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1.
PLoS One ; 8(1): e51460, 2013.
Article in English | MEDLINE | ID: mdl-23365635

ABSTRACT

A seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the Danish childhood immunization program (2+1 schedule) in October 2007, followed by PCV13 starting from April 2010. The nationwide incidence of IPD among children younger than 5 years nearly halved after the introduction of PCV7 in the program, mainly due to a decline in IPD caused by PCV7-serotypes. We report the results from a nationwide population-based cohort study of laboratory confirmed IPD cases in children younger than 5 years during October 1, 2007 to December 31, 2010 and describe the characteristics of children suspected to present with a vaccine failure. The period between April 19 and December 31, 2010 was considered a PCV7/PCV13 transitional period, where both vaccines were offered. We identified 45 episodes of IPD caused by a PCV7 serotype (23% of the total number) and 105 (55%) caused by one of the 6 additional serotypes in PCV13. Ten children had received at least one PCV7 dose before the onset of IPD caused by a PCV7 serotype. Seven children were considered to be incompletely vaccinated before IPD, but only three cases fulfilled the criteria of vaccine failure (caused by serotypes 14, 19F and 23F). One case of vaccine failure was observed in a severely immunosuppressed child following three PCV7 doses, and two cases were observed in immunocompetent children following two infant doses before they were eligible for their booster. None of the IPD cases caused by the additional PCV13 serotypes had been vaccinated by PCV13 and there were therefore no PCV13-vaccine failures in the first 8-months after PCV13 introduction in Denmark.


Subject(s)
Immunization Programs/statistics & numerical data , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/immunology , Streptococcus pneumoniae/immunology , Child, Preschool , Cohort Studies , Denmark/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Pneumococcal Infections/epidemiology , Pneumococcal Infections/immunology , Pneumococcal Infections/microbiology , Pneumococcal Vaccines/administration & dosage , Serotyping , Treatment Outcome , Vaccination , Vaccines, Conjugate
2.
Circ Cardiovasc Qual Outcomes ; 3(4): 395-405, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20530789

ABSTRACT

BACKGROUND: Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals. METHODS AND RESULTS: With the use of individual-level linkage of nationwide administrative registers, we identified a cohort of individuals without hospitalizations 5 years before first prescription claim of NSAIDs and without claimed drug prescriptions for selected concomitant medication 2 years previously. The risk of cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke associated with the use of NSAIDs was estimated by case-crossover and Cox proportional hazard analyses. The entire Danish population age 10 years or more consisted of 4,614,807 individuals on January 1, 1997, of which 2,663,706 (57.8%) claimed at least 1 prescription for NSAIDs during 1997 to 2005. Of these; 1,028,437 individuals were included in the study after applying selection criteria regarding comorbidity and concomitant pharmacotherapy. Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk. There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (odds ratio, 1.29; 95% confidence interval, 1.02 to 1.63), but naproxen was not associated with increased cardiovascular risk (odds ratio for cardiovascular death, 0.84; 95% confidence interval, 0.50 to 1.42). CONCLUSIONS: Individual NSAIDs have different degrees of cardiovascular safety, which must be considered when choosing appropriate treatment. In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals, whereas our results suggest that naproxen has a safer cardiovascular risk-profile.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Substance-Related Disorders/epidemiology , Substance-Related Disorders/etiology , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cardiovascular Diseases/mortality , Cardiovascular Diseases/physiopathology , Cause of Death , Cross-Over Studies , Denmark , Female , Humans , Male , Middle Aged , Risk Factors , Substance-Related Disorders/mortality , Substance-Related Disorders/physiopathology , Survival Analysis
3.
Eur Heart J ; 31(6): 684-90, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19933516

