Discontinuation of Infliximab Therapy in Patients with Crohn's Disease.

Infliximab Discontinuation in Patients with Crohn's DiseaseThis randomized controlled trial explores infliximab withdrawal in patients with Crohn's disease in clinical, biochemical, and endoscopic remission with long-term infliximab maintenance therapy. Time to relapse was significantly shorter among patients who discontinued infliximab than among those who continued therapy.

Medical treatment and COVID-19 related worries in patients with inflammatory bowel disease.

INTRODUCTION: The aim of this study was to explore changes in medical therapy and document the level of COVID-19-specific worries in patients with inflammatory bowel disease (IBD) during the COVID-19 epidemic in Denmark. METHODS: A cross-sectional survey including 619 IBD patients was conducted. Patients answered questionnaires regarding IBD, IBD medicine, sociodemographic information, mental health, and COVID-19-specific worries (response rate = 64.6%). RESULTS: In total, 14.3% of patients using IBD medication had paused or stopped their IBD treatment during the initial phase of the COVID-19 epidemic, the majority (61.4%) either due to remission or because of side-effects. Only five patients stated that COVID-19 contributed to their decision. The majority of patients (70.5%) expressed worries about an increased risk of infection with coronavirus-2 and worries that their IBD and/or IBD treatment might result in severe COVID-19. Women, patients taking immunomodulators and patients who considered their IBD to be severe were significantly more worried than the remaining population. Age, type of IBD, co-morbidity, level of education, work capacity and mental health were not associated with an increased level of COVID-19-specific worries. CONCLUSIONS: In this selected IBD population, medical IBD treatment was rarely stopped or paused during the initial phase of the COVID-19 epidemic even though 70% of the respondents expressed COVID-19-specific worries. These worries should, nevertheless, be addressed and the characteristics of the population who expressed concerns may be used in future targeted information to secure compliance. FUNDING: none. TRIAL REGISTRATION: not relevant.

Vitamin D deficiency in a European inflammatory bowel disease inception cohort: an Epi-IBD study.

BACKGROUND: Serum vitamin D level is commonly low in patients with inflammatory bowel disease (IBD). Although there is a growing body of evidence that links low vitamin D level to certain aspects of IBD such as disease activity and quality of life, data on its prevalence and how it varies across disease phenotype, smoking status and treatment groups are still missing. MATERIALS AND METHODS: Patients diagnosed with IBD between 2010 and 2011 were recruited. Demographic data and serum vitamin D levels were collected. Variance of vitamin D level was then assessed across different treatment groups, disease phenotype, disease activity and quality of life scores. RESULTS: A total of 238 (55.9% male) patients were included. Overall, 79% of the patients had either insufficient or deficient levels of vitamin D at diagnosis. Patients needing corticosteroid treatment at 1 year had significantly lower vitamin D levels at diagnosis (median 36.0 nmol/l) (P=0.035). Harvey-Bradshaw Index (P=0.0001) and Simple Clinical Colitis Activity Index scores (P=0.0001) were significantly lower in patients with higher vitamin D level. Serum vitamin D level correlated significantly with SIBQ score (P=0.0001) and with multiple components of SF12. Smokers at diagnosis had the lowest vitamin D levels (vitamin D: 34 nmol/l; P=0.053). CONCLUSION: This study demonstrates the high prevalence of low vitamin D levels in treatment-naive European IBD populations. Furthermore, it demonstrates the presence of low vitamin D levels in patients with IBD who smoke.

Occurrence of Anaemia in the First Year of Inflammatory Bowel Disease in a European Population-based Inception Cohort-An ECCO-EpiCom Study.

BACKGROUND AND AIMS: Anaemia is an important complication of inflammatory bowel disease [IBD]. The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis, in a European prospective population-based inception cohort. METHODS: Newly diagnosed IBD patients were included and followed prospectively for 1 year in 29 European and one Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization criteria. RESULTS: A total of 1871 patients (Crohn's disease [CD]: 686, 88%; ulcerative colitis [UC]: 1,021, 87%; IBD unclassified [IBDU] 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and, overall, 49% of CD and 39% of UC patients experienced at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed. CONCLUSIONS: Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting.

The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease.

