Rehospitalization For Myocardial Infarction Research Articles

Proton-Pump Inhibitors Are Associated With Increased Cardiovascular Risk Independent of Clopidogrel Use

Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel. To examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction. A nationwide cohort study based on linked administrative registry data. All hospitals in Denmark. All patients discharged after first-time myocardial infarction from 2000 to 2006. The primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year. Of 56 406 included patients, 9137 (16.2%) were re-hospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72). Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible. Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone.

Clopidogrel and PPI, warfarin management, and rural pharmacists' competence

Clopidogrel and PPI Stockl et al.1 concluded that “patients who received clopidogrel plus a PPI had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone.” Patients taking clopidogrel and a proton pump inhibitor (PPI) (n = 1,033) were compared with a matched group of patients taking clopidogrel alone. Propensity score matching corrected potential selection bias by balancing covariates between the two groups of patients. Patients included in the clopidogrel plus PPI group were dispensed a PPI with one or more days’ supply overlapping the index date and at least one refill within 90 days. The clopidogrel-alone group patients were not dispensed a PPI 90 days before or after the index date. Patients who received clopidogrel plus a PPI had a 93% higher risk of rehospitalization for myocardial infarction (MI) (adjusted hazard ratio 1.93 [95% CI 1.05–3.54]; P = 0.03) and a 64% higher risk of rehospitalization for MI or coronary stent placement (1.64 [1.16– 2.32]; P = 0.005) than patients receiving clopidogrel alone. Implications. Patients taking clopidogrel and a PPI were at higher risk of rehospitalization. Reduced action of clopidogrel may result from competitive metabolic effects of the PPIs on cytochrome P450 (CYP)2C19. Also, CYP2C19 variant allele carriers have lower capacity to metabolize clopidogrel into its active metabolite and inhibit platelet activation.2 Does the higher risk of rehospitalization associated with taking a PPI potentially have a genetic component? Further study is needed of therapy based on genetic testing among patients at high risk of acute gastrointestinal bleeding where a PPI is indicated.

Risk of Rehospitalization for Patients Using Clopidogrel With a Proton Pump Inhibitor

Recent pharmacodynamic and retrospective clinical analyses have suggested that proton pump inhibitors (PPIs) may modify the antiplatelet effects of clopidogrel bisulfate. We conducted a retrospective cohort study of persons enrolled in a multistate health insurance plan with commercial and Medicare clients to evaluate adverse clinical outcomes in patients using clopidogrel plus a PPI compared with clopidogrel alone. Patients who were discharged from the hospital after myocardial infarction (MI) or coronary stent placement and treated with clopidogrel plus a PPI (n = 1033) were matched 1:1 (using propensity scoring) with patients with similar cardiovascular risk factors treated with clopidogrel alone. Rehospitalizations for MI or coronary stent placement were evaluated for up to 360 days. A subanalysis was conducted to study the impact of pantoprazole sodium, the most used PPI. Patients who received clopidogrel plus a PPI had a 93% higher risk of rehospitalization for MI (adjusted hazard ratio, 1.93; 95% confidence interval, 1.05-3.54; P = .03) and a 64% higher risk of rehospitalization for MI or coronary stent placement (1.64; 1.16-2.32; P = .005) than did patients receiving clopidogrel alone. Increased risk of rehospitalization for MI or coronary stent placement was also observed for the subgroup of patients receiving clopidogrel plus pantoprazole (adjusted hazard ratio, 1.91; 95% confidence interval, 1.19-3.06; P = .008). Patients who received clopidogrel plus a PPI had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone. Prospective clinical trials and laboratory analyses of biochemical interactions are warranted to further evaluate the potential impact of PPIs on the efficacy of clopidogrel.