ABSTRACT

AIMS: To investigate if gender bias is present in today's setting of an early invasive strategy for patients with acute coronary syndrome in Denmark (population 5 million). METHODS AND RESULTS: We identified all patients admitted to Danish hospitals with acute coronary syndrome in 2005-07 (9561 women and 16 406 men). Cox proportional hazard models were used to estimate the gender differences in coronary angiography (CAG) rate and subsequent revascularization rate within 60 days of admission. Significantly less women received CAG (cumulative incidence 64% for women vs. 78% for men, P < 0.05), with a hazard ratio (HR) of 0.68 (95% CI 0.65-0.70, P < 0.0001) compared with men. The difference was narrowed after adjustment for age and comorbidity, but still highly significant (HR 0.82, 95% CI 0.80-0.85, P < 0.0001). Revascularization after CAG was less likely in women with an HR of 0.68 (95% CI 0.66-0.71, P < 0.0001) compared with men. More women (22%) than men (10%) (P < 0.0001) had no significant stenosis on their coronary angiogram. However, after adjustment for the number of significant stenoses, age, and comorbidity women were still less likely to be revascularized (HR 0.91, 95% CI 0.87-0.95, P < 0.0001). CONCLUSION: Women with ACS are approached in a much less aggressively invasive way and receive less interventional treatment than men even after adjusting for differences in comorbidity and number of significant stenoses.


Subject(s)
Acute Coronary Syndrome/therapy , Physical Examination/statistics & numerical data , Acute Coronary Syndrome/diagnosis , Aged , Bias , Coronary Angiography/statistics & numerical data , Denmark , Female , Hospitalization/statistics & numerical data , Humans , Male , Myocardial Revascularization/statistics & numerical data , Prospective Studies , Residence Characteristics , Sex Factors
4.
Arch Intern Med ; 169(2): 141-9, 2009 Jan 26.
Article in English | MEDLINE | ID: mdl-19171810

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Heart Failure/mortality , Myocardial Infarction/mortality , Aged , Aged, 80 and over , Female , Heart Failure/drug therapy , Humans , Male , Middle Aged , Myocardial Infarction/drug therapy , Risk Factors , Treatment Outcome
5.
Circulation ; 117(15): 1945-54, 2008 Apr 15.
Article in English | MEDLINE | ID: mdl-18378618

ABSTRACT

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 > or = 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 > or = 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.


Subject(s)
Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Myocardial Infarction/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/etiology , Comorbidity , Denmark/epidemiology , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Female , Forecasting , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/classification , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Male , Middle Aged , Myocardial Infarction/etiology , Proportional Hazards Models , Recurrence , Registries , Risk , Stroke/etiology , Stroke/mortality , Survival Analysis
6.
Pharmacoepidemiol Drug Saf ; 17(8): 822-33, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18383428

ABSTRACT

PURPOSE: To describe the nationwide pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) in the Danish population. METHODS: All Danish citizens aged 10 or above 1 January 1997 were included in the study. The national prescription registry was used to identify all claimed prescriptions for NSAIDs by the cohort until 2005. By individual-level-linkage of nationwide registries, information was acquired concerning hospitalizations, comorbidity, concomitant pharmacotherapy and socioeconomic factors. RESULTS: The population consisted of 4,614,807 individuals, of which 2,663,706 (57.8%) claimed at least one prescription for NSAID from 1997 to 2005. Ibuprofen and diclofenac were the most frequently used non-selective NSAIDs, whereas rofecoxib and celecoxib were the most frequently used selective cyclooxygenase-2 (COX-2) inhibitors. The usage was similar across all age groups. Female sex and increasing age was associated with increased use of NSAID. Factors predicting extensive NSAID use were: rheumatic disease (odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.69-1.90), gout agents (allopurinol) (OR = 2.54, CI: 2.44-2.64) and other pain medication (OR = 3.27, CI: 3.23-3.31). NSAIDs were most often prescribed for use for one distinct treatment interval and for a short period (overall inter-quartile range [IQR]: 9-66 days). High doses were used in a relatively large proportion of the population (8.9% for etodolac to 19.5% for celecoxib) and 54,373 (2.0%) claimed prescriptions for more than one NSAID at the same time. CONCLUSION: NSAIDs were commonly used in the Danish population. Since NSAIDs have been associated with increased cardiovascular risk, further research on the overall risk associated with these drugs on a national scale is needed.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Drug Utilization/trends , Adolescent , Adult , Aged , Aged, 80 and over , Child , Denmark , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Time Factors
7.
Med Care ; 46(1): 70-7, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18162858

