Non-adherence to secondary prevention medications increases mortality post MI

Adherence Tradeoff to Multiple Preventive Therapies and All-Cause Mortality After Acute Myocardial Infarction

Literature - Korhonen MJ, Robinson JG, Annis IE, et al. - J Am Coll Cardiol 2017;70:1543–54


Recent data show that approximately 40% of the patients who initiated ACE inhibitors, ARBs, beta-blockers (BB) or statins following hospitalization for acute myocardial infarction (AMI), became non-adherent during the first treatment year [1-4]. The clinical impact of trade-offs in adherence made among post-AMI preventive therapies is unclear. In this study, the effects of trade-offs in adherence to ACE inhibitors or ARBs, BB, and statins on all-cause mortality after AMI, was investigated in a large cohort of Medicare beneficiaries.

The eligibility criteria were: age ≥ 65 years, continuous enrollment for ≥ 365 days before and ≥ 180 days after the index AMI hospitalization, index AMI hospitalization between January 1, 2008, and December 31, 2010, survival for >180 days after the index hospitalization. The final study population included 90,869 patients who received ACE inhibitors or ARBs, BB, and statins within 30 days of the index hospital discharge.

The proportion of days covered (PDC) was calculated for 180 days following hospital discharge using dates and days of supply of the prescriptions filled. Patients with a PDC ≥ 80% were classified as adherent. There were 8 categories of trade-offs in medication adherence, depending on whether patients were adherent to all, some or none of the 3 preventive therapies.

Main results

  • 51.5% of patients were non-adherent to 1 or more of the 3 therapies during the 180-day adherence assessment period. 30.7% were non-adherent to ACE inhibitors/ARBs, 23.8% were non-adherent to BB, and 23.0% were non-adherent to statins.
  • The crude and adjusted mortality rates were at 1-year follow-up: 8.9% and 9.3% in patients who were adherent to all 3 therapies, 16.1% and 14.3% in patients who were non-adherent to all 3 therapies.
  • Those who were adherent to ACE inhibitors/ARBs and statins only had similar mortality as those adhering to all 3 therapies (adjusted HR: 0.98; 95%CI: 0.91 - 1.07).
  • Those who were non-adherent to all 3 therapies had the highest mortality (HR: 1.65; 95%CI: 1.54 - 1.76), followed by those who were adherent to BB only (HR: 1.32; 95%CI: 1.21 - 1.44), to statins only (HR: 1.26; 95%CI: 1.15 - 1.38), to ACE inhibitors/ARBs only (HR: 1.19; 95%CI: 1.07 - 1.32), to BB and statins only (HR: 1.17; 95%CI: 1.10 - 1.25), and to ACE inhibitors/ARBs and BB only (HR: 1.12; 95%CI: 1.04 - 1.21).


Post-AMI patients who are adherent to ACE inhibitors/ARBs and statins, but not to BB, have a similar mortality risk compared with those adherent to all 3 therapies. These data suggest that the use of BB for the secondary prevention post-MI may not provide an additional benefit on top of statins and ACE inhibitors/ARBs. Non-adherence to ACE inhibitors/ARB or statins and non-adherence to all 3 therapies was associated with a higher mortality.

Editorial comment

In their editorial article [5], Peterson and Navar, note that ‘medication adherence represents one of medicine’s greatest unsolved challenges.’, and comment on the limitations of the study published by Korhonen et al, which include the following:

  • The sole use of billing data does not account for all potential confounders.
  • Patients with insurance, who usually have improved adherence, and patients who never filled a prescription, were not included in the study.
  • PDC, as a measure of adherence, does not guarantee that patients have taken their medications.
  • The studied adherence period was short.

The authors conclude: ‘We believe that data from the current study should be a call to action. The field of medicine should learn from their colleagues in marketing, behavioral economics, and social science to identify which levers are most effective for improving patient medication adherence, and then test the impact of moving those levers in large outcomes trials. How many more studies documenting poor adherence do we need to see before we reach the tipping point?’


1. Lauffenburger JC, Robinson JG, Oramasionwu C, et al. Racial/ethnic and gender gaps in the use of and adherence to evidence based preventive therapies among elderly Medicare Part D beneficiaries after acute myocardial infarction. Circulation 2014;129:754–63.

2. Lenzi J, Rucci P, Castaldini I, et al. Does age modify the relationship between adherence to secondary prevention medications and mortality after acute myocardial infarction? A nested case control study. Eur J Clin Pharmacol 2015;71:243–50.

3. Choudhry NK, Setoguchi S, Levin R, et al. Trends in adherence to secondary prevention medications in elderly post-myocardial infarction patients. Pharmacoepidemiol Drug Saf 2008;17:1189–96.

4. Gislason GH, Rasmussen JN, Abildstrøm SZ, et al. Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction. Eur Heart J 2006;27:1153–8.

5. Peterson ED, Navar AM. ‘’Sticky’’ Issues for Adherence in Secondary Prevention. J Am Coll Cardiol 2017;70:1555-57.

Find this article online at J Am Coll Cardiol

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