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Contemporary Prescription Patterns of Adenosine Diphosphate Receptor Inhibitors in Acute Coronary Syndrome

Ellen B. Yin PharmD, BCPS
Huy Nguyen MD
Ishan Kamat MD
Maryam Bayat PharmD, BCPS
Mahboob Alam MD

INTRODUCTION

Dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) receptor inhibitor represents the corner-stone of treatment for acute coronary syndrome (ACS) and for patients undergoing percutaneous coronary intervention (PCI).1 Clopidogrel is historically the most commonly used ADP receptor inhibitor. However, clopidogrel has a complex metabolic pathway: It is a prodrug that requires a two-step oxidation process with multiple hepatic enzymes. The active metabolite of clopidogrel has a very short half-life and is rapidly eliminated if it does not bind to purinergic signaling receptor Y12 (P2Y12). Thus, there is an increased risk of stent thrombosis and recurrent cardiovascular events in poor responders.24 Therefore, in recent years, emphasis has been placed on using the newer, more potent ADP receptor inhibitors ticagrelor (Brilinta, AstraZeneca) and prasugrel.

Prasugrel is a once-daily irreversible P2Y12 ADP receptor antagonist indicated for the reduction of thrombotic cardiovascular events in patients with ACS who are to be managed with PCI. It is contraindicated in patients with active bleeding and prior transient ischemic attack or stroke. Caution should be used in prescribing prasugrel to patients 75 years of age or older, those weighing less than 60 kg, and those with planned coronary artery bypass graft (CABG) or other surgical procedures due to a higher risk of bleeding. Prasugrel has been shown to be especially beneficial in patients with diabetes or a history of myocardial infarction (MI).5 Its efficacy was established in the TRITON-TIMI 38 trial in patients with ACS who were scheduled for PCI. Prasugrel therapy was associated with significantly reduced rates of ischemic events in patients at an increased risk of major bleeding.6 However, it should be noted that in the TRILOGY ACS trial, the frequency of the composite primary endpoint (death from cardiovascular causes, MI, or stroke in patients younger than 75 years) was not significantly reduced in the prasugrel arm compared with the clopidogrel arm among patients with unstable angina (UA) or non–ST-segment elevation MI (NSTEMI) managed without revascularization. Both groups had similar risks of bleeding.7 As a result, prasugrel is indicated only for patients to be managed with PCI.5

Ticagrelor is a twice-daily reversible P2Y12 ADP receptor antagonist indicated for the reduction of thrombotic cardiovascular events in patients with ACS. It is contraindicated in patients with active bleeding, prior intracranial hemorrhage, and severe hepatic impairment. Moreover, a higher rate of dyspnea is reported with ticagrelor compared with the other ADP receptor antagonists.8 Its efficacy was established in the PLATO trial, in which the primary efficacy endpoint of death from vascular causes, MI, or stroke occurred in 9.8% of patients receiving ticagrelor compared with 11.7% of those receiving clopidogrel (hazard ratio[HR], 0.84; 95% confidence interval, 0.77–0.92; P < 0.001). No significant difference was found in the rates of overall major bleeding, but ticagrelor was associated with a higher rate of non–CABG-related major bleeding.9 In PEGASUS-TIMI 54, ticagrelor was shown to be beneficial when given with aspirin even beyond one year after MI, with reduced rates of cardiovascular death, MI, or stroke compared with placebo, but with higher rates of major bleeding.10

The American Heart Association’s ACS guidelines give no preference among ADP receptor inhibitors, but European ACS guidelines give preference to prasugrel and ticagrelor in patients managed with PCI.1,1113 Multiple studies using large registries in Australia and the U.S. have shown clopidogrel to be the most commonly prescribed antiplatelet agent in contemporary practice.1418 Nevertheless, there has been a trend toward increased prasugrel and ticagrelor use over time.1416 Prasugrel and ticagrelor were more likely to be prescribed to patients who were younger, male, had fewer comorbidities, and presented with STEMI.1418

With contemporary practice showing an increasing uptake of the novel ADP receptor inhibitors, controversies have surfaced regarding the use of these agents. Some issues revolve around the pretreatment of patients prior to angiography, in-hospital switching of agents, and use according to Food and Drug Administration (FDA)-approved labeling.1522

To better characterize ADP receptor inhibitor use at a large, quaternary academic medical center, this retrospective chart review assessed the contemporary use of these agents in ACS. This study aims to describe the characteristics of patients receiving one agent over another, to examine in-hospital switching patterns in patients previously on an antiplatelet prior to admission, and to determine how closely the FDA-approved labeling is followed.

