Blood Pressure Lowering Treatment Trialists' Collaboration Research Articles

Estimated impact of guidelines-based initiation of dual antihypertensive therapy on long-term cardiovascular outcomes in 1.1 million individuals.

Guidelines recommend initiation of dual combination antihypertensive therapy, preferably single-pill combination (SPC), in most patients with hypertension. Evidence on narrowing gaps in clinical practice relative to guidelines is limited. Monte Carlo simulation was applied to 1.1 million patients qualifying for dual combination therapy from a previously conducted retrospective analysis of clinical practice, hospital statistics, and national statistics in the UK. We provide 10-year Kaplan-Meier event rates for the primary endpoint representing a composite of nonfatal myocardial infarction, nonfatal stroke (ischemic or hemorrhagic), nonfatal heart failure hospitalization or cardiovascular death. Cox model results from a previously conducted study were utilized to estimate baseline risk, together with evidence on risk reduction from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) meta-analysis and published evidence on BP-lowering efficacy of antihypertensive therapies. In the overall population, estimated 10-year event rates for the primary endpoint in patients with 100% persistence in monotherapy were 17.0% for irbesartan (I) and 17.6% for ramipril (R). These rates were only modestly better than that observed in clinical practice (17.8%). In patients with 100% persistence in dual therapy, estimated event rates were 13.6% for combinations of Irbesartan+Amlodipine (ARR=8.7% compared to untreated) and 14.3% for Ramipril+Amlodipine (ARR=8.0% compared to untreated). The absolute risk of the primary endpoint was reduced by 15.9% in patients with ASCVD and 6.6% in those without ASCVD. Similarly, the absolute risk was reduced by 11.7% in diabetics and 7.8% in those without diabetes. This study represents the first to investigate guidelines-based treatment in hypertensive patients and demonstrates the opportunity for considerable risk reduction by ensuring recommended dual therapy in clinical practice, particularly in the form of SPC with high persistence, relative to no treatment or monotherapy.

SP-1: AGGRESSIVE BP MANAGEMENT IN OLDER ASIAN PEOPLE

With a rapidly aging population, adequate blood pressure (BP) control is critical for hypertension management and prevention of cardiovascular events. Impressive cardiovascular benefits have been observed with intensive BP control (SBP target, <120 mmHg) in the SPRINT (Systolic Blood Pressure Intervention Trial) study, even in patients 75 years of age or older. A most recent meta-analysis including 51 randomized trials with over 350,000 participants from the BPLTTC (The Blood Pressure Lowering Treatment Trialists’ Collaboration) showed that BP lowering is effective in older people for reducing major cardiovascular events. The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) study-a multicenter, randomized, controlled trial conducted in China, provided important evidence that intensive BP treatment (SBP target, 110 mmHg to < 130 mmHg) benefits older hypertensive patients (aged 60–80 years) and reduced the incidence of cardiovascular events than standard treatment (target 130 mmHg to < 150 mmHg). Because Asian people have a higher burden of hypertension and stroke than Caucasian people, intensive BP treatment has more advantages in reducing the risk of cardiovascular events including stroke in Asian hypertensive patients than in Caucasian people. Home BP monitoring is helpful to facilitate hypertension management for older patients. It should also be noted that clinical decision-making should be on a patient basis, such as fragility, diabetes, stroke, and other comorbidities, with tailored BP targets.

Blood pressure control according to type 2 diabetes status

The control of arterial hypertension is mandatory in people with and without type 2 diabetes. The Article by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), published in The Lancet Diabetes & Endocrinology.1 One-stage individual participant-level data meta-analysis of 51 major randomised controlled trials with information on type 2 diabetes status at baseline was performed. The included trials compared different antihypertensive drugs versus placebo or other classes of drugs, as well as intensive versus standard blood pressure-lowering strategies.

