U Fischer

Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis

INTRODUCTIONnUnexplained differences between classes of antihypertensive drugs in their effectiveness in preventing stroke might be due to class effects on intraindividual variability in blood pressure. We did a systematic review to assess any such effects in randomised controlled trials.nnnMETHODSnBaseline and follow-up data for mean (SD) of systolic blood pressure (SBP) were extracted from trial reports. Effect of treatment on interindividual variance (SD2) in blood pressure (a surrogate for within-individual variability), expressed as the ratio of the variances (VR), was related to effects on clinical outcomes. Pooled estimates were derived by use of random-effects meta-analysis.nnnFINDINGSnMean (SD) SBP at follow-up was reported in 389 (28%) of 1372 eligible trials. There was substantial heterogeneity between trials in VR (p<1 x 10(-40)), 68% of which was attributable to allocated drug class. Compared with other drugs, interindividual variation in SBP was reduced by calcium-channel blockers (VR 0.81, 95% CI 0.76-0.86, p<0.0001) and non-loop diuretic drugs (0.87, 0.79-0.96, p=0.007), and increased by angiotensin-converting enzyme (ACE) inhibitors (1.08, 1.02-1.15, p=0.008), angiotensin-receptor blockers (1.16, 1.07-1.25, p=0.0002), and beta blockers (1.17, 1.07-1.28, p=0.0007). Compared with placebo only, interindividual variation in SBP was reduced the most by calcium-channel blockers (0.76, 0.67-0.85, p<0.0001). Effects were consistent in parallel group and crossover design trials, and in analyses of dose-response. Across all trials, effects of treatment on VR of SBP (r2=0.372, p=0.0006) and on mean SBP (r2=0.328, p=0.0015) accounted for effects on stroke risk (eg, odds ratio 0.79, 0.71-0.87, p<0.0001, for VR< or =0.80), and both remained significant in a combined model.nnnINTERPRETATIONnDrug-class effects on interindividual variation in blood pressure can account for differences in effects of antihypertensive drugs on risk of stroke independently of effects on mean SBP.nnnFUNDINGnNone.

Acute post-stroke blood pressure relative to premorbid levels in intracerebral haemorrhage versus major ischaemic stroke: a population-based study

Summary Background It is often assumed that blood pressure increases acutely after major stroke, resulting in so-called post-stroke hypertension. In view of evidence that the risks and benefits of blood pressure-lowering treatment in acute stroke might differ between patients with major ischaemic stroke and those with primary intracerebral haemorrhage, we compared acute-phase and premorbid blood pressure levels in these two disorders. Methods In a population-based study in Oxfordshire, UK, we recruited all patients presenting with stroke between April 1, 2002, and March 31, 2012. We compared all acute-phase post-event blood pressure readings with premorbid readings from 10-year primary care records in all patients with acute major ischaemic stroke (National Institutes of Health Stroke Scale >3) versus those with acute intracerebral haemorrhage. Findings Of 653 consecutive eligible patients, premorbid and acute-phase blood pressure readings were available for 636 (97%) individuals. Premorbid blood pressure (total readings 13u2008244) had been measured on a median of 17 separate occasions per patient (IQR 8–31). In patients with ischaemic stroke, the first acute-phase systolic blood pressure was much lower than after intracerebral haemorrhage (158·5 mm Hg [SD 30·1] vs 189·8 mm Hg [38·5], p<0·0001; for patients not on antihypertensive treatment 159·2 mm Hg [27·8] vs 193·4 mm Hg [37·4], p<0·0001), was little higher than premorbid levels (increase of 10·6 mm Hg vs 10-year mean premorbid level), and decreased only slightly during the first 24 h (mean decrease from <90 min to 24 h 13·6 mm Hg). By contrast with findings in ischaemic stroke, the mean first systolic blood pressure after intracerebral haemorrhage was substantially higher than premorbid levels (mean increase of 40·7 mm Hg, p<0·0001) and fell substantially in the first 24 h (mean decrease of 41·1 mm Hg; p=0·0007 for difference from decrease in ischaemic stroke). Mean systolic blood pressure also increased steeply in the days and weeks before intracerebral haemorrhage (regression p<0·0001) but not before ischaemic stroke. Consequently, the first acute-phase blood pressure reading after primary intracerebral haemorrhage was more likely than after ischaemic stroke to be the highest ever recorded (OR 3·4, 95% CI 2·3–5·2, p<0·0001). In patients with intracerebral haemorrhage seen within 90 min, the highest systolic blood pressure within 3 h of onset was 50 mm Hg higher, on average, than the maximum premorbid level whereas that after ischaemic stroke was 5·2 mm Hg lower (p<0·0001). Interpretation Our findings suggest that systolic blood pressure is substantially raised compared with usual premorbid levels after intracerebral haemorrhage, whereas acute-phase systolic blood pressure after major ischaemic stroke is much closer to the accustomed long-term premorbid level, providing a potential explanation for why the risks and benefits of lowering blood pressure acutely after stroke might be expected to differ. Funding Wellcome Trust, Wolfson Foundation, UK Medical Research Council, Stroke Association, British Heart Foundation, National Institute for Health Research.

