and ACE inhibitors in patients above 75 years of age which gave this poor persistence, probably indicating a higher impact on the risk of hypokalemia and renal dysfunction in this older population."
When disease severity was determined according to the patient's dose of loop diuretic, persistence improved for spironolactone and statins with increased disease severity, but ACE inhibitors/ ARBs had the opposite effect, and use of beta blockers did not change.
Dr. Gislason said that poor persistence with treatment was associated with hazard ratios of 1.4 and 1.25 for ACE inhibitors/ ARBs and beta blockers, respectively. However, there was no significant effect relating to spironolactone, which, as he indicated, was interesting considering the clinical benefits of spironolactone.
"Also interestingly, we found that the drug that had the highest impact on mortality was the poor persistence with statin treatment, with a hazard ratio of 1.88… which is certainly above the clinical benefit of statin treatment," he said.
On the basis of this analysis, Dr. Gislason concluded that a systematic effort to increase initiation of therapy and to ensure titration to the appropriate doses is likely to provide important long-term benefits for these patients with chronic heart failure.
Study in press: Gislason et al., Circulation (in press).
[Presentation title: Poor Persistence of Evidence-Based Pharmacotherapy in Chronic Heart Failure Identifies High-Risk Patients and Is Associated With Increased Mortality. Abstract OP0445]
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