Effects of statin on hypertension patients: A systematic review and meta-analysis

Literature search strategy

We searched MEDLINE and the Cochrane Library Central Register of Controlled Trials (CENTRAL) for randomised controlled trials published between 1 January 2000 and 1 January 2022, using the search terms. Our search strategy varied by database, but covered the search term ‘statins and hypertension’. We conducted a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings, with no restrictions on language of publication or publication status. To achieve maximum sensitivity of the search strategy and to identify all studies, we manually screened the reference lists of all retrieved articles to further identify potentially relevant studies.

Study selection

To be included in the analysis, the original research articles had to meet the following criteria. (1) articles published in peer-reviewed journals and (2) journal articles with outcome measures related to hypertension. Exclusion criteria were.

(1) A research paper not written in English.

In addition, if there are multiple publications from the same queue, we extract the data from the largest or most recent dataset.

Data extraction and quality assessment

The following data were extracted: study characteristics, number of patients, clinical outcome results including SBP and DBP. Where available, the following details were extracted: first author, study title, country, year of publication, study design, study characteristics, sample size, mean age of patients and male/female ratio.

For the quality assessment, we considered the following domains: random sequence generation, allocation concealment, blinding (self-reporting), blinding (objective results), incomplete and selective reporting of results, and the presence of other biases. We assessed each domain separately and critically, and our score system is based on GRADE (Grading of Recommendations, Assessment, Development and Evaluations), which is a transparent framework for developing and presenting summaries of evidence and provides a systematic approach for making clinical practice recommendations. We classified them as low risk of bias, unclear risk or high risk of bias according to the criteria set out in the Cochrane Handbook. ⁸

Statistical analysis

Initially, we analysed all studies separately, replicating the originally reported findings using the methods described in the respective publications. Any inconsistencies were resolved with the authors of the original studies. To optimise the interpretability of our findings for continuous outcomes, we used network estimates of treatment effects to model the odds ratio (OR) of achieving a mean difference (MD), i.e. the smallest change in patient-reported outcomes that patients considered important. The broad Cochran’s Q statistic was used to assess homogeneity in multivariate meta-analyses. In detail, an I²value of 0% indicates no heterogeneity, 25% indicates low heterogeneity, 25–50% indicates moderate heterogeneity and 50% indicates high heterogeneity. In addition, a random effects model was used when heterogeneity was observed and a fixed effects model was used when no heterogeneity was modelled. Potential publication bias was assessed by visual inspection of funnel plots and Egger’s test for small study effects. Further sensitivity analyses were conducted to assess the robustness of the results via exponential skewing.

Search process

A total of 780 titles and abstracts were identified through the screening electronic search strategy, of which 8 were eligible for assessment. Eight studies describing 16 study groups met the inclusion criteria and were included in the meta-analysis.

After title and abstract review, 372 studies were excluded due to duplication and 400 studies were excluded because they did not meet inclusion criteria based on article type, study design, study population or relevant outcomes. After exclusion, eight articles were included in our meta-analysis. In total, we retrieved 8 studies that met all inclusion criteria (Figure 1).^9–16OPEN IN VIEWER

Characteristics of included studies

The sample sizes for the various studies ranged from 41 to 1946 people. A total of 3086 patients were included, of whom 1553 were treated with statins and 1533 were in the placebo group. The primary outcomes included SBP and DBP. Table 1 represents the detailed characteristics of the eight included studies.^9–16

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Table 1.

Baseline characteristics of included studies.

Study	Year	Type of study	Country	Ethnicity	Intervention	Mean age (years)	n
9	2012	RCT	Turkey	Caucasian	Placebo	62.80 ± 6.80	24
					Statin	61.80 ± 7.67	38
10	2008	RCT	USA	Caucasian	Placebo	57.7	973
					Statin	56.8	973
11	2010	RCT	Italia	Caucasian	Placebo	58.3 (6.5)	254
					Statin	58.3 (6.5)	253
12	2011	RCT	China	Mongoloid	Placebo	—	20
					Statin	—	21
13	2012	RCT	China	Mongoloid	Placebo	58 ± 6.5	37
					Statin	59 ± 7.7	43
14	2014	RCT	China	Mongoloid	Placebo	48.1 ± 7.0	102
					Statin	48.6 ± 7.2	102
15	2012	RCT	China	Mongoloid	Placebo	59 ± 7.7	59
					Statin	60 ± 18	59
16	2020	RCT	China	Mongoloid	Placebo	20.16 ± 4.4	64
					Statin	20.19 ± 4.46	64

Results of quality assessment

A qualitative assessment was conducted by using the Cochrane Risk of Bias tool to assess various indicators for each study (Figure S1). Scores ranged from 7 to 8, with nine studies scoring above 7. Given the bias summary, selection bias, detection bias and other biases were not an issue. Two trials were at risk of bias and seven were not (Figure S2).

Results of heterogeneity test

In eight studies involving 3086 patients, a comparison of systolic blood pressure (SBP) between the statin and placebo groups was reported. A meta-analysis showed a difference between the two groups (MD = 4.37, 95% CI [0.72, 8.02], p = .02, random effects model) (Figure 2).OPEN IN VIEWER

A meta-analysis was also performed on the diastolic blood pressure (DBP) of patients in the statin and placebo groups. The results showed no significant difference in DBP between the two groups (MD = 2.48, 95% CI [−2.00, 6.96], p = .28, random effects model) (Figure 3).OPEN IN VIEWER

Results of Sensitivity Analysis and Publication Bias

A total of eight studies reported SBP. The forest plots showed that the statin group was superior to the placebo group (MD = 4.37, 95% CI [0.72, 8.02], p = .02, p = .02, I² = 99%). We performed a sensitivity analysis by removing Beatrice’s 2008 study and the results were little changed, with I² = 92% from 99% (Figure 4), indicating that the results of the included articles were robust.OPEN IN VIEWER

We also drew a funnel plot to assess the publication bias of SBP between the statin and placebo groups; the plot shows its shape to be symmetrical. This result indicates that there was little publication bias in this meta-analysis (Figure S3).

Results of meta regression

From the results of meta regression, we found the main causes of high heterogeneity in SBP between the statin and placebo were age, gender and sample size (Table 2).

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Table 2.

Meta regression of included studies.

	Estimate	se	zval	pval	ci.lb	ci.ub
Country	0.3746	0.1951	1.9205	0.0548	−0.0077	0.7569
Age	−0.2389	0.0544	−4.3916	<.0001	−0.3455	−0.1323
Gender	3.2209	0.6701	4.8063	<.0001	1.9074	4.5343
Size	−0.0016	0.0003	−4.5833	<.0001	−0.0023	−0.0009

Limitation

This study also had some limitations. Firstly, dynamic changes in blood pressure were not analysed in this study. Secondly, due to the limited raw data, no further stratified comparisons of complications were made.