Summary of findings 1. Propionyl‐L‐carnitine compared to placebo for intermittent claudication.
| Propionyl‐L‐carnitine compared to placebo for intermittent claudication | ||||||
| Patient or population: people with intermittent claudication Setting: outpatient setting Intervention: propionyl‐L‐carnitine Comparison: placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | No. of participants (studies) | Certainty of evidence (GRADE) | Comments | |
| Risk with placebo/control | Risk with propionyl‐L‐carnitine | |||||
| Absolute claudication distance (MWD + PWT) (in meters) Follow‐up: 3 weeks to 1 year |
Mean change in ACD in placebo group was 59.89 m | MD 50.86 m higher (50.34 higher to 51.38 higher) | ‐ | 1121 (9 studies) | ⊕⊕⊕⊝ moderatea | |
| Initial claudication distance (PFWD + COT) (in meters) Follow‐up: 90 days to 1 year |
Mean change in ICD in placebo group was 32.24 m | MD 32.98 m higher (32.6 higher to 33.37 higher) | ‐ | 1151 (9 studies) | ⊕⊕⊕⊝ moderatea | |
| Quality of life Follow‐up: 6 months |
Mean change in QoL score in placebo group was 0.01 | MD 0.06 higher (0.05 higher to 0.07 higher) | ‐ | 126 (1 study) | ⊕⊕⊕⊝ moderateb | |
| Progression of disease (to Fontaine stage III or IV, or necessity for intervention (endovascular or surgery)) Follow‐up: 1 year |
1 study evaluated progression of disease: 5/242 (2%) PLC participants evolved from Fontaine stage II to stage III (rest pain) vs 10/243 (4%) placebo participants; 2/242 (0.8%) PLC participants evolved to Fontaine stage IV (critical ischemia) vs 0/243 (0%) placebo participants | 485 (1 study) |
⊕⊕⊝⊝ lowc |
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| Side effects of propionyl‐L‐carnitine regimen Follow‐up: 6 months to 1 year |
Brevetti 1995: 7 AEs in placebo group and 5 AEs in PLC group not requiring drug discontinuation. Nausea and gastric pain were the most frequent side effects; 11 AEs resulting in drug discontinuation occurred in the PLC group, and 3 in the placebo group. According to study authors, medical problems requiring drug discontinuation in the PLC group were unrelated to study medication Brevetti 1999: 27 PLC participants discontinued the study because of the occurrence of serious AEs (mainly cardiac and peripheral vascular). In the placebo group, 30 AEs required study discontinuation. 38 AEs not requiring drug discontinuation occurred in the PLC group vs 98 in the placebo group; flu syndrome was the most frequent AE without a difference in occurrence between arms Coto 1992: 3 AEs requiring study interruption in the PLC group and 6 in the placebo group. The most common AE was abdominal pain Hiatt 2001 and Hiatt 2011: no mention of important differences in side effects between 2 intervention arms: 70% of PLC participants and 68% of placebo participants experienced 1 or more AEs; AEs that affected more than 5% of participants in either group with a ratio > 1.5 PLC vs placebo included nausea, diarrhea, bronchitis, and back pain Signorelli 2006b: no AEs |
1303 (6 studies) |
⊕⊕⊕⊝ moderated |
Overall, PLC appears to be a safe and well‐tolerated drug, as no significant differences with placebo can be found in studies with follow‐up from 6 months to 1 year | ||
| Ankle brachial index (ABI) Follow‐up: 4 months to 1 year |
Mean ABI in control group was ‐0.02 | MD 0.09 higher (0.08 higher to 0.09 higher) | ‐ | 369 (4 studies) | ⊕⊕⊕⊝ moderatee |
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| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ABI: ankle brachial index; ACD: absolute claudication distance; AE: adverse event; CI: confidence interval; COT: claudication onset time; ICD: initial claudication distance; MD: mean difference; MWD: maximum waking distance; PFWD: pain‐free walking distance; PLC: propionyl‐L‐carnitine; PWT: peak walking time; QoL: quality of life. | ||||||
| GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
aDowngraded by one level due to high heterogeneity between studies. Furthermore, the overall estimate of effect reflects mainly results of the studies of Brevetti (largest numbers of participants); however in these studies, subgroups were not reported (?publication bias) and there was a marked center effect. Overall results were relatively consistent among studies. The same remarks apply for all outcomes. bDowngraded by one level because this was investigated in only one study. cDowngraded by two levels because this outcome was investigated in only one study and the absolute number of events in this study was low. dDowngraded by one level because causal relationship of different adverse events was not fully explained. eDowngraded by one level because this outcome was investigated in a small number of studies (four studies).