Table.
GRADE Evaluation of interventions for Peripheral arterial disease.
| Important outcomes | Cardiovascular events, Claudication distance/time, Mortality, Physiological measures , Post-intervention patency, Quality of life | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of treatments for people with chronic peripheral arterial disease? | |||||||||
| 9 (3019) | Mortality | Antiplatelet agents versus placebo or control | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for large diabetic population reducing generalisability of results and small number of comparators |
| at least 42 (at least 9214) | Cardiovascular events | Antiplatelet agents versus placebo or control | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for composite outcome in two reviews (inclusion of vascular death in vascular events) and combined regimens (aspirin plus dipyridamole) included in two reviews |
| 5 (1077) | Claudication distance/time | Antiplatelet agents versus placebo or control | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results Directness point deducted for restricting population to moderate intermittent claudication |
| at least 14 (at least 3226) | Post-intervention patency | Antiplatelet agents versus placebo or control | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results in some reviews |
| 6 (10,024) | Cardiovascular events | Antiplatelet agents other than aspirin (alone or in combination with aspirin) versus aspirin alone | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for subgroup analysis of larger study. Directness point deducted for use of a composite outcome (review and RCT included mortality in event rate) |
| at least 9 (at least 656) | Claudication distance/time | Exercise versus usual care/placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for blinding flaws. Directness point deducted for range of different forms of exercise included |
| 8 (285) | Physiological measures | Exercise versus usual care/placebo | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Directness points deducted for range of different interventions and length of treatment included; and 1 RCT restricting population to males. |
| 1 (156) | Quality of life | Exercise versus usual care/placebo | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for different results for different outcomes with different types of exercise |
| 2 (934) | Claudication distance/time | Exercise as part of a multicomponent intervention versus usual care or placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and subjective assessment of outcome in largest RCT |
| 3 (203) | Claudication distance/time | Different types of exercise versus each other | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for no statistical assessment between groups |
| 3 (590) | Mortality | Bypass surgery versus percutaneous transluminal angioplasty (PTA) | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting and use of non-cumulative follow-up data in 1 large RCT. Directness point deducted for inclusion of different disease states |
| at least 2 (at least 525) | Post-intervention patency | Bypass surgery versus percutaneous transluminal angioplasty (PTA) | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting. Directness point deducted for inclusion of different disease states |
| 1 (86) | Post-intervention patency | Bypass surgery versus percutaneous transluminal angioplasty (PTA) plus stent placement | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 3 (31,195) | Mortality | Statins versus placebo | 4 | 0 | –1 | –1 | 0 | Low | Consistency points deducted for different results with different statins. Directness point deducted for small proportion of people with peripheral arterial disease, which may affect generalisability of results |
| 4 (at least 23,211) | Cardiovascular events | Statins versus placebo | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for use of a composite outcome (some outcomes assessed included fatal cardiovascular events) and because in two RCTs people with peripheral arterial disease represented only a small proportion of the total assessed, which may affect generalisability of results |
| 5 (1442) | Claudication distance/time | Statins versus placebo | 4 | –1 | –1 | –1 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for uncertainty of benefit for different outcomes. Directness point deducted for statistical uncertainty regarding significance of baseline differences in 1 RCT so results may not be generalisable to the full population |
| 1 (354) | Physiological measures | Statins versus placebo | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for no statistical analysis of between group differences. Directness point deducted for limited number of drugs assessed (only atorvastatin) |
| 1 (354) | Quality of life | Statins versus placebo | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results. |
| 3 (154) | Claudication distance/time | Percutaneous transluminal angioplasty (PTA) versus no percutaneous intervention | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data. Consistency point deducted for different results at different end points |
| 2 (118) | Quality of life | Percutaneous transluminal angioplasty (PTA) versus no percutaneous intervention | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Consistency point deducted for different results for different outcomes |