AIM: The aims of The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease are to ensure that biological therapy and the clinical management of patients with inflammatory bowel disease (IBD) receiving biological treatment are in accordance with the national clinical guidelines and, second, the database allows register-based clinical epidemiological research. STUDY POPULATION: The study population comprises all Danish patients with IBD (both children and adults) with ulcerative colitis, Crohn's disease, and IBD unclassified who receive biological therapy. Patients will be enrolled consecutively when biological treatment is initiated. MAIN VARIABLES: The variables in the database are: diagnosis, time of diagnosis, disease manifestation, indication for biological therapy, previous biological and nonbiological therapy, date of visit, clinical indices, physician's global assessment, pregnancy and breastfeeding (women), height (children), weight, dosage (current biological agent), adverse events, surgery, endoscopic procedures, and radiology. DESCRIPTIVE DATA: Eleven clinical indicators have been selected to monitor the quality of biological treatment. For each indicator, a standard has been defined based on the available evidence. National results will be published in an annual report and local results on a quarterly basis. The indicators will be reported as department-specific proportions with 95% confidence intervals, and the national average will be provided for comparison. An estimated 1,200-1,300 new biological therapies are initiated each year in Danish patients with IBD. CONCLUSION: The database will be available for research during 2016. Data will be made available by The Danish Clinical Registries (www.rkkp.dk).

Placebo-Controlled Discontinuation of Long-Term Acid-Suppressant Therapy: A Randomised Trial in General Practice.

Objective. To investigate whether patients on long-term antisecretory medication need to continue treatment to control symptoms. Methods. A double-blinded randomised placebo-controlled trial in general practices in Denmark. Patients aged 18-90 who were treated with antisecretory drugs on a long-term basis were randomized to esomeprazole 40 mg or identical placebo. Outcome measures were time to discontinuation with trial medication due to failed symptom control analysed as survival data. The proportion of patients stopping trial medication during the one-year follow-up was estimated. Results. A total of 171 patients were included with a median prior duration of antisecretory treatment of four years (range: 0.5 to 14.6 years). 86 patients received esomeprazole 40 mg and 85 patients received placebo. At 12 months, statistically significantly more patients in the placebo group had discontinued (73% (62/85)) compared with the esomeprazole group (21% (18/86); p < 0.001). Conclusions. Long-term users of antisecretory drugs showed a preference for the active drug compared to placebo. However, 27% of patients continued on placebo throughout the study and did not need to reinstitute usual treatment. One in five patients treated with esomeprazole discontinued trial medication due to unsatisfactory symptom control. Discontinuation of antisecretory treatment should be considered in long-term users of antisecretory drugs. This trial is registered with Trial registration ClinicalTrials.gov ID: NCT00120315.

Costs and resource utilization for diagnosis and treatment during the initial year in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom Study.

BACKGROUND: No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe. METHODS: The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (€) using the Danish Health Costs Register. RESULTS: One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohn's disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was €5,408,174 (investigations: €2,042,990 [38%], surgery: €1,427,648 [26%], biologicals: €781,089 [14%], and standard treatment: €1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohn's disease: investigations €1803 (€2160) (P = 0.44), surgery €11,489 (€13,973) (P = 0.14), standard treatment €1027 (€824) (P = 0.51), and biologicals €7376 (€8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations €1189 ( €1518) (P < 0.01), surgery €18,414 ( €12,395) (P = 0.18), standard treatment €896 ( €798) (P < 0.05), and biologicals €5681 ( €72) (P = 0.51). CONCLUSIONS: In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.

Initial disease course and treatment in an inflammatory bowel disease inception cohort in Europe: the ECCO-EpiCom cohort.

BACKGROUND: The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort. METHODS: Patients were followed-up every third month during the first 12 (±3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu). RESULTS: In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn's disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe. DISCUSSION: In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.

Sex- and age-related differences in clinical outcome after primary percutaneous coronary intervention.

AIMS: To compare the outcome after primary percutaneous coronary intervention (PPCI) according to sex and age, including comparison of sex- and age-specific mortality of PPCI patients with that of the general population. METHODS AND RESULTS: This population-based follow-up study included 7,385 STEMI patients treated with PPCI and 42,965 matched general population controls. The primary outcome was the composite endpoint of mortality, reinfarction, and stroke at 30 days, one year, and two years. Women were older and had a more adverse baseline risk profile than men. The risks of the composite endpoint after 30 days, one year, and two years were 9.1%, 16.0%, and 20.0%, respectively, for women compared to 5.8%, 10.6%, and 14.0% for men (adjusted hazard ratio [HR] [30 days]=1.16 [0.95-1.41], adjusted HR [one year]=1.18 [1.02-1.37], and adjusted HR [two years]=1.14 [0.99-1.30]). The risk of an adverse outcome increased similarly among women and men with increasing age. When comparing patients and controls, we found a higher mortality among patients up to 90 days after PPCI. However, after 90 days, the mortality among the PPCI patients was comparable to the mortality in the general population in all sex and age groups. CONCLUSIONS: Clinical outcome after PPCI was comparable in men and women after controlling for possible confounding. After 90 days post-PPCI, the mortality of treated patients was comparable to the mortality of the general population, independent of sex and age.

