Clopidogrel Prescription Research Articles

Delay in filling first prescription for clopidogrel after coronary stenting increases risk of death and myocardial infarction

Delay in filling first prescription for clopidogrel after coronary stenting increases risk of death and myocardial infarction

Prolonged clopidogrel use improves clinical outcomes following drug eluting but not bare metal stent implantation

Purpose: Current guidelines recommend clopidogrel for 6-12 months following drug eluting stent (DES) implantation. The role of clopidogrel beyond 12 months is unclear. Methods: We linked hospital administrative, community pharmacy and cardiac revascularization data to determine clopidogrel use and outcomes for all patients receiving a coronary stent in British Columbia 2004 - 2006 with follow-up to 5 years. Cox proportional hazard regression analysis was performed to determine the effect of prolonged clopidogrel use (>12 months) on outcomes. Patients who died ≤12 months from index stent placement were excluded. Results: 15,629 patients were included in the study. Of 3,599 patients who received at least 1 DES and 12030 patients who received only bare metal stents (BMS), 1326 (37%) and 2121 (18%) respectively filled a prescription for clopidogrel >12 months from the index procedure. The mean duration of clopidogrel prescription in patients who received clopidogrel >12 months was 406±35 days in the DES group and 407±37 days in the BMS group, compared with 217±115 days (p<0.0001) and 117±116 days (p<0.0001) respectively for those who did not. Compared with ≤12 months clopidogrel, prolonged clopidogrel use was associated with a reduction in mortality (HR 0.67, 95% CI [0.46–0.98], p=0.038), mortality and readmission for myocardial infarction combined (HR 0.70, 95% CI [0.54–0.92], p=0.01) and an indication of a reduction in readmission for myocardial infarction alone (HR 0.70, 95% CI [0.49–1.00], p=0.051) in patients treated with DES, but not with BMS alone. ![Figure][1] Conclusions: In contrast to BMS, clopidogrel use beyond 12 months following DES implantation was associated with improved clinical outcomes. Our data support a longer duration of clopidogrel therapy for patients treated with DES. [1]: pending:yes

Nurse-led Early Triage (NET) study of chest pain patients: a long term evaluation study of a service development aimed at improving the management of patients with non-ST-elevation acute coronary syndromes

Patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) are at risk of early death. This may be reduced by timely assessment and treatment. The purpose of this study was to evaluate if Nurse-led Early Triage (NET) in the coronary care unit (CCU) can improve time to assessment and management of NSTE-ACS patients. Data on 79 consecutive chest pain patients admitted pre-NET to the acute admissions unit (AAU) and on 103 patients admitted in the first six months of the NET service in CCU, was re-examined and compared to subsequent data obtained on 92 patients admitted via NET five years later, in order to re-evaluate the service. NET resulted in significant improvements in: the number of patients with chest pain who had their 12-lead electrocardiogram (ECG) performed within 10 min of admission (94% vs 32%, p<0.001); the number of high-risk NSTE-ACS patients prescribed clopidogrel (72% vs 42%, p<0.01); and the number being managed in CCU (82% vs 34%, p<0.01). Comparison of the NET service at five years with the pre-NET service demonstrated measurable benefits were sustained (p<0.01) for the same comparative end points. There were no significant differences in these end-points of time to ECG, clopidogrel prescription nor management in CCU for high-risk patients between the NET groups at six months and five years, demonstrating that current triage is as effective as when first introduced. This study demonstrated the positive impact of nurse-led early triage for NSTE-ACS patients and that initial benefits have been sustained.

Abstract 285: Impact of Prescription Refill Reminders for Clopidogrel Therapy in Patients Receiving Drug-Eluting Stents

