Long-Term Follow-Up After Acute Myocardial Infarction According to Beta-Blocker Dose.

OBJECTIVE: Our purpose was to examine the association between beta-blocker dose and mortality following acute myocardial infarction. METHODS: This nationwide cohort study enrolled all patients admitted for first-time acute myocardial infarction in Denmark between July 1, 2004 and December 31, 2014, using the Danish National Patient Registry. Patients alive 15 days after admission were followed until death, emigration, or December 31, 2014. Patients were categorized according to daily beta-blocker consumption (0%, >0%-12.5%, >12.5%-25%, >25%-50%, >50%-100%, or >100% of the currently recommended target dose) based on prescriptions registered in the Danish National Database of Reimbursed Prescriptions. Doses were continuously updated during follow-up. Mortality rate ratios (MRRs) were computed and adjusted for confounders using Cox proportional hazard regression. RESULTS: Among 65,125 patients followed, any beta-blocker dose was associated with significant mortality reduction compared with no treatment (adjusted MRR ≤ 0.92 [95% confidence interval {CI}: 0.86-0.98]). The largest reduction was observed within the first year for beta-blocker doses >25%-50% (adjusted MRR = 0.55 [95% CI: 0.50-0.60]). After 1 year, doses >50%-100% were associated with the largest mortality reduction (adjusted MRR = 0.58 [95% CI: 0.50-0.67]), but it did not differ significantly from that associated with doses >25%-50% (adjusted MRR = 0.68 [95% CI: 0.61-0.77]). CONCLUSIONS: Any beta-blocker dose was associated with significant mortality reduction following acute myocardial infarction compared with no treatment. Doses >25%-50% of the currently recommended target dose were associated with maximal mortality reduction within the first year after acute myocardial infarction, suggesting that higher doses are unnecessary.

Significant regional variation in use of implantable cardioverter-defibrillators in Denmark.

AIMS: Implantable cardioverter-defibrillator (ICD) treatment prevents sudden cardiac death in high-risk patients. This study examined geographical variation in ICD implantation rates in Denmark and potential causes of variation. METHODS AND RESULTS: We obtained numbers of ICD implantations in the 5 Danish regions and 98 municipalities during 2007-13 from the Danish Pacemaker and ICD Registry. Standardized implantation rates (SIRs) were computed as ICD implantations per 1 000 000 person-years, and age- and gender-standardized to the Danish population. We examined associations of the municipal SIR with mean age and Charlson Comorbidity Index score of ICD recipients, percentage of implantations with primary prophylactic indication, and distance from patient residency to ICD implanting centre. Based on 7192 ICD implantations, the nationwide SIR was 186 [95% confidence interval (CI) 182-190], ranging from 170 (95% CI 158-183) in the North Denmark Region to 206 (95% CI 195-218) in the Region of Zealand. Municipalities with higher patient comorbidity scores, higher percentages of implantations with primary prophylactic indication, and shorter distances to ICD implanting centres, had higher SIRs [differences between SIRs of municipalities in highest and lowest quartiles 22 (95% CI 10-34), 45 (95% CI 33-58), and 35 (95% CI 24-47), respectively]. Regional differences in SIRs decreased over time and had become insignificant during 2011-13. CONCLUSION: Implantable cardioverter-defibrillator implantation rates in Denmark varied significantly between regions but variation decreased during 2007-13. Geographical variation was associated with differences in patient comorbidity score, variation in use of primary prophylactic ICD treatment, and distance to ICD implanting centre.

Venous thromboembolism in patients with implantable cardioverter-defibrillators.

AIMS: To examine the incidence of venous thromboembolism (VTE) and its risk factors among patients with implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS: All first-time ICD recipients in Denmark during 2000-12 were identified from medical databases. Incident VTEs were ascertained, overall and according to gender, age, Charlson Comorbidity Index score (no, moderate, or severe comorbidity), prior pacemaker or cardiac resynchronization therapy (CRT-D) implantation, and ICD type (single-chamber, dual-chamber, or CRT-D). We computed the risk of VTE within 3 months and 5 years of implantation, taking death into account as a competing risk. We used Cox proportional hazards regression to compute hazard ratios as estimates of incidence rate ratios (IRRs). Among 8132 ICD recipients, 136 VTEs were diagnosed during up to 13 years of follow-up (median = 3.0 years). The VTE incidence rate was thus 4.5 per 1000 person-years [95% confidence interval (CI): 3.7-5.2]. Venous thromboembolism risk was 0.3% (95% CIs ranging from 0.1 to 0.7%) within 3 months following ICD implantation regardless of comorbidity level. Within 5 years following implantation it was 1.4% (95% CI: 0.8-2.3%), 1.3% (1.0-1.8%), and 3.2% (95% CI: 2.4-4.1%) for patients with no, moderate, and severe comorbidity, respectively. Overall, severe comorbidity conferred a 2.7-fold higher incidence rate ratio than no comorbidity (95% CI: 1.6-4.6). Incidence rate ratios did not differ by gender, age, or ICD type. CONCLUSION: Three-month risk of VTE following ICD implantation was 0.3% regardless of comorbidity level. Five-year risk of VTE following ICD implantation was 1.9% and more than twice as high for patients with severe comorbidity as for patients without comorbidity.