METHODS

Study Design and Participants

This retrospective observational study was conducted at a large, quaternary academic medical center and approved by the local institutional review board. Electronic health records were used to compare patients who were treated with ticagrelor, prasugrel, or clopidogrel for a principal diagnosis of new-onset ACS between January 2014 and December 2014. Patients with International Classification of Diseases, 9th revision, codes of 410 and 411 for acute MI and other acute and subacute forms of ischemic heart disease were identified through the University Health System Consortium database. Patient data were anonymized in accordance with Health Insurance Portability and Accountability Act (HIPAA) requirements. All authors had full access to the study data.

To qualify for inclusion in the study, patients had to be at least 18 years old with an admitting diagnosis of STEMI, NSTEMI, or UA. Exclusion criteria included undergoing CABG; never receiving ticagrelor, prasugrel, or clopidogrel during hospitalization; and undergoing coronary angiography with no significant coronary artery disease.

To examine the contemporary use of ADP receptor inhibitors, the following data were collected: patient demographics (age, gender, body mass index, race, payer type); medical history; admitting diagnosis; ACS management strategy; service of prescribing physician; location of ADP receptor inhibitor loading dose; concurrent medications; history of antiplatelet use; changes to antiplatelet choice during hospitalization or at discharge; and antiplatelet function test results, if available. Inadequate platelet function inhibition was defined as greater than 60% platelet activity via the Bio/Data platelet function screen analyzer, PAP-8E, 2010.

Clinical outcomes data included intensive care unit (ICU)/cardiac critical care unit (CCU) length of stay (LOS); hospital LOS; in-hospital, all-cause, and cardiovascular mortality; and all-cause and ACS 30-day readmissions to the study hospital.

Statistical Analysis

A two-sided P value of less than 0.05 was considered significant for all statistical tests. Categorical data were presented as counts and percentages compared with chi-square or Fisher’s exact test. Continuous data with normal and skewed distribution were presented as means plus or minus standard deviation and medians (first to third quartile), respectively. Normally distributed continuous data were compared using the Kruskal-Wallis test, and skewed data and continuous data were compared using ANOVA. A multinomial logistic regression was done to examine relevant covariates. All statistical analysis was performed using GraphPad InStat 3.0, 2016 (La Jolla, California).

RESULTS

Patients

415 patients met the inclusion criteria. Of those patients, 140 were excluded: 64 patients for management with CABG and 76 patients who did not receive any ADP receptor inhibitors or had no clinically significant coronary artery disease per coronary angiography. Therefore, a total of 275 patients were included in the study for analysis.

Factors Associated With Antiplatelet Choice

Table 1 shows patient demographics, comorbidities, and antiplatelet prescribed on admission. The initial choice of antiplatelet agent upon hospitalization was clopidogrel (52%) followed by ticagrelor (26%) and prasugrel (22%). Patients who received clopidogrel, compared with patients who received prasugrel and ticagrelor, were more likely to be female (36%, 21%, and 18%, respectively; P < 0.01), 75 years of age or older (22%, 7%, and 10%, respectively; P = 0.01), or be insured by Medicare (50%, 28%, and 32%, respectively; P < 0.01). Patients prescribed clopidogrel, compared with those prescribed prasugrel and ticagrelor, had a higher prevalence of comorbidities: coronary artery disease (65%, 46%, and 38%, respectively; P < 0.01), ischemic stroke (17%, 3%, and 4%, respectively; P < 0.01), peripheral vascular disease (20%, 5%, and 7%, respectively; P < 0.01), heart failure (33%, 10%, and 10%, respectively; P < 0.01), chronic kidney disease (36%, 2%, and 10%, respectively; P < 0.01), and prior CABG (34%, 13%, and 11%, respectively; P < 0.01).