| at least 2 (at least 240) | Claudication distance/time | Percutaneous transluminal angioplasty (PTA) plus stent versus PTA alone | 4 | –1 | –1 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for statistical heterogeneity. Directness points deducted for uncertainty of interventions in PTA alone group and restricting population to superficial femoral disease. |
| at least 6 (at least 520) | Post-intervention patency | Percutaneous transluminal angioplasty (PTA) plus stent versus PTA alone | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for different diagnostic criteria. Directness points deducted for uncertainty of interventions in PTA alone group and restricting population to superficial femoral disease in one systematic review |
| at least 3 (at least 291) | Physiological measures | Percutaneous transluminal angioplasty (PTA) plus stent versus PTA alone | 4 | –1 | –1 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for statistical heterogeneity. Directness points deducted for uncertainty of interventions in PTA alone group and restricting population to superficial femoral disease. |
| 1 (208) | Quality of life | Percutaneous transluminal angioplasty (PTA) plus stent versus PTA alone | 4 | –2 | 0 | –2 | 0 | Very low | Quality points deducted for incomplete reporting of results and not specifying quality of life score used. Directness points deducted for uncertainty of interventions in PTA alone group and restricting population to superficial femoral disease. |
| 2 (177) | Claudication distance/time | Percutaneous transluminal angioplasty (PTA) plus routine stent versus PTA plus selective stent | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for excluding acute critical limb ischaemia in 1 RCT |
| 4 (628) | Post-intervention patency | Percutaneous transluminal angioplasty (PTA) plus routine stent versus PTA plus selective stent | 4 | –1 | –1 | –2 | 0 | Very low | Quality point deducted for unclear methods of measuring restenosis in 1 RCT. Consistency point deducted for conflicting results between RCTs assessing restenosis alone. Directness points deducted for assessment of composite outcome in one RCT and excluding acute critical limb ischaemia in 1 RCT |
| 1 (73) | Physiological measures | Percutaneous transluminal angioplasty (PTA) plus routine stent versus PTA plus selective stent | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for RCT excluding acute critical limb ischaemia |
| 2 (383) | Quality of life | Percutaneous transluminal angioplasty (PTA) plus routine stent versus PTA plus selective stent | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and short follow-up |
| 1 (37) | Post-intervention patency | Percutaneous transluminal angioplasty (PTA) alone versus PTA plus statins | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and RCT being underpowered to detect a clinically important result |
| 12 (5674) | Cardiovascular events | Cilostazol versus placebo | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for inclusion of three studies in the review with people without peripheral arterial disease, which may affect generalisabilty of results. |
| 8 (1659) | Claudication distance/time | Cilostazol versus placebo | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for methodological weaknesses of RCTs included in meta-analysis and one RCT not reporting method of randomisation. Consistency point deducted for different results with different doses |
| 4 (939) | Physiological measures | Cilostazol versus placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for methodological weaknesses of RCTs included in meta-analysis and one subsequent RCT not reporting method of randomisation. Directness point deducted for RCT restricting population |
| at least 4 (at least 1229) | Quality of life | Cilostazol versus placebo | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for methodological weakness of RCTs and incomplete reporting of results. Consistency point deducted for different results with different measures of quality of life |
| 1 (322) | Mortality | Prostaglandins versus placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for statistically significant difference in adherence rates between treatment and placebo groups. Directness point deducted for population limited to critical limb ischaemia |
| 5 (400) | Claudication distance/time | Prostaglandins versus placebo | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for statistical heterogeneity, incomplete reporting of results, and poor methodological quality in some RCTS |
| at least 7 (at least 1040) | Post-intervention patency | Prostaglandins versus placebo | 4 | –1 | –1 | –1 | 0 | Very low | Quality point deducted for methodological flaws. Consistency point deducted for conflicting results between studies. Directness point deducted for use of composite outcomes |
| 2 (277) | Claudication distance/time | Prostaglandins versus pentoxifylline | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for poor quality methods in the RCTs and incomplete reporting of results |
| 2 (240) | Physiological measures | Prostaglandins versus pentoxifylline | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for poor quality methods in the RCTs and incomplete reporting of results |
| 8 (1299) | Claudication distance/time | Pentoxifylline versus placebo | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for poor follow-up and incomplete reporting of results |
| 1 (417) | Claudication distance/time | Pentoxifylline versus cilostazol | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for poor follow-up |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.