title: Effect of Perindopril on Cerebral and Renal Perfusion in Stroke Patients With Carotid Disease Comparison of the Effect of Perindopril and Acebutolol on Cerebral Hemodynamics in Hypertensive Patients Should hypertension be treated after acute stroke? A randomized controlled trial using single photon emission computed tomography. Long-Term Angiotensin-Converting Enzyme Inhibitor Perindopril Therapy Improves Cerebral Perfusion Reserve in Patients With Previous Minor Stroke Blood pressure and risk of headache: a prospective study of 22 685 adults in Norway Hemodynamic Influences of Losartan on the Brain in Hypertensive Patients Verapamil prophylaxis of migraine. A double-blind, placebo-controlled study. Cerebral hemodynamics in young hypertensive subjects and effects of atenolol treatment Comparison of isradipine and enalapril effects on regional carotid circulation in patients with hypertension with unilateral internal carotid artery stenosis. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. The effect of losartan on global and focal cerebral perfusion and on renal function in hypertensives in mild early ischaemic stroke Amlodipine compared to nitrendipine in hypertensive patients: the effects on toleration in relationship to the onset of action.
abstract: Background and Purpose — The purpose of this study was to investigate the effect of the angiotensin-converting enzyme inhibitor perindopril on mean arterial blood pressure ( MABP ) , cerebral blood flow ( CBF ) , and glomerular filtration rate in hypertensive stroke patients with moderate to severe internal carotid artery ( ICA ) disease or ICA occlusion . Methods — Twenty-four nonacute ischemic stroke patients who had MABP readings > 100 mm Hg and moderate to severe ICA stenosis or occlusion were r and omized to receive perindopril 4 mg daily or placebo for 14 days . MABP , ICA flow , and both middle cerebral artery ( MCA ) velocity and resistance index were measured before dose , at 5 time points over the subsequent 24 hours , and finally at 2 weeks . Brain hexamethyl propylene amine oxide single photon emission computed tomography scans were performed before drug administration and at time of peak drug effect ( 6 to 8 hours ) after the first dose . Glomerular filtration rate was measured with 51Cr EDTA before medication and at 14 days . Results — A placebo-corrected BP fall of 17/10 mm Hg was seen ( P = 0.017 ) , which was maximal at 5.5 hours . No significant change in ICA flow or MCA velocity was seen between groups . No significant change in hemispheric CBF was seen . The mean change from baseline in the treated group was −0.79 mL · 100 g−1 · min−1 ( 95 % confidence interval [ CI ] , 1.65 to −3.23 ) ; mean change in the placebo group was −1.9 mL · 100 g−1 · min−1 ( 95%CI , 3.02 to −6.92 ) . Peri-infa rct CBF was similarly unaffected . One of the treated patients developed transient acute renal impairment and was withdrawn from the study on day 4 . Conclusions — Perindopril lowers BP without lowering CBF in hypertensive stroke patients with moderate to severe ICA stenosis or occlusion ; monitoring of this patient population for the complications of renal artery stenosis should be considered Abstract Purpose : The aim of the study was to compare effect of perindopril ( 4 mg once a day ) versus acebutolol ( 400 mg once a day ) on cerebral hemodynamics in hypertensive patients . Methods : Thirty untreated patients with mild-to-mode-rate hypertension were studied . Drug influences on Doppler-derived parameters from the cerebral blood flow ( CBF ) velocity wave form were evaluated in a r and omized , double blind , cross-over , placebo controlled study . The mean CBF velocity , pulsatility index ( PI ) , cerebrovascular resistance and index of CBF were calculated from concomitant transcranial Doppler measurements and systemic blood pressure . Results : Acebutolol and perindopril significantly decreased systolic , diastolic and mean blood pressure in relation to placebo . The mean value of CBF velocity increased to a comparable level after both drugs ( 54.9 ± 9.1 cm/s on placebo vs 62.8 ± 14.5 cm/s on perindopril p < 0.01 and 61.4 ± 9.2 cm/s on acebutolol , p < 0.01 ) . Also , the cerebrovascular resistance index decreased similarly after both drugs ( 2.26 ± 0.35 on placebo vs 1.68 ± 0.42 on perindopril p < 0.01 and 1.7 ± 0.36 on acebutolol p < 0.01 ) . The calculated CBF index increased significantly after each drug ( 25.23 ± 7.99 on placebo vs 33.98 ± 11.23 p < 0.01 on perindopril and 30.90 ± 8.04 on acebutolol p < 0.01 ) . However , perindopril augmented the CBF index more effectively than acebutolol ( p < 0.05 ) . Conclusions : Among patients with mild-to-moderate