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Meta-Analysis
. 2020 Oct 5;10(10):e036960.
doi: 10.1136/bmjopen-2020-036960.

Antihypertensive therapies in moderate or severe aortic stenosis: a systematic review and meta-analysis

Jonathan Sen  1   2 , Erin Chung  3 , Christopher Neil  1   2 , Thomas Marwick  4   2
Affiliations
Meta-Analysis

Antihypertensive therapies in moderate or severe aortic stenosis: a systematic review and meta-analysis

Jonathan Sen et al. BMJ Open. .

Abstract

Background: Hypertension confers a poor prognosis in moderate or severe aortic stenosis (AS), however, antihypertensive therapy (AHT) is often not prescribed due to the perceived deleterious effects of vasodilation and negative inotropes.

Objective: To assess the efficacy and safety outcomes of AHT in adults with moderate or severe AS.

Design: Systematic review and meta-analysis.

Data sources: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and grey literature were searched without language restrictions up to 9 September 2019.

Study eligibility criteria, appraisal and synthesis methods: Two independent reviewers performed screening, data extraction and risk of bias assessments from a systematic search of observational studies and randomised controlled trials comparing AHT with a placebo or no AHT in adults with moderate or severe AS for any parameter of efficacy and safety outcomes. Conflicts were resolved by the third reviewer. Meta-analysis with pooled effect sizes using random-effects model, were estimated in R.

Main outcome measures: Mortality, Left Ventricular (LV) Mass Index, systolic blood pressure, diastolic blood pressure and LV ejection fraction RESULTS: From 3025 publications, 31 studies (26 500 patients) were included in the qualitative synthesis and 24 studies in the meta-analysis. AHT was not associated with mortality when all studies were pooled, but heterogeneity was substantial across studies. The effect size of AHT differed according to drug class. Renin-angiotensin-aldosterone system inhibitors (RAASi) were associated with reduced risk of mortality (Pooled HR 0.58, 95% CI 0.43 to 0.80, p=0.006), The differences in changes of haemodynamic or echocardiographic parameters from baseline with and without AHT did not reach statistical significance.

Conclusion: AHT appears safe, is well tolerated. RAASi were associated with clinical benefit in patients with moderate or severe AS.

Keywords: adult cardiology; hypertension; valvular heart disease.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from Australian Government Research Training Program (Research Scholarship) for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1
Flow diagram of study selection.
Figure 2
Figure 2
Risk-of-bias assessment of randomised controlled trials. Risk-of-bias summary (A) and graph (B).
Figure 3
Figure 3
Forest plot of the effect of antihypertensive therapies on all-cause mortality at follow-up. ACEi, ACE inhibitor; BB, beta-blockers.
Figure 4
Figure 4
Forest plot of the effect of antihypertensive therapies on HR of all-cause mortality at follow-up. ACEi, ACE inhibitor; AS, aortic stenosis; RAAS, renin-angiotensin and aldosterone systems.
Figure 5
Figure 5
Forest plot of the effect of antihypertensive therapies on (A) change in Left Ventricular Mass Index (LVMI) and (B) post-LVMI. RAAS, renin–angiotensin and aldosterone systems; SMD, standardised mean difference.
Figure 6
Figure 6
Forest plot of the effect of antihypertensive therapies on change in (A) systolic blood pressure and (B) diastolic blood pressure during follow-up. RAAS, renin-angiotensin and aldosterone systems; SMD, standardised mean difference.
Figure 7
Figure 7
Forest plot of the effect of antihypertensive therapies on change in left ventricular ejection fraction during follow-up. RAAS, renin–angiotensin and aldosterone systems; SMD, standardised mean difference.
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