Dimensions of socioeconomic status and clinical outcome after primary percutaneous coronary intervention.

BACKGROUND: The association between low socioeconomic status (SES) and high mortality from coronary heart disease is well-known. However, the role of SES in relation to the clinical outcome after primary percutaneous coronary intervention remains poorly understood. METHODS AND RESULTS: We studied 7385 patients treated with primary percutaneous coronary intervention. Participants were divided into high-SES and low-SES groups according to income, education, and employment status. The primary outcome was major adverse cardiac events (cardiac death, recurrent myocardial infarction, and target vessel revascularization) at maximum follow-up (mean, 3.7 years). Low-SES patients had more adverse baseline risk profiles than high-SES patients. The cumulative risk of major adverse cardiac events after maximum follow-up was higher among low-income patients and unemployed patients compared with their counterparts (income: hazard ratio, 1.68; 95% CI, 1.47-1.92; employment status: hazard ratio, 1.75; 95% CI, 1.46-2.10). After adjustment for patient characteristics, these differences were substantially attenuated (income: hazard ratio, 1.12; 95% CI, 0.93-1.33; employment status: hazard ratio, 1.27; 95% CI, 1.03-1.56). Further adjustment for admission findings, procedure-related data, and medical treatment during follow-up did not significantly affect the associations. With education as the SES indicator, no between-group differences were observed in the risk of the composite end point. CONCLUSIONS: Even in a tax-financed healthcare system, low-SES patients treated with primary percutaneous coronary intervention face a worse prognosis than high-SES patients. The poor outcome seems to be largely explained by differences in baseline patient characteristics. Employment status and income (but not education level) were associated with clinical outcomes.

Treatment of acute ulcerative colitis with infliximab, a retrospective study from three Danish hospitals.

BACKGROUND: In acute steroid-refractory ulcerative colitis, rescue therapy with infliximab has become a therapeutic option in patients facing colectomy. Data on efficacy and safety in this setting are sparse. METHODS: Patients with ulcerative colitis and acute and severe steroid-refractory disease, who were given infliximab as rescue therapy, were identified by a review of patients' records and databases of infliximab-treated patients. Data on patient background, concomitant medication, endoscopic and laboratory results, clinical activity and adverse events were collected. RESULTS: Fifty-six patients, all admitted because of high disease activity of short duration, and failing high-dose glucocorticoid treatment, received infliximab treatment and were followed up for a median of 538 days (range 2-1769). Colectomy was avoided in 61% of cases. No fatalities were observed. Concomitant medication at the end of follow-up indicated a low number of relapses in patients without colectomies. CONCLUSIONS: Our results show a lasting benefit of infliximab rescue therapy in 61% of patients with acute, steroid-refractory ulcerative colitis, a low incidence of late colectomies, and low frequency of steroid use in patients who avoided colectomy. High levels of C-reactive protein on admittance and at the first infliximab infusion were associated with colectomy. Our study adds to the growing experience of infliximab treatment of patients with acute, steroid-refractory ulcerative colitis.

Cyclooxygenase-2, multidrug resistance 1, and breast cancer resistance protein gene polymorphisms and inflammatory bowel disease in the Danish population.

OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) are characterized by an impaired mucosal defence to normal constituents of the intestinal flora and a dysregulated inflammatory response. The purpose of the study was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in these processes were associated with CD and UC. MATERIAL AND METHODS: Allele frequencies of the cyclooxygenase 2 (COX-2/PTGS2/PGHS2) G-765C and breast cancer resistance protein (BCRP/ABCG2) C421A as well as allele and haplotype frequencies of multidrug resistance 1 (MDR1, ABCB1) SNPs G2677T/A, C3435T and G-rs3789243-A (intron 3) were assessed in a Danish case-control study comprising 373 CD and 541 UC patients and 796 healthy controls. RESULTS: Carriers of the homozygous COX-2 and MDR1 intron 3 variant had a relatively high risk of CD, odds ratio (95% CI) (OR (95% CI))=2.86 ((1.34-5.88) p=0.006) and 1.39 ((0.99-1.92) p=0.054), respectively, and for UC of 2.63 ((1.33-5.26) p=0.005) and 1.28 ((0.96-1.51) p=0.093), respectively, assuming complete dominance. No association was found for BCRP or other MDR1 SNPs, or for selected MDR1 haplotypes. No effect-modification of smoking habit at the time of diagnosis was found. CONCLUSIONS: An effect of the COX-2 polymorphism on both CD and UC was shown which is compatible with the presence of a recessive allele in linkage equilibrium with the SNP marker in the COX-2 gene. The polymorphism located in intron 3 of the MDR1 gene showed a weak association with CD, and a marginally suggestive association with UC.