Purpose: Premature discontinuation of antiplatelet therapy in ACS patients receiving a drug-eluting stent (DES) can be associated with increased morbidity and mortality. The purpose of this study was to determine if refill notification reminders for clopidgrel by a pharmacist would improve long term adherence and outcomes for patients receiving a DES. Methods: A prospective, randomized, controlled study was conducted to evaluate adherence to clopidogrel for up to one year in ACS patients receiving a DES. Patients randomized to the Pharmacist Reminder group were contacted by a pharmacist on a monthly basis with a refill reminder for their clopidogrel prescription and the ability to discuss any medication issues. Patients randomized to the No Reminder group did not receive any refill reminder notification from a pharmacist. Both groups were contacted at 6 and 12 months to complete a follow-up survey. Pharmacy refill records were evaluated to determine monthly adherence and actual out-of-pocket expenses for clopidogrel up to one year after enrollment. Adherence was assessed by both the proportion of months covered (PMC) and complete continuous adherence over 1 year. A PMC of &gt;80% was considered adherent. Patients were enrolled from September 2007 to August 2009. Assuming premature discontinuation rates of 5% and 14% for Pharmacist Reminder and No Reminder groups respectively, 120 patients were required to detect significance with an alpha level of 0.05 and a power of 0.80. Results: A total of 114 patients were enrolled in the study with 53% (N=60) patients in the No Reminder group and 47% (N=54) in the Pharmacist Reminder group. The majority of patients were male (75%) with an average age of 62 years. Approximately 18% had a previous stent and had taken clopidogrel previously. Of the total population, 89% were adherent (102/114) with a PMC &gt;80%, 2.6% (3/114) had a PMC 60-79%, and 7.9% (9/114) had a PMC &lt;60%. Similarly, 88% (100/114) had complete continuous adherence to clopidogrel over 1 year. More patients in the Pharmacist Reminder group had continuous adherence to clopidogrel over 1 year (91% vs. 85%, p=NS) and a PMC &gt;80% (93% vs. 87%, p=NS) compared to the No Reminder group. More patients who were not adherent to clopidogrel reported recent hospitalizations through follow-up (33% vs. 10%, p=NS). No significant improvement in long term adherence to clopidogrel was found through pharmacist reminder on a monthly basis, however the enrollment goal was not met and other factors could have influenced adherence. Conclusions: For patients receiving a DES for ACS, 1 in 9 patients was nonadherent to clopidogrel at 1 year. Pharmacist refill reminder can positively impact long term adherence to clopidogrel. Nonadherence to clopidgrel was associated with a higher rate of hospitalization. Further research is necessary to determine which factors impact long term adherence to clopidogrel in patients receiving a DES.

Abstract 332: Persistent Use Of Evidence-Based Medications After Discharge Among Patients With Non-ST Elevation Myocardial Infarction Treated At Academic Versus Non-Academic Hospitals

Background: While academic hospitals are more likely to apply evidence-based therapies in-hospital for patients with non-ST elevation myocardial infarction (NSTEMI) than non-academic hospitals, differences in post-discharge persistence of evidence-based medications have never been evaluated. Methods: We examined 3,184 NSTEMI patients over age 65 treated at 250 hospitals in 2006 in the CRUSADE registry linked to Medicare part D pharmacy data. Using multivariable Poisson regression adjusting for case mix, we compared continued filling of prescriptions for beta-blockers, ACEI/ARB, clopidogrel, and statins at 90 days and 1 year post-discharge between patients treated at academic and non-academic hospitals. Results: Patients treated at academic hospitals were more frequently non-white (19% vs. 8%, p&lt;0.001), but age (median 76 years) and gender (53% female) were not significantly different from patients treated at non-academic hospitals. Patients at academic hospitals were more likely to have a Charlson score &gt;4 (36% vs. 30%, p=0.001), yet the rates of in-hospital PCI (48%) and CABG (8%) were similar between groups. Rates of persistence to evidence-based medications did not differ substantially between patients treated at academic vs. non-academic hospitals at 90 days or 1 year (Table). Persistence to all drug classes prescribed at discharge was low and not significantly different between academic and non-academic hospitals at 90 days (46% vs. 45%, p=0.44 with adjusted incidence rate ratio (IRR)=0.99 (0.95,1.04) and at 1-year (39% vs. 39%, p=0.93, adjusted IRR=1.02 (0.98,1.07)). There were no significant differences in index hospitalization duration (median 4 days, interquartile range (IQR) 3-6 for both, p=0.51) and time to first post-discharge cardiac follow-up visit (median 28 days [IQR 15-54] vs. 28 days [IQR 16-56], p=0.25) between patients treated at academic vs. non-academic hospitals. Conclusion: Rates of persistence to evidence-based medications were similar between older NSTEMI patients treated at academic vs. non-academic hospitals, and may reflect similar in-hospital treatment and post-discharge cardiac follow-up. However, persistence rates are low both early and late post-discharge, highlighting a continued need for quality improvement efforts to optimize post-MI management.