hypertension  both acebutolol and perindopril beneficially decreased cerebrovascular resistance and increased the CBF index in comparison with placebo . The increase of CBF index was greater after perindopril than acebutolol , which suggests a more significant improvement in cerebral perfusion by perindopril . The non-invasive transcranial Doppler ultrasonography method of CBF velocity measurement may contribute to choosing optimal antihypertensive therapies and to monitor their effect OBJECTIVE To determine if previously hypertensive patients with acute ischemic stroke should be treated with antihypertensive medication in the immediate poststroke period . DESIGN R and omized double-blind , placebo-controlled trial . SETTING Sixteen consecutive hypertensive patients ( four men and 12 women ; mean age , 66 years [ age range , 46 to 83 years ] ) with middle cerebral artery infa rct ion within 72 hours of onset and blood pressure between 170 and 220 mm Hg(systolic ) and 95 and 120 mm Hg ( diastolic ) . INTERVENTION Placebo ( n = 6 ) , nicardipine hydrochloride ( 20 mg [ n = 5 ] ) , captopril ( 12.5 mg [ n = 3 ] ) , or clonidine hydrochloride ( 0.1 mg [ n = 2 ] ) given every 8 hours for 3 days . MAIN OUTCOME MEASURES Decline in blood pressure , change in cerebral blood flow as measured by single photon emission computed tomography , and clinical change as determined by the National Institutes of Health Stroke Scale . RESULTS Blood pressure fell significantly in both the drug-treated group as a whole and in those patients receiving placebo ( P < .001 ) . There was no difference in blood pressure levels between these two groups throughout the study period . Patients receiving nicardipine had a consistently lower pressure than the other groups . A significant negative relationship was noted between the maximum blood pressure fall and improvement in cerebral blood flow . There were four patients whose blood pressure dropped by more than 16 % of the baseline value on any 24 hours in the first 3 days . All either failed to increase or actually decreased their cerebral blood flow to the affected area . Three of these patients were treated with nicardipine . There was no significant difference in clinical course between the placebo- and drug-treated groups as a whole . CONCLUSIONS Hypertensive ischemic stroke patients with a moderate elevation of blood pressure in the first few days may not require antihypertensive therapy . Nicardipine and possibly other calcium channel blockers may cause an excessive fall in blood pressure and impair cerebral blood flow in these patients and should therefore be used with caution Background and Purpose — Angiotensin-converting enzyme ( ACE ) inhibitor – based therapy reduces the recurrence of stroke . The present study assessed the effects of long-term ACE inhibitor therapy on cerebral circulation in patients with previous minor stroke . Methods — After a run-in period , 19 patients were r and omized to ACE inhibitor therapy ( n=9 ; 4 mg of perindopril daily ; mean age , 64±8 years ; mean systolic/diastolic blood pressure [BP]±SD , 133±12/77±9 mm Hg ) or placebo therapy ( n=10 ; mean age , 66±9 years ; mean BP , 139±10/78±8 mm Hg ) . Cerebral blood flow ( CBF ) was measured during hypercapnia , normocapnia , and hypocapnia using a positron emission tomography with H215O at entry into the study and after 3 to 12 months . Cerebral perfusion reserve ( CPR ) was defined as percent CBF response to a 1 mm Hg change in arterial partial pressure of CO2 between hypercapnia and hypocapnia . Results — Systolic/diastolic BP and CBF during normocapnia showed no significant changes between entry and completion of the trial in the perindopril and placebo groups . Mean value of CPR showed a significant increase in the perindopril group ( from 3.7±1.7%/mm Hg to 4.8±1.7%/mm Hg ; P < 0.05 ) but not in the placebo group ( from 4.1±0.8%/mm Hg to 4.2±0.6%/mm Hg ; NS ) . Statistical parametric mapping analysis also showed global and significant increase ( P < 0.01 , uncorrected ) in CPR in the perindopril group alone . Conclusions — Long-term ACE inhibitor – based therapy had a beneficial effect on the cerebral circulation by improving CPR in patients with previous minor stroke Objectives : Prevalence studies of the association between blood pressure and headache have shown conflicting results . The aim was to analyse the relation between blood pressure and risk of headache in a prospect i ve study . Methods : A total of 22 685 adults not likely to have headache , had their baseline blood pressure measured in 1984–6 , and responded to a headache question naire at follow up 11 years later ( 1995–7 ) . The relative risk of headache ( migraine or non-migrainous headache ) was estimated in relation to blood pressure at baseline . Results : Those with a systolic blood pressure of 150 mm Hg or higher had 30 % lower risk ( risk ratio (RR)=0.7 , 95 % CI 0.6–0.8 ) of having non-migrainous headache at follow up compared with those with systolic pressure lower than 140 mm Hg . For diastolic blood pressure , the risk of non-migrainous headache decreased with increasing values , and these findings were similar for both sexes , and were not influenced by use of antihypertensive medication . For migraine , there was no clear association with blood pressure . Conclusion : In the first prospect i ve study of blood pressure and the risk of headache , high systolic and diastolic pressures were associated with reduced risk of non-migrainous headache . One possible explanation may be the phenomenon of hypertension associated hypalgesia , which probably involves the baroreflex system influencing nociception in the brain stem or spinal cord The effects of angiotensin II receptor blockers on cerebral hemodynamics in humans have not been well eluci date d. The present study evaluated the effects of losartan on cerebral hemodynamics in hypertensive patients using positron emission tomography . Ten patients with essential hypertension ( mean age , 60.8 years ) were examined . In each patient , regional cerebral blood flow was measured by [ O-15 ] labeled water positron emission tomography before and after the oral administration of losartan for 8 to 23 weeks . In 8 patients , the baseline regional cerebral blood flow measurement was followed by 1,000 mg of acetazolamide challenge to measure the cerebral perfusion reserve . Systemic blood pressures before and after treatment were 153.8±10.8/96.0±6.5 mmHg ( systolic mean±SD/diastolic mean±SD ) and 133.4±11.2/83.6±6.5 mmHg , respectively ; this difference was significant . The baseline global cerebral blood flow values before and after treatment were 38.4±6.9 ml/min/100 g and 38.2±8.2 ml/min/100 g , respectively ; this difference was not significant . The results of the global cerebral blood flow response to the acetazolamide challenges were not statistically different before and after treatment . A regional analysis showed no statistical difference in regional cerebral blood flow or cerebral perfusion reserve throughout the brain before and after treatment . Losartan 's effect on reducing the blood pressure did not affect either the baseline regional cerebral blood flow or the cerebral perfusion reserve in patients with mild to moderate hypertension . The inclusion of losartan in anti-hypertensive regimens could be advantageous for cerebral circulation in patients with essential hypertension We undertook a double-blind , placebo-controlled study to determine the effectiveness of verapamil hydrochloride for the prophylaxis of  migraine . Twelve patients were given either verapamil hydrochloride  , 80 mg four times daily , or placebo in r and om order during two consecutive three-month periods . Migraine frequency , severity , and duration were quantified by daily logs and monthly question naires . Ten of the 12 patients had fewer migraines during verapamil therapy . Migraine frequency decreased from 6.7 to 3.8 migraines per patient per month , for a mean decrease of 49 % . Headache unit index fell from an average of 0.61 to 0.44 . We conclude that verapamil is effective in the prophylaxis of migraine and that verapamil might be considered one alternative in the development of a regimen for the prophylaxis of migraine The aim of this study was to evaluate changes in cerebral hemodynamics in young patients with uncomplicated hypertension before and after effective antihypertensive treatment with a beta-blocker drug . Changes in mean flow velocity in the middle cerebral artery from normal condition to hypercapnia were evaluated by means of a transcranial Doppler in 42 hypertensive patients and 21 healthy subjects comparable for age and sex distribution . We obtained hypercapnia with breath-holding and evaluated cerebrovascular reactivity with the breath-holding index ( BHI ) . After a baseline evaluation ( time 0 ) , patients were r and omly assigned to a placebo ( group 1 ) or atenolol ( group 2 ) therapy . The evaluation was repeated after 30 ( time 1 ) and 60 ( time 2 ) days of treatment . Before treatment , hypertensive patients had significantly lower BHI values ( 0.96 + /- 0.1 group 1 and 0.85 + /- 0.3 group 2 ) than controls ( 1.69 + /- 0.4 ) ( P < 0.0001 ) . During treatment , mean blood pressure significantly decreased in group 2 patients . In the same group , BHI values significantly increased with respect to the pre-treatment