Table 2.
Significant associations of interventions with the risk for sudden cardiac death, in meta-analyses of randomized controlled trials.
| Reference | Risk/Protective factor | Exposed/Unexposed as in included MA | K | n/N | Metric | ES (95% CI) | p-value | PI include null value | I2 | SSE | ESB | High RoB | GLE | AMSTAR 2 Quality |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Heart failure or LV dysfunction population | ||||||||||||||
| Peck et al. (34) | Implantable cardioverter defibrillator (ICD) use, in patients with LV dysfunction | ICD use or not | 4 | 261/4,269 | RR | 0.40 (0.31, 0.51) | 4.21 x 1013 | No | 0% | No | No | <25% | High | High |
| Le (35) | Aldosterone antagonist use, in patients with HF | Use or not | 5 | 456/8,301 | RR | 0.81 (0.67, 0.98) | 0.031 | Yes | 7.7% | No | NP | <25% | High | High |
| Bapoje (36) | Mineralocorticoid receptor antagonist (MRA) use, in patients with left ventricular (LV) dysfunction | MRA use or not | 6 | 709/11,654 | OR | 0.76 (0.65, 0.89) | 0.001 | No | 0% | Yes | No | <25% | High | High |
| Fernandes (37) | Sodium-glucose cotransporter-2 (SGLT-2) inhibitor use, in patients with diabetes or HF | SGLT-2 use or not | 8 | 187/45,483 | OR | 0.72 (0.54/0.97) | 0.031 | Yes | 0% | No | NP | <25% | High | High |
| Kolodziejczak et al. (38) | ICD use, in patients with IHD and non-IHD | ICD use or conventional therapy | 7 | 336/3,959 | HR | 0.41 (0.31, 0.54) | 9.07 x 1011 | No | 0% | No | No | >25% | Moderate | High |
| Gama (39) | ICD use, in patients with HF | ICD use or not | 6 | 1,946/2,197 | RR | 0.49 (0.40, 0.61) | 5.46 x 1011 | No | 0% | Yes | NP | >25% | Moderate | High |
| Peck et al. (34) | ACEi and beta-blocker use, in patients with LV dysfunction | Use or not | 10 | 2,824/36,172 | RR | 0.89 (0.81, 0.98) | 0.014 | Yes | 31.7% | No | Yes | >25% | Moderate | High |
| Al-Gobari (40) | Beta-blocker use, in patients with heart failure (HF) | Beta-blocker use or not | 26 | 1,597/24,554 | OR | 0.69 (0.62, 0.77) | 2.79 x 10−2 | No | 0% | No | Yes | <25% | Moderate | Moderate |
| Chatterjee (41) | Beta-blocker use, in patients with HF | Beta-blocker use or comparator | 6 | 787/8,960 | OR | 0.73 (0.63, 0.85) | 3.9 x 105 | No | 0% | No | No | <25% | Moderate | Moderate |
| Peck et al. (34) | MRA use, in patients with LV dysfunction using ACEi and/or beta-blockers | MRA use or not | 3 | 691/11,032 | RR | 0.79 (0.68, 0.91) | 0.001 | Yes | 0% | No | No | <25% | Moderate | High |
| Claro (42) | Amiodarone use, in patients with heart failure | Amiodarone use or not | 11 | 526/4,306 | RR | 0.79 (0.67, 0.92) | 0.004 | No | 0% | No | NP | >25% | Low | Critically low |
| Coronary Artery disease population | ||||||||||||||
| Kolodziejczak et al. (38) | ICD use, in patients with ischemic heart disease (IHD) | ICD use or conventional therapy | 4 | 246/2,282 | HR | 0.39 (0.28, 0.55) | 5.95 x 10−8 | No | 0% | No | No | >25% | Moderate | High |
| Fernandes (43) | Trans-endocardial stem cell injection, in patients with chronic IHD | Injection or not | 10 | 7/422 | OR | 0.19 (0.04, 0.86) | 0.031 | Yes | 0% | Yes | NP | >25% | Moderate | High |
| Fernandes (43) | Trans-endocardial stem cell injections with other cells, in patients with chronic IHD | Injection or not | 4 | 14/422 | OR | 0.24 (0.07, 0.89) | 0.033 | Yes | 0% | No | NP | >25% | Moderate | High |