Details regarding inpatient antiplatelet choice are shown in Table 2 and Figure 1. Patients who suffered a STEMI were more likely to be prescribed prasugrel and ticagrelor than clopidogrel (59%, 46%, and 22%, respectively; P < 0.01). Patients medically managed with or without angiography were more likely to receive clopidogrel than prasugrel or ticagrelor. The majority of patients receiving prasugrel or ticagrelor were managed with PCI. Only one patient medically managed with prasugrel did not have a previous stent. Prasugrel and ticagrelor were solely prescribed by cardiologists, except in one instance where prasugrel was prescribed by an emergency department (ED) physician. Internal medicine and ED physicians were more likely to prescribe clopidogrel.

PCI management details are shown in Table 3. Of the 275 patients analyzed, 200 were managed with PCI. Of those 200 patients, 41% received clopidogrel, 26% received prasugrel, and 34% received ticagrelor. Patients managed with a drug-eluting stent were more likely to receive prasugrel or ticagrelor. Patients prescribed prasugrel or ticagrelor were more likely to also receive a glycoprotein IIB/IIIA inhibitor in the catheterization laboratory compared with those prescribed clopidogrel (44%, 33%, and 16%, respectively; P < 0.01). There was no difference in heparin or bivalirudin use in the catheterization laboratory based on antiplatelet choice (P = 0.86 and P = 0.55, respectively).

When running a multinomial logistic regression with relevant covariates, significant variables describing antiplatelet prescription choice included indication (STEMI versus NSTEMI/UA), management of ACS, antiplatelet choice prior to admission, presence of heart failure, and chronic kidney disease.

Loading Doses

The majority of patients who were managed with PCI received a loading dose immediately before, during, or after the procedure. Loading doses included ticagrelor 180 mg, prasugrel 60 mg, clopidogrel 300 mg, or clopidogrel 600 mg. Of the patients who received a clopidogrel loading dose, 72% received the 600-mg dose. Most loading doses were administered in the catheterization laboratory either after angiography or after PCI (Table 3). Patients who did not receive a loading dose were either previously loaded with a different antiplatelet agent or were previously on an antiplatelet agent prior to hospitalization.

Of the 19 patients who were switched from one agent to another during hospitalization, six patients received a loading dose with the initial agent and were then reloaded with a different agent. Patients switched from ticagrelor or prasugrel to clopidogrel were reloaded with the 300-mg clopidogrel dose instead of the 600-mg dose.

Concomitant Medications on Discharge

Concomitant drugs prescribed on discharge are presented in Table 4. More than 90% of patients in each group were prescribed aspirin with antiplatelet therapy on discharge. No patients in the ticagrelor group were prescribed an aspirin dose greater than 81 mg on discharge compared with 11% of patients in both the clopidogrel and prasugrel groups. About 10% of patients in each group were discharged on an oral anticoagulant. Based on prior medical history, this was likely due to atrial fibrillation. There was no significant difference among the groups regarding the choice between warfarin and a target-specific oral anticoagulant. About 20% to 30% of patients were discharged on a proton pump inhibitor, and about 10% of patients were discharged on an H2 antagonist. The choice of proton pump inhibitor did not differ among the groups, with 9% of the clopidogrel group prescribed omeprazole or esomeprazole on discharge. The majority of patients were discharged on a statin, beta blocker, and angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker regardless of antiplatelet choice.

Adherence to FDA-Approved Dosing

Table 2 presents antiplatelet use outside of the FDA-approved prescribing information based on relative or absolute contraindications. Clopidogrel was prescribed outside of FDA recommendations 13% of the time: 12 patients were discharged on omeprazole/esomeprazole, four patients were discharged on nonsteroidal anti-inflammatory drugs (NSAIDs), and two patients were discharged on more than 75 mg daily of clopidogrel. Prasugrel was prescribed outside of FDA recommendations 13% of the time: two patients were dosed higher than the recommended dose, two patients had a history of stroke, one patient had no PCI or history of stent placement, one patient received prasugrel before angiography, and two patients were discharged on NSAIDs. Ticagrelor was prescribed outside of FDA recommendations in 4% of patients: one patient had a history of intracranial hemorrhage, one patient had liver dysfunction, and one patient was discharged on NSAIDs.

