Structured appraisal of studies quantifying the risk for idiopathic pulmonary embolus in adults with schizophrenia taking antipsychotic drugs
| Walker 1997 (cohort study of national registry)6 |
Parkin 2003 (case-control study)5 |
Zornberg 2000 (case-control study)7 |
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|---|---|---|---|
| Are the results valid? | |||
| Were the patients and controls similar? | Yes. Internal control (current v past users) | Not adequately reported. Analysis adjusted for oestrogen exposure. Controls were randomly selected from age and sex matched cohort | No. Controls had higher rates of hypertension, smoking, and current oral contraceptive use |
| Were outcomes and exposures measured in the same way? | Yes. Outcome of fatal pulmonary embolus determined by review of death certificates. | Yes. Outcome of fatal pulmonary embolus determined by necropsy in most patients | Yes. Extracted from UK general practice research database. Outcome of venous thromboembolism requiring hospitalisation for anticoagulation determined by one of several objective tests |
| Was follow-up long enough and complete? | Mean days of observation was over two months in both groups of interest; 92% had usable death certificates | At least 1 month of exposure, maximum duration of exposure of 3 months | At least 1 month of exposure and mean duration of follow-up of 6.8 years |
| Does the association satisfy simple rules for causation: | |||
| Temporal relationship correct? | Yes | Yes | Yes |
| Dose-response? | No data | No data | No |
| “Dechallenge-rechallenge”? | No data | No data | No data |
| Biological plausibility? | Increase in weight and sedation from clozapine might increase risk for pulmonary embolus | None proposed | None proposed |
| What are the results? | |||
| How strong is the association between exposure and outcome (risk ratios or odds ratios)? | Standardised mortality risk ratio for current versus past clozapine users 5.25 (based on 18 v 1 deaths due to pulmonary embolus) | Adjusted odds ratios for current versus no exposure to antipsychotics | Adjusted odds ratios for current versus no exposure to first generation antipsychotics |
| Lower potency: 20.8 | Lower potency: 24.1 | ||
| Any (first generation) antipsychotic: 13.3 | Higher potency: 3.3 | ||
| How precise is the estimate of risk (95% confidence intervals)? | Not reported | Lower potency: 1.7 to 259.0 |
Lower potency: 3.3 to 172.7 |
| Any antipsychotic: 2.3 to 76.3 | Higher potency: 0.8 to 13.2 | ||
| How relevant are the results? | |||
| Are the results applicable to this patient? | Yes. He would have met entry criteria for this study | Yes. Cases and controls had no known risk factors for venous thromboembolism | Yes. Cases and controls had no known risk factors for venous thromboembolism |
| What is the magnitude of risk to this patient? | Given lack of confidence intervals, cannot estimate maximum risk for clozapine | Study suggests lower risk for high potency typical antipsychotics | Study suggests lower risk for high potency typical antipsychotics |
| Patient’s preferences? Alternatives? | See text | ||