Beta-Blocker Therapy Early After Myocardial Infarction: A Comparison Between Medication at Hospital Discharge and Subsequent Pharmacy-Dispensed Medication.

BACKGROUND: Beta-blocker (BB) therapy after myocardial infarction (MI) reduces all-cause mortality. OBJECTIVE: The aim of this study was to investigate BB dosing patterns and compliance following MI. METHODS: Using medical patient files and nationwide databases, we identified 100 patients who were discharged following MI in 2012 from Aarhus University Hospital, Denmark, and subsequently redeemed one or more BB prescriptions within 6 months. We obtained information about all BB medication prescribed at discharge and all BB prescriptions redeemed until 31 December 2013. Daily BB doses were computed as percentages of the target doses used in clinical trials documenting the efficacy of BBs after MI. Four dose groups were defined: ≤12.5, >12.5-25, >25-50, and >50 % of target dose. The proportion of patients in each dose group was ascertained at and following discharge, as was the proportion that changed dose group following discharge. RESULTS: The median study period was 400 days (interquartile range [IQR] 318-486 days). At discharge, 8 % of daily doses were >50 % of target dose while 80 % were ≤25 % of target dose. At first prescription redemption, 71.7 % of patients moved to a higher dose group (median dose change = 33.4 % [IQR 2.0-115.1]). Still, comparing final daily doses to discharge doses, 40.2 % did not change dose group (median dose change -5.7 % [IQR -18.0 to 4.2]). Only 31.5 % reached a final daily dose >50 % of target dose. CONCLUSIONS: Target dose BB treatment was infrequently achieved at discharge following MI. Despite dose up-titration early after discharge, most patients did not receive target dose BB treatment approximately 1 year following MI.

Thirteen-year nationwide trends in use of implantable cardioverter-defibrillators and subsequent long-term survival.

BACKGROUND: Long-term trends in use of implantable cardioverter-defibrillators (ICDs) and outcomes are rare. OBJECTIVE: We examined 13-year nationwide trends in ICD implantation and survival rates in Denmark. METHODS: Using medical databases, we identified all first time ICD recipients in Denmark during 2000-2012 (N = 8460) and ascertained all-cause mortality. We computed standardized annual implantation rates and mortality rate ratios according to age, sex, comorbidity level, indication, and device type. RESULTS: The standardized annual implantation rate increased from 42 per million persons in 2000 to 213 per million persons in 2012 (from 34 to 174 for men and from 8 to 39 for women). The increase was driven by secondary prophylactic ICDs until 2006 and primary prophylactic ICDs thereafter. The increase occurred particularly in older patients and those with a high level of comorbidity. Independent of indication, 76% of all patients with ICD were alive after 5 years. Men had a higher mortality rate compared with women (mortality rate ratio 1.28; 95% confidence interval 1.10-1.49). Compared with low comorbidity level, moderate, severe, and very severe comorbidity levels were associated with 1.6-, 2.5-, and 4.9-fold increased mortality rates, respectively. The most influential individual comorbidities were heart failure, diabetes, liver disease, and renal disease. CONCLUSION: The annual implantation rate of ICDs increased 5-fold in Denmark between 2000 and 2012. The rate increase occurred for both men and women, but particularly in the elderly and patients with severe comorbidity. Five-year survival probability was high, but severe comorbidity and male sex were associated with shorter survival.

Implantable cardioverter-defibrillators and subsequent cancer risk: a nationwide population-based cohort study.