Rationale for Switching Agents

Figures 2, 3, and 4 show when antiplatelet agents were switched either upon admission or discharge and the corresponding rationale. Prior to hospitalization, 94 of the 275 included patients were on clopidogrel (81%), prasugrel (12%), or ticagrelor (7%). Upon hospitalization, 16 patients were switched from clopidogrel to a newer ADP-receptor inhibitor due to restenosis of a previous stent or inadequate platelet inhibition and placement of a new stent. Three patients were switched from a newer ADP receptor inhibitor to clopidogrel due to concerns about bleeding or cost. Three patients were switched from prasugrel to ticagrelor or vice versa for restenosis of a previous stent.

At discharge, six of the 143 patients on inpatient clopidogrel were switched to a newer ADP receptor inhibitor due to inadequate platelet inhibition on clopidogrel, placement of a new stent, or returning patients to their preadmission home medication regimen. Nine of the 126 patients on inpatient ticagrelor were switched to clopidogrel at discharge due to concerns about bleeding or cost. Two patients were switched from ticagrelor to prasugrel at discharge for compliance and contraindication (history of liver disease). Two patients were discharged on clopidogrel 75 mg twice daily rather than once daily due to suboptimal platelet inhibition.

Sixty-two patients had platelet function studies performed, with five patients (8%) being switched from clopidogrel to a newer ADP receptor inhibitor or twice-daily clopidogrel based on the results. Only one patient had follow-up platelet function studies performed that showed suppressed platelet function after changing to ticagrelor.

Clinical Outcomes

Table 5 shows clinical outcomes. Median ICU/CCU and hospital LOS were longer in the clopidogrel group. All-cause in-hospital mortality, cardiovascular in-hospital mortality, 30-day readmissions for ACS, and all-cause 30-day readmissions were not significantly different among the groups. There were no readmissions for stroke, and only one patient was readmitted with hematuria in the clopidogrel group.

DISCUSSION

Factors Associated With Antiplatelet Choice

Based on our results, clopidogrel is the most commonly prescribed ADP receptor antagonist in all patients presenting with ACS, regardless of management strategy. However, in the subgroup of patients managed with PCI, physicians prescribed all three agents with similar frequency. In contrast, large database registry studies have reported that the ratio of clopidogrel use relative to novel ADP receptor antagonist use in ACS is about 70:30, with each novel agent constituting an approximately equal portion.14,15,17,18 The higher rate of prescription of novel agents in our study compared with previous studies may reflect an increased adoption of ticagrelor and prasugrel due to growing clinician familiarity with these newer drugs. 14,15

Consistent with previous literature, our study shows clopidogrel was more likely to be prescribed to older female patients with more comorbidities, including history of coronary artery disease, ischemic stroke, heart failure, peripheral vascular disease, and chronic kidney disease.1418,20 This may be due to concern about increased bleeding risk in older patients seen with prasugrel and ticagrelor. Several studies, including one from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry, show that prasugrel was used in the healthiest subset of patients, whereas clopidogrel was used in the highest-risk cohort.14,15,18 Prasugrel is recommended for patients with diabetes or prior MI due to better outcomes, as demonstrated by a post-hoc analysis in the TRITON-TIMI 38 trial.6 These patient factors did not affect prasugrel prescription patterns in our study and may reflect an underutilization of prasugrel in contemporary practice in these two important patient subgroups. Based on the PLATO trial, in every major subgroup of patients, ticagrelor was associated with a significant reduction in ischemic events and also significantly reduced overall mortality compared with clopidogrel.9 Furthermore, in patients with high-risk features (65 years of age or older, diabetes mellitus, a second prior spontaneous MI, multivessel coronary disease, or chronic renal failure), ticagrelor use beyond one year after an initial MI showed ischemic benefit versus aspirin therapy alone.10 In contrast, in the CHARISMA trial, clopidogrel plus aspirin failed to prevent atherothrombotic events compared with aspirin alone in high-risk patients.24 Prasugrel and ticagrelor have shown greater efficacy in patients who were at the highest risk of recurrent ischemic events; however, this study shows that, in contemporary practice, both ticagrelor and prasugrel were prescribed to patients with a lower risk profile and may reflect underutilization of these more potent agents.14,15

