Antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia: A systemic review and meta-analysis of randomized studies

PLOS ONE RESEARCH ARTICLE Antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia: A systemic review and meta-analysis of randomized studies Sungjae Lee1, Seungwon Yang2‡*, Min Jung Chang ID1,2,3‡* 1 Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, Republic of Korea, 2 Department of Pharmacy and Yonsei Institute of Pharmaceutical Science, College of Pharmacy, Yonsei University, Incheon, Republic of Korea, 3 Department of Industrial Pharmaceutical Science, Yonsei University, Incheon, Republic of Korea a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Lee S, Yang S, Chang MJ (2021) Antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia: A systemic review and meta-analysis of randomized studies. PLoS ONE 16(11): e0260391. https://doi.org/ 10.1371/journal.pone.0260391 Editor: Mansueto Gomes Neto, Universidade Federal da Bahia, BRAZIL Received: July 20, 2020 Accepted: November 9, 2021 Published: November 24, 2021 Copyright: © 2021 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. ‡ SY and MJC contributed equally as corresponding authors. * (MJC); (SY) Abstract Some studies have suggested the antihypertensive effects of statins, a class of lipid-lowering agents, particularly in patients with hypertension. However, the evidence for the role of statins in blood pressure (BP) lowering is controversial, and no meta-analysis of rosuvastatin therapy has been conducted to assess its BP-lowering effects. Therefore, the aim of this meta-analysis of randomized controlled trials (RCTs) was to investigate the effects of rosuvastatin on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with hypertension. We systematically searched the electronic databases MEDLINE, EMBASE, and Cochrane Library to identify RCTs in which patients were assigned to groups of rosuvastatin plus antihypertensive agents vs. antihypertensive agents. The three authors independently selected the studies, extracted data, and assessed methodological quality. We included five RCTs in this meta-analysis with 288 patients treated with rosuvastatin and 219 patients without rosuvastatin. The mean DBP in the rosuvastatin group was significantly lower than that in the non-rosuvastatin group by −2.12 mmHg (95% confidence interval (CI) −3.72 to −0.52; Pfixed-effects model = 0.009; I2 = 0%, Pheterogeneity = 0.97). Rosuvastatin treatment also lowered the mean SBP compared with the non-rosuvastatin treatment by −2.27 mmHg, but not significantly (95% CI − 4.75 to 0.25; Pfixed-effects model = 0.08; I2 = 0%, Pheterogeneity = 0.82). In this study, we reviewed the antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia. We demonstrated a modest significant reduction of DBP and a trend toward a lowered SBP in patients with hypertension with rosuvastatin therapy. Rosuvastatin could be beneficial to control hypertension and, consequently, contribute toward reducing the risk of cardiovascular events in patients with hypertension and dyslipidemia. Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. PLOS ONE | https://doi.org/10.1371/journal.pone.0260391 November 24, 2021 1 / 12 PLOS ONE Antihypertensive effects of rosuvastatin in patients with hypertension and dyslipidemia Introduction Cardiovascular disease (CVD), the leading cause of death globally, accounted for more than 17.6 million deaths in 2016 [1]. Of many risk factors, hyperlipidemia, with elevated lipoprotein levels, and arterial hypertension, with elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP), are among the major risk factors that are independently or positively associated with the development of CVD, including myocardial infarction, stroke, and congestive heart failure [2, 3]. In a large proportion of patients, hyperlipidemia coexists with hypertension [4–6]. Furthermore, patients who have concomitant hyperlipidemia and hypertension are at a higher risk of CVD than patients who have hyperlipidemia or hypertension alone. Therefore, the combination therapy of antihypertensive agents with statins has been used for the control of both BP and the blood cholesterol level [7]. Recently, studies have demonstrated that statins, a class of lipid-lowering agents that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, are associated with an unexpected reduction in BP in patients with hypertension [8–10]. The underlying mechanism of the BP-lowering effect of statins could be related to the modulation of endothelial function and vascular oxidative stress [9]. A reduction in BP conferred by statin treatment could provide additional cardiovascular protection in patients with hypertension [10]. However, studies on the effects of statins on BP have shown conflicting results, possibly owing to the heterogeneity of the antihypertensive agents, different initial BP levels, and different age groups used [11–13]. Additionally, although rosuvastatin is one of the most potent and commonly prescribed statins for the treatment of hyperlipidemia, the effects of rosuvastatin have not been analyzed in previous meta-analyses that report the antihypertensive effects of statins [14]. Therefore, this meta-analysis was conducted to investigate whether rosuvastatin can lower DBP and SBP in patients with hypertension and dyslipidemia. Materials and methods We followed the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines to report the study design, search strategy, data analysis, and results of this meta-analysis (S1 Appendix). Using a standardized pilot-tested form, two authors (SL and MJC) independently checked the fulfillment of study eligibility, assessed the risk of bias, and conducted the extraction of data from each eligible study. Disagreements were resolved by consensus in the presence of a third author (SL, SY, and MJC). Study selection We included randomized controlled trials (RCTs) that investigated the effect of rosuvastatin on BP. Studies were eligible if they met the following criteria: (1) participants: patients with hypertension; (2) intervention: rosuvastatin treatment; (3) comparison: standard care or placebo; (4) outcome: changes in DBP or SBP measurements from the baseline to the end-oftreatment period. We excluded studies where we were unable to calculate the mean difference of the DBP and SBP measurements between the baseline and the end-of-treatment period in the intervention a (...truncated)