Mutations in CARD15 and smoking confer susceptibility to Crohn's disease in the Danish population.

OBJECTIVE: Three CAspase Recruitment Domain (CARD15) mutations have shown to predispose to Crohn's disease in Caucasian populations. The aim of this study was to investigate the mutation frequency in patients with inflammatory bowel disease and in healthy controls in Denmark. MATERIAL AND METHODS: Genotyping of the three common CARD15 mutations was carried out on 388 patients with Crohn's disease, 565 patients with ulcerative colitis and 796 healthy controls using real-time PCR. Allele and genotype frequencies in the three groups were compared. A possible additive effect of smoking on CARD15 mutations was also examined. RESULTS: Carrying at least one CARD15 mutation was significantly more common in patients with Crohn's disease compared with healthy controls (21% versus 10%; p <0.001). A gene-dosage effect was observed (ORadj.smoking 22.2; p <0.001 for carrying two CARD15 mutations versus ORadj.smoking 1.8; p=0.01 for carrying one CARD15 mutation). The 1007insC protein truncating mutation was the major contributing mutation. Ileal involvement was more common in Crohn's disease patients with CARD15 mutations as opposed to patients without CARD15 mutations (ORadj.smoking 3.6; p <0.001). Smoking was independently associated with Crohn's disease (OR 1.8; p <0.001), but no multiplicative effect of smoking on CARD15 genotypes was found. CONCLUSIONS: In the Danish population, CARD15 mutations were found to be associated with Crohn's disease, hence supporting the hypothesis of a genetic component contributing to the disease. Further research for other genes possibly involved in Crohn's disease may result in the use of genetic testing for diagnosis or treatment of Crohn's disease in the future.

Assessment of experimental pain from skin, muscle, and esophagus in patients with chronic pancreatitis.

OBJECTIVES: Comprehensive experimental methods are of major relevance assessing pain mechanisms in patients with chronic pain. Chronic pancreatitis is thought to involve the sensory response in other visceral organs and somatic tissue. We, therefore, aimed at exploring the pain mechanisms in chronic pancreatitis (CP) using a multimodal and multitissue stimulation approach. METHODS: Ten patients (mean age, 50 years) with CP and 13 healthy controls (mean age, 35 years) participated. None of the patients took analgesics regularly. All were exposed to multimodal (mechanical, thermal, and electrical) experimental pain in the skin, muscles, and esophagus. RESULTS: The patients were hyposensitive to mechanical stimulations of the skin (P = 0.001), but there were no differences in the pain to thermal and electrical stimulations. In the muscle and esophagus, no differences in pain thresholds were found. The difference between single and repeated stimulations reflecting the degree of central sensitization was 17% in controls and 36% in patients (P = 0.001). The referred pain area to electrical stimulation was 30.1 cm2 in the patients and 7.7 cm2 for the controls (P = 0.02). CONCLUSIONS: The findings suggest that the balance among central hyperexcitability, neuroplastic changes, and descending pain-modulating pathways may explain the pain response to experimental multimodal stimulations in CP. This will likely also reflect the clinical pain mechanisms and may have important impact in selection of treatment, where drugs with potential effects on these mechanisms should be used.

Differential effect of opioids in patients with chronic pancreatitis: an experimental pain study.

OBJECTIVE: Animal experiments and clinical observations have indicated a different working profile of oxycodone compared to morphine, and it has previously been shown that oxycodone attenuates visceral pain better than morphine. The objective of this study was to test the effects of oxycodone and morphine on experimental pain in patients with pain caused by chronic pancreatitis. MATERIAL AND METHODS: Ten patients took part in this blinded, cross-over study. The analgesic effects of morphine (30 mg, oral), oxycodone (15 mg, oral) and placebo were tested against multimodal (mechanical, thermal and electrical) experimental pain in the skin, muscles and oesophagus. Pain was assessed at baseline and 30, 60 and 90 min after drug administration. RESULTS: In the skin and muscles, oxycodone was more effective than placebo and morphine on mechanically (skin: F=12.4, p<0.001, muscle: F=11.0, p<0.001) and thermally (skin: F=8.5, p<0.001) evoked pain. In oesophageal heat pain, the effect of morphine was equal to that of placebo, while oxycodone attenuated pain better than both morphine and placebo (F=9.5, p<0.001). Both morphine and oxycodone were more effective in attenuating mechanical pain in the oesophagus than placebo (F=8.6, p<0.001). After electrical stimulation no differences were seen between the opioids and placebo in any tissue studied. CONCLUSIONS: Oxycodone was a stronger analgesic than morphine in several pain modalities in the skin, muscle and oesophagus.