In our cohort, prasugrel and ticagrelor were more likely to be prescribed to patients who presented with STEMI. This is likely because patients presenting with STEMIs tend to be younger and male, have fewer comorbidities, and are more likely to have a PCI.16,23 Patients requiring glycoprotein IIB/IIIA inhibitors during the catheterization procedure were also more likely to receive prasugrel or ticagrelor. This could reflect the use of the more potent ADP receptor inhibitors in patients with a greater risk of ischemic complications and is consistent with contemporary practices described in the literature.14,15

Another factor affecting antiplatelet choice is cost. In this study, prasugrel and ticagrelor were more likely to be prescribed to patients with commercial insurance. Conversely, patients with Medicare were more likely to receive clopidogrel. However, patients in the Medicare group were also older, which may be a confounder when looking at the kind of payer driving prescription patterns. Clinical trials have shown that patients prescribed prasugrel and ticagrelor have better outcomes compared with those prescribed clopidogrel. However, many patients are unable to afford the more expensive medications. The increased drug costs of using prasugrel or ticagrelor instead of clopidogrel may be offset by a reduction in medical costs and improved quality of life. Several economic analyses have been performed favoring prasugrel and ticagrelor over clopidogrel.2528 In a U.S.-based study over a median follow-up of 15 months, average total costs (including drug costs) were $221 lower per patient with prasugrel mainly because of lower rates of rehospitalizations involving PCIs.25 Using prasugrel also yielded an incremental cost-effectiveness ratio of $9,727 per life-year gained. Similarly, in another U.S.-based study, one year of therapy with ticagrelor relative to generic clopidogrel cost $29,665 per quality-adjusted life year gained, with a 98.7% likelihood of being cost-effective at a willingness-to-pay threshold of $100,000.26 Similar results were seen in European and Asian studies in which ticagrelor and prasugrel were shown to be more cost-effective.27,28 On the other hand, although analyses have shown that the newer agents are more cost-effective overall, the financial impact on pharmacy budgets could be substantial with widespread adoption of these more expensive agents.

Loading Doses

Pretreatment with ADP receptor antagonists before coronary angiography is controversial. American ACS guidelines recommend starting ADP receptor antagonists “as soon as possible,” but the ACCOAST study has shown that pretreatment with prasugrel prior to angiography increased bleeding events without reducing ischemic events for up to 30 days.1,11,23 Furthermore, a needed CABG procedure may be delayed upon intake of an ADP receptor antagonist. Fan et al. published a database study looking at pretreatment prescribing patterns in contemporary U.S. practice. Pretreatment with an ADP receptor antagonist was observed in 23% of patients receiving PCI, with a trend toward lower rates of pretreatment over time with ticagrelor and prasugrel. 16 Similarly, 82% of patients in our study who received PCI received an ADP receptor antagonist after angiography or after the catheterization procedure.

When examining clopidogrel loading doses, we found that 72% of patients receiving a clopidogrel loading dose received 600 mg despite the FDA-labeled indication for 300 mg. Pharmacokinetic studies have shown that loading with 600 mg resulted in higher plasma concentrations of the active metabolite and lower values for ADP-induced platelet aggregation four hours after drug administration.29 Clinically, this has translated into better outcomes as shown in a study looking at STEMI patients undergoing PCI. The 600-mg dose was associated with improvements in procedural angiographic endpoints and one-year clinical outcomes.30

Guidelines were recently published in Circulation based on expert consensus about switching between oral agents. These guidelines suggest that in the acute/early phase (30 days or less from the index event), switching should occur with the administration of a loading dose in most cases, excepting patients who are de-escalating therapy because of bleeding. For those patients, a maintenance dose of clopidogrel should be considered.31 In our study, six of 19 patients were reloaded after switching from another ADP receptor antagonist. This demonstrates variability in contemporary practice and slow uptake of current guidelines.