ABSTRACT

OBJECTIVE: To examine temporal trends in hospital use of secondary preventive medicine after discharge for first acute myocardial infarction (AMI) in Denmark. DESIGN: Observational study from national administrative databases of 60,339 patients who survived a first AMI at 73 acute-care hospitals during 1995-2004. OUTCOME MEASURES: At least 1 prescription claim for angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, or statins within 90 days of discharge for AMI. FINDINGS: The odds ratios between hospitals in the highest and lowest deciles, adjusted for age, gender, period, income, comorbidity, concomitant, and prior pharmaceutical therapy, in 1995 were 8.5 [95% confidence interval (CI), 5.5-12.2] for beta-blockers, 3.0 (2.3-3.7) for ACE inhibitors, and 6.2 (4.1-8.8) for statins. By 2004, the hospital variation had decreased for beta-blockers (3.2; 2.3-4.0) and statins (4.2; 3.0-5.5) but had increased for ACE inhibitors (3.8; 2.7-4.9). All the changes over time were significant (P < 0.001). Geographical characteristics of the hospital explained 32% of the variation in use of beta-blockers in 2004 and 27% in 1995, 39% of the variation in use of ACE inhibitors in 2004 and 3% in 1995, and 29% of the variation in use of statins and 19% in 1995. CONCLUSIONS: Hospital use of secondary preventive medicine after discharge for AMI varied substantially. Hospital variation in use of beta-blockers and statins decreased with time whereas variation in use of ACE inhibitors increased. This may be attributed to gradually better agreement for the use of beta-blockers and statins and lesser agreement for the use of ACE inhibitors.


Subject(s)
Cardiovascular Agents/therapeutic use , Hospital Administration , Myocardial Infarction/drug therapy , Patient Discharge/statistics & numerical data , Preventive Health Services/statistics & numerical data , Adult , Aged , Aged, 80 and over , Continuity of Patient Care/statistics & numerical data , Drug Utilization , Female , Humans , Male , Middle Aged , Myocardial Infarction/mortality , Socioeconomic Factors , Time Factors
8.
J Epidemiol Community Health ; 61(12): 1091-7, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18000133

ABSTRACT

OBJECTIVE: To study the initiation of and long-term refill persistency with statins and beta-blockers after acute myocardial infarction (AMI) according to income and education. DESIGN AND SETTING: Linkage of individuals through national registers of hospitalisations, drug dispensation, income and education. PARTICIPANTS: 30 078 patients aged 30-74 years surviving first hospitalisation for AMI in Denmark between 1995 and 2001. MAIN OUTCOME MEASURES: Initiation of statin or beta-blocker treatment (out-patient claim of prescriptions within 6 months of discharge) and refill persistency (first break in treatment lasting at least 90 days, and re-initiation of treatment after a break). RESULTS: When simultaneously estimating the effect of income and education on initiation of treatment, the effect of education attenuated and a clear income gradient remained for both drugs. Among patients aged 30-64 years, high income (adjusted hazard ratio (HR) 1.27; 95% confidence interval (CI) 1.19-1.35) and medium income (HR 1.13; 95% CI 1.06-1.20) was associated with initiation of statin treatment compared with low income. The risk of break in statin treatment was lower for patients with high (HR 0.73; 95% CI 0.66-0.82) and medium (HR 0.82; 95% CI 0.74-0.92) income compared with low income, whereas there was a trend in the opposite direction concerning a break in beta-blocker treatment. There was no gradient in re-initiation of treatment. CONCLUSION: Patients with low compared with high income less frequently initiated preventive treatment post-AMI, had worse long-term persistency with statins, but tended to have better persistency with beta-blockers. Low income by itself seems not to be associated with poor long-term refill persistency post-AMI.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocardial Infarction/prevention & control , Patient Compliance , Adrenergic beta-Antagonists/economics , Adult , Aged , Confidence Intervals , Denmark , Drug Costs , Educational Status , Female , Health Surveys , Hospitalization , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/economics , Income , Male , Middle Aged , Myocardial Infarction/drug therapy , Proportional Hazards Models , State Medicine/organization & administration
9.
Cardiovasc Drugs Ther ; 21(6): 449-57, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17955357

