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ImportanceÌý The use of evidence-based medication therapy in patients after acute myocardial infarction (AMI) improves long-term prognosis, yet the current rates of adherence are poor.

ObjectiveÌý To determine whether earlier outpatient follow-up after AMI is associated with higher rates of medication adherence.

Design, Setting, and ParticipantsÌý A retrospective analysis was conducted of 20 976 Medicare patients older than 65 years discharged alive after an AMI between January 2, 2007, and October 1, 2010, from 461 Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines hospitals in the United States. Patients were grouped based on the timing of first follow-up clinic visit within 1 week, 1 to 2 weeks, 2 to 6 weeks, or more than 6 weeks after hospital discharge. Data analysis was conducted from September 26, 2014, to April 22, 2015.

Main Outcomes and MeasuresÌý Medication adherence was defined as the proportion of days with more than 80% coverage using Medicare Part D prescription fill records and was examined at 90 days and 1 year after discharge for β-blockers, platelet P2Y₁₂ receptor inhibitors, statins, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

ResultsÌý Among 20 976 Medicare-insured patients discharged alive after acute MI, 10 381 (49.5%) were men; mean (SD) age was 75.8 (7.5) years. The median time to the first outpatient follow-up visit after hospital discharge was 14 days (interquartile range, 7-28 days). Overall, the first follow-up clinic visit occurred 1 week or less after discharge in 5542 (26.4%) patients, 1 to 2 weeks in 5246 (25.0%), 2 to 6 weeks in 6830 (32.6%), and more than 6 weeks in 3358 (16.0%) individuals. Rates of medication adherence for secondary prevention therapies ranged from 63.4% to 68.7% at 90 days and 54.4% to 63.5% at 1 year. Compared with patients with follow-up visits within 1 week, those with follow-up in 1 to 2 weeks and 2 to 6 weeks had no significant difference in medication adherence; however, patients with follow-up more than 6 weeks after discharge had lower adherence at both 90 days (56.8%-61.3% vs 64.7%-69.3%; P < .001) and 1 year (49.5%-57.7% vs 55.4%-64.1%; P < .001). Patients with delayed follow-up more than 6 weeks were more likely to reside in communities with lower household incomes and educational levels (both P < .001); however, their clinical characteristics were similar to those of patients with earlier follow-up. After adjusting for these differences, delayed follow-up of more than 6 weeks remained associated with lower medication adherence at 90 days (odds ratio [OR], 0.74 [95% CI, 0.70-0.78]) and 1 year (OR, 0.79 [95% CI, 0.73-0.85]) compared with follow-up of 6 weeks or less.

Conclusions and RelevanceÌý Delayed outpatient follow-up beyond the first 6 weeks after AMI is associated with worse short-term and long-term patient medication adherence. These data support the concept that medication adherence is modifiable via improved care transitions.

Approximately 1 million Americans are hospitalized for acute myocardial infarction (AMI) annually; of these, 470 000 are expected to have a recurrent major adverse cardiovascular event.¹ Current guidelines recommend secondary prevention with aspirin, β-blockers, statins, platelet P2Y₁₂ receptor inhibitors, and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), all of which have demonstrated long-term survival benefits for post-AMI patients.² However, nonadherence to these medications following AMI occurs frequently and is associated with increased risks of mortality and hospital readmission.^3,4

Readmission risk is a current challenge in health care among patients after an AMI; approximately 1 in 5 Medicare beneficiaries are readmitted within 30 days after AMI discharge.⁵ Hospitals, policymakers, and payers have placed greater focus on strategies such as early outpatient follow-up for hospitalized patients to prevent adverse events. Up to 50% of patients readmitted to the hospital have not had an outpatient physician visit prior to their readmission and patients without timely follow-up may be up to 10 times more likely to be rehospitalized.^6-8 For these reasons, early follow-up is now incorporated into provider payment models and national quality improvement guidelines.⁹ To our knowledge, whether timing of outpatient follow-up is associated with medication adherence among patients after AMI has not been previously studied.

Using the Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines (ACTION Registry–GWTG) linked with longitudinal Medicare Part D prescription fill data, we sought to examine the association between timing of the first outpatient follow-up visit after AMI hospitalization and downstream medication adherence. We hypothesized that earlier follow-up with a health care professional may increase adherence owing to more timely clinical assessment, medication review, adverse effect monitoring, dose adjustment, patient education, and refilling of prescriptions.

