Abstract
Objectives:Vasodilating antihypertensives prevent stroke and potentially cerebral small vessel disease but their effects on cerebrovascular haemodynamics beyond blood pressure lowering are unclear.Methods:We searched PubMed, Medline, Embase, Cinahl, Psychinfo, Health Business Elite and Health Management Information Consortium for randomized studies of vasodilating medications, compared to no treatment or nonvasodilators, that reported effects on cerebral blood flow (CBF), mean blood flow velocity (MFV) or cerebrovascular reactivity. Absolute and standardized mean differences (SMD) were combined by inverse-variance weighted fixed or random-effects meta-analysis stratified by study design, population characteristics and vasodilator class.Results:In 35 studies reporting 57 comparisons, there was a reduction in SBP (−4.13 mmHg, −7.55 to −0.71, P = 0.018) but no change in MFV (ΔMFV 1.11, confidence interval −0.93 to 3.14, P = 0.29, 23 comparisons). MFV increased in patients with underlying conditions (3.41, 0.24 to 6.57, P = 0.04) but not in healthy study participants (−1.27, −5.18 to 2.64, P = 0.68), with no differences by vasodilating drug class. Cerebral pulsatility index was reduced across all studies (Δ pulsatility index −0.04, −0.07 to −0.02, P = 0.001; Δ pulsatility index -SMD −0.32, −0.47 to −0.16, P < 0.001), except in studies reporting responses to single drug doses (Δ pulsatility index 0.00, −0.09 to −0.08, P = 0.93). Despite evidence of reporting and publication bias, there was an apparent consistent reduction in CBF with vasodilators (CBF-SMD −0.24, −0.46 to −0.02, P = 0.03) with a significant increase in cerebrovascular reactivity-SMD (0.48, 0.13–0.83, P = 0.007).Conclusions:Despite reducing SBP, vasodilators did not significantly impair absolute CBF but improved cerebrovascular pulsatility and reactivity, suggesting therapeutic potential in preventing stroke and cerebral small vessel disease.
Highlights
Blood pressure (BP)-lowering treatment significantly reduces the risk of recurrent stroke [1] and probably reduces cerebral small vessel disease [2]
In 35 studies reporting 57 comparisons, there was a reduction in SBP (À4.13 mmHg, À7.55 to À0.71, P 1⁄4 0.018) but no change in mean blood flow velocity (MFV) (DMFV 1.11, confidence interval À0.93 to 3.14, P 1⁄4 0.29, 23 comparisons)
MFV increased in patients with underlying conditions (3.41, 0.24 to 6.57, P 1⁄4 0.04) but not in healthy study participants (À1.27, À5.18 to 2.64, P 1⁄4 0.68), with no differences by vasodilating drug class
Summary
Blood pressure (BP)-lowering treatment significantly reduces the risk of recurrent stroke [1] and probably reduces cerebral small vessel disease [2]. Antiplatelet medications with pleiotropic vasodilating actions (cilostazol [5], dipyridamole [6]) appear to reduce recurrent stroke more than expected from their antiplatelet effects alone. These differences may be because of systemic effects on BP variability [1] or central aortic BP [7], but could reflect the transmission of systemic haemodynamic effects to the cerebral circulation [8] or direct effects of treatment on cerebrovascular haemodynamics [9]. Studies have been underpowered, have not meta-analyzed results because of insufficient studies with significant heterogeneity and have focused on specific conditions, drugs or specific physiological
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