Abstract 5607: Risk of Re-hospitalization for Patients Using Clopidogrel With a Proton Pump Inhibitor

Background: Recent pharmacodynamic and retrospective clinical analyses have suggested that proton pump inhibitors (PPIs) may modify the antiplatelet effects of clopidogrel. Methods: We conducted a retrospective cohort study of persons enrolled in a large multi-state health insurance plan with commercial and Medicare clients to evaluate adverse clinical outcomes for patients using clopidogrel plus PPI compared to clopidogrel alone. Using propensity scoring methodology, patients discharged from the hospital for myocardial infarction (MI) or coronary stent placement and treated with clopidogrel plus PPI were matched 1:1 with patients with similar cardiovascular risk factors treated with clopidogrel alone. Re-hospitalizations for MI or coronary stent placement were evaluated over a period of up to 360 days. A subanalysis was conducted to study the impact of pantoprazole, the most prescribed PPI. Results: Rates of re-hospitalization for MI or coronary stent placement were higher for clopidogrel plus PPI versus clopidogrel alone (Table ). Patients receiving clopidogrel plus PPI had 92% higher risk of re-hospitalization for MI and 53% higher risk of re-hospitalization for MI or coronary stent placement than patients receiving clopidogrel alone. Increased risk of re-hospitalization for MI or coronary stent placement was also observed for the subgroup of clopidogrel plus PPI patients receiving pantoprazole. Conclusion: Patients receiving clopidogrel plus PPI had significantly higher risk of re-hospitalization for MI or coronary stent placement than patients receiving clopidogrel alone. Prospective clinical trials and laboratory analyses of biochemical interactions are warranted to further evaluate the potential impact of PPIs on the efficacy of clopidogrel. Rates and Risk of Hospitalization for MI or Coronary Stent Placement

Effects of Angiotensin‐Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Therapy After Hospital Discharge on Subsequent Rehospitalization for Acute Myocardial Infarction and Heart Failure

American College of Cardiology/American Heart Association guidelines recommend angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy following acute myocardial infarction (MI) or development of heart failure (HF). This study estimated the effects of initiating these therapies after hospitalization for MI or HF on subsequent 1-year rehospitalization rates for MI or HF. A retrospective multivariate analysis of medical claims for 14,327 patients receiving and 7905 not receiving an ACEI or ARB after discharge for MI or HF was conducted. Rehospitalization for MI or HF was lower for treated vs untreated patients (MI: odds ratio [OR]=0.53, P<.001; HF: OR=0.52, P<.001). Rehospitalization was lower in treated patients with high medication compliance (medication possession ratio [MPR]>80%) and medium compliance (MPR 40%-79%) vs patients with low compliance (ORs for MI: high=0.54, medium=0.69; P<.001); ORs for HF: high=0.38, medium=0.62; P<.001). In conclusion, ACEI or ARB therapy initiated after hospitalization for MI or HF reduced risk of rehospitalization, and greater risk reduction was achieved with higher medication compliance.

C‐reactive protein, interleukin‐6, secretory phospholipase A2 group IIA and intercellular adhesion molecule‐1 in the prediction of late outcome events after acute coronary syndromes

We investigated whether levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A(2) group IIA (sPLA(2)-IIA) and intercellular adhesion molecule-1 (ICAM-I) predict late outcomes in patients with acute coronary syndromes (ACS). Prospective longitudinal study. CRP (mg L(-1)), IL-6 (pg mL(-1)), sPLA(2)-IIA (ng mL(-1)) and ICAM-1 (ng mL(-1)) were measured at days 1 (n = 757) and 4 (n = 533) after hospital admission for ACS. Their relations to mortality and rehospitalization for myocardial infarction (MI) and congestive heart failure (CHF) were determined. Coronary Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. Patients with ACS alive at day 30; median follow-up 75 months. Survival was related to day 1 levels of all markers. After adjustment for confounders, CRP, IL-6 and ICAM-1, but not sPLA(2)-IIA, independently predicted mortality and rehospitalization for CHF. For CRP, the hazard ratio (HR) was 1.3 for mortality (95% confidence interval (CI): 1.1-1.5, P = 0.003) and 1.4 for CHF (95% CI: 1.1-1.9, P = 0.006). For IL-6, HR was 1.3 for mortality (95% CI: 1.1-1.6, P < 0.001) and 1.4 for CHF (95% CI: 1.1-1.8, P = 0.02). For ICAM-1, HR was 1.2 for mortality (95% CI: 1.0-1.4, P = 0.04) and 1.3 for CHF (95% CI: 1.0-1.7, P = 0.03). No marker predicted MI. Marker levels on day 4 provided no additional predictive value. In patients with ACS, CRP, IL-6, sPLA(2)-IIA and ICAM-1 are associated with long-term mortality and CHF, but not reinfarction. CRP, IL-6 and ICAM-1 provide prognostic information beyond that obtained by clinical variables.