AIMS: Despite increasing use of implantable cardioverter-defibrillators (ICDs) and reports linking selected bio-implants with cancer, the cancer risk associated with implanted ICDs remains unknown. The objective of our study was to examine cancer risk among ICD recipients. METHODS AND RESULTS: We conducted a population-based cohort study using medical registries covering the entire Danish population. We identified all first-time ICD recipients during the period of 2000-11 and determined their subsequent cancer incidence. Standardized incidence ratios (SIRs) were computed by comparing observed cancer incidence in the ICD cohort with expected cancer incidence based on national incidence rates according to age, sex, and year of diagnosis. A total of 6723 ICD recipients were followed for up to 12 years (median 2.8 years) and contributed a total of 23 254 person-years of follow-up. Compared with the general population, ICD recipients had a slightly elevated overall risk of cancer [SIR = 1.1 (95% confidence interval (CI): 1.0-1.2)]. This was driven by the cancer risk among patients with ischaemic heart disease (IHD) [SIR = 1.1 (95% CI: 1.0-1.3)], which, as expected, was particularly elevated for tobacco-related cancers [SIR = 1.4 (95% CI: 1.2-1.6)]. Importantly, ICD recipients without IHD were not at increased cancer risk [SIR = 1.0 (95% CI: 0.8-1.3)]. CONCLUSION: This nationwide population-based cohort study with up to 12-year follow-up did not indicate a causal relation between ICD implantation and cancer. However, more follow-up data are needed to entirely rule out risks for individual cancer types.

A comparison of platelet function tests and thromboxane metabolites to evaluate aspirin response in healthy individuals and patients with coronary artery disease.

Individualised antiplatelet therapy and platelet function testing have attracted considerable clinical interest, but several aspects of test performance have not been thoroughly evaluated. We investigated repeatability and concordance of light transmission aggregometry (LTA) induced with arachidonic acid (AA) 1.0 mM, PFA-100 induced with collagen/epinephrine, multiple electrode aggregometry (MEA) induced with AA 0.5 or 0.75 mM and VerifyNow Aspirin. Patients with stable coronary artery disease (n=43) and healthy individuals (n=21) were included. All tests were performed in duplicate at baseline in healthy individuals and in duplicate for four days in all study participants during aspirin treatment. Serum and urinary thromboxane metabolites were measured several times to evaluate cyclooxygenase-1 inhibition by aspirin. MEA was most sensitive for aspirin as treatment induced a 12-fold difference in AA-induced platelet aggregation. Coefficients of variation for duplicate measurements at baseline (0.4-12%), during aspirin treatment (3-46%) and for day-to-day variability (3-37%) differed markedly between tests and were lowest for VerifyNow. The prevalence of aspirin low-responsiveness also differed between tests (0-9%) and the agreement was low: kappa

Monitoring aspirin therapy with the Platelet Function Analyzer-100.

OBJECTIVE: Low platelet response to aspirin has been reported to be associated with a high incidence of vascular events. The reported prevalence of aspirin low-responsiveness varies, which may be explained by poor reproducibility of the methods used to evaluate aspirin response and low compliance. The Platelet Function Analyzer-100 (PFA-100) is a commonly used platelet function test. We aimed to assess the reproducibility of the PFA-100 and the agreement with optical platelet aggregometry (OPA) in healthy volunteers and in patients with coronary artery disease (CAD) treated with low-dose aspirin. MATERIAL AND METHODS: Twenty-one healthy volunteers and 43 patients with CAD took part in the study. During treatment with aspirin 75 mg daily, all participants had platelet function assessed in duplicate with the PFA-100 and OPA on 4 consecutive days. Additionally, platelet function was assessed before aspirin treatment in healthy subjects. Serum-thromboxane B(2) (S-TxB(2)) was measured to assess compliance. RESULTS: In healthy volunteers not receiving aspirin, duplicate measurements resulted in coefficients of variation (CV) of 7.9 % for the PFA-100 and 5.2 % for OPA. During aspirin treatment, CVs were significantly higher (healthy volunteers: PFA-100: 15.6 %, OPA: 19.2 %; patients: PFA-100: 26.6 %, OPA: 16.8 %). Two of the 64 participants were classified as aspirin low-responders with both methods, indicating poor agreement (Kappa coefficient 0.05). Compliance was excellent, as S-TxB(2) was completely inhibited in all participants. CONCLUSIONS: Aspirin treatment affects the reproducibility of both PFA-100 and OPA. This imprecision should be considered carefully if the methods are used for monitoring aspirin treatment. Additionally, these methods do not identify the same individuals as being aspirin low-responders.