Clopidogrel and the possibility of drug–drug interaction in primary health care

IntroductionClopidogrel ineffectiveness is a serious problem in antiplatelet therapy. Many factors may contribute to this phenomenon. One of them is clopidogrel drug–drug interaction with CYP2C19 and CYP3A4 enzyme inhibitors. The main goal of this descriptive study was to assess the prevalence of cases of clopidogrel–drug interactions in the primary health care physicians' practices. Materials and methodsDuring 2010–2011, 80 patients receiving clopidogrel antiplatelet therapy from primary care physicians' clinical practices were involved in this study. By using questionnaires and case histories, the following information was collected: Age, gender, clinical diagnoses, and medications used. ResultsIn the current study, drugs were used that could potentially influence the effect of clopidogrel: Omeprazole, lipophilic statins, calcium channel blockers (CCB). There was a different use of the above-mentioned drugs before and after the initiation of the clopidogrel therapy, e.g., 12 (15.0%) and 44 (55.0%) patients used proton pump inhibitors (PPI) before and after the clopidogrel therapy accordingly (P = 0.16; χ2 = 1.91). However, pantoprazole was recommended more often than other PPI. The use of the potential CYP3A4 inhibitors – lipophilic statins and CCB – was increased after the prescription of clopidogrel too. Concomitant use of statins (mainly atorvastatin) with clopidogrel was observed in 75 (93.8%) patients and the use of CCB (mainly amlodipine) – in 33 (41.3%) patients. ConclusionIn the primary health care practices, it is revealed that there is co-medication of clopidogrel with weak CYP3A4 inhibitors, such as lipophilic statins and amlodipine, and with the moderate CYP2C19 inhibitor – omeprazole. The latter co-medication is potentially harmful and it is very important to inform the first care professionals about the opportunity to change omeprazole to pantoprazole, which does not influence clopidogrel biotransformation.

What you need to know about pharmacogenomics

MRS. C, 62, IS ADMITTED to the hospital after experiencing an acute myocardial infarction. Her management includes percutaneous coronary intervention (PCI) and a prescription for clopidogrel. She tolerates the procedure well and is admitted to the ICU for close observation. Over the next 48 hours, s

Comparison of Current Treatment Practices for Preserved and Reduced Left Ventricular Ejection Fraction: The New Zealand Heart Failure Registry

have required coronary bypass grafting*, had higher right ventricular pressure* and lower weight* (*p< 0.05). With worseningCKD, therewas a trend towardsmore gastrointestinal bleeding, iron deficiency, diabetes, significant mitral regurgitation, prescription of clopidogrel, spironolactone and frusemide, as well as reduced defibrillator implantation and warfarin use. Conclusion: CKD is associated poor prognostic factors in CHF. Many of those identified increase cardiovascular demand in CHF, impacting on symptoms, survival and rehospitalisaton. CHF patients with CKD should be identified, investigated for these co-morbidities and treated aggressively as they have multiple risk factors for poor outcome. http://dx.doi.org/10.1016/j.hlc.2013.05.171

Clinical Outcomes and Cardiovascular Responses According to Exercise Training Intensity in Heart Failure Patients: A Systematic Review and Meta-analysis

have required coronary bypass grafting*, had higher right ventricular pressure* and lower weight* (*p< 0.05). With worseningCKD, therewas a trend towardsmore gastrointestinal bleeding, iron deficiency, diabetes, significant mitral regurgitation, prescription of clopidogrel, spironolactone and frusemide, as well as reduced defibrillator implantation and warfarin use. Conclusion: CKD is associated poor prognostic factors in CHF. Many of those identified increase cardiovascular demand in CHF, impacting on symptoms, survival and rehospitalisaton. CHF patients with CKD should be identified, investigated for these co-morbidities and treated aggressively as they have multiple risk factors for poor outcome. http://dx.doi.org/10.1016/j.hlc.2013.05.171

Healthcare Utilization of Patients With Acute Coronary Syndrome in Germany.

