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The American Journal of Managed Care April 2017
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Medication Burden in Patients With Acute Coronary Syndromes
Eric A. Wright, PharmD, MPH; Steven R. Steinhubl, MD; J.B. Jones, PhD, MBA; Pinky Barua, MSc, MBA; Xiaowei Yan, PhD; Ryan Van Loan, BA; Glenda Frederick, BA; Durgesh Bhandary, MS; and David Cobden, Ph

Medication Burden in Patients With Acute Coronary Syndromes

Eric A. Wright, PharmD, MPH; Steven R. Steinhubl, MD; J.B. Jones, PhD, MBA; Pinky Barua, MSc, MBA; Xiaowei Yan, PhD; Ryan Van Loan, BA; Glenda Frederick, BA; Durgesh Bhandary, MS; and David Cobden, Ph
Patients endure heavy medication complexity following hospital discharge for acute coronary syndrome.
Table 2 displays the medication use by number and frequency used in the peri-hospitalization period. On average, patients were prescribed 8.6 medications on admission, which increased by an average of 2.8 medications to 11.4 on discharge (P <.001). Similar increased medication burden was found for patients after discharge (within 90 days after discharge) compared with at admission (mean difference = 2.5; P <.001). Among those with both discharge and 90-day follow-up data (n = 3285), total medications per patient at discharge (11.7 ± 5.3) was slightly higher than during the posthospitalization period (mean difference = 0.4; P = .02).

Most patients throughout the peri-hospitalization period were prescribed regularly scheduled medications. On admission, over 35% were taking a medication only once a day, as needed, or no medications (Figure 2). This proportion dropped to less than 10% at discharge. In total, 90.5% of patients at discharge were taking at least 1 medication twice a day or more, but this proportion dropped slightly, to 81.2%, at follow-up (P <.001).

Cardioprotective medication use during the index ACS peri-hospitalization period is reported in Table 3. On admission to the hospital, less than 5% of patients were taking all 5 medication classes. Statins were the highest used medication class, with 52.2% of patients prescribed a statin prior to admission, followed by any use of aspirin at 51.4%. P2Y12 receptor inhibitors were the least prescribed medication class prior to admission (16.1%). Cardioprotective medication use increased across all 5 medication classes from admission to discharge. There was a relative increase in use from admission to discharge of 76% for aspirin, 72% for statins, 85% for beta-blockers, and 29% for ACE inhibitors or ARBs. P2Y12 receptor inhibitor use increased 4-fold. ACE inhibitor or ARB use only slightly increased from admission to discharge (44.1%-56.8%) and was the least prescribed agent among the 5 classes on discharge (Figure 2). Patients admitted for an STEMI (n = 1602; 69.5%) were 2.2 times (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.9-2.5) more likely to have all 5 medications prescribed at discharge compared with an NSTEMI, and 3.1 times (OR, 3.1, 95% CI, 2.6-3.7) more likely compared with unstable angina.

DISCUSSION

In this retrospective observational analysis of patients with ACS in a rural integrated delivery system, we found the medication burden among this group to be high on admission and to increase significantly in number and complexity thereafter. To our knowledge, this is the first report that quantifies the total medication use burden, as a patient transitions care from hospital admission through the discharge and postdischarge process after being given a diagnosis of ACS. Specifically, we found that our patients increase the number of medications from admission to discharge and are taking a median of 11 medications daily, with 9 of every 10 patients taking at least 1 scheduled medication twice a day or more.

Although these results confirm the high medication burden of patients being discharged following ACS diagnosis, they most likely underestimate the real medication totals and administration frequencies experienced by patients. We intentionally restricted our medication totals to traditional medications to reduce variability being introduced by usage of self-prescribed medications and potential bias introduced from patient recall and incomplete EHR capture of other nonprescribed alternative medications. The actual extent of this exclusion on our medication use is uncertain, as the use of complementary and alternative medicine varies widely, ranging in prevalence from 4% to 68%.12 In addition, although we captured the frequency of dosing of medications, we were unable to capture the actual times of day that medications were taken;  several medications may be taken just once a day, some are typically taken in the morning (eg, beta-blockers), whereas others are commonly taken in the evening (eg, statins). Therefore, only capturing how many times a day a medication is taken will not capture the daily dosing frequency burden for an individual patient. Ultimately, our study results demonstrate a high medication burden for total medications and administration frequency per day, which is likely even more complex than our analysis could accurately describe.

As anticipated, we found significant increases in the prescribing of evidence-based cardioprotective medications during and following an ACS hospitalization, with approximately doubling of the use of beta-blockers, aspirin, and statins and nearly quadrupling of P2Y12 receptor inhibitor use from admission to discharge. Despite this, only a minority of patients received all 5 classes of medications on discharge. As this study was conducted over a period of 5 years, beginning in 2008, temporal effects may explain some of these shortcomings (eg, low use of high-intensity statins prior to 2013 due to treatment to a low-density lipoprotein cholesterol goal of <70 mg/dL versus American College of Cardiology/American Heart Association updated guidelines recommending use of high-dose, high-intensity statins independent of the cholesterol-lowering effect), but may better reflect inertia in implementing best practice guidelines within this population.

