Summary of findings for the main comparison. Ezetimibe for the prevention of cardiovascular disease and all‐cause mortality events.
| Ezetimibe plus other lipid‐modifying drugs compared to other lipid‐modifying drugs alone or plus placebo for the prevention of cardiovascular disease and all‐cause mortality events | ||||||
| Patient or population: people with cardiovascular disease or at high risk of cardiovascular disease Setting: inpatients or outpatient Intervention: ezetimibe plus other lipid‐modifying drugs (statin or fenofibrate) Comparison: other lipid‐modifying drugs (statin or fenofibrate) alone or plus placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with other lipid‐modifying drugs alone or plus placebo | Risk with Ezetimibe plus other lipid‐modifying drugs | |||||
| Major adverse cardiovascular events (MACE) follow‐up: range 1 years to 6 years | Study population | RR 0.94 (0.90 to 0.98) | 21,727 (10 RCTs) | ⊕⊕⊕⊝ MODERATE 1 | The data were obtained from studies comparing ezetimibe plus statin versus statin alone. The IMPROVE‐IT study carried 88.8% of the weight. |
|
| 284 per 1,000 | 267 per 1,000 (256 to 278) | |||||
| All‐cause mortality follow‐up: range 1 years to 6 years | Study population | RR 0.98 (0.91 to 1.05) | 21,222 (8 RCTs) | ⊕⊕⊕⊕ HIGH | The IMPROVE‐IT study carried 94.6% of the weight. Two additional studies reported that no deaths occurred, and one study reported the total deaths but did not provide data by treatment arm. |
|
| 123 per 1,000 | 120 per 1,000 (112 to 129) | |||||
| Myocardial infarction (non‐fatal) follow‐up: range 1 years to 6 years | Study population | RR 0.88 (0.81 to 0.95) | 21,145 (6 RCTs) | ⊕⊕⊕⊝ MODERATE 1 | The data were obtained from studies comparing ezetimibe plus statin versus statin alone. The IMPROVE‐IT study carried 97.8% of the weight, and also provided data on any MI (HR 0.87, 95% CI 0.80 to 0.95) and fatal MI (HR 0.84, 95% CI 0.55 to 0.1.27). Two additional studies reported that no MI events occurred. |
|
| 105 per 1,000 | 92 per 1,000 (85 to 100) | |||||
| Stroke (non‐fatal) follow‐up: range 1 years to 6 years | Study population | RR 0.83 (0.71 to 0.97) | 21,205 (6 RCTs) | ⊕⊕⊕⊝ MODERATE 1 | The data were obtained from studies comparing ezetimibe plus statin versus statin alone. The IMPROVE‐IT study carried 89.4% of the weight, and also provided data on any stroke (HR 0.86, 95% CI 0.73 to 1.00), ischaemic stroke (HR 0.79, 95% CI 0.67 to 0.94), haemorrhagic stroke (HR 1.38, 95% CI 0.93 to 2.04) and fatal stroke (HR 1.22, 95% CI 0.81 to 1.82). One additional study reported that no stroke events occurred. |
|
| 32 per 1,000 | 27 per 1,000 (23 to 31) | |||||
| Cardiovascular mortality follow‐up: range 1 years to 6 years | Study population | RR 1.00 (0.89 to 1.12) | 19,457 (6 RCTs) | ⊕⊕⊕⊝ MODERATE 2 | The IMPROVE‐IT study carried 98.4% of the weight. Four additional studies reported that no cardiovascular death occurred and one study reported total cardiac deaths but did not provide data by treatment arm. |
|
| 56 per 1,000 | 56 per 1,000 (50 to 63) | |||||
| Adverse events ‐ hepatopathy follow‐up: range 1 to 6 years | Study population | RR 1.14 (0.96 to 1.35) | 20,687 (4 RCTs) | ⊕⊕⊝⊝ LOW 1 3 | The data were obtained from studies comparing ezetimibe plus statin versus statin alone. The IMPROVE‐IT study carried 89.6% of the weight. Ten additional studies reported no occurrence in the levels of ALT and/or AST being more than or equal 3 x ULN. |
|
| 22 per 1,000 | 26 per 1,000 (22 to 30) | |||||
| Adverse events ‐ myopathy follow‐up: range 1 years to 6 years | Study population | RR 1.31 (0.72 to 2.38) | 20,581 (3 RCTs) | ⊕⊝⊝⊝ VERY LOW 1 4 | The data were obtained from studies comparing ezetimibe plus statin versus statin alone. The IMPROVE‐IT study carried 52.5% of the weight. Thirteen additional studies reported that none of the participants in either group developed a CK level more than or equal 10 x ULN. |
|
| 2 per 1,000 | 2 per 1,000 (1 to 4) | |||||
| *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). CI: Confidence interval; HR: hazard ratio; RR: Risk ratio | ||||||
| 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 | ||||||
1 Downgraded by one level due to risk of bias.
2 Downgraded by one level due to imprecision (the 95% CI exclude serious harm, but included the null).
3 Downgraded by one level due to imprecision (the 95% CI of the overall effect included both no effect and important harm).
4 Downgraded by two levels due to imprecision (few events and wide CI).