A population-based case-cohort study of drug-associated agranulocytosis
ABSTRACT Agranulocytosis is a life-threatening disorder, often caused by drugs. Incidences or risks of drug-induced agranulocytosis are not well known, since it is rare.
To determine the risk of drug-associated agranulocytosis as a reason for admission to Dutch hospitals, we performed a population-based case-cohort study. Hospital discharge data came from the Dutch Centre for Health Care Information, Utrecht, which contains data on all general and university hospitals in the Netherlands. The reference cohort consisted of all persons in the catchment area of the Pharmaco Morbidity Record Linkage System (PHARMO RLS) in the Netherlands, composing a population of approximately 220 000 to 484 000 persons from 1987 through 1990. All admissions during that period with agranulocytosis or related diagnoses were included in the study (n = 923). The potential causes of agranulocytosis were assessed in all cases classified as probable or possible agranulocytosis.
Discharge summaries were received of 753 admissions, of which 678 contained enough information for analysis. Of the 678,108 were classified as "agranulocytosis probable" or as "agranulocytosis possible." In 75 of these 108 cases, agranulocytosis had been the reason for admission. Fifteen patients had used methimazole within 10 days before developing agranulocytosis; 2, carbimazole; 9, sulfasalazine; 8, sulfamethoxazole-trimethoprim; 4, clomipramine hydrochloride; and 2, dipyrone with analgesics, yielding adjusted relative risks of agranulocytosis of 114.8 (for thyroid inhibitors combined) (95% confidence interval [CI], 60.5-218.6), 74.6 (95% CI, 36.3-167.8), 25.1 (95% CI, 11.2-55.0),20.0 (95% CI, 6.1-57.6), and 26.4 (95% CI, 4.4-11.1), respectively.
The highest relative risks were found for thyroid inhibitors, sulfamethoxazole-trimethoprim, sulfasalazine, clomipramine, and dipyrone combined with analgesics.
Article: Agranulocytosis and pyrazolone.The Lancet 07/1984; 1(8392):1471. DOI:10.1016/S0140-6736(84)91966-4 · 39.21 Impact Factor
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ABSTRACT: The International Agranulocytosis and Aplastic Anemia Study (IAAAS) of analgesic-induced risks of blood dyscrasias represents the current "state of the art" in case-control pharmacoepidemiology. We present a conceptual framework for examining the goal, methods, and analysis of an epidemiologic study of drug risks and review the IAAAS within this framework. In our view, the new risk estimates reported by the IAAAS are not inherently more accurate than existing ones, nor have they been measured in clinically and sociodemographically relevant groups of patients over the anticipated course of therapy. Thus, the reported risks cannot be used to guide clinical or regulatory decisions concerning available treatment options for such patients. Furthermore, we believe that the IAAAS methods for selection of cases and controls, ascertainment of exposure, and data analysis may well have led to invalid estimates even for those risks that are reported. We hope that closer attention to the conceptual framework we suggest and the methodologic issues we raise will enable future case-control pharmacoepidemiologic studies to provide more useful and accurate answers to questions concerning the adverse effects of drugs.Journal of Chronic Diseases 02/1987; 40(12):1073-85. DOI:10.1016/0021-9681(87)90073-7
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ABSTRACT: The risks of agranulocytosis and aplastic anemia in relation to the use of cardiovascular drugs were estimated in a population-based case-control study conducted in Israel and Europe (total population, 23 million). Cardiovascular drug use in the week before onset of illness was compared between 270 patients hospitalized with agranulocytosis and 1870 hospitalized control subjects. Propranolol (relative risk, 2.5), dipyridamole (3.8), digoxin (2.5), and acetyldigoxin (9.9) were significantly associated with agranulocytosis. The excess risks attributable to these drugs ranged from one to three cases per 10 million persons exposed for up to 1 week. Increased risks were also observed for cinepazide (used by six cases and no control subjects), procainamide (7, 1), and aprindine (5, 1); based on crude relative risk estimates, the excess risks for the latter two drugs were approximately three per million persons exposed for up to 1 week. The use of cardiovascular drugs in a 5-month period ending 1 month before hospital admission was compared between 152 patients with aplastic anemia and 2180 control subjects. Furosemide was the only significantly associated drug (relative risk, 3.1); the excess risk attributable to any exposure in a 5-month interval was 1.7 per million.Clinical Pharmacology & Therapeutics 04/1991; 49(3):330-41. DOI:10.1038/clpt.1991.37 · 7.39 Impact Factor