Adherence to FDA-Approved Dosing

Our study showed that ADP receptor antagonists were prescribed several times outside the recommended use per FDA-approved prescribing information based on relative or absolute contraindications. Nine percent of the clopidogrel group received omeprazole or esomeprazole even though this is considered a major drug–drug interaction. Although the significance of the interaction is still controversial, the FDA warns against concomitant use due to possible reduction in clopidogrel active metabolite levels and antiplatelet activity. However, no known studies have demonstrated increased risks in cardiovascular events due to this interaction.32,33 Two patients in our study were prescribed a higher dose of clopidogrel upon discharge due to inadequate platelet inhibition. However, a study comparing prasugrel with daily clopidogrel and twice-daily clopidogrel showed no benefit to dosing clopidogrel twice daily. This may be due to the small sample size and lack of power to detect differences.34 In our cohort, prasugrel was prescribed outside the prescribing information in 11% of cases compared with the 6% to 50% rate reported in the literature.15,17,18 Therefore, the use of ADP receptors outside of FDA recommendations is not uncommon and may be an area for quality improvement efforts.

Rationale for Switching Agents

In the TRANSLATE ACS study, post-discharge antiplatelet switching was examined in 8,672 MI patients discharged after PCI in the U.S. Within one year after MI, 7.6% of patients switched agents. The majority of patients, approximately 90%, switched from ticagrelor or prasugrel to clopidogrel, with the reason cited most often being cost.20 In the GRAPE study, conducted in Greece, in-hospital antiplatelet switching occurred in 35.5% of patients, with about 90% switching from clopidogrel to ticagrelor or prasugrel. Bleeding rates were higher, but fewer major adverse cardiovascular events occurred in patients switched from clopidogrel to prasugrel or ticagrelor. It should be noted that Greece has universal health care and medication cost was not a large burden for patients.21 In comparison, only 7.2% of our patients were switched to a different agent. Many were on clopidogrel upon admission but were switched to a newer agent due to new stent placement. This brings into question why more patients were not switched to a newer agent as seen in GRAPE, and whether medication costs were considered in making the decision not to switch.

Study Limitations

Although our results are consistent with those from larger retrospective studies, our study was limited by the sample size.1418 The analysis of chosen antiplatelet did not consider procedural characteristics, such as stratified risk of PCI. In addition, clinical outcomes such as major cardiac adverse events and bleeding rates as a result of antiplatelet choice were not examined. However, these outcomes would likely have been no different among groups based on the small sample size and lack of power to detect such differences. In addition, we could only collect information on readmissions to the study hospital and could not account for readmissions to other hospitals. Furthermore, we had excluded patients who were later determined to be more appropriate candidates for CABG. This would have excluded patients who potentially did not do well on the antiplatelet of choice and had a failed PCI or subsequent stent stenosis that later required CABG. We decided to exclude these patients because they were unlikely to be discharged on dual antiplatelet therapy after CABG. Another limitation was our inclusion of patients previously on antiplatelet agents prior to admission. A majority of patients were on clopidogrel prior to admission, so this was likely an influence on physician prescribing patterns upon admission. However, we wanted to determine whether antiplatelet choice prior to admission would influence prescription patterns, and it appears that it does.

CONCLUSION

In this study, clopidogrel was the most commonly prescribed ADP receptor inhibitor, followed by ticagrelor and prasugrel. Physicians prescribed clopidogrel for patients who were more likely to be female, elderly, insured by Medicare and with more comorbidities. Patients presenting with STEMI and those to be managed with PCI were more likely to be prescribed prasugrel or ticagrelor. The majority of patients received a loading dose upon hospitalization, mostly in the catheterization laboratory after angiography or after a PCI procedure. In-hospital switching of antiplatelet agents was infrequent and driven by considerations of cost, bleeding, inadequate platelet inhibition, and new stent placement. Hospital LOS was slightly longer in patients prescribed clopidogrel, but there was no difference in in-hospital mortality or 30-day readmission rates among groups. A small number of patients were being prescribed these agents outside of FDA-approved dosing. Clinical studies and economic studies have favored the use of prasugrel and ticagrelor; however, our study shows that these new agents may be underutilized, especially among the highest-risk patients who might benefit most.