evaluation : 1.39 + /- 0.2 at time 1 and 1.44 + /- 0.2 at time 2 ( P < 0.0001 ) . On the contrary , mean blood pressure and BHI values remained unchanged in the placebo group . Furthermore , BHI values were significantly higher in group 2 than in group 1 patients at times 1 ( P < 0.001 ) and 2 ( P < 0.0001 ) . These findings suggest that hypertension causes reduced capability of cerebral vessels to adapt to functional changes . This condition , which is reversible after treatment , could be implicated in the increased susceptibility to ischemic stroke in hypertension This r and omized , double-blind , placebo-controlled study was aim ed at detecting cerebrovascular effects of isradipine and enalapril in patients with moderate hypertension depending on the presence and grade on unilateral stenosis of internal carotid artery ( ICA ) . We evaluated carotid vascular resistance by using Doppler analysis and regional cerebral blood flow ( rCBF ) by using 133Xe-clearance technique before and after a single 5-mg oral dose of isradipine , enalapril , or placebo . Their effects were r and omly and consecutively tested in 73 patients with essential hypertension subdivided into three groups : without carotid occlusive lesions , with moderate ( 50 - 75 % ) , and with severe ( 76 - 99 % ) unilateral asymptomatic ICA stenosis . There were no differences in age , gender , and antihypertensive effects of the drugs between these three subgroups . Three major variants of cerebrovascular drug effects were observed : absence of changes ( variant I ) , decrease in carotid vascular resistance with increase in rCBF and elimination of side-to-side asymmetry ( variant II ) , and increase in carotid vascular resistance with further reduction of rCBF ipsilaterally ICA stenosis , and increased side-to-side asymmetry ( variant III ) . Frequency of variant III was significantly higher in patients with severe ICA stenosis .  Enalapril produced variant I of cerebrovascular effects in most patients examined ; variant III was observed only in 13 % of patients with severe ICA stenosis . Isradipine produced variant I of cerebrovascular effects much less frequently than did enalapril . For this drug , variant II was most typical in patients without ICA stenosis and with moderate ICA stenosis . In 43.5 % of patients with severe ICA stenosis , however , isradipine produced reduction of cerebral perfusion . Presumably the presence of ICA stenosis , especially > 75 % , increases the risk of cerebrovascular disorders in antihypertensive therapy . In patients with severe ICA stenosis , treatment with enalapril appears to be safer than that with isradipine CONTEXT There is a paucity of effective , well-tolerated drugs available for migraine prophylaxis . OBJECTIVE To determine whether treatment with the angiotensin II receptor blocker c and esartan is effective as a migraine-prophylactic drug . DESIGN AND SETTING R and omized , double-blind , placebo-controlled crossover study performed in a Norwegian neurological outpatient clinic from January 2001 to February 2002 . PATIENTS Sixty patients aged 18 to 65 years with 2 to 6 migraine attacks per month were recruited mainly from newspaper advertisements . INTERVENTIONS A placebo run-in period of 4 weeks was followed by two 12-week treatment periods separated by 4 weeks of placebo washout . Thirty patients were r and omly assigned to receive one 16-mg c and esartan cilexetil tablet daily in the first treatment period followed by 1 placebo tablet daily in the second period . The remaining 30 received placebo followed by c and esartan . MAIN OUTCOME MEASURES The primary end point was number of days with headache ; secondary end points included hours with headache , days with migraine , hours with migraine , headache severity index , level of disability , doses of triptans , doses of analgesics , acceptability of treatment , days of sick leave , and quality -of-life variables on the Short Form 36 question naire . RESULTS In a period of 12 weeks , the mean number of days with headache was 18.5 with placebo vs 13.6 with c and esartan ( P = .001 ) in the intention-to-treat analysis ( n = 57 ) . Some secondary end points also favored c and esartan , including hours with headache ( 139 vs 95 ; P<.001 ) , days with migraine ( 12.6 vs 9.0 ; P<.001 ) , hours with migraine ( 92.2 vs 59.4 ; P<.001 ) , headache severity index ( 293 vs 191 ; P<.001 ) , level of disability ( 20.6 vs 14.1 ; P<.001 ) and days of sick leave ( 3.9 vs 1.4 ; P = .01 ) , although there were no significant differences in health-related quality of life . The number of c and esartan responders ( reduction of > or = 50 % compared with placebo ) was 18 ( 31.6 % ) of 57 for days