BackgroundThe aim of this study was to determine the health care utilization of patients with acute coronary syndrome (ACS) of one German statutory health insurance. The utilization of ambulatory services as well as of inpatient rehabilitation should be regarded. Moreover, the study should reveal the prescription of drugs for secondary prevention. Here, patients showing guideline corresponding prescriptions should be compared with patients without such prescriptions.MethodsA retrospective claims data analysis of one German statutory health insurance was conducted. Health care utilization was considered in the first year after an index hospitalization due to ACS. Beneficiaries for whom an ICD-10 discharge diagnosis of ACS was reported between January 1st 2007 and December 31st 2009 were included. In order to reveal differences in health care utilization depending on the type of ACS (STEMI versus NSTEMI/UA) stratified analyses were performed. Another stratification was done for patients with and without defined drug prescriptions.ResultsFrom 45,188 patients with ACS almost three quarters were assigned to the group of NSTEMI/UA. For 8.9% of all ACS patients (18.74% STEMI, 8.89% NSTEMI/UA), inpatient post-hospital rehabilitation related to ACS was recorded. Ambulatory care related to CHD diagnosis was utilized by 77.6% of patients, more often by STEMI than by NSTEMI/UA patients. For 36.7% and 45.7% of ACS patients, a prescription of aspirin or clopidogrel was recorded, respectively, 79.4% of STEMI patients received at least one prescription for antiplatelet drugs, the corresponding proportion of NSTEMI/UA was 59.8%. A considerable part of patients without prescription dropped out within the first 90 days after the index event.ConclusionsA claims data analysis of one German statutory health insurance fund showed that health care utilization of ACS patients varied depending on the ACS type. It is necessary to distinguish between STEMI and NSTEMI/UA patients when discussing the ambulatory drug utilization.

Genetic Polymorphisms and Drug Interactions Leading to Clopidogrel Resistance: Why the Asian Population Requires Special Attention

ABSTRACTIschemic heart disease and stroke are the two leading causes of death worldwide. Antiplatelet therapy plays the most significant role in the management of these cardiovascular and cerebrovascular occlusive events to prevent recurrent ischemic attack. Clopidogrel, an antiplatelet drug, is widely prescribed either alone or in combination with aspirin as dual antiplatelet therapy for the prevention of vascular occlusive events. The antiplatelet response to clopidogrel varies widely. Hyporesponders and nonresponders are likely to have adverse cardiovascular events during follow-up. Some drugs, such as proton pump inhibitors (omeprazole), calcium channel blockers, selective serotonin reuptake inhibitors (nefazadone), coumarin derivatives (phenprocoumon), benzodiazepines, sulfonylurea, erythromycin, and itraconazole, decrease the antiplatelet effect of clopidogrel when administered concomitantly. Decreased response to clopidogrel is common among Asians due to genetic polymorphisms associated with clopidogrel resistance, and it is nearly 70% in some of the Asian communities. It is necessary to study Asian populations, because there are a large number of Asians throughout the world due to increased migration. Current guidelines do not make genetic testing or platelet response testing mandatory prior to clopidogrel prescription. Therefore, it is important for clinicians treating Asian patients to keep in mind the interindividual variability in response to clopidogrel when prescribing the drug.

T6 Thrombocytosis is Associated with Increased Short and Long Term Mortality After Exacerbation of Chronic Obstructive Pulmonary Disease

IntroductionThere is increasing evidence suggesting that platelets play a significant role in inflammation in addition to their established role in thrombosis. Systemic inflammation is linked to poor short and long...

Clopidogrel treatment and the incidence and severity of community acquired pneumonia in a cohort study and meta-analysis of antiplatelet therapy in pneumonia and critical illness

Platelet activation results in the release and upregulation of mediators responsible for immune cell activation and recruitment, suggesting that platelets play an active role in immunity. Animal models and retrospective data have demonstrated benefit of antiplatelet therapy on inflammatory mediator expression and clinical outcomes. This study sought to characterize effects of clopidogrel on the incidence and severity of community-acquired pneumonia (CAP). A retrospective cohort study was conducted of Kentucky Medicaid patients (2001-2005). The exposed cohort consisted of patients receiving at least six consecutive clopidogrel prescriptions; the non-exposed cohort was comprised of patients not prescribed clopidogrel. Primary endpoints included incidence of CAP and inpatient treatment. Secondary severity endpoints included mortality, intensive care unit admission, mechanical ventilation, sepsis, and acute respiratory distress syndrome/acute lung injury. CAP incidence was significantly greater in the exposed cohort (OR 3.39, 95% CI 3.27-3.51, p < 0.0001) that remained after adjustment (OR 1.48, 95% CI 1.41-1.55, p < 0.0001). Inpatient treatment was more common in the exposed cohort (OR 1.96, 95% CI 1.85-2.07, p < 0.0001), but no significant difference remained after adjustment. Trends favoring the exposed cohort were found for the secondary severity endpoints of mechanical ventilation (p = 0.07) and mortality (p = 0.10). Pooled analysis of published studies supports these findings. While clopidogrel use may be associated with increased CAP incidence, clopidogrel does not appear to increase--and may reduce--its severity among inpatients. Because this study was retrospective and could not quantify all variables (e.g., aspirin use), these findings should be explored prospectively.