ABSTRACT

BACKGROUND: Use of invasive revascularization [percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG)] after acute myocardial infarction (AMI) in Denmark increased between 1996 and 2004. We investigated how this affected socioeconomic differences in their use. MATERIALS AND METHODS: All patients aged 30-74 years in hospital for a first AMI in Denmark between 1996 and 2004 were included. Cox proportional hazard models were used to estimate the association between individual income (tertiles) and education (>12, 10-12 and <10 years) and time to revascularization within 6 months. Revascularization was stratified into CABG, acute PCI (within 2 days of admission) and non-acute PCI (after the third day). RESULTS: A total of 38,803 patients were included. In 1996-1998, 6.8% received CABG, 9.3% non-acute PCI and 2.4% acute PCI; in 2002-2004, these numbers were 11.8, 36.1 and 29.1%. CABG was more likely to be performed for patients with a high income [hazard ratio (HR), 1.18; 95% confidence interval (CI), 1.08-1.28] or a medium income (HR, 1.16; 95% CI, 1.07-1.25) than for those with a low income throughout the period. A similar income gradient was seen for non-acute PCI, but not for acute PCI, for which no gradient was seen. No educational gradient was found for CABG, and that for non-acute and acute PCI decreased during the period; by the end of the period, more patients with low than high education received acute PCI. CONCLUSION: In the universal health care system of Denmark, income differences in CABG and non-acute PCI persisted, whereas no such differences were seen for acute PCI.


Subject(s)
Angioplasty, Balloon, Coronary/statistics & numerical data , Coronary Artery Bypass/statistics & numerical data , Delivery of Health Care , Myocardial Infarction/therapy , Socioeconomic Factors , Adult , Aged , Denmark , Female , Humans , Male , Middle Aged
10.
Circulation ; 116(7): 737-44, 2007 Aug 14.
Article in English | MEDLINE | ID: mdl-17646585

ABSTRACT

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), beta-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 beta-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, beta-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.


Subject(s)
Cardiac Output, Low/drug therapy , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/therapeutic use , Adult , Angiotensin II Type 2 Receptor Blockers , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Cardiac Output, Low/mortality , Denmark , Drug Prescriptions/statistics & numerical data , Evidence-Based Medicine , Hospital Mortality , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Patient Compliance , Spironolactone/administration & dosage , Spironolactone/therapeutic use , Time Factors , Treatment Outcome
11.
JAMA ; 297(2): 177-86, 2007 Jan 10.
Article in English | MEDLINE | ID: mdl-17213401

ABSTRACT

CONTEXT: The extent to which drug adherence may affect survival remains unclear, in part because mortality differences may be attributable to "healthy adherer" behavioral attributes more so than to pharmacological benefits. OBJECTIVE: To explore the relationship between drug adherence and mortality in survivors of acute myocardial infarction (AMI). DESIGN, SETTING, AND PARTICIPANTS: Population-based, observational, longitudinal study of 31 455 elderly AMI survivors between 1999 and 2003 in Ontario. All patients filled a prescription for statins, beta-blockers, or calcium channel blockers, with the latter drug considered a control given the absence of clinical trial-proven survival benefits. MAIN OUTCOME MEASURES: Patient adherence was subdivided a priori into 3 categories--high (proportion of days covered, > or =80%), intermediate (proportion of days covered, 40%-79%), and low (proportion of days covered, <40%)--and compared with long-term mortality (median of 2.4 years of follow-up) using multivariable survival models (and propensity analyses) adjusted for sociodemographic factors, illness severity, comorbidities, and concomitant use of evidence-based therapies. RESULTS: Among statin users, compared with their high-adherence counterparts, the risk of mortality was greatest for low adherers (deaths in 261/1071 (24%) vs 2310/14,345 (16%); adjusted hazard ratio, 1.25; 95% confidence interval, 1.09-1.42; P = .001) and was intermediary for intermediate adherers (deaths in 472/2407 (20%); adjusted hazard ratio, 1.12; 95% confidence interval, 1.01-1.25; P = .03). A similar but less pronounced dose-response-type adherence-mortality association was observed for beta-blockers. Mortality was not associated with adherence to calcium channel blockers. Moreover, sensitivity analyses demonstrated no relationships between drug adherence and cancer-related admissions, outcomes for which biological plausibility do not exist. CONCLUSION: The long-term survival advantages associated with improved drug adherence after AMI appear to be class-specific, suggesting that adherence outcome benefits are mediated by drug effects and do not merely reflect an epiphenomenon of "healthy adherer" behavioral attributes.