ACTION Registry–GWTG is a US quality improvement registry that includes patients at participating hospitals with a primary diagnosis of either ST-segment elevation MI (STEMI) or non–ST-segment elevation MI (NSTEMI).¹⁰ Data are abstracted from the medical record and include demographics, medical history, in-hospital procedures and therapies, clinical events before discharge, and medications prescribed at discharge (datacollection). Because information was collected without unique patient identifiers in ACTION Registry–GWTG, we used 5 indirect identifiers in combination (date of birth, sex, hospital identifier, date of admission, and date of discharge) to link patients older than 65 years with Medicare claims data (methods previously described).¹¹ The Duke University Medical Center institutional review board granted a waiver of informed consent and authorization for this study.

Our study cohort was drawn from all patients in the linked database who were discharged between January 2, 2007, and October 1, 2010 (n = 72 587). A previous study¹² showed that approximately half of Medicare-insured patients who experienced AMI were enrolled in the Part D prescription coverage plan during this study period. To examine medication adherence, we included only patients enrolled in Medicare Part D at least 90 days before discharge (n = 23 475) so that we could accurately classify patients who continued to take medications filled prior to the index AMI as adherent. We excluded 16 patients who died in the hospital or 37 who were transferred to another acute care facility, a skilled nursing facility or hospice, and 273 patients who were not discharged with a prescription for at least 1 evidence-based post-AMI medication including a β-blocker, statin, platelet P2Y₁₂ receptor inhibitor, or ACEI or ARB. We also excluded 136 patients whose first follow-up visit was the same day as discharge, 1283 patients who died or lost Medicare coverage within 90 days of discharge, and 754 nonindex AMI hospitalizations for patients with multiple AMI presentations. Our final study population included 20 976 AMI patients discharged from 461 US hospitals.

The first outpatient clinic visit was defined as the first appointment after hospital discharge with either a cardiology, primary care, internal medicine, or family practice health care professional, including those in advanced practice settings. This information was determined from Medicare data using carrier claim line items. Our primary outcomes of interest were medication adherence at 90 days and 1 year from discharge. Using Medicare Part D prescription filling data, which includes drug name, dosage, date dispensed, and days supplied, we assessed adherence to the following guideline-recommended secondary prevention medication classes among those prescribed at index AMI discharge: β-blocker, statin, platelet P2Y₁₂ receptor inhibitor, and ACEI or ARB. Adherence to aspirin was not assessed owing to its over-the-counter availability and lack of thorough monitoring with available prescription data. Medication adherence was defined using Part D prescription fill data as the proportion of days covered of at least 80% for each medication, similar to previous studies.^13,14 Adherence at 1 year was assessed among patients who were alive and enrolled in Medicare Part D at that time.

Patients were categorized into 1 of 4 prespecified groups based on timing of the first outpatient clinic visit from discharge: 1 week or less, 1 to 2 weeks, 2 to 6 weeks, and more than 6 weeks. Patient characteristics, including medical history, risk factors, and in-hospital treatment, were compared among groups. Categorical variables are presented as frequencies (percentages) and differences between groups were assessed using χ² rank-based group means score statistics (Cochran-Mantel-Haenszel test). Continuous variables are presented as median values (interquartile range) and were compared using χ² tests 1-df rank correlation.

We presented the proportion of patients adherent to each medication by categories of first outpatient follow-up time overall, then stratified by first visit with a cardiologist or a noncardiologist. We then compared medication adherence of each group referenced to the earliest follow-up group (≤1 week). To assess the adjusted association, we fitted mixed-effects logistic regression models for composite adherence, treating each medication as an opportunity for adherence. Thus, each patient was included in the model up to 4 times depending on the number of medications prescribed at discharge. Clustering owing to the hospital was accounted for by a hospital random effect, and correlation between repeated opportunities on the same patients was modeled by a compound symmetric residual covariance structure. Covariates for adjustment included age, race, sex, socioeconomic status variables (percentage of persons aged ≥25 years with a high school diploma, percentage of persons ≥25 with >4 years of college, median home value, and median household income obtained from the Area Resource File based on the zip code of patient residence), weight, history of AMI, prior coronary artery bypass graft (CABG) surgery, prior stroke, diabetes mellitus, hypertension, dyslipidemia, prior heart failure, current dialysis, current smoking, and transfer-in status. In addition, whether the patient received percutaneous coronary intervention (PCI) with a drug-eluting stent, PCI with a bare metal stent, CABG surgery, or medical management was added to the model covariate list. We repeated these analyses comparing medication adherence of patients with follow-up of longer than 6 weeks with those with follow-up of 6 weeks or less.