Gastrointestinal Events with Clopidogrel: A Nationwide Population-Based Cohort Study

Clopidogrel prevents cardiovascular events, but has been linked with adverse gastrointestinal (GI) complications, particularly bleeding events. We aimed to investigate the risk of adverse GI events in patients treated with clopidogrel. A nationwide population-based cohort study based on linkage of three administrative registries in Denmark. All individuals who redeemed at least one prescription of clopidogrel from 1996 to 2008 were included as exposed subjects (n = 77,503). For each exposed subject, three matched controls were randomly selected from the background population (n = 232,510). Follow-up began on January 1, 1996, and was censored on December 31, 2007, or if patients emigrated or died. The study endpoint was the occurrence of any gastritis, GI ulcer or bleeding. Analyses were adjusted for comorbidity and medication. Regardless of dose, adjusted odds ratios associating clopidogrel use with the study endpoint were statistically significant and followed a dose-response pattern. The crude absolute risk of GI events were: never users: 2.2 %; <0.1 defined daily dose (DDD) of clopidogrel per day: 7.1 %; 0.1-0.39 DDD: 6.0 %; 0.4-0.79 DDD: 5.7 %; ≥0.80 DDD: 4.4 %. Adjusted odds ratios were: <0.1 DDD: 1.34, 95 % CI: 1.26-1.42; 0.1-0.39 DDD: 1.58, 95 % CI: 1.48-1.68; 0.4-0.79 DDD: 1.91, 95 % CI: 1.77-2.06; ≥0.80 DDD: 1.77, 95 % CI: 1.66-1.89, all p-values < 0.01. Depending on the dose, numbers needed to harm ranged from 58 to 33 patients receiving 12 months of clopidogrel treatment. The well-known cardioprotective effect of clopidogrel must be carefully weighed against an increased risk of GI events.

Rehospitalization following percutaneous coronary intervention for commercially insured patients with acute coronary syndrome: a retrospective analysis

BackgroundWhile prior research has provided important information about readmission rates following percutaneous coronary intervention, reports regarding charges and length of stay for readmission beyond 30 days post-discharge for patients in a large cohort are limited. The objective of this study was to characterize the rehospitalization of patients with acute coronary syndrome receiving percutaneous coronary intervention in a U.S. health benefit plan.MethodsThis study retrospectively analyzed administrative claims data from a large US managed care plan at index hospitalization, 30-days, and 31-days to 15-months rehospitalization. A valid Diagnosis Related Group code (version 24) associated with a PCI claim (codes 00.66, 36.0X, 929.73, 929.75, 929.78–929.82, 929.84, 929.95/6, and G0290/1) was required to be included in the study. Patients were also required to have an ACS diagnosis on the day of admission or within 30 days prior to the index PCI. ACS diagnoses were classified by the International Statistical Classification of Disease 9 (ICD-9-CM) codes 410.xx or 411.11. Patients with a history of transient ischemic attack or stroke were excluded from the study because of the focus only on ACS-PCI patients. A clopidogrel prescription claim was required within 60 days after hospitalization.ResultsOf the 6,687 ACS-PCI patients included in the study, 5,174 (77.4%) were male, 5,587 (83.6%) were <65 years old, 4,821 (72.1%) had hypertension, 5,176 (77.4%) had hyperlipidemia, and 1,777 (26.6%) had diabetes. At index hospitalization drug-eluting stents were the most frequently used: 5,534 (82.8%). Of the 4,384 patients who completed the 15-month follow-up, a total of 1,367 (31.2%) patients were rehospitalized for cardiovascular (CV)-related events, of which 811 (59.3%) were revascularization procedures: 13 (1.0%) for coronary artery bypass graft and 798 (58.4%) for PCI. In general, rehospitalizations associated with revascularization procedures cost more than other CV-related rehospitalizations. Patients rehospitalized for revascularization procedures had the shortest median time from post-index PCI to rehospitalization when compared to the patients who were rehospitalized for other CV-related events.ConclusionsFor ACS patients who underwent PCI, revascularization procedures represented a large portion of rehospitalizations. Revascularization procedures appear to be the most frequent, most costly, and earliest cause for rehospitalization after ACS-PCI.

