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Long-term compliance with pharmacotherapy in patients with acute myocardial infarction and chronic heart failure

Gunnar H. Gislason M.D.

SUMMARY

During the last 10-15 years new treatment opportunities have improved the survival for patients with cardiovascular disease. Although treatment strategies recommend therapy, there has been increased awareness of undertreatment of cardiovascular disease, especially among subgroups of patients. Therefore, this thesis analysed the nature of undertreatment and long-term compliance in patients with acute myocardial infarction (MI) and chronic heart failure (HF), in order to identify potential areas for future interventions. The thesis had the following objectives: 1) to analyze initiation of treatment with beta-blockers, ACE inhibitors and statins in patients discharged after first hospitalization with acute myocardial infarction during 1995-2002; 2) to analyze initiation of treatment with beta-blockers, ACE inhibitors, statins and spironolactone in patients discharged after first hospitalization with heart failure during 1995-2004; 3) to analyze long-term compliance with beta-blockers, ACE inhibitors and statins in patients with acute myocardial infarction and additionally spironolactone in patients with chronic heart failure; and 4) to analyze association of poor compliance with pharmacological treatment and mortality in chronic heart failure. A total of 55,315 patients with MI and 107,092 patients with HF hospitalized for the first time were identified in the Danish National Patient Registry and included in the studies. Treatment initiation with beta-blockers, ACE inhibitors, statins, and additionally spironolactone in patients with HF, after discharge was established in the Danish Registry of Medicinal Product Statistics. All subsequent prescriptions dispensed from pharmacies were identified to determine long-term compliance. Multiple logistic regression models were used to analyze initiation of treatment and Cox proportional-hazard models to analyse long-term compliance and mortality.  This thesis demonstrates substantial increase in the use of beta-blockers and statins post-AMI in Denmark, and a more moderate increase in the use of ACE inhibitors. The increase in beta-blocker use was most prominent among patients presumed to have heart failure, whereas the reverse was true for ACE inhibitors. Especially younger patients (< 65 years) reached high levels of statin use.  For both MI patients and patients with HF early initiation of treatment was associated with good long-term compliance, but if treatment was not initiated shortly after discharge the chance of ever starting treatment was low. Dosages used were in general 50% of recommended target dosages, and were seldom adjusted during long-term treatment. There was general undertreatment of elderly patients, women and patients with diabetes, but older age or comorbidity did not impair long-term compliance. Notably, multiple drug treatment or increased severity of HF was not associated with poorer compliance. After 5 years of treatment 58% of patients with MI and 65% with HF were still receiving beta-blockers, 75% and 82% ACE inhibitors, 79 and 82% statins 56% spironolactone and above 80% statins, respectively. Poor compliance (a break in treatment of at least 90 days) with beta-blockers, ACE inhibitors and statins was associated with higher mortality in patients with HF, with hazard ratios (95% CI) for death of 1.25 (1.19-1.32), 1.37 (1.31-1.42) and 1.88 (1.67-2.12) for respectively beta-blockers, ACE inhibitors and statins. To conclude, this thesis demonstrates that long-term drug compliance was good once medication was started in patients with MI and HF, but treatment dosages were far below recommended dosages. Increased number of concomitant medications or increased severity of did not worsen compliance, but poor compliance was associated with increased mortality. Focus on early treatment initiation, reaching appropriate dosages and long-term compliance is likely to provide long-term benefits.