The effect of various types and doses of statins on C-reactive protein levels in patients with dyslipidemia or coronary heart disease: A systematic review and network meta-analysis

Abstract

Objective: The objective of this study was to measure the efficacy of various types and dosages of statins on C-reactive protein (CRP) levels in patients with dyslipidemia or coronary heart disease.

Methods: Randomized controlled trials were searched from PubMed, Embase, Cochrane Library, OpenGray, and ClinicalTrials.gov. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for data extraction and synthesis. The pairwise meta-analysis compared statins and controls using a random-effects model, and a network meta-analysis compared the types and dosages of statins using the Bayesian random-effects model. The PROSPERO registration number is CRD42021242067.

Results: The study included 37 randomized controlled trials with 17,410 participants and 20 interventions. According to the pairwise meta-analysis, statins significantly decreased CRP levels compared to controls (weighted mean difference [WMD] = -0.97, 95% confidence interval [CI] [-1.31, -0.64], P < 0.0001). In the network meta-analysis, simvastatin 40 mg/day appeared to be the best strategy for lowering CRP (Rank P = 0.18, WMD = -4.07, 95% CI = [-6.52, -1.77]). The same was true for the high-sensitivity CRP, non-acute coronary syndrome (ACS), <12 months duration, and clear measurement subgroups. In the CRP subgroup (rank P = 0.79, WMD = -1.23, 95% CI = [-2.48, -0.08]) and ≥12-month duration subgroup (Rank P = 0.40, WMD = -2.13, 95% CI = [-4.24, -0.13]), atorvastatin 80 mg/day was most likely to be the best. There were no significant differences in the dyslipidemia and ACS subgroups (P > 0.05). Node-splitting analysis showed no significant inconsistency (P > 0.05), except for the coronary heart disease subgroup.

Conclusion: Statins reduced serum CRP levels in patients with dyslipidemia or coronary heart disease. Simvastatin 40 mg/day might be the most effective therapy, and atorvastatin 80 mg/day showed the best long-term effect. This study provides a reference for choosing statin therapy based on LDL-C and CRP levels.

Keywords: C-reactive protein; coronary heart disease; dyslipidemia; network meta-analysis; statin.

Figure 1

Flow diagram of the study selection progress.

Figure 2

Risk of bias graph of the included studies.

Figure 3

Forest plot of pairwise meta-analysis between statins and control. Note: PRV 40: Pravastatin 40 mg/d; RSV 10: Rosuvastatin 10 mg/d; Rosuvastatin 20 mg/d; ATV 10: Atorvastatin 10 mg/d; SIV 20: Simvastatin 20 mg/d; SIV 10: Simvastatin 10 mg/d; SIV 40: Simvastatin 40 mg/d; SIV 80: Simvastatin 80 mg/d; RSV 5: Rosuvastatin 5 mg/d; ATV 40: Atorvastatin 40 mg/d; PRV 10: Pravastatin 10 mg/d; ATV 80: Atorvastatin 80 mg/d; ATV 20: Atorvastatin 20 mg/d.

Figure 4

Network evidence plot on CRP. The size of nodes is directly proportional to the number of studies. The lines link two direct-comparison interventions, their thickness is proportional to the number of comparisons, and the green links represent at least one double-blind comparison. PTV 4: Pitavastatin 4 mg/d; PTV 2: Pitavastatin 2 mg/d; PTV 1: Pitavastatin 1 mg/d; PRV 40: Pravastatin 40 mg/d; PRV 20: Pravastatin 20 mg/d; PRV 10: Pravastatin 10 mg/d; ATV 80: Atorvastatin 80 mg/d; ATV 5: Atorvastatin 5 mg/d; ATV 40: Atorvastatin 40 mg/d; ATV 20: Atorvastatin 20 mg/d; ATV 10: Atorvastatin 10 mg/d; SIV 80: Simvastatin 80 mg/d; SIV 40: Simvastatin 40 mg/d; SIV 20: Simvastatin 20 mg/d; SIV 10: Simvastatin 10 mg/d; RSV 5: Rosuvastatin 5 mg/d; RSV 40: Rosuvastatin 40 mg/d; RSV 20: Rosuvastatin 20 mg/d; RSV 10: Rosuvastatin 10 mg/d.