| Domanski (44) | Angiotensin converting enzyme inhibitor (ACEI) use, in patients with recent MI | ACEi use or not | 15 | 900/15,103 | OR | 0.80 (0.70, 0.91) | 0.001 | No | 0% | No | No | NR | Low | Critically low |
| Claro (42) | Amiodarone use, in post myocardial infarction (MI) patients | Amiodarone use or not | 6 | 140/3,377 | RR | 0.65 (0.46, 0.91) | 0.011 | Yes | 0% | No | NP | >25% | Low | Critically low |
| Zhao (45) | Omega-3 fatty acid (OFA) use, in high-incidence MI subgroup | OFA use or not | 4 | 305/13,168 | RR | 0.52 | 0.027 | Yes | 33.7% | Yes | No | NR | Low | Critically low |
| Zhao (45) | OFA use, in low-incidence MI subgroup | OFA use or not | 4 | 149/7,829 | RR | 1.39 (1.01, 1.92) | 0.045 | Yes | 0% | No | NP | NR | Low | Critically low |
| Khoueiry (46) | OFA use, in patients with recent MI | OFA use or not | 5 | 286/13,126 | OR | 0.69 (0.55, 0.88) | 0.003 | Yes | 0% | No | NP | NR | Low | Critically low |
| Non-ischemic cardiomyopathy population | ||||||||||||||
| Peck et al. (34) | ACEi and beta-blocker use, in patients with LV dysfunction without recent MI | Use or not | 9 | 2,461/29,540 | RR | 0.91 (0.82, 1.00) | 0.050 | Yes | 29.9% | No | No | <25% | High | High |
| Kolodziejczak et al. (38) | ICD use, in patients with non-ischemic heart disease (non-IHD) | ICD use or conventional therapy | 3 | 90/1,677 | HR | 0.44 (0.28, 0.69) | 3.41 x 10−4 | Yes | 0% | No | No | >25% | Moderate | High |
| Siddiqui, (47) | ICD and cardiac resynchronization therapy with ICD (CRT-D), in patients with non-IHD | CRT-D or medical management | 3 | 90/1,677 | OR | 0.44 (0.28, 0.70) | 0.001 | Yes | 0% | No | No | >25% | Moderate | High |
| Hypertensive population | ||||||||||||||
| Hebert (48) | Epithelial sodium channel inhibitors combined with a thiazide diuretic | Use or not | 3 | 100/5,761 | OR | 0.61 (0.39, 0.95) | 0.029 | Yes | 0% | No | NP | NR | Low | Critically low |
| High risk population for SCD | ||||||||||||||
| Claro (42) | Amiodarone use, for primary prevention | Amiodarone use or not | 17 | 666/ 8,386 | RR | 0.76 (0.66, 0.88) | 1.98 x 10−4 | No | 0% | No | NP | >25% | Low | Critically low |
| Levantesi (49) | Statin use | Statin use or not | 10 | 688/22,275 | OR | 0.79 (0.67, 0.94) | 0.008 | Yes | 9.8% | No | No | NR | Low | Critically low |
| Other categories | ||||||||||||||
| Chen (50) | OFA use, in non-guidelines-adjusted therapy subgroup | OFA use or not | 6 | 308/14,219 | RR | 0.67 (0.54, 0.84) | 0.001 | No | 0% | Yes | No | <25% | Moderate | Critically low |
CE, class of evidence; CI, confidence interval; ES, effect size; ESB, excess significance bias; GLE: GRADE level of evidence; GRADE: GRADE, Grading of Recommendations Assessment, Development and Evaluation; I2, heterogeneity; K, number of studies for each factor; LS, largest study with significant effect; n, number of cases; N, total number of cohort per factor; NA, not assessable; NP, not pertinent, because the number of observed studies is less than the expected; NR, not reported; OR, odds ratio; PI, prediction interval; RoB, risk of bias; RR, risk ratio; SCD: sudden cardiac death; SSE, small study effects.