Pernille Buch

Diabetes Patients Requiring Glucose-Lowering Therapy and Nondiabetics With a Prior Myocardial Infarction Carry the Same Cardiovascular Risk A Population Study of 3.3 Million People

Background— Previous studies reveal major differences in the estimated cardiovascular risk in diabetes mellitus, including uncertainty about the risk in young patients. Therefore, large studies of well-defined populations are needed. Methods and Results— All residents in Denmark ≥30 years of age were followed up for 5 years (1997 to 2002) by individual-level linkage of nationwide registers. Diabetes patients receiving glucose-lowering medications and nondiabetics with and without a prior myocardial infarction were compared. At baseline, 71 801 (2.2%) had diabetes mellitus and 79 575 (2.4%) had a prior myocardial infarction. Regardless of age, age-adjusted Cox proportional-hazard ratios for cardiovascular death were 2.42 (95% confidence interval [CI], 2.35 to 2.49) in men with diabetes mellitus without a prior myocardial infarction and 2.44 (95% CI, 2.39 to 2.49) in nondiabetic men with a prior myocardial infarction (P=0.60), with nondiabetics without a prior myocardial infarction as the reference. Results for women were 2.45 (95% CI, 2.38 to 2.51) and 2.62 (95% CI, 2.55 to 2.69) (P=0.001), respectively. For the composite of myocardial infarction, stroke, and cardiovascular death, the hazard ratios in men with diabetes only were 2.32 (95% CI, 2.27 to 2.38) and 2.48 (95% CI, 2.43 to 2.54) in those with a prior myocardial infarction only (P=0.001). Results for women were 2.48 (95% CI, 2.43 to 2.54) and 2.71 (95% CI, 2.65 to 2.78) (P=0.001), respectively. Risks were similar for both diabetes types. Analyses with adjustments for comorbidity, socioeconomic status, and prophylactic medical treatment showed similar results, and propensity score–based matched-pair analyses supported these findings. Conclusions— Patients requiring glucose-lowering therapy who were ≥30 years of age exhibited a cardiovascular risk comparable to nondiabetics with a prior myocardial infarction, regardless of sex and diabetes type. Therefore, requirement for glucose-lowering therapy should prompt intensive prophylactic treatment for cardiovascular diseases.

Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction.

Background— 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. Methods and Results— 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. Conclusions— 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.

Rising rates of hospital admissions for atrial fibrillation.

Background: Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality. We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospective population-based cohort study spanning 2 decades (the Copenhagen City Heart Study). Methods: The study included baseline data collected in 1981 through 1983 on 10,955 persons age 40 to 79 years and baseline data collected in 1991 through 1994 on 7212 persons age 40 to 79 years. We used hospital diagnosis data from the Danish National Hospital Discharge Register to determine the rate of first hospital admission for atrial fibrillation during 7 years following each of the 2 baseline data collecting periods. Changes in admission rates were analyzed using Cox proportional hazard models. Results: During the 2 7-year periods, 379 subjects were admitted with a hospital diagnosis of atrial fibrillation. The rate of hospital admissions for atrial fibrillation increased among both men and women from the first to the second period (relative risk = 1.6; 95% confidence interval = 1.3–1.9 [adjusted for age, sex, prior myocardial infarction, arterial hypertension, diabetes mellitus, electrocardiographic left ventricular hypertrophy, decreased lung function, smoking, height, and weight]). Conclusion: During the latest 10 to 20 years, there has been a 60% increase in hospital admissions for atrial fibrillation independent of changes in known risk factors. This increase could result from changes in admission threshold or coding practices, or it could reflect a genuine increase in the population incidence of atrial fibrillation.

Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure.