Hypoalgesia to experimental visceral and somatic stimulation in painful chronic pancreatitis.

OBJECTIVES: To gain more information of the pain mechanisms in chronic pancreatitis we applied standardized experimental pain stimulation of the duodenum, oesophagus and the skin in 12 healthy controls and 13 patients with chronic pancreatitis and typical pain attacks. METHODS: Using endoscopy a guide wire was positioned into the horizontal part of the duodenum, and a probe with a distal balloon was introduced over the guide wire. Mechanical stimuli were given as tonic (38 ml/min) or phasic (increasing volume steps of 5 ml delivered for 60 s) distensions of the balloon. After stimulation of the duodenum, the distal oesophagus was stimulated with the same protocol. Finally, the skin was stimulated with 'single and repeated burst' electrical stimuli reflecting activation of peripheral and central pain mechanisms. RESULTS: The stimuli reliably evoked both painful and non-painful local and referred sensations. The patients had hyposensitivity to both tonic and phasic mechanical stimuli of the duodenum and the oesophagus (P=0.001). Hypoalgesia was also observed to single and repeated electrical skin stimuli in the patients, most evident for repeated stimuli (P=0.001). The evoked referred pain did not differ between the groups, but the patients used on average more words from the McGill Pain Questionnaire to describe the pain evoked in the duodenum (P=0.02). CONCLUSIONS: Generalized hypoalgesia to experimental visceral and somatic stimulations was found in chronic pancreatitis. The findings suggest that the activation and modulation of central mechanisms is fundamental in pancreatic pain, and future studies should address the effect of analgesics with central effects in the treatment of these patients.

Five-year cardiovascular and all-cause mortality, and myocardial infarction in all subjects referred for exercise testing in two Danish counties.

OBJECTIVE: To examine the association between exercise test results and the 5-year cardiovascular and all-cause mortality, and myocardial infarction, in patients referred for exercise testing because of known or suspected coronary heart disease. DESIGN: A study of all patients (N = 2763) who in 1996 had an exercise test in two Danish counties (900000 inhabitants). Data and follow-up were based on medical records and general administrative healthcare and population registries. RESULTS: Abnormal tests, compared with normal ones, were associated with an increased adjusted cardiovascular mortality ratio of 1.77 (95% confidence interval (CI): 1.19-2.63), all-cause mortality ratio of 1.46 (95% CI: 1.11-1.93), and myocardial infarction ratio of 1.71 (95% CI: 1.28-2.28). Inconclusive tests, compared with normal ones, were associated with an increased adjusted all-cause mortality ratio of 1.52 (95% CI: 1.05-2.20) and myocardial infarction ratio of 1.67 (95% CI: 1.12-2.56). A history of myocardial infarction increased the cardiovascular death ratio by 1.51 (95% CI: 1.05-2.16) and the myocardial infarction ratio by 2.39 (95% CI: 1.84-3.10). CONCLUSION: Over a 5-year period, the result of the bicycle exercise test was clearly associated with both mortality and risk of myocardial infarction. An inconclusive test may deserve special attention.

Prescription of anti-anginal drugs in relation to exercise tests and coronary angiography. A 1-year population-based study of two Danish counties.

BACKGROUND: The cardiac diagnostic examination activity in a population should ideally mirror age and gender characteristics of the prevalence of ischemic heart disease. In this study, the prescription of anti-anginal drugs in relation to morbidity and mortality brought on by ischemic heart disease, and in relation to exercise tests and coronary angiography, is analyzed. METHODS: The study population comprised two Danish counties with a total of 896,954 inhabitants. We obtained data on all prescriptions of nitrates, adrenergic beta-antagonists, and calcium channel blockers from regional pharmaceutical registers. Data on all patients who took an exercise test or underwent coronary angiography were derived from regional health authority registers. Data on ischemic heart mortality and on the incidence of myocardial infarction were gathered from the national register of causes of death and hospital registers. RESULTS: Only patients receiving nitrates had an age and gender profile matching that of those who died from ischemic heart disease or who suffered from myocardial infarction (correlation coefficients 0.95-0.99). Judging from the prescription of nitrates, relatively few elderly patients, especially women older than 60-69 years, were referred for a cardiac examination. CONCLUSIONS: The prescription of nitrates seems useful as a surrogate marker for ischemic heart disease. Elderly patients, especially women, seem to be treated with anti-anginal medication without any diagnostic evaluation.