Blood Pressure Reduction and Secondary Stroke Prevention: A Systematic Review and Metaregression Analysis of Randomized Clinical Trials.
Current recommendations do not specifically address the optimal blood pressure (BP) reduction for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention. For all reported events during each eligible study period, we calculated the corresponding risk ratios to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. On the basis of the reported BP values, we performed univariate metaregression analyses according to the achieved BP values under the random-effects model (Method of Moments) for those adverse events reported in ≥10 total subgroups of included randomized controlled clinical trials. In pairwise meta-analyses, antihypertensive treatment lowered the risk for recurrent stroke (risk ratio, 0.73; 95% confidence interval, 0.62-0.87; P<0.001), disabling or fatal stroke (risk ratio, 0.71; 95% confidence interval, 0.59-0.85; P<0.001), and cardiovascular death (risk ratio, 0.85; 95% confidence interval, 0.75-0.96; P=0.01). In metaregression analyses, systolic BP reduction was linearly related to the lower risk of recurrent stroke (P=0.049), myocardial infarction (P=0.024), death from any cause (P=0.001), and cardiovascular death (P<0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (P=0.026) and all-cause mortality (P=0.009). Funnel plot inspection and Egger statistical test revealed no evidence of publication bias. The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebrovascular and cardiovascular events. Strict and aggressive BP control seems to be essential for effective secondary stroke prevention.
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Aristeidis H
AH
Katsanos
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Angeliki
A
Filippatou
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Efstathios
E
Manios
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Spyridon
S
Deftereos
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
John
J
Parissis
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Alexandra
A
Frogoudaki
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Agathi-Rosa
AR
Vrettou
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Ignatios
I
Ikonomidis
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Maria
M
Pikilidou
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Odysseas
O
Kargiotis
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Konstantinos
K
Voumvourakis
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Anne W
AW
Alexandrov
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.).
Andrei V
AV
Alexandrov
From the Second Department of Neurology (A.H.K., A.F., K.V., G.T.) and Second Department of Cardiology (S.D., J.P., A.F., A.-R.V., I.I.), Attikon University Hospital, School of Medicine, University of Athens, Greece; Department of Neurology, University of Ioannina School of Medicine, Greece (A.H.K.); Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, University of Athens, Greece (E.M.); First Department of Internal Medicine, Hypertension Excellence Center, AHEPA University Hospital, Thessaloniki, Greece (M.P.); Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece (O.K.); Department of Neurology, University of Tennessee Health Science Center, Memphis (A.W.A., A.V.A., G.T.); Australian Catholic University, Sydney, Australia (A.W.A.); and International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic (G.T.). tsivgoulisgiorg@yahoo.gr.
Georgios
G
Tsivgoulis
D001794:Blood Pressure / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D040242:Risk Reduction Behavior; D055502:Secondary Prevention / Q000379:methods*; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*
D007004:Hypoglycemic Agents
antihypertensive agents; blood pressure; meta-analysis; regression analysis; stroke