Figures and Tables

Choice of Inpatient Antiplatelet Therapy and ACS Management Strategy (N = 275)

PCI = percutaneous coronary intervention

Choice of Antiplatelet Therapy Prior to Hospitalization/at Discharge (n = 94)

Rationale for Switching Prior-to-Hospitalization Antiplatelet Therapy During Inpatient Stay (n = 94)

Rationale for Switching Inpatient Antiplatelet Therapy on Discharge (n = 262)

Baseline Characteristics Based on Selected Inpatient Antiplatelet (N = 275)

Clopidogrel (n = 143) Prasugrel (n = 61) Ticagrelor (n = 71) P Value

Age, mean ± SD, years 65.9 ± 12.2 60.6 ± 9.9 60.2 ± 11.9 < 0.01

Sex, male, n (%) 91 (64) 48 (79) 58 (82) < 0.01

BMI, mean ± SD, kg/m2 28.8 ± 5.8 30.4 ± 7.6 28.9 ± 4.9 0.2

Race, n (%)
 Caucasian 65 (45) 40 (66) 40 (56) 0.02
 African-American 38 (27) 8 (13) 12 (17) 0.06
 Hispanic 27 (19) 8 (13) 8 (11) 0.29
 Other 13 (9) 5 (8) 11 (16) 0.28

Age ≥ 75 years, n (%) 31 (22) 4 (6.6) 7 (10) 0.01

Weight < 60 kg, n (%) 15 (10) 4 (6.6) 0 (0) 0.02

Payer type, n (%)
 Commercial 48 (34) 31 (51) 42 (59) < 0.01
 Medicaid 11 (8) 4 (6) 3 (4) 0.63
 Medicare* 72 (50) 17 (28) 23 (32) < 0.01
 Other 12 (8) 9 (15) 3 (4) 0.1

Past medical history, n (%)
 Coronary artery disease 93 (65) 28 (46) 27 (38) < 0.01
 Diabetes 74 (50) 25 (41) 26 (37) 0.08
 Ischemic stroke 24 (17) 2 (3) 3 (4) < 0.01
 Hemorrhagic stroke 2 (1.4) 0 (0) 2 (3) 0.4
 Atrial fibrillation 14 (10) 5 (8) 5 (7) 0.79
 Peripheral vascular disease 28 (20) 3 (5) 5 (7) < 0.01
 Heart failure 47 (33) 6 (10) 7 (10) < 0.01
 Hypertension 122 (85) 46 (75) 56 (79) 0.2
 Hyperlipidemia 86 (60) 34 (56) 34 (49) 0.2
 Liver disease 2 (1.4) 0 (0) 1 (1.4) 0.6
 Chronic kidney disease 51 (36) 1 (2) 7 (10) < 0.01
 Prior PCI 58 (41) 24 (39) 19 (27) 0.13
 Prior CABG 49 (34) 8 (13) 8 (11) < 0.01

BMI = body mass index; CABG = coronary artery bypass graft; PCI = percutaneous coronary intervention; SD = standard deviation.

*All Medicare patients, including Medicare Advantage and Medicare Supplemental.

Includes charity cases, the uninsured, and patients where no payment data were available in the chart.

Use of Antiplatelet Therapy Based on Inpatient Antiplatelet (N = 275)

Clopidogrel (n = 143) Prasugrel (n = 61) Ticagrelor (n = 71) P Value

Indication, n (%)
 STEMI 31 (22) 36 (59) 33 (46) < 0.01
 UA/NSTEMI 112 (78) 25 (41) 38 (54) < 0.01

Management of ACS, n (%)
 Medical management only 24 (17) 3 (5) 1 (1.4) < 0.01
 Angiography with PCI 81 (57) 52 (85) 67 (94) < 0.01
 Angiography with medical management 38 (26) 6 (10) 3 (4) < 0.01

Inappropriate use per FDA prescribing information, n (%) 18 (13) 8 (13) 3 (4) 0.13

ACS = acute coronary syndrome; FDA = Food and Drug Administration; NSTEMI = non–ST-segment elevation myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-segment elevation myocardial infarction; UA = unstable angina.