Risk of Death or Reinfarction Associated With the Use of Selective Cyclooxygenase-2 Inhibitors and Nonselective Nonsteroidal Antiinflammatory Drugs After Acute Myocardial Infarction

The selective cyclooxygenase-2 (COX-2) inhibitors and other nonselective nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk, but the risk in patients with established cardiovascular disease is unknown. We analyzed the risk of rehospitalization for acute myocardial infarction (MI) and death related to the use of NSAIDs including selective COX-2 inhibitors in patients with prior MI. All patients with first-time MI between 1995 and 2002 as well as all prescription claims for NSAIDs after discharge were identified from nationwide Danish administrative registers. The risk of death and rehospitalization for MI associated with the use of selective COX-2 inhibitors and nonselective NSAIDs was studied with the use of multivariable proportional hazards models and case-crossover analysis. A total of 58 432 patients were discharged alive and included in the study; 9773 experienced rehospitalization for MI, and 16 573 died. A total of 5.2% of patients received rofecoxib, 4.3% celecoxib, 17.5% ibuprofen, 10.6% diclofenac, and 12.7% other NSAIDs. For any use of rofecoxib, celecoxib, ibuprofen, diclofenac, and other NSAIDs, the hazard ratios and 95% confidence intervals for death were 2.80 (2.41 to 3.25; for rofecoxib), 2.57 (2.15 to 3.08; for celecoxib), 1.50 (1.36 to 1.67; for ibuprofen), 2.40 (2.09 to 2.80; for diclofenac), and 1.29 (1.16 to 1.43; for other NSAIDS); there were dose-related increases in risk of death for all of the drugs. There were trends for increased risk of rehospitalization for MI associated with the use of both the selective COX-2 inhibitors and the nonselective NSAIDs. Selective COX-2 inhibitors in all dosages and nonselective NSAIDs in high dosages increase mortality in patients with previous MI and should therefore be used with particular caution in these patients.

Cardiovascular outcome in hospitalized patients with minimal troponin I elevation and normal creatine phosphokinase

Background: Among patients with acute coronary syndrome, elevated cardiac troponin and creatine phosphokinase MB fraction levels have both prognostic and diagnostic values. However, in hospitalized patients, cardiac biomarkers are measured in a variety of clinical situations including but not limited to acute coronary syndrome. Moreover, these patients may have elevated troponin levels with no increase in creatine phosphokinase MB fraction levels. Objective: To evaluate the cardiovascular outcome of acutely ill, hospitalized patients with minimal troponin I increase with normal creatine phosphokinase MB fraction. Methods: We identified 64 patients retrospectively from our database with minimal troponin I increase and normal creatine phosphokinase MB fraction hospitalized between November 1998 and April 2000. Discharged patients were questioned about re-hospitalization for myocardial infarction, unstable coronary syndrome, congestive heart failure and percutaneous coronary intervention by means of a structured questionnaire. For those patients who died during hospitalization, data were collected from hospital records. For patients who died at home or at a different institution, a surviving relative completed the questionnaire. Primary outcomes were death, myocardial infarction and the need for revascularization or re-hospitalization. Results: Composite endpoint of death, myocardial infarction, percutaneous coronary intervention or coronary artery bypass grafting and re-hospitalization for cardiac cause occurred in 35.95% of patients within 1 year. Conclusions: There is a significant composite event rate of death, myocardial infarction or re-hospitalization for cardiac causes in acutely ill, hospitalized patients with normal creatine phosphokinase MB fraction and minimally elevated troponin I, regardless of the cause for hospitalization.