J Stroke.  2021 Jan;23(1):1-11. 10.5853/jos.2020.02698.

Role of Blood Pressure Management in Stroke Prevention: A Systematic Review and Network Meta-Analysis of 93 Randomized Controlled Trials

• Zhong XL
• Dong Y
• Xu W
• Huang YY
• Wang HF
• Zhang TS
• Sun L
• Tan L
• Dong Q
• Yu JT

• KMID: 2512351
• DOI: http://doi.org/10.5853/jos.2020.02698

Abstract

Background and Purpose
The present study aimed to compare the efficacy and tolerability of different blood pressure (BP)-lowering strategies.
Methods
Randomized controlled trials that compared various antihypertensive treatments and stroke outcomes were included. Eligible trials were categorized into three scenarios: single or combination antihypertensive agents against placebos; single or combination agents against other agents; and different BP-lowering targets. The primary efficacy outcome was the risk reduction pertaining to strokes. The tolerability outcome was the withdrawal of drugs, owing to drug-related side effects (PROSPERO registration number CRD42018118454 [20/12/2018]).
Results
The present study included 93 trials (average follow-up duration, 3.3 years). In the pairwise analysis, angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) were inferior to calcium channel blockers (CCBs) (odds ratio [OR], 1.123; 95% confidence interval [CI], 1.008 to 1.252) (OR, 1.261; 95% CI, 1.116 to 1.425) for stroke prevention, BB was inferior to angiotensin II receptor blockers (ARB) (OR, 1.361; 95% CI, 1.142 to 1.622), and diuretics were superior to ACEi (OR, 0.871; 95% CI, 0.771 to 0.984). The combination of ACEi+CCB was superior to ACEi+diuretic (OR, 0.892; 95% CI, 0.823 to 0.966). The network meta-analysis confirmed that diuretics were superior to BB (OR, 1.34; 95% CI, 1.11 to 1.58), ACEi+diuretic (OR, 1.47; 95% CI, 1.02 to 2.08), BB+CCB (OR, 2.05; 95% CI, 1.05 to 3.79), and renin inhibitors (OR, 1.87; 95% CI, 1.25 to 2.75) for stroke prevention. Regarding the tolerability profile, the pairwise analysis revealed that ACEi was inferior to CCB and less tolerable, compared to the other treatments.
Conclusions
Monotherapy using diuretics, CCB, or ARB, and their combinations could be employed as first-line treatments for stroke prevention in terms of efficacy and tolerability.

Keyword

Antihypertensive agents; Stroke; Meta-analysis

Figure

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  Figure 1. Flow diagram depicting the study selection.

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  Figure 2. Significance of systolic blood pressure reduction pertaining to multiple outcomes. OR, odds ratio; CI, confidence interval; MI, myocardial infarction.

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  Figure 3. Association of blood pressure lowering and stroke prevention, categorized in accordance with the multiple study characteristics. OR, odds ratio; CI, confidence interval; CVD, cardiovascular disease; DM, diabetes mellitus; SBP, systolic blood pressure.

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  Figure 4. (A) Network of the studies included in the review with the available direct comparisons regarding efficacy. (B) Network of the studies included in the review with the available direct comparisons regarding tolerability. The width of the lines and the size of the nodes are proportional to the number of studies compared in each pair of treatments and the total sample size pertaining to each treatment, respectively. ARB, angiotensin II receptor blocker; ACEi, angiotensin-converting enzyme inhibitor; CCB, calcium channel blocker; BB, beta-blocker.

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  Figure 5. Comparative efficacy and tolerability of all blood pressure lowering treatments in stroke prevention, as per the network meta-analyses. Effect sizes represent summary odds ratios and 95% credible intervals. In the upper triangle (efficacy in stroke prevention), values greater than 1 favor the treatment in the corresponding row, whereas values less than 1 favor the treatment in the corresponding column. In the lower triangle (tolerability), values greater than 1 favor the treatment in the corresponding column, whereas values less than 1 favor the treatment in the corresponding row. Significant results are in bold and underlined. CCB, calcium channel blocker; ARB, angiotensin II receptor blocker; ACEi, angiotensin-converting enzyme inhibitor; BB, beta-blocker.

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  Figure 6. Cluster ranking for efficacy and tolerability of blood pressure lowering treatments in network meta-analyses. Each color represents a group of treatments that belong to the same cluster. Treatments located on the upper right corner are more effective and acceptable, compared to the other treatments. ARB, angiotensin II receptor blocker; BB, beta-blocker; CCB, calcium channel blocker; ACEi, angiotensin-converting enzyme inhibitor.

Reference

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