BACKGROUND Accumulating evidence indicates increased cardiovascular risk associated with nonsteroidal anti-inflammatory drug (NSAID) use, in particular in patients with established cardiovascular disease. We studied the risk of death and hospitalization because of acute myocardial infarction and heart failure (HF) associated with use of NSAIDs in an unselected cohort of patients with HF. METHODS We identified 107,092 patients surviving their first hospitalization because of HF between January 1, 1995, and December 31, 2004, and their subsequent use of NSAIDs from individual-level linkage of nationwide registries of hospitalization and drug dispensing by pharmacies in Denmark. Data analysis was performed using Cox proportional hazard models adjusted for age, sex, calendar year, comorbidity, medical treatment, and severity of disease, and propensity-based risk-stratified models and case-crossover models. RESULTS A total of 36,354 patients (33.9%) claimed at least 1 prescription of an NSAID after discharge; 60,974 (56.9%) died, and 8970 (8.4%) and 39,984 (37.5%) were hospitalized with myocardial infarction or HF, respectively. The hazard ratio (95% confidence interval) for death was 1.70 (1.58-1.82), 1.75 (1.63-1.88), 1.31 (1.25-1.37), 2.08 (1.95-2.21), 1.22 (1.07-1.39), and 1.28 (1.21-1.35) for rofecoxib, celecoxib, ibuprofen, diclofenac, naproxen, and other NSAIDs, respectively. Furthermore, there was a dose-dependent increase in risk of death and increased risk of hospitalization because of myocardial infarction and HF. Propensity-based risk-stratified analysis and case-crossover models yielded similar results. CONCLUSIONS NSAIDs are frequently used in patients with HF and are associated with increased risk of death and cardiovascular morbidity. Inasmuch as even commonly used NSAIDs exerted increased risk, the balance between risk and benefit requires careful consideration when any NSAID is given to patients with HF.

Persistent Use of Evidence-Based Pharmacotherapy in Heart Failure Is Associated With Improved Outcomes

Background— Undertreatment with recommended pharmacotherapy is a common problem in heart failure and may influence prognosis. We studied initiation and persistence of evidence-based pharmacotherapy in 107 092 patients discharged after first hospitalization for heart failure in Denmark from 1995 to 2004. Methods and Results— Prescriptions of dispensed medication and mortality were identified by an individual-level linkage of nationwide registers. Inclusion was irrespective of left ventricular function. Treatment with renin-angiotensin inhibitors (eg, angiotensin-converting enzyme inhibitors and angiotensin-2 receptor blockers), &bgr;-blockers, spironolactone, and statins was initiated in 43%, 27%, 19%, and 19% of patients, respectively. Patients who did not initiate treatment within 90 days of discharge had a low probability of later treatment initiation. Treatment dosages were in general only 50% of target dosages and were not increased during long-term treatment. Short breaks in therapy were common, but most patients reinitiated treatment. Five years after initiation of treatment, 79% patients were still on renin-angiotensin inhibitors, 65% on &bgr;-blockers, 56% on spironolactone, and 83% on statins. Notably, multiple drug treatment and increased severity of heart failure was associated with persistence of treatment. Nonpersistence with renin-angiotensin inhibitors, &bgr;-blockers, and statins was associated with increased mortality with hazard ratios for death of 1.37 (95% CI, 1.31 to 1.42), 1.25 (95% CI, 1.19 to 1.32), 1.88 (95% CI, 1.67 to 2.12), respectively. Conclusions— Persistence of treatment was high once medication was started, but treatment dosages were below recommended dosages. Increased severity of heart failure or increased number of concomitant medications did not worsen persistence, but nonpersistence identified a high-risk population of patients who required special attention. A focused effort on early treatment initiation, appropriate dosages, and persistence with the regimen is likely to provide long-term benefit.