Prespecified secondary analyses examined medication adherence stratified by the following categories: sex (women vs men), age (≥75 vs <75 years), revascularization therapy during the index hospitalization (CABG, PCI, or medical management), and estimated mortality risk (ACTION Registry–GWTG mortality risk score tertiles). A test for interaction between timing of follow-up and each category was performed with adjusted logistic regression models using the covariates noted above to determine whether the association of early follow-up with each outcome differed in each category. A significance level of P < .05 and 2-sided tests were used for all analyses. Analyses were performed with SAS, version 9.2 (SAS Institute Inc). Data analysis was conducted from September 26, 2014, to April 22, 2015.

Among 20 976 Medicare-insured patients discharged alive after AMI, 10 381 (49.5%) were men and the mean (SD) age was 75.8 (7.5) years. The median time to the first outpatient follow-up visit was 14 days (interquartile range, 7-28 days). Overall, 5542 (26.4%) patients had their follow-up visit within the first week after discharge, 5246 (25.0%) had their first follow-up visit between 1 and 2 weeks after discharge, and 6830 (32.6%) had their first follow-up visit between 2 and 6 weeks after discharge. By 6 weeks after discharge, 3358 (16.0%) of the patients had not yet had a follow-up visit. Among the 20 332 first follow-up visits, 9693 (47.7%) were with a cardiologist.

A description of patient characteristics stratified by time to first follow-up visit is reported in Table 1. Patients with longer times to their first follow-up appointment were more likely to be men, black, and live in communities with lower median household income, lower median home value, and lower rates of high school and college educational levels compared with patients with earlier follow-up visits. Overall morbidity, as defined by a Charlson Comorbidity Index¹⁵ score of 4 or higher, did not differ significantly between follow-up groups. Patients with later follow-up times were less likely to have undergone PCI and more likely to have undergone CABG surgery during their index AMI hospitalization. There were no major differences in the rates of in-hospital complications, such as cardiogenic shock, heart failure, or major bleeding among the different follow-up groups. At discharge, we observed high rates of evidence-based medication prescription among all follow-up groups for aspirin, β-blockers, and statins (Table 2).

As shown in Figure 1, even when the medications were prescribed at discharge, adherence to each of the evidence-based medications was low. Adherence rates at 90 days and 1 year after discharge were 68.7% and 61.1%, respectively, for β-blockers, 63.8% and 54.4% for ACEIs or ARBs, 63.4% and 55.8% for statins, and 64.2% and 63.5% for platelet P2Y12 inhibitors. Table 3 reports medication adherence at 90 days and 1 year after discharge stratified by timing of the first follow-up visit. Observed adherence rates were not substantially different between patients with follow-up visits within 1 week, 1 to 2 weeks, and 2 to 6 weeks but were lowest among those with follow-up times longer than 6 weeks across all medications. This association persisted among patients who were directly admitted to the hospital and those who were transferred from another hospital (eTable 1 in the Supplement).

The proportion of patients with the first follow-up visit more than 6 weeks after discharge associated with patients who were adherent compared with those who were not adherent to each medication at 90 days and 1 year is presented in the eFigure in the Supplement. Among patients whose first follow-up appointment was more than 6 weeks after discharge, medication adherence rates were slightly higher for those whose first visit was with a cardiologist than a noncardiologist. Among all patients whose first visit was with a cardiologist, there was no significant difference in medication adherence between follow-up groups (eTable 2 in the Supplement).

After multivariable adjustment, there remained no significant differences in medication adherence for patients seen between 1 to 2 weeks and 2 to 6 weeks after discharge compared with those seen 1 week or less after discharge. However, patients whose first visit was more than 6 weeks after discharge had significantly lower rates of medication adherence at both 90 days and 1 year. We repeated this analysis dichotomizing at 6 weeks, and found similarly lower medication adherence in patients with follow-up at more than 6 weeks after discharge compared with those with follow-up at 6 weeks or less (odds ratio [95% CI], 0.74 [0.70-0.78] for medication adherence at 90 days and 0.79 [0.73-0.85] at 1 year). Adjusted odds ratios for adherence to individual medications are reported in eTable 3 in the Supplement.

In prespecified subgroup analyses, we found that follow-up more than 6 weeks after discharge was associated with lower medication adherence at 90 days and 1 year after stratifying by age, sex, in-hospital revascularization therapy, and predicted mortality risk (Figure 2). The only subgroup that did not show an association between delayed follow-up and lower medication adherence was the group of patients who underwent CABG surgery during their index hospital stay.