Although we identified measurable increases in the usage of cardioprotective medications during hospitalization, little additional changes were made in the postdischarge period despite apparent gaps in recommended cardioprotective medications. These findings should help to bolster support for more inpatient initiation and adjustment of therapy to reduce these gaps prior to discharge. It should also alarm healthcare professionals that few additional changes to cardioprotective medications are made in the postdischarge period, signifying a need to provide better transitional guidance to outpatient providers and for outpatient providers to assist with recommended medication use in the postdischarge period. Best practice approaches to transitional care may include a combination of multidisciplinary care, enhanced use of health information technology, and/or focused care with pharmacists.13,14

These results provide insights into the extent of the total medication burden patients with ACS experience throughout their peri-hosptialization period and have direct implications on current practice, future research, and policy. In particular, even with our conservative estimates for total medications, patients with ACS are being discharged, on average, with over 11 medications unrestricted to the underlying reason for hospitalization—namely the ACS event. Hence, patients must coordinate new, changing, and discontinued medications in their already complex medication regimen following hospitalization. Providers should therefore be acutely sensitive to the changes being made throughout hospitalization, reconciling medications and engaging patients as they move through the peri-hospitalization period to ensure patient understanding of the modifications and coordination of medications post discharge.

Although not directly measured in this study, medication adherence is a major problem in patients post hospitalization for ACS5; both primary (first fill) and secondary medication nonadherence are large impediments to improved outcomes following ACS. Our study will help to assist providers, health systems, and policy makers in understanding the extent to which new or adjusted cardioprotective medications play a role in the overall medication burden of patients post discharge. Efforts to assist patients in the transition process prior to discharge, such as ensuring appropriate medication selection titration and follow-up, providing complete medication reconciliation, and counseling patients on adherence while paying particular attention to medication complexity, may help reduce gaps in care.

Limitations

Caution should be used in extrapolating our results to that of other healthcare systems and settings as the population (eg, predominantly white, rural population), culture, and practice at Geisinger may not necessarily reflect that of other healthcare systems. The ACS breakdown and use of cardioprotective medications within our patient cohort, however, are broadly consistent with other observational studies.7,8,15,16 Perhaps more dissimilar was our finding of a highly comorbid population, including a high proportion of heart failure patients (24.33%). These results imply that our average patient with ACS is already highly complex. We are unclear if this was a reflection of the hospital type, high prehospitalization comorbid management, or higher prevalence rate among our index ACS population.

Our analysis is limited by the nature of EHR data and our extraction for this analysis. For pre- and postadmission data, the ability to ensure complete collection of utilization and outcome data is limited because the EHR only captures data from encounters that occur within the Geisinger network of ambulatory and inpatient facilities. For example, postdischarge follow-up that occurs at a non-Geisinger site would not be included in our analysis. Also, the definition of an index ACS event did not exclude prevalent patients from inclusion in the cohort, since a patient with prior ACS may still have an index hospitalization if they had an event prior to 2008, or were admitted to a non-Geisinger facility during the given period. Our electronic capture of PTA, in-hospital, and discharge medication lists allows for intraperson comparisons of medication-related measures, but is subject to missing information bias caused by incomplete or inaccurate capture of PTA medications. Specifically, PTA lists were composed of a combination of patient self-report and electronic medication lists derived from orders placed in the EHR, whereas the discharge assessments relied on medication lists alone. Missing, incomplete, or outdated medication lists could have affected the comparisons of preadmission and discharge medications. For example, we assumed that the small numbers of patients with no PTA or EHR medications were not taking any medications on admission. However, it is possible that some patients were on medications but did not report this information when presenting at the hospital, resulting in underestimation of PTA medication use.

CONCLUSIONS

The burden of medication use from hospital admission to discharge among patients with ACS is complex and increases throughout the peri-hospitalization period. Cardioprotective medication use, even in an integrated delivery system, can be improved. Efforts to increase evidenced-based medication use and assist patients with complex medication regimens prior to and after discharge could improve care among this population.

Author Affiliations: Geisinger Health System (EAW, SRS, XY, RVL, GF), Danville, PA; Scripps Translational Science Institute (SRS), La Jolla, CA; Sutter Health Research, Development, and Dissemination (JBJ, XY); University of Missouri Health Care (PB), Colombia, MO; US Medical Affairs, AstraZeneca (DB, DC), Wilmington, DE.

Source of Funding: This study was supported by a grant from AstraZeneca.

Author Disclosures: Dr Wright received a grant from AstraZeneca. Dr Jones has previously received research grants from AstraZeneca and Boehringer Ingelheim. Dr Cobden and Mr Bhandary are employed by AstraZeneca, which develops and manufactures medicines that are indicated for cardiovascular diseases (including BRILINTA, a product indicated for the treatment of ACS). He has also attended meetings by ACC, AHA, and QCOR. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (EAW, SRS, JBJ, DC, DB, XY); acquisition of data (SRS); analysis and interpretation of data (EAW, SRS, JBJ, DC, PB, DB, XY, RVL, GF); drafting of the manuscript (EAW, SRS, JBJ, DC, PB, DB, GF, XY); critical revision of the manuscript for important intellectual content (EAW, SRS, JBJ, RVL, DC, DB); statistical analysis (PB, XY); obtaining funding (EAW, SS, DC, DB, JBJ); administrative, technical, or logistic support (RVL, JBJ, DC, DB, GF); and supervision (EAW).

Address Correspondence to: Eric A. Wright, PharmD, MPH, Geisinger Health System, 190 Welles St, Ste 128, Forty Fort, PA 18704. E-mail: ewright2@geisinger.edu. 
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