Subject(s)
Myocardial Infarction/drug therapy , Patient Compliance , Survivors , Adrenergic beta-Antagonists/therapeutic use , Aged , Calcium Channel Blockers/therapeutic use , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Longitudinal Studies , Male , Survival Analysis
12.
Circulation ; 113(25): 2906-13, 2006 Jun 27.
Article in English | MEDLINE | ID: mdl-16785336

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cyclooxygenase 2 Inhibitors/adverse effects , Cyclooxygenase 2 Inhibitors/therapeutic use , Myocardial Infarction/drug therapy , Myocardial Infarction/mortality , Aged , Aged, 80 and over , Celecoxib , Confidence Intervals , Cross-Over Studies , Denmark , Diclofenac/adverse effects , Diclofenac/therapeutic use , Dose-Response Relationship, Drug , Female , Humans , Ibuprofen/adverse effects , Ibuprofen/therapeutic use , Lactones/adverse effects , Lactones/therapeutic use , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Patient Readmission , Proportional Hazards Models , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Recurrence , Registries , Retrospective Studies , Risk Factors , Sulfonamides/adverse effects , Sulfonamides/therapeutic use , Sulfones/adverse effects , Sulfones/therapeutic use
13.
J Epidemiol Community Health ; 60(4): 351-6, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16537354

ABSTRACT

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.


Subject(s)
Educational Status , Income , Myocardial Infarction/mortality , Acute Disease , Adult , Aged , Denmark/epidemiology , Female , Hospital Mortality , Humans , Male , Middle Aged , Proportional Hazards Models , Prospective Studies
14.
Eur Heart J ; 27(10): 1153-8, 2006 May.
Article in English | MEDLINE | ID: mdl-16399775

ABSTRACT

AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995 and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials, and dosages did not increase during the observation period. Patients who did not start treatment shortly after discharge had a low probability of starting treatment later. CONCLUSION: The main problem with underuse of recommended treatment after AMI is that treatment is not initiated at an appropriate dosage shortly after AMI. A focused effort in the immediate post-infarction period would appear to provide long-term benefit.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocardial Infarction/drug therapy , Patient Compliance , Aged , Denmark , Female , Humans , Male , Multivariate Analysis , Myocardial Infarction/mortality , Treatment Outcome
15.
Scand Cardiovasc J ; 39(1-2): 42-9, 2005 Apr.
Article in English | MEDLINE | ID: mdl-16097413

ABSTRACT

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 > or = 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 > 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.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Coronary Restenosis/drug therapy , Myocardial Infarction/drug therapy , Age Factors , Confidence Intervals , Coronary Angiography , Coronary Restenosis/diagnostic imaging , Coronary Restenosis/mortality , Denmark , Drug Utilization/trends , Female , Follow-Up Studies , Health Care Surveys , Humans , Incidence , Male , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/mortality , Odds Ratio , Practice Patterns, Physicians' , Probability , Registries , Sensitivity and Specificity , Severity of Illness Index , Sex Factors , Survival Rate
16.
Br J Clin Pharmacol ; 60(2): 150-8, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16042668

ABSTRACT

AIMS: To study outpatient statin use after first acute myocardial infarction (AMI) in Denmark between 1995 and 2002 and to determine the predictors of statin use. METHODS: This is a nationwide population-based study using administrative registries. Patients with first AMI between 1995 and 2002 older than 30 years of age and alive 6 months after discharge (n = 45 219) were identified through the National Patient Registry. The statins purchased by these patients within 6 months after discharge were determined using the Registry of Medicinal Product Statistics, a nationwide prescription database. RESULTS: Statin use following AMI increased from 13% in 1995 to 61% in 2002. In 2002, 81% of patients aged 30-64 years used statins. Older patients used fewer statins, but use increased more among patients aged 75-84 years: from 1.3% to 43%. Use in elderly patients did not differ according to gender in 2000-02, but young men used more than younger women. In 2000-02, patients with diabetes (odds ratio (OR): 0.84; 95% confidence interval (CI): 0.74-0.95) and with heart failure (OR: 0.70; 95% CI: 0.64-0.76) were undertreated; this trend was present throughout the period. CONCLUSIONS: In this nationwide study, younger patients after AMI had high statin use in 2002, but high-risk patients such as those with diabetes and heart failure were still being undertreated.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocardial Infarction/drug therapy , Adult , Age Distribution , Aged , Aged, 80 and over , Ambulatory Care/methods , Atorvastatin , Denmark/epidemiology , Female , Heptanoic Acids/therapeutic use , Humans , Male , Middle Aged , Myocardial Infarction/epidemiology , Population Surveillance/methods , Pravastatin/therapeutic use , Pyrroles/therapeutic use , Registries , Sex Distribution , Simvastatin/therapeutic use
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