IDF21-0652 Blood pressure-lowering for prevention of major cardiovascular diseases in persons with and without type 2 diabetes

Background: There is insufficient randomised evidence as to whether the effect of blood pressure (BP)-lowering treatment differs in people with type 2 diabetes versus those without this metabolic condition, particularly at a normal or high-normal BP level. Aim: To investigate the effects of BP-lowering treatment on the risk of major cardiovascular events in people with and without type 2 diabetes, and by baseline levels of systolic and diastolic BP. Method: We used the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) to conduct a one-stage individual participant data meta-analysis of major randomised trials. The primary outcome was total major cardiovascular events, defined as the first occurrence of fatal or non-fatal stroke or cerebrovascular disease, fatal or non-fatal myocardial infarction, and heart failure causing death or requiring hospitalisation. The analysis was stratified for type 2 diabetes status at baseline, and baseline categories of systolic BP (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg) and diastolic BP from <70 mm Hg to ≥110 mm Hg diastolic). Cox proportional hazard model stratified by the trial was used to estimate hazard ratio (HR). A Poisson regression model with an identity link was used to calculate the absolute risk reduction (ARR). Results: Data for 358,533 participants (58.4% men) from 51 randomised clinical trials were included in the analysis, in which 28.8% (n=103,325) of the participants had diagnosis of type 2 diabetes at baseline. Baseline mean systolic/diastolic BPs were 149/84 mm Hg in participants with type 2 diabetes (n=103,325) and 153/88 mm Hg in participants without type 2 diabetes (n=255,208). The incidence risks of primary events during the study follow-up time in participants with and without type 2 diabetes were 16.5% and 10.2%, respectively. Over 4.2 years of median follow-up, a fixed value of 5-mm Hg reduction in systolic BP was associated with a lower risk of major cardiovascular events both in participants with type 2 diabetes (HR 0.94 [95% CI 0.91 to 0.98]; ARR -0.015 [95% CI -0.020 to -0.010]) and in those without history of type 2 diabetes (HR 0.89 [95% CI 0.87 to 0.92]; ARR =-0.016 [95% CI -0.018 to -0.013]). In stratified analyses, we did not find reliable evidence for heterogeneity of treatment effects by baseline systolic or diastolic BP level in participants with or without type 2 diabetes (all P for interaction > 0.78). Discussion: The effect of BP reduction for primary and secondary prevention of major cardiovascular events was broadly comparable among people with and without type 2 diabetes, with no clinically important evidence that the level of systolic or diastolic BP at baseline is a determinant of treatment effect. Recommendations by guidelines on different BP reduction treatment in people with and without diabetes, or initiation of BP reduction therapy at a specific BP threshold, are not substantiated by these findings. This work will be presented on behalf of the Blood Pressure Lowering Treatment Trialists' Collaboration. Working group: Milad Nazarzadeh, Zeinab Bidel, Dexter Canoy, Emma Copland, Abbas Dehghan, Derrick A Bennett, George Davey Smith, Rury R. Holman, Mark Woodward, Ajay Gupta, Amanda Adler, Naveed Sattar, Richard J McManus, Koon Teo, Barry R Davis, John Chalmers, Carl J. Pepine, Kazem Rahimi.

Do recent meta-analyses truly prove that treatment with blood pressure-lowering drugs is beneficial at any blood pressure value, no matter how low? A critical review.

Current European guidelines for the management of hypertension and on cardiovascular disease prevention place the threshold for pharmacological treatment at a SBP level of 140 mmHg or above, with the exception of patients at very high risk (mainly because of coronary heart disease). This is in agreement with the current definition of hypertension, that is, the level of blood pressure at which the benefits of treatment outweigh the risks of treatment, as documented by clinical trials. This rationale and definition was recently challenged by meta-analyses using individual participant-level data from 48 randomized trials by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC). The authors calculated for a fixed 5 mmHg pharmacological reduction of SBP an overall 10% risk reduction for major cardiovascular events. It was concluded that there was no reliable evidence of heterogeneity of treatment effects by baseline SBP categories; that the effect was independent from the presence of cardiovascular disease; applied also to old and very old individuals up to 84 years or beyond; and that BP-lowering was also beneficial in individuals with normal or high-normal SBP down to a baseline SBP less than 120 mmHg. In this report, we identify and discuss a number of shortcomings of the BPLTTC meta-analyses. In our view, the conclusions by the BPLTTC must be -together with accompanying suggestions to abandon the definition of hypertension - strongly rejected as they are not justified and may be harmful for cardiovascular health in individuals without hypertension.

Time to remove hypertension from our vocabulary?

Hypercholesterolaemia has not been part of our clinical vocabulary for several decades, so why has hypertension not gone the same way? The latest individual participant-level data meta-analysis from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC)1 is yet another nail in the coffin for hypertension. The new study included 51 trials, with 358 707 participants (149 211 [41·6%] women and 209 496 [58·4%] men) aged 21–105 years, who had 42 947 major cardiovascular events during approximately 4 years of follow-up.

Blood pressure-lowering treatment for the prevention of cardiovascular events in patients with atrial fibrillation: An individual participant data meta-analysis.

Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline. The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), in which individual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in individuals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF.

Investigating the stratified efficacy and safety of pharmacological blood pressure-lowering: an overall protocol for individual patient-level data meta-analyses of over 300 000 randomised participants in the new phase of the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC)

IntroductionPrevious research from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) and others has shown that pharmacological blood pressure (BP)- lowering substantially reduces the risk of major cardiovascular events, including...

Blood pressure-lowering treatment strategies based on cardiovascular risk versus blood pressure: A meta-analysis of individual participant data.

BackgroundClinical practice guidelines have traditionally recommended blood pressure treatment based primarily on blood pressure thresholds. In contrast, using predicted cardiovascular risk has been advocated as a more effective strategy to guide treatment decisions for cardiovascular disease (CVD) prevention. We aimed to compare outcomes from a blood pressure-lowering treatment strategy based on predicted cardiovascular risk with one based on systolic blood pressure (SBP) level.Methods and findingsWe used individual participant data from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) from 1995 to 2013. Trials randomly assigned participants to either blood pressure-lowering drugs versus placebo or more intensive versus less intensive blood pressure-lowering regimens. We estimated 5-y risk of CVD events using a multivariable Weibull model previously developed in this dataset. We compared the two strategies at specific SBP thresholds and across the spectrum of risk and blood pressure levels studied in BPLTTC trials. The primary outcome was number of CVD events avoided per persons treated. We included data from 11 trials (47,872 participants). During a median of 4.0 y of follow-up, 3,566 participants (7.5%) experienced a major cardiovascular event. Areas under the curve comparing the two treatment strategies throughout the range of possible thresholds for CVD risk and SBP demonstrated that, on average, a greater number of CVD events would be avoided for a given number of persons treated with the CVD risk strategy compared with the SBP strategy (area under the curve 0.71 [95% confidence interval (CI) 0.70–0.72] for the CVD risk strategy versus 0.54 [95% CI 0.53–0.55] for the SBP strategy). Compared with treating everyone with SBP ≥ 150 mmHg, a CVD risk strategy would require treatment of 29% (95% CI 26%–31%) fewer persons to prevent the same number of events or would prevent 16% (95% CI 14%–18%) more events for the same number of persons treated. Compared with treating everyone with SBP ≥ 140 mmHg, a CVD risk strategy would require treatment of 3.8% (95% CI 12.5% fewer to 7.2% more) fewer persons to prevent the same number of events or would prevent 3.1% (95% CI 1.5%–5.0%) more events for the same number of persons treated, although the former estimate was not statistically significant. In subgroup analyses, the CVD risk strategy did not appear to be more beneficial than the SBP strategy in patients with diabetes mellitus or established CVD.ConclusionsA blood pressure-lowering treatment strategy based on predicted cardiovascular risk is more effective than one based on blood pressure levels alone across a range of thresholds. These results support using cardiovascular risk assessment to guide blood pressure treatment decision-making in moderate- to high-risk individuals, particularly for primary prevention.

Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review.

BackgroundMany national and international guidelines recommend that the initiation of blood pressure (BP)-lowering drug treatment for the primary prevention of cardiovascular disease (CVD) should no longer be based on BP level alone, but on absolute cardiovascular risk. While BP-lowering drug treatment is beneficial in high-risk individuals at any level of elevated BP, clinicians are concerned about legacy effects on patients with low-to-moderate risk and mildly elevated BP who remain “untreated”.ObjectiveWe aim to investigate the legacy effect of delayed BP-lowering pharmacotherapy in middle-aged individuals (45-65 years) with mildly elevated BP (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg) stratified by absolute risk for primary prevention of CVD, but particularly in the low-risk (<10% five-year absolute risk) group.MethodsRandomized trials of BP-lowering therapy versus placebo or pretreated subjects in active comparator studies with posttrial follow-up will be identified using a 2-step process. First, randomized trials of BP-lowering therapy will be identified by (1) retrieving the references of trials included in published systematic reviews of BP-lowering therapy, (2) retrieving studies published by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), and (3) checking studies referenced in the 1993 World Health Organization/International Society of Hypertension meeting memorandum on BP management. Posttrial follow-up studies will then be identified by forward citation searching the randomized trials identified in step 1 through Web of Science. The search will include randomized controlled trials with at least 1-year in-trial period and a posttrial follow-up phase. Age is the major determinant of absolute cardiovascular risk, so the participants in our review will be restricted to middle-aged adults who are more likely to have a lower cardiovascular risk profile. The primary outcome will be all-cause mortality. Secondary outcomes will include cardiovascular mortality, fatal stroke, fatal myocardial infarction, and death due to heart failure.ResultsThe searches for existing systematic reviews and BPLTTC studies were piloted and modified. The study is expected to be completed before June 2018.ConclusionsThe findings of this study will contribute to the body of knowledge concerning the beneficial, neutral, or harmful effects of delayed BP-lowering drug treatment on the primary prevention of CVD in patients with mildly elevated BP and low-to-moderate CVD risk.Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews: CRD42017058414; https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017058414 (Archived by WebCite® at http://www.webcitation.org/6t6sa8O2Q)

Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis.

Effects of blood pressure reduction in persons with grade 1 hypertension are unclear. To investigate whether pharmacologic blood pressure reduction prevents cardiovascular events and deaths in persons with grade 1 hypertension. Trials included in the BPLTTC (Blood Pressure Lowering Treatment Trialists' Collaboration) and trials identified from a previous review and electronic database searches. Patients without cardiovascular disease with blood pressures in the grade 1 hypertension range (140 to 159/90 to 99 mm Hg) who were randomly assigned to an active (antihypertensive drug or more intensive regimen) or control (placebo or less intensive regimen) blood pressure-lowering regimen. Individual-patient data from BPLTTC trials and aggregate data from other trials were extracted. Risk of bias was assessed for all trials. Individual-patient data involved 10 comparisons from trials where most patients had diabetes, and aggregate data involved 3 comparisons from trials of patients without diabetes. The average blood pressure reduction was about 3.6/2.4 mm Hg. Over 5 years, odds ratios were 0.86 (95% CI, 0.74 to 1.01) for total cardiovascular events, 0.72 (CI, 0.55 to 0.94) for strokes, 0.91 (CI, 0.74 to 1.12) for coronary events, 0.80 (CI, 0.57 to 1.12) for heart failure, 0.75 (CI, 0.57 to 0.98) for cardiovascular deaths, and 0.78 (CI, 0.67 to 0.92) for total deaths. Results were similar in secondary analyses. Withdrawal from treatment due to adverse effects was more common in the active groups. Blood pressure reductions and numbers of events were small. Blood pressure-lowering therapy is likely to prevent stroke and death in patients with uncomplicated grade 1 hypertension. Swedish Heart-Lung Foundation, Swedish Research Council, Australian Research Council, and National Health and Medical Research Council of Australia.

Blood pressure-dependent and independent effects of amlodipine and angiotensin receptor blockers on the risk of stroke

