Summary of findings for the main comparison. Fixed‐dose combination therapy for the prevention of atherosclerotic cardiovascular diseases (ASCVD).
| Fixed‐dose combination therapy for the prevention of atherosclerotic cardiovascular diseases (ASCVD) | ||||||
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Patient or population: adults older than 18 years, with no restriction regarding presence of ASCVD; participants generally had elevated risk of ASCVD (as estimated by the presence of at least one abnormal cardiovascular risk factor) without prevalent CVD (two studies included > 10% of participants with prior ASCVD) Settings: outpatient Intervention: fixed‐dose combination therapy of varying drug combinations ranging from two to five drugs Comparison: usual care, placebo, or active drug therapy | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk based on event rates or mean changes from baseline in the comparator group | Corresponding risk | |||||
| Comparator group, including placebo, usual care, or active drug comparator | Fixed‐dose combination therapy | |||||
|
All‐cause mortality Median follow‐up range: 9 to 23 months |
Total | RR = 1.10 (0.64 to 1.89) |
5300 (5 studies) |
⊕⊕⊝⊝ Lowa,b | Low event rates among trials that were not designed nor powered to detect differences in clinical outcomes. Four of the five trials included had high‐quality usual care as the comparator group | |
| 10 per 1000 |
11 per 1000 (6 to 19) |
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ASCVD event, such as fatal or non‐fatal myocardial infarction or stroke. Median follow‐up range: 8 weeks to 23 months |
Total | RR = 1.26 (0.95 to 1.66) | 4517 (6 studies) |
⊕⊕⊝⊝ Lowa,b | Low event rates among trials that were not designed nor powered to detect differences in clinical outcomes. Four of the five trials included had high‐quality usual care as the comparator group | |
| 37 per 1000 |
46 per 1000 (35 to 61) |
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Any investigator‐defined adverse event Median follow‐up range: 6 weeks to 23 months |
271 per 1000 |
314 per 1000 (295 to 339) |
RR = 1.16 (1.09 to 1.25) |
6906 (11 studies |
⊕⊕⊕⊝ Moderatec | We would expect the rate of adverse events to be higher with fixed‐dose combination compared with placebo, and the difference between fixed‐dose combination and usual care depends on what care is provided |
|
Systolic blood pressure, mmHg Median follow‐up range: 6 weeks to 12 months |
The mean change in systolic blood pressure ranged across control groups from ‐17.9 mmHg to 0.9 mmHg | The mean difference in change in systolic blood pressure between the intervention and comparator groups was ‐6.34 mmHg (95% CI ‐9.03 to ‐3.64) | 7638 (13 studies) |
⊕⊕⊕⊝ Moderated | ||
|
Total cholesterol, mmol/L Median follow‐up range: 6 weeks to 23 months |
The mean change in total cholesterol ranged across control groups from ‐1.6 mmol/L to 0.2 mmol/L. | The mean difference in change in total cholesterol between the intervention and comparator groups was ‐0.61 mmol/L (‐0.88 to ‐0.35) | 6565 (11 studies) |
⊕⊕⊝⊝ Lowd,e | ||
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LDL cholesterol, mmol/L Median follow‐up range: 6 weeks to 23 months |
The mean change in LDL cholesterol ranged across control groups from ‐1.4 mmol/L to 0.1 mmol/L | The mean difference in change in LDL cholesterol between the intervention and comparator groups was ‐0.70 mmol/L (95% CI ‐0.98 to ‐0.41) | 7153 (12 studies) |
⊕⊕⊕⊝ Moderated | ||
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Adherence, variable definitions Median follow‐up range: 9 to 23 months |
534 per 1000 |
769 per 1000 (673 to 882) |
RR = 1.44 (1.26 to 1.65) | 3835 (4 studies) |
⊕⊕⊕⊝ Moderateb | All four trials included had high‐quality comparator care as the comparator group either as usual care or provision of individual drug components |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is the outcomes of the study control arms. The corresponding risk (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). ASCVD = atherosclerotic cardiovascular disease; CI: confidence interval; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. | ||||||
aDowngraded by one level due to imprecision due to low event rates. bDowngraded one level due to indirectness of evidence, including high quality 'usual care' as comparator group in four of five trials study limitations, which may not be comparable to settings where fixed‐dose combination therapy might be deployed, including low‐ and middle‐income country settings with low treatment rates. cDowngraded one level due to indirectness of evidence, including different comparators that could be usual care, placebo, or active comparator. dDowngraded one level due to heterogeneity likely due to different participants, fixed‐dose combinations, and comparator groups. eDowngraded one level due to reporting bias demonstrated through funnel plot asymmetry.