eTable 4. Quality of evidence based on the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) and results for each endpoint.
| Quality assessment | Number of events and number of patients | Effect | Quality of evidence | ||||||
|---|---|---|---|---|---|---|---|---|---|
| No. of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Ezetimibe 10 mg/day + statin 10–80 mg/day | Statin 10–80 mg/day | Risk ratio (95% CI) | |
| Cardiovascular morbidity in high-risk patients after acute coronary syndrome (follow-up: 84 months) | |||||||||
| 1*1 | RCT | not high | not high | not high | not high | 2572/9067 (33%) | 2742/9077 (35%) | HR: 0.94 [0.89; 0.99] | + + + + high |
| Cardiovascular morbidity in hyperlipidemic patients with atherosclerosis without acute coronary syndrome (follow-up: 6–24 months) | |||||||||
| 3*2 | RCT | high*3 | not high | not high | very high*4 | 4/22 (18%) | 2/22 (10%) | RR: 2.22 [0.36; 13.62] | very low + |
| Cardiovascular mortality (follow-up: 6–84 months)) | |||||||||
| 2 | RCT | high*3 | not high | not high | not high | 538/9092 (6%) | 538/9102 (6%) | HR: 1.00 [0.89; 1.12] | moderate + + + |
| All-cause mortality in high-risk patients after acute coronary syndrome (follow-up: 84 months) | |||||||||
| 1 | RCT | not high | not high | not high | not high | 1215/9067 (15%) | 1231/9077 (15%) | HR: 0.99 [0.91; 1.07] | + + + + high |
| All-cause mortality in hyperlipidemic patients with atherosclerosis without acute coronary syndrome | |||||||||
| 1 | RCT | high*3 | not high | not high | very high*4 | 0/104 (0%) | 0/110 (0%) | RR not calculable | very low + |
| Quality of life – no evidence identified | |||||||||
| Number of adverse events (follow-up: 6 months) | |||||||||
| 3 | RCT | not high | not high | not high | high*5 | 5769/9574 (60%) | 5643/9380 (60%) | RR: 0.98 [0.89; 1.07] | moderate + + + |
| Number of serious adverse events (follow-up: 6 months) | |||||||||
| 3 | RCT | not high | not high | not high | very high*4 | 3672/9628 (38%) | 3662/9440 (39%) | RR: 1.09 [0.77; 1.55] | low + + |
| Study discontinuation due to adverse events (follow-up: 6–12 months) | |||||||||
| 6 | RCT | high*6 | not high | not high | high*5 | 32/699 (5%) | 26/499 (5%) | RR: 0.85 [0.51; 1.43] | low + + |
GRADE, Grading of Recommendations Assessment, Development and Evaluation; HR, Hazard Ratio; CI, confidence interval; RCT, randomized controlled trial; RR, risk ratio
*1This study reports both a composite endpoint and individual endpoints (myocardial infarction, revascularization, unstable angina pectoris). Since the composite endpoint was the study’s primary endpoint, it was reported here.
*2Cardiovascular morbidity was reported in three RCTs (in one study as a composite endpoint, in the other studies as single endpoints [myocardial infarction, revascularization, stent thrombosis]). Since the data were not combined in a meta-analysis, the results of the study which evaluated a composite endpoint (death, myocardial infarction, stroke, and transient ischemic attack), are reported here. In the two other studies, the incidence of cardiovascular events was comparably low in both treatment groups.
*3Randomization, concealed assignment, blinding at times unclear
*4The confidence interval contains effect estimates that can indicate both an advantage and a disadvantage for ezetimibe-statin therapy. The number of subjects is very small; thus, the results may be due to random effects and lack of power. Result rates very low.
*5The confidence interval contains effect estimates that can indicate both an advantage and a disadvantage for ezetimibe-statin therapy.
*6Randomization was unclear and no blinding was carried out.