Mortality after acute myocardial infarction according to income and education

Objective: To study how income and educational level influence mortality after acute myocardial infarction (AMI). Design and setting: Prospective analysis using individual level linkage of registries in Denmark. Participants: All patients 30–74 years old hospitalised for the first time with AMI in Denmark in 1995–2002. Main outcome measures: Relative risk (RR) of 30 day mortality and long term mortality (31 days until 31 December 2003) associated with income (adjusted for education) or educational level (adjusted for income) and further adjusted for sex, age, civil status, and comorbidity. Results: The study identified 21 391 patients 30–64 years old and 16 169 patients 65–74 years old. The 30 day mortality was 7.0% among patients 30–64 years old and 15.9% among those 65–74 years old. Among patients surviving the first 30 days, the long term mortality was 9.9% and 28.3%, respectively. The adjusted RR of 30 day mortality and long term mortality among younger patients with low compared with high income was 1.54 (95% confidence interval 1.36 to 1.79) and 1.65 (1.45 to 1.85), respectively. The RR of 30 day and long term mortality among younger patients with low compared with high education was 1.24 (1.03 to 1.50) and 1.33 (1.11 to 1.59), respectively. The RR of 30 day and long term mortality among older patients with low compared with high income was 1.27 (1.15 to 1.41) and 1.38 (1.27 to 1.50), respectively. Older high and low education patients did not differ in mortality. Conclusion: This study shows that both educational level and income substantially and independently affect mortality after AMI, indicating that each indicator has specific effects on mortality and that these indicators are not interchangeable.

Temporal decline in the prognostic impact of a recurrent acute myocardial infarction 1985 to 2002

Objective: To investigate trends in case-fatality and prognostic impact from recurrent acute myocardial infarction (re-AMI) during 1985–2002. Design: Retrospective cohort study using nationwide administrative data from Denmark. Settings: National registries on hospital admissions and causes of death were linked to identify patients with first AMI, re-AMI and subsequent prognosis. Patients: Patients ⩾30 years old with a discharge diagnosis of AMI during 1985–2002 were tracked for first hospital admission for re-AMI 1 year after discharge. Main outcome measures: One-year case-fatality. Results: 166 472 patients were identified with a first AMI; 14 123 developed re-AMI. One-year crude case-fatality from first AMI/re-AMI was 39% versus 43% in 1985–1989 and 25% versus 29% in 2000–2002, respectively. In 1985–89, 35 795 patients survived to discharge (71%); of these 2.5% experienced reinfarction within 30 days (early reinfarction) and an additional 9.0% reinfarction within days 31–365 (late re-AMI). Re-AMI carried a poor prognosis in 1985–1989 compared to no re-AMI with age- and sex-adjusted relative risk of 1-year case-fatality of 7.5 (95% CI: 6.9 to 8.5) from early re-AMI and 11.7 (95% CI: 11.0 to 12.4) from late re-AMI. In 2000–2002, 23 552 patients (86%) survived to discharge; 4.4% had early re-AMI and 6.6% late re-AMI. Adjusted relative risk of 1-year case-fatality had declined to 2.1 (95% CI: 1.9 to 2.5) from early re-AMI and 5.6 (95% CI: 5.1 to 6.2) from late re-AMI compared to patients without reinfarction. Conclusion: Prognosis after AMI has improved substantially during the latest two decades and extends to patients with re-AMI.

Nationwide trends in the prescription of beta-blockers and angiotensin-converting enzyme inhibitors after myocardial infarction in Denmark, 1995–2002

Objectives To study the use of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) in Denmark from 1995 to 2002. Design Information about patients with first AMI aged ≥30 years and the dispensing of beta-blockers and ACE inhibitors from pharmacies within 30 d from discharge was obtained from the National Patient Registry and the Danish Registry of Medicinal Product Statistics. Results Beta-blocker use increased from 38.1% of patients in 1995 to 67.9% in 2002 (OR=3.85, CI: 3.58–4.13). Women, elderly patients and patients taking loop-diuretics and antidiabetic drugs received beta-blockers less frequently, but patients taking loop-diuretics or antidiabetic drugs had the greatest increase. ACE inhibitor use increased from 24.5 to 35.5% (OR=1.86, CI: 1.72–2.01). Women, patients aged <60 years or ≥80 years and patients not taking loop-diuretics received ACE inhibitors less frequently, but patients not taking loop-diuretics had the greatest increase. Conclusions Beta-blocker use increased markedly post-AMI from 1995 to 2002, whereas ACE inhibitor use increased modestly. The results suggested undertreatment of women, elderly patients and people with diabetes.

Different prognostic impact of systolic function in patients with heart failure and/or acute myocardial infarction

To study the prognostic importance of left ventricular systolic function in patients with heart failure (HF) and acute myocardial infarction (AMI) with respect to the presence of prior heart failure and known ischemic heart disease.