J Rawles1, J Light. 1. Medicines Assessment Research Unit, University of Aberdeen, Foresterhill.
Abstract
STUDY OBJECTIVES: (1) To measure the quality of life and the loss of quality adjusted days (QADS) after suspected acute myocardial infarction in patients who received thrombolytic treatment either at home or in hospital. (2) To compare the loss of QADS as a trial endpoint with the conventional endpoints of mortality and Q-wave infarction. DESIGN: Randomised double blind parallel group trial of anistreplase (30 U given intravenously) and placebo given either at home or in hospital. SETTING:Rural practices in Grampian admitting patients to teaching hospitals in Aberdeen. PATIENTS: A total of 311 patients with suspected acute myocardial infarction and no contraindications to thrombolytic treatment seen at home within four hours of the onset of symptoms. MEASUREMENTS AND MAIN RESULTS:Loss of quality adjusted days (QADS) in the first 100 days after suspected myocardial infarction (365 QADS = 1 QALY) was the main outcome measure. Compared with later administration in hospital, anistreplase at home resulted in a relative reduction of mortality of 49% (95% confidence interval 3.95%, 2p = 0.04), and a relative reduction of 26% in the proportion of survivors with infarction who had Q-waves (95% CI 7.44%, 2p = 0.007). During the 100 day follow up, the median loss of QADS was 25 for all patients. This loss was significantly greater in those who died than in survivors (65 v 18, 2p < 0.001), and in survivors with infarction than in survivors without infarction (26 v 13, 2p < 0.01). However, there was no significant difference in loss of QADS in those with infarction with or without Q-waves (29 v 21, NS), and the median loss of QADS was not significantly different in those who had thrombolytic treatment at home or in hospital (median difference 0, 95% CI -5, +4 QADS). CONCLUSIONS:Loss of QADS had two serious limitations as an outcome measure: it was less sensitive than mortality and it failed to reflect physiological benefit. Palliative treatment with no physiological effect would have resulted in a greater gain in QADS (or QALYs) than did early thrombolytic treatment. Extreme caution is required in accepting a gain in QALYs as a valid outcome measure for health care.
RCT Entities:
STUDY OBJECTIVES: (1) To measure the quality of life and the loss of quality adjusted days (QADS) after suspected acute myocardial infarction in patients who received thrombolytic treatment either at home or in hospital. (2) To compare the loss of QADS as a trial endpoint with the conventional endpoints of mortality and Q-wave infarction. DESIGN: Randomised double blind parallel group trial of anistreplase (30 U given intravenously) and placebo given either at home or in hospital. SETTING: Rural practices in Grampian admitting patients to teaching hospitals in Aberdeen. PATIENTS: A total of 311 patients with suspected acute myocardial infarction and no contraindications to thrombolytic treatment seen at home within four hours of the onset of symptoms. MEASUREMENTS AND MAIN RESULTS: Loss of quality adjusted days (QADS) in the first 100 days after suspected myocardial infarction (365 QADS = 1 QALY) was the main outcome measure. Compared with later administration in hospital, anistreplase at home resulted in a relative reduction of mortality of 49% (95% confidence interval 3.95%, 2p = 0.04), and a relative reduction of 26% in the proportion of survivors with infarction who had Q-waves (95% CI 7.44%, 2p = 0.007). During the 100 day follow up, the median loss of QADS was 25 for all patients. This loss was significantly greater in those who died than in survivors (65 v 18, 2p < 0.001), and in survivors with infarction than in survivors without infarction (26 v 13, 2p < 0.01). However, there was no significant difference in loss of QADS in those with infarction with or without Q-waves (29 v 21, NS), and the median loss of QADS was not significantly different in those who had thrombolytic treatment at home or in hospital (median difference 0, 95% CI -5, +4 QADS). CONCLUSIONS: Loss of QADS had two serious limitations as an outcome measure: it was less sensitive than mortality and it failed to reflect physiological benefit. Palliative treatment with no physiological effect would have resulted in a greater gain in QADS (or QALYs) than did early thrombolytic treatment. Extreme caution is required in accepting a gain in QALYs as a valid outcome measure for health care.