In this contemporary, national survey of patients with AMI who had Medicare prescription coverage, almost 1 in 3 patients were no longer adherent to evidence-based medications prescribed at discharge as early as 90 days after AMI; medication adherence rates decreased further by 1 year. Compared with patients who had follow-up within 6 weeks of discharge, those whose first follow-up was more than 6 weeks had significantly worse medication adherence at 90 days and 1 year.

During the past several years, there have been significant efforts to improve the quality of care of patients with AMI. The American College of Cardiology and American Heart Association^16-18 have developed clinical performance measures and quality improvement programs to quantify and promote the utilization of evidence-based treatments. As a result of these efforts, adherence to evidence-based therapies during the index hospitalization among patients with AMI has reached near perfect levels. Given these improvements, attention has increasingly emphasized postdischarge secondary prevention. Prior studies showed that long-term adherence to evidence-based medications remains suboptimal. A meta-analysis¹⁹ of patients treated before 2007 demonstrated 66% adherence to secondary prevention medications after 2 years; more recent estimates have been as low as 37% to 49%.²⁰ Our data found medication adherence rates of 63.4% to 68.7% at 90 days and 54.4% to 63.5% at 1 year despite persons possessing prescription coverage. Even though rates of medication adherence in patients with AMI increased over time between the 1990s and 2003,²¹ our study suggests that rates of long-term medication adherence have not improved recently.

Among patients who experienced AMI, medication nonadherence has been associated^3,22-24 with adverse clinical outcomes and increased health care costs. For these reasons, national organizations, including the National Committee for Quality Insurance and the Centers for Medicare & Medicaid Services, are placing greater focus on medication adherence as an outcome measure.²⁵ Many current quality improvement initiatives have focused on early follow-up as a means of improving transition of care. The benefit of early follow-up has been noted in studies^26,27 documenting lower rates of 30-day readmission in patients with congestive heart failure and chronic lung disease; however, this association was not seen among elderly patients with NSTEMI.²⁸ Extending this concept, we investigated how timing of postdischarge follow-up is associated with medication adherence in patients with AMI. Our data indicated that adherence to evidence-based medications for AMI in patients with follow-up longer than 6 weeks from discharge was significantly lower at 90 days and 1 year compared with adherence in patients with follow-up within 1 week. No significant differences in medication adherence were noted between patients with follow-up between 1 and 6 weeks compared with those with follow-up within 1 week.

Lower adherence for patients with follow-up more than 6 weeks after discharge was observed for all medication classes included in our study. A prior study²⁹ showed that patients with AMI whose follow-up visits were within 30 days of hospital discharge had higher usage rates of β-blockers at 6 months compared with those who did not have a follow-up visit within this period, but usage rates of statins, aspirin, and ACEIs or ARBs were similar. In our study, Medicare Part D prescription-filling data provided a more objective quantification of post-AMI medication adherence—more than just patient self-reported use.

Despite robust multivariable analyses, we cannot exclude the possibility of residual confounding. The greatest differences between patients with follow-up 6 weeks after hospital discharge and those with earlier follow-up were observed in measures of socioeconomic status. Compared with patients whose first discharge visit was earlier, those with follow-up more than 6 weeks after hospital discharge resided in communities with lower household incomes, home values, and educational levels. Previous studies^30,31 have shown that low-income patients are at an increased risk of medication nonadherence owing to cost, despite having prescription drug coverage, and are more likely to stop taking medications owing to a lack of perceived benefit than are patients with higher incomes. Many patients of lower socioeconomic status are also likely to have significant barriers to health care (eg, lack of transportation, poor medical literacy, and inadequate social support) that were not fully captured in the socioeconomic variables we adjusted for, and these barriers likely contribute to the association between timing of follow-up and medication adherence. The latest follow-up group also had higher proportions of patients who were black, and race was included in our list of adjusted covariates. Significantly lower medication adherence was consistently observed in the later follow-up group, despite stratifying by age, sex, and predicted mortality risk score.

Patients who had later follow-up times were more likely to be transferred from another hospital than were patients who had earlier follow-up times. However, in both directly admitted and transferred patients, we found consistent results between the timing of follow-up and downstream medication adherence. Patients with follow-up more than 6 weeks after discharge had no significant difference in medication adherence when their first visit was with a cardiologist compared with those with an earlier follow-up time. Cardiologists may be more likely to switch medication formulation or dose in response to patient-reported adverse effects instead of discontinuing evidence-based medications. Patients seeing a cardiologist may be more motivated to adhere to cardioprotective medications when reminded of their recent AMI. Patients who underwent CABG surgery during their index hospital stay did not have lower medication adherence with later follow-up; this finding may be related to the occurrence of routine surgical follow-up or postoperative rehabilitation, which were not included in our definition of follow-up.