Costs and outcomes associated with clopidogrel discontinuation in Medicare beneficiaries with acute coronary syndrome in the coverage gap

BackgroundCurrent guidelines for acute coronary syndrome recommend clopidogrel for an optimal period of 12 months in order to reduce the risk of reinfarction and mortality. Premature clopidogrel discontinuation has been associated with higher rates of rehospitalization, coronary stent thrombosis, and mortality. No data exist regarding the effect of the Medicare Part D coverage gap on medical costs and outcomes in Medicare beneficiaries who discontinue their clopidogrel upon entering the coverage gap.MethodsBeneficiaries with a Medicare Advantage plan in 2009 who had a diagnosis of acute coronary syndrome were taking clopidogrel 75 mg daily, and reached the gap in the same year representing the study sample. From this cohort, those who filled at least two prescriptions for clopidogrel (continued) versus those that did not (discontinued) while in the gap were compared with regard to outcomes related to acute coronary syndrome and expenditure 30 days after the last prescription was filled and during any time while in the gap. Descriptive and multivariate analyses were used to compare these differences.ResultsA total of 1365 beneficiaries with acute coronary syndrome met the inclusion criteria, of which 705 beneficiaries entered into the coverage gap, wherein 103 (14.6%) and 602 (85.4%) of beneficiaries discontinued and continued clopidogrel, respectively. Compared with those who continued clopidogrel during the gap, beneficiaries who discontinued clopidogrel showed a higher trend in the number of hospitalizations related to acute coronary syndrome and emergency room visits, albeit not statistically significant. Those who discontinued clopidogrel showed a higher mean adjusted cost per member per month in hospitalizations ($3604) related to acute coronary syndrome and outpatient visits ($1144) related to acute coronary syndrome and total medical costs ($5614), albeit not statistically significant.ConclusionMedicare beneficiaries who face large out-of-pocket costs for clopidogrel while in the coverage gap and discontinue therapy may experience adverse events related to acute coronary syndrome.

Effect of the Clopidogrel–Proton Pump Inhibitor Drug Interaction on Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome

To examine the effect of the drug interaction between clopidogrel and proton pump inhibitors (PPIs) on the risk of an adverse cardiovascular event. Population-based, retrospective cohort study. IMS LifeLink Health Plan administrative claims database. A total of 10,101 patients aged 18 years or older with a diagnosis of acute coronary syndrome (ACS) made during a hospitalization or emergency department visit between 2001 and 2008 and who had their first clopidogrel prescription within 90 days after their ACS diagnosis were included in the study. Patients were stratified according to concurrent use (clopidogrel plus PPI group) or no use (clopidogrel alone group) of the following PPIs: esomeprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole. Data were collected on baseline patient demographic and clinical characteristics. Patients were followed from their first clopidogrel prescription until they experienced an adverse cardiovascular event, defined as inpatient hospitalization or emergency department visits for myocardial infarction, percutaneous coronary intervention, or intermediate coronary syndrome; were disenrolled; discontinued clopidogrel; or reached the end of the study period. Using a propensity scoring method, the clopidogrel plus PPI group was matched in a 1:1 ratio with the clopidogrel alone group. Exposure to overlapping clopidogrel-PPI prescriptions was modeled as a time-dependent covariate. The Cox hazards regression model was used to estimate the risk of an adverse cardiovascular event in the clopidogrel plus PPI group versus the clopidogrel alone group. Propensity score matching resulted in 2674 patient pairs. In the propensity score-matched sample, the mean age was 61.30 years, with a mean follow-up of 268 days, and 70.04% were male. Concurrent use of clopidogrel with a PPI was associated with a significantly increased risk of a cardiovascular adverse event (hazard ratio 1.438, 95% confidence interval 1.237-1.671) compared with clopidogrel alone. Concurrent use of clopidogrel plus a PPI was associated with a significant increase in risk of an adverse cardiovascular event in patients with ACS. Large randomized studies are needed to confirm this finding. Until then, clinicians should prescribe the concurrent use of these two drugs cautiously.