Identification of missed hypertension and hypertensive arteriopathy with home versus ambulatory blood pressure measurement in patients with TIA or minor stroke

Impaired cognitive function is often reported in patients with carotid artery stenosis. Revascularization by transcervical carotid artery stenting (CAS) with flow reversal is associated with increased cognition regardless of age, asymtomatic status, previous stroke events, baseline brain parenchyma status, and contralateral carotid artery stenosis. The findings of this preliminary prospective study suggest that transcervical CAS and stenting with flow reversal for cerebral protection is a safe technique that will improve, or at least not worsen, cognitive performance.Impaired cognitive function is often reported in patients with carotid artery stenosis. Revascularization by transcervical carotid artery stenting (CAS) with flow reversal is associated with increased cognition regardless of age, asymtomatic status, previous stroke events, baseline brain parenchyma status, and contralateral carotid artery stenosis. The findings of this preliminary prospective study suggest that transcervical CAS and stenting with flow reversal for cerebral protection is a safe technique that will improve, or at least not worsen, cognitive performance.

Response of Day-to-Day Home Blood Pressure Variability by Antihypertensive Drug Class After Transient Ischemic Attack or Nondisabling Stroke

Background and Purpose— Visit-to-visit variability in systolic blood pressure (SBP) is associated with an increased risk of stroke and was reduced in randomized trials by calcium channel blockers and diuretics but not by renin–angiotensin system inhibitors. However, time of day effects could not be determined. Day-to-day variability on home BP readings predicts stroke risk and potentially offers a practical method of monitoring response to variability-directed treatment. Methods— SBP mean, maximum, and variability (coefficient of variation=SD/mean) were determined in 500 consecutive transient ischemic attack or minor stroke patients on 1-month home BP monitoring (3 BPs, 3× daily). Hypertension was treated to a standard protocol. Differences in SBP variability from 3 to 10 days before to 8 to 15 days after starting or increasing calcium channel blockers/diuretics versus renin–angiotensin system inhibitors versus both were compared by general linear models, adjusted for risk factors and baseline BP. Results— Among 288 eligible interventions, variability in SBP was reduced after increased treatment with calcium channel blockers/diuretics versus both versus renin–angiotensin system inhibitors (−4.0 versus 6.9 versus 7.8%; P=0.015), primarily because of effects on maximum SBP (−4.6 versus −1.0 versus −1.0%; P=0.001), with no differences in effect on mean SBP. Class differences were greatest for early-morning SBP variability (3.6 versus 17.0 versus 38.3; P=0.002) and maximum (−4.8 versus −2.0 versus −0.7; P=0.001), with no effect on midmorning (P=0.29), evening (P=0.65), or diurnal variability (P=0.92). Conclusions— After transient ischemic attack or minor stroke, calcium channel blockers and diuretics reduced variability and maximum home SBP, primarily because of effects on morning readings. Home BP readings enable monitoring of response to SBP variability-directed treatment in patients with recent cerebrovascular events.

Reporting of consistency of blood pressure control in randomized controlled trials of antihypertensive drugs: a systematic review of 1372 trial reports.

Objective: Hypertension is a powerful treatable risk factor for stroke. Reports of randomized controlled trials (RCTs) of antihypertensive drugs rightly concentrate on clinical outcomes, but control of blood pressure (BP) during follow-up is also important, particularly given that inconsistent control is associated with a high risk of stroke and that antihypertensive drug classes differ in this regard. Methods: We performed a systematic review of reporting of BP control in RCTs of antihypertensive drugs. We searched bibliographic databases (1950–2009) for systematic reviews of RCTs of BP-lowering and identified the main report of all trials. Results: We identified 94 larger trials (>100 participants/arm, >1-year follow-up) and 1278 smaller/shorter trials. Ninety-one (96.8%) larger trials reported some data on mean BP during follow-up, but none reported effects on the consistency of control of BP over time. Although 81 (86.2%) larger trials reported group distribution of BP at baseline (usually SD), only 22 (23.4%) reported such data at any follow-up visit. Eleven (11.7%) larger trials reported group distribution of the change in BP from baseline to follow-up, but 61 (64.9%) reported no data at all on group distribution of BP at follow-up. Thirty-nine (41.5%) trials reported the proportion of patients reaching some BP target during follow-up, but no trial reported data on the consistency of control to target within individuals over time. Similar proportions were observed in the 1278 smaller/short trials. Conclusion: Reporting of BP control is limited in RCTs of BP-lowering drugs. We suggest reporting guidelines.