Use of secondary prevention pharmacotherapy after first myocardial infarction in patients with diabetes mellitus.

BACKGROUND: Despite recommended pharmacotherapies the use of secondary prevention therapy after myocardial infarction (MI) remains suboptimal. Patients with diabetes mellitus (DM) have worse prognosis after MI compared to patients without DM and aggressive secondary prevention pharmacotherapy in this population is therefore warranted. We examined the changes in use of evidence-based secondary prevention pharmacotherapy in patients with and without DM discharged after first MI. METHODS: All patients aged 30 years or older admitted with first MI in Denmark during 1997-2006 were identified by individual-level linkage of nationwide registries of hospitalizations. Univariate and multivariate logistic regression models were used to identify patient characteristics associated with initiation of acetylsalicylic acid, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, ß-blockers, and clopidogrel within 90 days, and statins within 180 days of discharge, respectively. RESULTS: A total of 78,230 patients were included, the mean age was 68.3 years (SD 13.0), 63.5% were men and 9,797 (12.5%) had diabetes. Comparison of claimed prescriptions in the period 1997-2002 and 2003-2006 showed significant (p < 0.001) increases in claims for acetylsalicylic acid (38.9% vs. 69.7%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (38.7% vs. 50.4%), ß-blockers (69.2% vs. 77.9%), clopidogrel (16.7% vs. 66.3%), and statins (41.3% vs. 77.3%). During 2003-2006, patients with DM claimed significantly less acetylsalicylic acid (odds ratio [OR] 0.81 [95% confidence interval [CI] 0.74-0.88) and clopidogrel (OR 0.91 [95% CI 0.83-1.00]) than patients without DM. CONCLUSIONS: Despite sizeable increase in use of evidence-based secondary prevention pharmacotherapy after MI from 1997 to 2006, these drugs are not used in a substantial proportion of subjects and patients with DM received significantly less antiplatelet therapy than patients without DM. Increased focus on initiation of secondary prevention pharmacotherapy after MI is warranted, especially in patients with DM.

Psoriasis and risk of atrial fibrillation and ischaemic stroke: a Danish Nationwide Cohort Study.

AIMS: Psoriasis is a chronic inflammatory disease and inflammation contributes to the pathogenesis of atrial fibrillation (AF) and ischaemic stroke. We therefore investigated the risk of these endpoints in patients with psoriasis. METHODS AND RESULTS: Cohort study of the entire Danish population followed from 1997 to 2006 by individual-level-linkage of nationwide prospectively recorded registers. Multivariable Poisson's regression and sensitivity analyses were used to assess the psoriasis-related risk of AF and ischaemic stroke. A total of 36 765 patients with mild psoriasis and 2793 with severe psoriasis were compared with 4 478 926 individuals, i.e., the reference population. In patients with mild psoriasis, the adjusted rate ratios (RRs) for AF were 1.50 (1.21-1.86) and 1.16 (1.08-1.24) in patients aged <50 and ≥50 years, respectively. Patients with severe psoriasis had a higher risk of AF with RRs 2.98 (1.80-4.92) in patients aged <50 years and 1.29 (1.01-1.65) in patients aged ≥50 years. Patients with psoriasis also demonstrated a disease severity-dependent increased risk of ischaemic stroke, i.e. RRs 1.97 (1.66-2.34) and 2.80 (1.81-4.34) in patients aged <50 years with mild and severe psoriasis, and RRs 1.13 (1.04-1.21) and 1.34 (1.04-1.71) in patients aged ≥50 years with mild and severe psoriasis, respectively. A range of sensitivity analyses yielded comparable results. CONCLUSION: Psoriasis is associated with increased risk of AF and ischaemic stroke. These novel results add to a growing body of evidence, suggesting that patients with psoriasis could be considered at increased cardiovascular risk.

Comparable long-term mortality risk associated with individual sulfonylureas in diabetes patients with heart failure.

AIMS: The aim was to investigate the outcomes of individual sulfonylureas in patients with heart failure (HF). METHODS: All patients hospitalized with HF for the first time in 1997-2006, alive 30 days after discharge, and who received anti-diabetic monotherapy with glimepiride (n=1097), glibenclamide (glyburide) (n=1031), glipizide (n=557), gliclazide (n=251), or tolbutamide (n=541) were identified from nationwide registers. Risk of all-cause mortality was assessed by multivariable Cox regression models. RESULTS: Over the median observational time of 744 (Inter Quartile Range 268-1451) days, 2242 patients (64%) died. The analysis demonstrated similar hazard ratio (HR) for mortality for treatment with glimepiride (1.10 [95% confidence interval 0.92-1.33]), glibenclamide (1.12 [0.93-1.34]), glipizide (1.14 [0.93-1.38]), tolbutamide (1.04 [0.85-1.26]), and gliclazide (reference). Grouped according to pancreatic specificity, i.e., with tolbutamide, glipizide, and gliclazide as specific, and glibenclamide, and glimepiride as non-specific agents, no differential prognosis was found between the two groups (HR 1.04 [0.96-1.14], for non-specific, compared to pancreas specific agents). The prognosis was not dependent on prior acute myocardial infarction or ischemic heart disease (p for interactions >0.3). CONCLUSIONS: In current clinical practice, it is unlikely that there are considerable differences in risk of mortality associated with individual sulfonylureas in patients with heart failure.