Clopidogrel Use and Hospital Quality in Medically Managed Patients With Non–ST-Segment–Elevation Myocardial Infarction

Clopidogrel prescription is a class I guideline recommendation for medically managed patients with non-ST-segment-elevation myocardial infarction (NSTEMI). However, clopidogrel has historically been underused in this population. We evaluated contemporary rates of its use and evaluated associated factors, with a particular focus on hospital quality of myocardial infarction (MI) care. We examined clopidogrel prescription rates among 23 186 patients with NSTEMI discharged from 382 US hospitals between October 2009 and March 2011. Associations between clopidogrel prescription and various patient and hospital factors, including hospital quality of MI care, were determined with regression modeling. Of the sample, 54.9% of eligible patients with NSTEMI received clopidogrel prescription at hospital discharge. Variation in rate by hospital was large, ranging from 22% to 97%. A variety of patient and hospital factors were associated with clopidogrel prescription. Hospital quality of MI care demonstrated modest association with clopidogrel prescription (odds ratio, 0.68; 95% CI, 0.54-0.85) between the lowest and highest hospital quality quartile) and accounted for 5.7% of the variation in prescription rates. Clopidogrel prescription is significantly underused in the medically managed NSTEMI population and demonstrates wide variability by hospital. Although hospital quality of MI care is associated with its use, the findings suggest that it only has a modest effect. Therefore, efforts to improve clopidogrel use likely will require measures beyond improving the overall hospital quality of MI care.

Effect of a safety alert in the electronic prescription program: PPI-clopidogrel interaction†

BackgroundA growing body of evidence suggests that proton pump inhibitors (PPIs) may adversely interact with clopidogrel, diminishing the antiplatelet effect. The potential for increased risk of thrombotic complications warrants cautious...

Abstract 253: Comparative Effectiveness of Clopidogrel in Medically Managed Patients with Unstable Angina and non-ST Segment Myocardial Infarction

Background: The CURE trial demonstrated improved outcomes with the addition of clopidogrel to aspirin in unstable angina (UA) or NSTEMI, leading to guideline adoption and widespread use. Although the role of clopidogrel after PCI is well studied, 40-50% of patients with UA/NSTEMI are medically managed, i.e., without revascularization during the index hospitalization. The effectiveness and optimal duration in real-world medically managed patients is unknown. Methods: We conducted a retrospective cohort study of all adult members of Kaiser Permanente of Northern California, a large, integrated health care delivery system, without known CAD or prior clopidogrel use who presented with UA/NSTEMI from 2003-2008 and did not receive revascularization (PCI or CABG) during the index hospitalization or within 7 days post-discharge (i.e., “medically managed”). We measured the association between use of clopidogrel within 7 days of discharge with subsequent all-cause mortality and MI at 2 years of follow up. Outcomes were examined in unmatched and propensity-matched multivariable Cox regression analyses, adjusted for demographics, comorbidities, longitudinal medication use and secular trends. Results: We identified 18,771 patients (mean age 69.3 years; 42.4% women) with incident UA (34.7%) or NSTEMI (65.3%) followed for a mean 2.5 years after the initial event. Clopidogrel prescription within 7 days of discharge was observed for 34.5% of the sample. Among these, the mean duration of continuous clopidogrel use was 255 days. An additional 1.6% filled a clopidogrel prescription between 7 and 30 days after discharge, and 5.0% filled a prescription after 30 days. During the first 2-years of follow up, patients prescribed clopidogrel within the first 7 days after discharge had lower unadjusted rates of all-cause mortality (7.5% vs 19.2%, p &lt; 0.001; HR = 0.42, 95% CI [0.38-0.45]) and subsequent MI (6.5% vs 8.2%, p = 0.002; HR = 0.85 [0.76-0.95]). In multivariable Cox regression models, clopidogrel users had lower risk of 2-year all-cause mortality (HR = 0.65, [0.60-0.71]) but similar rates of MI (HR = 1.07, [0.96-1.20]). Propensity-matched models demonstrated similar results. A sensitivity analysis in which clopidogrel use was defined by initiation within 30-days post-discharge also demonstrated similar results. Conclusions: In a large community-based sample of patients with incident medically managed UA/NSTEMI, receipt of early post-discharge clopidogrel was independently associated with lower rates of death but similar rates of MI. Future research should identify the subset of patients who experience the greatest net clinical benefit with clopidogrel after UA/NSTEMI as well as the optimal duration of treatment.