Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: A systematic review and meta-analysis

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/)Aims:The value of elective coronary revascularisation plus medical therapy over medical therapy alone in managing stable patients with coronary artery disease is debated. We reviewed all trials comparing the two strategies in this population. Methods and results:From inception through November 2020, Medline, Embase, Google Scholar and other databases were searched for randomised trials comparing revascularisation to medical therapy alone in clinically stable coronary artery disease patients. Treatment effects were measured by rate ratios (RR) with 95% confidence intervals using random-effects models. Cardiac mortality was the prespecified primary endpoint. Spontaneous myocardial infarction (MI) and its association with cardiac mortality were secondary endpoints. Further endpoints included all-cause mortality, any MI and stroke. Longest follow-up data were abstracted. The study is registered with PROSPERO (CRD42021225598). Twenty-five trials involving 19,806 patients (10,023 randomised to revascularisation plus medical therapy and 9,783 to medical therapy alone) were included. Compared to medical therapy alone, revascularisation was associated with a lower risk of cardiac death (RR 0.79 [0.67-0.93], p<0.01) and spontaneous MI (RR 0.74 [0.64-0.86], p<0.01). By meta-regression, the cardiac death risk reduction after revascularisation, compared to medical therapy alone, was linearly associated with follow-up duration (RR per 4-year follow-up: 0.81 [0.69-0.96], p=0.008) and spontaneous MI absolute difference (p=0.01). Trial sequential and sensitivity analyses confirmed the reliability of the cardiac mortality findings. All cause mortality (0.94 [0.87-1.01], p=0.11), any MI (p=0.14) and stroke risk (p=0.30) did not differ significantly between strategies. Conclusion:In stable coronary artery disease patients, randomisation to elective coronary revascularisation plus medical therapy led to reduced cardiac mortality compared to medical management alone. The cardiac survival benefit after revascularisation improved with longer follow-uptimes and was associated with fewer spontaneous MIs.Peer reviewedFinal Published versio

Prevention of contrast-induced acute kidney injury in patients undergoing cardiovascular procedures : a systematic review and network meta-analysis

BACKGROUND: Interventional diagnostic and therapeutic procedures requiring intravascular iodinated contrast steadily increase patient exposure to the risks of contrast-induced acute kidney injury (CIAKI), which is associated with death, nonfatal cardiovascular events, and prolonged hospitalization. The aim of this study was to investigate the efficacy of pharmacological and non-pharmacological treatments for CIAKI prevention in patients undergoing cardiovascular invasive procedures with iodinated contrast.METHODS AND FINDINGS: MEDLINE, Google Scholar, EMBASE and Cochrane databases as well as abstracts and presentations from major cardiovascular and nephrology meetings were searched, up to 22 April 2016. Eligible studies were randomized trials comparing strategies to prevent CIAKI (alone or in combination) when added to saline versus each other, saline, placebo, or no treatment in patients undergoing cardiovascular invasive procedures with administration of iodinated contrast. Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. Eighteen strategies aimed at CIAKI prevention were identified. The primary outcome was the occurrence of CIAKI. Secondary outcomes were mortality, myocardial infarction, dialysis and heart failure. The data were pooled using network meta-analysis. Treatment estimates were calculated as odds ratios (ORs) with 95% credible intervals (CrI). 147 RCTs involving 33,463 patients were eligible. Saline plus N-acetylcysteine (OR 0.72, 95%CrI 0.57-0.88), ascorbic acid (0.59, 0.34-0.95), sodium bicarbonate plus N-acetylcysteine (0.59, 0.36-0.89), probucol (0.42, 0.15-0.91), methylxanthines (0.39, 0.20-0.66), statin (0.36, 0.21-0.59), device-guided matched hydration (0.35, 0.12-0.79), prostaglandins (0.26, 0.08-0.62) and trimetazidine (0.26, 0.09-0.59) were associated with lower odds of CIAKI compared to saline. Methylxanthines (0.12, 0.01-0.94) or left ventricular end-diastolic pressure-guided hydration (0.09, 0.01-0.59) were associated with lower mortality compared to saline.CONCLUSIONS: Currently recommended treatment with saline as the only measure to prevent CIAKI during cardiovascular procedures may not represent the optimal strategy. Vasodilators, when added to saline, may significantly reduce the odds of CIAKI following cardiovascular procedures

Cardiac mortality, adequate power, and objective inclusion of the entire evidence are key to accurately define the long-term effect of revascularisation vs. medical therapy alone in stable coronary syndromes

This commentary refers to 'Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis', by E.P. Navarese et al., https:// doi.org/10.1093/eurheartj/ehab246; 'When a meta-analysis equals a single large-scale trial with meaningful follow-up', by E.P. Navarese et al., https://doi:10.1093/eurheartj/ ehab460; and the discussion pieces 'Cardiac death should be the primary endpoint for revascularisation trials and meta analyses', by H.D. White, https://doi.org/10.1093/ eurheartj/ehab676; `In the pool: dilution or drowning?

Should we consider low LDL-cholesterol a marker of in-hospital bleeding in patients with acute coronary syndrome undergoing percutaneous coronary intervention?

Aims Emerging evidence has linked cholesterol metabolism with platelet responsiveness. We sought to examine the dose-response relationship between low-density lipoprotein cholesterol (LDL-C) and major in-hospital bleeds in acute coronary syndrome (ACS) patientsMethods and results Among 42 378 ACS patients treated with percutaneous coronary intervention (PCI) enrolled in 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from 2014 to 2019, a total of 615 major bleeds, 218 ischaemic events, and 337 deaths were recorded. After controlling for baseline variables, a non-linear relationship was observed for major bleeds, with the higher risk at lower LDL-C levels. No dose-response relationship was identified for ischaemic events and mortality. A threshold value of LDL-C &lt;70 mg/dL was associated with an increased risk for major bleeds (adjusted odds ratio: 1.49; 95% confidence interval: 1.21-1.84) in multivariable-adjusted logistic regression models and in propensity score-matched cohorts. The results were consistent in multiple sensitivity analyses. Among ticagrelor-treated patients, the LDL-C threshold for increased bleeding risk was observed at &lt;88 mg/dL, whereas for clopidogrel-treated patients, the threshold was &lt;54 mg/dL. Across a full spectrum of LDL-C levels, the treatment effect size associated with ticagrelor vs. clopidogrel on major bleeds favoured clopidogrel at lower LDL-C levels, but no difference at higher LDL-C levelsConclusions In a nationwide ACS registry, a non-linear association was identified between LDL-C levels and major in-hospital bleeds following PCI, with the higher risk at lower levels. As the potential for confounding may exist, further studies are warranted

When a meta-analysis equals a single large-scale trial with meaningful follow-up

N/