Drug-induced heart failure

AbstractHeart failure is a clinical syndrome that is predominantly caused by cardiovascular disorders such as coronary heart disease and hypertension. However, several classes of drugs may induce heart failure in patients without concurrent cardiovascular disease or may precipitate the occurrence of heart failure in patients with preexisting left ventricular impairment. We reviewed the literature on drug-induced heart failure, using the MEDLINE database and lateral references. Successively, we discuss the potential role in the occurrence of heart failure of cytostatics, immunomodulating drugs, antidepressants, calcium channel blocking agents, nonsteroidal anti-inflammatory drugs, antiarrhythmics, beta-adrenoceptor blocking agents, anesthetics and some miscellaneous agents. Drug-induced heart failure may play a role in only a minority of the patients presenting with heart failure. Nevertheless, drug-induced heart failure should be regarded as a potentially preventable cause of heart failure, although sometimes other priorities do not offer therapeutic alternatives (e.g., anthracycline-induced cardiomyopathy). The awareness of clinicians of potential adverse effects on cardiac performance by several classes of drugs, particularly in patients with preexisting ventricular dysfunction, may contribute to timely diagnosis and prevention of drug-induced heart failure

Patients with an ApoE <i>ε</i>4 allele require lower doses of coumarin anticoagulants

Objective: Vitamin K is an essential cofactor for the synthesis of several blood coagulation factors. It has been suggested that the apolipoprotein E (ApoE) genotype has profound effects on vitamin K status. Therefore, we investigated whether this common genetic polymorphism influenced dose requirements and effects of coumarin anticoagulants. Methods: We did a cohort study in 1637 patients from an outpatient anticoagulation clinic treated with acenocoumarol or phenprocoumon. Results: To attain the same level of anticoagulation, patients with genotype ε4/ε4 and genotype ε3/ε4 required respectively 3.4 mg (95%CI: -6.0 to -0.9) and 0.8 mg (95%CI: -1.6 to 0.1) acenocoumarol per week less than patients with genotype ε3/ε3. Patients homozygous for the ε2 allele required 3.5 mg (95%CI: 0.1 to 6.9) acenocoumarol per week more than patients with genotype ε3/ε3. The acenocoumarol maintenance dose showed a gene dose effect of the ε4 allele, but not of the ε2 allele. No significant dose difference was observed for phenprocoumon, possibly because of low numbers. Conclusion: The ApoE genotype affects the dose requirements of acenocoumarol.</p

Patients with an ApoE <i>ε</i>4 allele require lower doses of coumarin anticoagulants

Objective: Vitamin K is an essential cofactor for the synthesis of several blood coagulation factors. It has been suggested that the apolipoprotein E (ApoE) genotype has profound effects on vitamin K status. Therefore, we investigated whether this common genetic polymorphism influenced dose requirements and effects of coumarin anticoagulants. Methods: We did a cohort study in 1637 patients from an outpatient anticoagulation clinic treated with acenocoumarol or phenprocoumon. Results: To attain the same level of anticoagulation, patients with genotype ε4/ε4 and genotype ε3/ε4 required respectively 3.4 mg (95%CI: -6.0 to -0.9) and 0.8 mg (95%CI: -1.6 to 0.1) acenocoumarol per week less than patients with genotype ε3/ε3. Patients homozygous for the ε2 allele required 3.5 mg (95%CI: 0.1 to 6.9) acenocoumarol per week more than patients with genotype ε3/ε3. The acenocoumarol maintenance dose showed a gene dose effect of the ε4 allele, but not of the ε2 allele. No significant dose difference was observed for phenprocoumon, possibly because of low numbers. Conclusion: The ApoE genotype affects the dose requirements of acenocoumarol.</p

Overanticoagulation associated with combined use of antibacterial drugs and acenocoumarol or phenprocoumon anticoagulants

