Table 1 Summary of the two included studies
From: Cilostazol for the prevention of pneumonia: a systematic review
| Study and country | Yamaya et al. 2001 [16], Japan | Shinohara et al. 2006 [10], Japan |
|---|---|---|
| Population | History of cerebral infarction but not bedridden | History of cerebral infarction, age < 80 years |
| Mean age | Mean age: 76.5 ± 2.1 years | Mean age: 65.0 ± 8.7 years |
| Gender | No statement about gender | Female 34.4% |
| Risk factors | No statement about risk factors for pneumonia | No statement about risk factors for pneumonia |
| Criteria for diagnosis of pneumonia | New pulmonary infiltrate seen on chest radiographs (assessed by two radiologists not involved in the study) and one of the following: cough, body temperature > 37.8 °C, subjective dyspnea | Description by attending physician in the medical chart, chest radiographs and blood test |
| Intervention and control (n, allocated) | I: cilostazol 100 mg per day (n: not stated) | I: cilostazol 200 mg per day (n: 547) |
| C: no active treatment (n: not stated) | C: placebo (n: 548) | |
| 328 patients were allocated in total but the number of patients in each group at allocation was not reported | ||
| Intervention period | 3 years | 3.3 years on average |
| Number of patients analyzed | I = 125, C = 145, see comments | I = 531, C = 533, see comments |
| Outcomes | Pneumonia | Pneumonia |
| I: 12 (9.6%), C: 35 (24.1%) | I: 3 (0.56%), C: 15 (2.8%) | |
| RR = 0.40 (95% CI 0.22–0.73)** | RR = 0.20 (95% CI 0.06–0.69)** | |
| Cerebral infarction | Cerebral infarction [17] | |
| I: 9 (7.2%), C: 24 (16.6%) | I: 30 (5.6%), C: 57 (10.7%) | |
| RR = 0.43 (95% CI 0.21–0.90)* | RR = 0.53 (95% CI 0.34–0.81)* | |
| Bleeding | Bleeding [17] | |
| I: 12 (9.6%), severity of the bleeding events was not reported | Fatal intracranial hemorrhage | |
| C: No statement about adverse events | I: 0, C: 1 | |
| Nonfatal intracranial hemorrhage | ||
| I: 4 (0.75%), C: 6 (1.1%) | ||
| Other bleeding | ||
| I: 15a (2.8%), C: 11 (2.1%) | ||
| Risk of bias | ||
| Random sequence generation | Low | Low |
| Allocation concealment | Unclear: Inadequate description | Low |
| Blinding of participants and personnel | High: Open-label trial | Low |
| Blinding of outcome assessment | Low | Unclear: Post-hoc analysis of a RCT [17] |
| Incomplete outcome data | High: As-treated analysis | Unclear: Reasons for dropouts were unclear |
| Selective reporting | High: No protocol available, No statement about adverse events in the control group | High: Post-hoc analysis of a RCT [17] |
| Other bias | Unclear: No statement about funding | Unclear: No statement about funding but original RCT [17] was supported by Otsuka Pharmaceutical |
| Comments | Reported in a Letter to the Editor | 1095 patients were randomized but 31 patients were excluded from analysis because of “serious protocol violations” |
| 328 patients were randomized but 58 patients were excluded from analysis; 31 patients died from causes other than pneumonia; additionally, 27 patients in cilostazol group dropped out because of adverse events | Of 1064 patients, about half of the patients discontinued the treatment (I: 54%, C: 49%) | |