Our study has several limitations. Given the retrospective design of the study, it is not possible to determine whether late follow-up contributed directly to lower medication use. Residual confounding likely existed because there may be many variables that affect both outpatient follow-up and medication use that could not be quantified in our data source. Follow-up appointments may also have been scheduled but not attended; our data included only clinic encounters that took place. Patients who missed their appointment would be more likely to have late follow-up and could be expected to exhibit behaviors that would result in lower medication adherence. Administrative data do not capture the rationale for medication discontinuation; therefore, we cannot distinguish between appropriate medication discontinuation (eg, acute kidney injury in the setting of ACEI or ARB use) and nonadherence. Finally, our data source measures medication adherence based on prescriptions filled; it is not possible to determine whether patients used the medications.

Our study has several implications for the clinical care of patients with AMI. The data show that adherence to evidence-based therapies among patients after AMI remains low and suggest that greater focus on medication adherence is needed to improve patient outcomes. Scheduling follow-up within 6 weeks of hospital discharge, especially with a cardiologist, may also be a strategy to help improve medication adherence. Patients who do not attend a clinic visit within the first 6 weeks after discharge may benefit from other interventions designed to enhance medication adherence. Strategies that have been demonstrated^29,32-34 to improve outcomes in patients after AMI include patient involvement with transitions of care, discharge contracts, inclusion of inpatient and outpatient care, and care that involves primary care physicians and cardiologists. Because patients with lower socioeconomic status seem to be at higher risk for delayed follow-up and low medication adherence after an AMI, increased attention should be placed on this group before and after hospital discharge.

In older patients hospitalized for AMI, our study demonstrates that long-term adherence to medications indicated for secondary risk prevention after AMI remains low in all patient groups despite their established benefit. However, we found that medication adherence may be modifiable through improved care transitions following hospital discharge. Specifically, attending the first follow-up appointment within 6 weeks of discharge was associated with greater 90-day and 1-year medication adherence.

Corresponding Author: Tracy Y. Wang, MD, MHS, MSc, Duke Clinical Research Institute, Duke University Hospital, 2400 Pratt St, Durham, NC 27703 (tracy.wang@duke.edu).

Accepted for Publication: January 4, 2016.

Published Online: March 23, 2016. doi:10.1001/jamacardio.2016.0001.

Author Contributions: Ms McCoy and Dr Wang had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Faridi, Thomas, Wang.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Faridi, McCoy, Wang.

Critical revision of the manuscript for important intellectual content: Faridi, Peterson, Thomas, Enriquez, Wang.

Statistical analysis: Faridi, McCoy, Thomas.

Administrative, technical, or material support: Faridi, Peterson, Wang.

Study supervision: Faridi, Peterson, Wang.

Conflict of Interest Disclosures: Dr Peterson reports institutional grant support from the American College of Cardiology, American Heart Association, Eli Lilly, and Janssen; consulting fees (including continuing medical education) from Merck & Co, Boehringer Ingelheim, Genentech, Janssen, and Sanofi. Dr Wang reports receiving research grant support from Eli Lilly, Daiichi Sankyo, Astra Zeneca, Bristol Myers Squibb, Boston Scientific, Gilead, GlaxoSmithKline, and Regeneron; and paid consulting services for Eli Lilly, Astra Zeneca, and Premier. No other disclosures were reported.

Funding/Support: The data linkage was supported by Centers for Education and Research on Therapeutics grant U19HS021092 from the Agency for Healthcare Research and Quality.

Role of the Funder/Sponsor: The Agency for Healthcare Research and Quality had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: Dr Thomas is the Assistant Editor for statistics for JAMA Cardiology. She was not involved in the editorial evaluation or decision to accept this article for publication. This research used data from the American College of Cardiology Foundation’s National Cardiovascular Data Registry (NCDR). The views expressed in this manuscript represent those of the authors and do not necessarily represent the official views of the NCDR or its associated professional societies.

Additional Information: Acute Coronary Treatment and Intervention Network Registry—Get With the Guidelines is an initiative of the American College of Cardiology Foundation and the American Heart Association, with partnering support from the Society of Chest Pain Centers, the American College of Emergency Physicians, and the Society of Hospital Medicine.