Background: Several case reports associated combined use of coumarins and antibacterial drugs with overanticoagulation. Despite the fact that these drugs are frequently prescribed concurrently, there is little quantitative information on the risks of such complications. Objective: To study which antibacterial drugs are associated with overanticoagulation during therapy with coumarins. Design: Population-based cohort study in a sample of the Rotterdam Study. Subjects: All patients who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991 through December 31, 1998 and for whom INR data were available. Methods: Patients were followed until an INR ≥ 6.0, the end of their treatment, death or end of the study period. Proportional hazards regression analysis was used to estimate the risk of an INR ≥ 6.0 in relation to concomitant use of an oral anticoagulant and antibacterial drugs after adjustment for several potentially confounding factors such as age, gender, hepatic dysfunction, malignancies, and heart failure. Results: Of the 1124 patients in the cohort, 351 developed an INR ≥ 6.0. The incidence rate was 6.9 per 10,000 treatment days. Sulfamethoxazole combined with trimethoprim most strongly increased the risk of overanticoagulation with an adjusted relative risk of 20.1 (95% CI: 10.7-37.9). Stratification showed that the induction period of overanticoagulation varied between different antibacterial drugs. Conclusion: In this study among outpatients of an anticoagulation clinic using acenocoumarol or phenprocoumon, several antibacterial drugs strongly increased the risk of overanticoagulation. Awareness of these drug interactions and more frequent monitoring of INR values during the initial stages of antibacterial drug therapy are warranted to minimize the risk of bleeding complications.</p

Overanticoagulation associated with combined use of antibacterial drugs and acenocoumarol or phenprocoumon anticoagulants

Background: Several case reports associated combined use of coumarins and antibacterial drugs with overanticoagulation. Despite the fact that these drugs are frequently prescribed concurrently, there is little quantitative information on the risks of such complications. Objective: To study which antibacterial drugs are associated with overanticoagulation during therapy with coumarins. Design: Population-based cohort study in a sample of the Rotterdam Study. Subjects: All patients who were treated with acenocoumarol or phenprocoumon in the study period from April 1, 1991 through December 31, 1998 and for whom INR data were available. Methods: Patients were followed until an INR ≥ 6.0, the end of their treatment, death or end of the study period. Proportional hazards regression analysis was used to estimate the risk of an INR ≥ 6.0 in relation to concomitant use of an oral anticoagulant and antibacterial drugs after adjustment for several potentially confounding factors such as age, gender, hepatic dysfunction, malignancies, and heart failure. Results: Of the 1124 patients in the cohort, 351 developed an INR ≥ 6.0. The incidence rate was 6.9 per 10,000 treatment days. Sulfamethoxazole combined with trimethoprim most strongly increased the risk of overanticoagulation with an adjusted relative risk of 20.1 (95% CI: 10.7-37.9). Stratification showed that the induction period of overanticoagulation varied between different antibacterial drugs. Conclusion: In this study among outpatients of an anticoagulation clinic using acenocoumarol or phenprocoumon, several antibacterial drugs strongly increased the risk of overanticoagulation. Awareness of these drug interactions and more frequent monitoring of INR values during the initial stages of antibacterial drug therapy are warranted to minimize the risk of bleeding complications.</p

A population-based case-cohort study of drug-associated agranulocytosis

Background: 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. Methods: 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. Results: Discharge summaries were received of 753 admissions, of which 678 contained enough information for analysis. Of the 678,108 were classified as 'agranulocytosis probable' oras '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. Conclusions: The highest relative risks were found for thyroid inhibitors, sulfamethoxazole-trimethoprim, sulfasalazine, clomipramine, and dipyrone combined with analgesics

Thiazide Diuretics and the Risk for Hip Fracture

Background: Since most hip fractures are related to osteoporosis, treating accelerated bone loss can be an important strategy to prevent hip fractures. Thiazides have been associated with reduced age-related bone loss by decreasing urinary calcium excretion. Objective: To examine the association between dose and duration of thiazide diuretic use and the risk for hip fracture and to study the consequences of discontinuing use. Design: Prospective population-based cohort study. Setting: The Rotterdam Study. Participants: 7891 individuals 55 years of age and older. Measurements: Hip fractures were reported by the general practitioners and verified by trained research assistants. Details of all dispensed drugs were available on a day-to-day basis. Exposure to thiazides was divided into 7 mutually exclusive categories: never use, current use for 1 to 42 days, current use for 43 to 365 days, current use for more than 365 days, discontinuation of use since 1 to 60 days, discontinuation of use since 61 to 120 days, and discontinuation of use since more than 120 days. Results: 281 hip fractures occurred. Relative to nonuse, current use of thiazides for more than 365 days was statistically significantly associated with a lower risk for hip fracture (hazard ratio, 0.46 [95% CI, 0.21 to 0.96]). There was no clear dose dependency. This lower risk disappeared approximately 4 months after thiazide use was discontinued. Conclusions: Thiazide diuretics protect against hip fracture, but this protective effect disappears within 4 months after use is discontinued