Effects of oral glucose-lowering drugs on long term outcomes in patients with diabetes mellitus following myocardial infarction not treated with emergent percutaneous coronary intervention--a retrospective nationwide cohort study.

BACKGROUND: The optimum oral pharmacological treatment of diabetes mellitus to reduce cardiovascular disease and mortality following myocardial infarction has not been established. We therefore set out to investigate the association between individual oral glucose-lowering drugs and cardiovascular outcomes following myocardial infarction in patients with diabetes mellitus not treated with emergent percutaneous coronary intervention. MATERIALS AND METHODS: All patients aged 30 years or older receiving glucose-lowering drugs (GLDs) and admitted with myocardial infarction (MI) not treated with emergent percutaneous coronary intervention in Denmark during 1997-2006 were identified by individual-level linkage of nationwide registries of hospitalizations and drug dispensing from pharmacies. Multivariable Cox regression models adjusted for age, sex, calendar year, comorbidity, and concomitant pharmacotherapy were used to assess differences in the composite endpoint of non-fatal MI and cardiovascular mortality between individual GLDs, using metformin monotherapy as reference. RESULTS: The study comprised 9876 users of GLDs admitted with MI. The mean age was 72.3 years and 56.5% of patients were men. A total of 3649 received sulfonylureas and 711 received metformin at admission. The average length of follow-up was 2.2 (SD 2.6) years. A total of 6,171 patients experienced the composite study endpoint. The sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide were associated with increased risk of cardiovascular mortality and/or nonfatal MI with hazard ratios [HRs] of 1.31 (95% confidence interval [CI] 1.17-1.46), 1.19 (1.06-1.32), 1.25 (1.11-1.42), and 1.18 (1.03-1.34), respectively, compared with metformin. Gliclazide was the only sulfonylurea not associated with increased risk compared with metformin (HR 1.03 [0.88-1.22]). CONCLUSIONS: In patients with diabetes mellitus admitted with MI not treated with emergent percutaneous coronary intervention, monotherapy treatment with the sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide was associated with increased cardiovascular risk compared with metformin monotherapy.

Heart failure severity, as determined by loop diuretic dosages, predicts the risk of developing diabetes after myocardial infarction: a nationwide cohort study.

AIMS: Heart failure (HF) is associated with increased insulin resistance, but the consequences of HF for development of diabetes are not well studied. The aim of the present study was to investigate the relationship between HF severity and risk of developing diabetes in a nationwide cohort of patients with myocardial infarction (MI). METHODS AND RESULTS: Patients discharged from first-time MI during 1997-2006 and not previously treated with glucose-lowering medications (GLM) or loop diuretics were identified from Danish nationwide registers. Heart failure severity was determined by loop diuretic dosage after discharge. Patients were followed until first claimed prescription of GLM, death, or until the end of 2006. The cohort comprised 50 874 patients. A total of 3006 (6%) had mild (loop-diuretic dosage≤40 mg/day), 5383 (11%) moderate (>40-120 mg/day), and 1127 (2%) severe (>120 mg/day) HF. During follow-up, 2531 (5%) patients developed diabetes. Increasing HF severity was associated with increased risk of diabetes, but the use of renin-angiotensin system inhibitors (RASi) attenuated the risk (P-value for interaction between the HF group and RASi<0.05). Compared with no HF, the adjusted hazard ratios (95% confidence interval) for the development of diabetes were 1.34 (1.11-1.63), 1.63 (1.40-1.90), and 1.68 (1.25-2.25) for mild, moderate, and severe HF with RASi treatment; and 1.45 (1.13-1.88), 1.90 (1.56-2.33), and 3.02 (2.01-4.54) for mild, moderate, and severe HF without RASi treatment. CONCLUSION: Heart failure predicts the development of diabetes in a severity-dependent manner among patients with MI. Focus on increased predisposition to diabetes is warranted and needs further investigations.

Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study.

BACKGROUND: Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel. OBJECTIVE: 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. DESIGN: A nationwide cohort study based on linked administrative registry data. SETTING: All hospitals in Denmark. PATIENTS: All patients discharged after first-time myocardial infarction from 2000 to 2006. MEASUREMENTS: 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. RESULTS: 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). LIMITATIONS: Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible. CONCLUSION: 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.