Management of Patients Receiving Primary PCI by Inpatient Antiplatelet (N = 200)

Clopidogrel (n = 81) Prasugrel (n = 52) Ticagrelor (n = 67) P Value

Drug-eluting stent, n (%) 70 (86) 50 (96) 64 (96) 0.06
Bare metal stent, n (%) 10 (12) 1 (2) 2 (3) 0.02
POBA, n (%) 1 (1) 1 (2) 1 (1) 0.95

Received loading dose, n (%) 75 (93) 46 (88) 65 (97) 0.19

Location of loading dose, n (%)
 Prior to PCI 27 (33) 7 (13) 8 (12) < 0.01
 After PCI 54 (67) 45 (87) 59 (88) < 0.01

Antithrombotic use in catheterization laboratory, n (%)
 Glycoprotein IIB/IIIA inhibitor 13 (16) 23 (44) 22 (33) < 0.01
 Heparin 42 (52) 27 (52) 32 (47) 0.86
 Bivalirudin 38 (47) 22 (43) 35 (52) 0.55

PCI = percutaneous coronary intervention; POBA = plain old balloon angioplasty.

Concomitant Drugs Prescribed on Discharge (N = 262)

Clopidogrel (n = 136) Prasugrel (n = 57) Ticagrelor (n = 69) P Value

Aspirin, n (%) 128 (94) 52 (91) 68 (99) 0.18
 81 mg 113 (83) 46 (81) 68 (99) < 0.01
 162 mg 1 (1) 0 (0) 0 (0) 0.63
 325 mg 14 (10) 6 (11) 0 (0) 0.02

NSAIDs, n (%) 4 (3) 2 (4) 1 (1.5) 0.75
Warfarin, n (%) 12 (9) 3 (5) 7 (10) 0.60
Rivaroxaban, n (%) 2 (1.5) 2 (4) 0 (0) 0.28
Apixaban, n (%) 1 (1) 0 (0) 0 (0) 0.63

Proton pump inhibitor, n (%) 49 (36) 13 (23) 18 (26) 0.12
 Omeprazole/esomeprazole 12 (9) 5 (9) 4 (6) 0.73
 Other 37 (27) 8 (14) 14 (21) 0.12
H2 antagonist, n (%) 13 (10) 6 (11) 6 (9) 0.94

Statin, n (%) 128 (94) 56 (98) 63 (91) 0.25
 High-intensity* 90 (66) 40 (70) 48 (71) 0.82
 Medium-intensity* 34 (25) 15 (26) 14 (21) 0.68
 Low-intensity* 4 (3) 1 (2) 1 (1.5) 0.76

Beta blocker, n (%) 122 (89) 50 (88) 63 (93) 0.8

ACE/ARB, n (%) 95 (70) 45 (79) 44 (65) 0.18

ACE = angiotensin-converting enzyme; ARB = angiotensin-receptor blocker; NSAID = nonsteroidal anti-inflammatory drug.

*Based on the 2013 American College of Cardiology/American Heart Association guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults.35

Outcomes Based on Inpatient Antiplatelet (N = 275)

Clopidogrel (n = 143) Prasugrel (n = 61) Ticagrelor (n = 71) P Value

ICU LOS, median (IQR), days 2 (1–4) 1 (1–2) 2 (1–3) 0.04
Hospital LOS, median (IQR), days 5 (3–7) 3 (2–5) 4 (2–5) < 0.01
All-cause mortality, n (%) 6 (4.2) 2 (3) 1 (1.4) 0.55
Cardiovascular mortality, n (%) 6 (4.2) 2 (3) 1 (1.4) 0.55
30-day readmission for ACS, n (%) 11 (8) 5 (8) 2 (3) 0.31
All-cause 30-day readmission, n (%)* 27 (20) 8 (14) 9 (13) 0.4

ACS = acute coronary syndrome; ICU = intensive care unit; IQR = interquartile range; LOS = length of stay.

*One patient was readmitted for hematuria in the clopidogrel group; there were no readmissions for stroke.

Author bio: 
Dr. Yin is a Clinical Pharmacist at CHI Baylor St. Luke’s Medical Center in Houston, Texas. Drs. Nguyen and Kamat are Medical Residents at the Baylor College of Medicine in Houston. Dr. Bayat is Clinical Pharmacy Manager at the University of Texas Medical Branch in Galveston, Texas. Dr. Alam is a Cardiologist at Baylor College of Medicine.

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