Comparative effectiveness of influenza vaccination dosing strategies for cardiovascular protection: a systematic review and network meta-analysis of randomised controlled trials.
Abstract
Background
Influenza vaccination is recommended for cardiovascular secondary prevention, but the comparative effectiveness of different dose strategies remains incompletely characterised.
Methods
We searched MEDLINE, Embase, and CENTRAL for randomised trials comparing high-dose (HD-IIV), double standard-dose, standard-dose (SD-IIV), and no vaccination in adults with established cardiovascular disease. A pairwise meta-analysis (SD-IIV versus no vaccination) and a network meta-analysis comparing all four dosing strategies were performed. The primary endpoint was the trial-reported composite cardiovascular endpoint. Secondary endpoints were all-cause death, cardiovascular death, myocardial infarction, stroke, and heart failure hospitalisation. Risk ratios (RR) were pooled under random-effects models.
Results
Ten trials enrolling 131,908 participants were included. In the pairwise analysis, SD-IIV was associated with a significantly lower risk of the composite cardiovascular endpoint (RR, 0.74; 95% confidence interval [CI], 0.61-0.90), all-cause death (0.75; 0.64-0.89), cardiovascular death (0.63; 0.42-0.93), and myocardial infarction (0.76; 0.62-0.94) compared with no vaccination. No significant reductions were observed for stroke (1.06; 0.72-1.54) or heart failure hospitalisation (0.96; 0.60-1.54). In the network meta-analysis, SD-IIV ranked highest across mortality and composite endpoints while HD-IIV ranked highest for heart failure hospitalisation and stroke, though no head-to-head dose comparison reached statistical significance.
Conclusions
Influenza vaccination was associated with lower risks of cardiovascular events, all-cause death, cardiovascular death, and myocardial infarction in patients with cardiovascular disease, with mortality benefits concentrated in trials enrolling patients during acute cardiovascular admission. Higher-dose formulations did not demonstrate incremental cardiovascular benefit over standard-dose vaccination, although a directional advantage for HD-IIV against heart failure hospitalisation was observed in a single trial and requires confirmation.