with headache and 23 ( 40.4 % ) of 57 for days with migraine . Adverse events were similar in the 2 periods . CONCLUSION In this study , the angiotensin II receptor blocker c and esartan provided effective migraine prophylaxis , with a tolerability profile comparable with that of placebo Background Secondary prevention of stroke with antihypertensive drugs is now st and ard practice , but it is unclear how soon after a cerebrovascular event antihypertensive therapy should be initiated or re-started . Due to impaired cerebral autoregulation , changes in systemic blood pressure may be reflected in cerebral perfusion , especially in hypertensive patients immediately post-stroke . Conversely , early initiation in hospital may better assure continued long-term treatment . We have investigated the effect of the angiotensin II receptor antagonist ( ARA ) losartan on mean arterial blood pressure ( MABP ) , global and focal cerebral blood flow ( CBF ) , and glomerular filtration rate ( GFR ) in hypertensive patients 2–7 days after stroke . Methods Twenty-four patients without occlusive carotid disease but with MABP between 110 and 145 mmHg were studied within 2–7 days of ischaemic stroke/transient ischaemic attack ( TIA ) . They were r and omized to receive either placebo or losartan ( 25 or 50 mg daily ) . MABP and internal carotid artery ( ICA ) flow were measured at baseline , over the following 24 h and at 2 weeks . Brain hexamethylpropyleneamine oxime single photon emission computed tomography ( HMPAO SPECT ) was performed before dosing and at the estimated time of peak drug effect ( 6–8 h after the first dose ) . GFR was measured at baseline and at 2 weeks . Results The mean National Institutes of Health ( NIH ) score of r and omized patients was 2.6 ; losartan was generally well tolerated and no patient suffered a deterioration in neurological function . A mean placebo-corrected intra-subject reduction in MABP of 9.5 mmHg was observed in treated patients from 1–12 h ( P = 0.0001 ) , with a maximal fall of 18.1 mmHg at 9 h post-dose ( P = 0.002 ) . No change occurred in ICA flow , or cortical or hemispheric CBF measured by HMPAO SPECT . No significant change in GFR was seen within or between groups . Discussion Losartan may be introduced within 2–7 days of mild stroke in hypertensive patients in whom significant carotid occlusive disease has been excluded without affecting global or regional CBF , or affecting GFR Amlodipine and nitrendipine are calcium antagonists of the 1,4-dihydropyridine group which differ in their pharmacokinetic and pharmacodynamic properties . The clinical relevance of these differences was investigated in a study design ed to compare the efficacy and safety of once-daily amlodipine ( 5 mg ) and nitrendipine ( 20 mg ) in patients with mild-to-moderate essential hypertension . Ambulatory blood pressure monitoring and conventional measurements showed that amlodipine and nitrendipine produced comparable reductions in blood pressure after 4 weeks of treatment . However , the onset of the antihypertensive effect was gradual for amlodipine , while most of the reduction achieved at the end of treatment with nitrendipine was seen after the first dose . There were no significant changes in heart rate with amlodipine , but significant increases occurred during the first 6 h of nitrendipine treatment . Amlodipine was associated with a significantly lower incidence of vasodilator-related adverse effects at initiation of therapy ( headache , flushing , tachycardia ) compared with nitrendipine , which may reflect its slower onset of action . The different pharmacodynamic and toleration profiles of amlodipine and nitrendipine at therapeutically equivalent doses suggest that amlodipine may have advantages in the treatment of hypertension , especially in terms of the low incidence of acute side effects , which may ultimately translate into improved patient compliance
target: Antihypertensive drugs reduce headache but it is unclear whether there are differences between drug classes .
  Calcium channel blockers ( CCBs ) decrease variability in systolic blood pressure ( SBPV ) and stroke risk more than other classes , possibly due to decreased vascular tone .
  If so , there might be a correlation between drug-class effects on variability in SBP and on headache .
  Antihypertensive drugs reduce headache but the effect differs between classes , corresponding to their effects on SBPV and the risk of stroke .
  This may partly be explained by consistent antihypertensive class effects on vascular tone in the peripheral ( variability ) and cerebrovascular circulations ( headache )
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