Calcium channel blockers (CCBs) by the use of amlodipine substantially reduce the risk of stroke, and the benefit of initial treatment with this drug versus other antihypertensive drugs could be largely, though not entirely, explained by blood pressure differences between randomized groups of trials [1]. When contrasted with a long-acting CCB, amlodipine, angiotensin receptor blockers (ARBs) are less effective in lowering blood pressure and also demonstrate inferiority for the prevention of stroke [1]. It remains uncertain, however, whether mechanisms independent of blood pressure also affect the size of the treatment benefit, and there have been few formal attempts to investigate any such classand drug-specific effects. Using data from trials of amlodipine or ARBs that were included in recent meta-analyses [2,3], we conducted analyses to determine the relative contribution of blood-pressure-dependent and independent mechanisms to the reduction in risk of stroke produced by these drugs. Instead of comprehensive electronic and manual searches, we identified 10 and 17 odds ratios (ORs) for stroke from randomized controlled trials of amlodipine (77,093 individuals) and ARBs (104,360 individuals), respectively, from the comprehensive metaanalyses [2,3] (Table 1). We used sophisticated methods designed by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) [4]. For each trial, the mean difference in follow-up systolic blood pressure levels between the randomized groups was sought. The association between the difference in follow-up systolic blood pressure levels and the log OR for stroke was investigated using random-effects meta-regression analysis with inverse variance weighting. Initially, using a single regression model, separate regression lines were fitted for trials in which amlodipine or ARBs were the treatment. The slopes of these lines were compared, so as to test for a differential effect of blood pressure reduction on risk in trials of amlodipine compared with ARBs. If these slopes were not significantly different (pN0.05), a parallel lines regression model was fitted, which assumes equal effects of blood pressure reduction with amlodipine and ARBs. Using this model, the null hypothesis of no separation between the 2 parallel lines was tested to explore whether there was evidence of a differential effect of amlodipine and ARBs independent of blood pressure lowering. Assumptions of linear associations between differences in follow-up blood pressure levels and log ORs were tested using standard graphical methods. Analyses were carried out using the metareg routine in STATA version 8.0 (Stata Corporation, College Station, Texas). In the single regression model, the association between the magnitude of reduction in blood pressure and the size of relative risk reduction were similar for amlodipine and ARBs (p=0.326). In the parallel lines regression model, treatment with amlodipine or ARBs achieved a 4.0% (95% confidence interval [CI]; 1.2% to 7.0%; p=0.007) reduction in the risk for each 1 mm Hg reduction in blood pressure (Fig. 1). At zero blood pressure reduction, the estimated relative risk reduction with amlodipine was 11.9% (95% CI, 4.4% to 18.7%; p=0.004). However, ARBs did not confer any additional protection beyond that conferred by blood pressure reduction alone. There was a significant difference between amlodipine and ARBs in terms of their likelihood of providing protection independent of blood pressure lowering (p=0.010), suggesting greater protection with amlodipine than ARBs. The size of blood pressure reduction achieved with amlodipine or ARBs was directly associated with the size of the reductions in the risk of stroke. In addition, although treatment with amlodipine provided an additional 11.9% relative risk reduction beyond that explained by the observed blood pressure differences, no such effect was observed for ARBs. This cerebroprotective effect of amlodipine was significantly greater than any such effect produced by ARBs. These findings extend those previously reported by Wang et al. [1], who plotted only 5 ORs for amlodipine trials and 5 ORs for ARB trials and performed meta-regression analyses separately for trials involving amlodipine and ARB groups. The present analyses provide much more reliable information about the blood pressure-dependent and independent effects of amlodipine and ARBs. The analyses included 10 ORs for amlodipine trials and 17 ORs for ARB trials and involved more sophisticated statistical methods (parallel lines regression model) specifically aimed at the identification of blood pressure-dependent and independent components of the treatment effects. For the risk of stroke, metaregression analyses by the BPLTTC [4] showed similar blood pressure-dependent effects of angiotensin-converting enzyme inhibitors and ARBs but no blood pressure-independent effects for both drug classes. Maximization of the benefit for stroke may be achieved with a regimen that includes amlodipine together with other drugs in an effort to optimize the size of the blood pressure reduction achieved. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010;144:1–2).

Safety and Efficacy of Imidapril in the Treatment of Essential Hypertension

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are one of the renin angiotensin system (RAS) inhibitors widely used for the treatment of hypertension. Recently, Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) meta-analysis showed that ACEIs had the blood pressure independent beneficial effects on coronary heart events. In this review, we summarized our current knowledge about ACEIs especially imidapril and re-evaluated ACEIs among other RAS inhibitors (RASIs) because ACEIs have wide ranges of beneficial effects in addition to the ACE inhibition which other RASIs do not have such as the up-regulation of bradykinin level, substance P level, the inhibition of matrix metalloproteinase (MMP) activity and stabilization of coronary plaque.

Angiotensin receptor blockers: baseline therapy in hypertension?

The provocative editorial by Verma and Strauss in the BMJ 5 years ago1 stating that angiotensin receptor blockers (ARBs) ‘may increase myocardial infarction—and patients may need to be told’ caused a tempest in the teapot and led to extensive scrutiny of outcome data with this drug class. In 2007 the blood pressure-lowering treatment trialists collaboration found that there were similar blood pressure-dependent effects of angiotensin-converting enzyme (ACE) inhibitors and ARBs for the risk of stroke, coronary heart disease, and heart failure.2 The authors cautioned, however, that only for ACE inhibitors but not for ARBs, was there evidence of a blood pressure-independent effect on the risk of major coronary disease events. Also, ONTARGET, a thorough, double-blind prospective randomized trial, documented equal outcome efficacy of an ARB and an ACE inhibitor in a high-risk population, although there was a trend for better stroke prevention in the ARB (telmisartan) arm and better coronary artery disease prevention in the ACE inhibitor (ramipril) arm.3 When analysing these studies and including the most recent ARB trials such as TRANSCEND,4 PRoFESS,5 CASE-J trial,6 HIJ-CREATE,7 JIKEI,8 and KYOTO,9 we found, in a database of ∼100 000 patients from 26 randomized non-heart failure trials of ARBs, a 13% reduction in the risk of stroke ( P = 0.022) ( Figure 1 ) but a trend towards increased risk of myocardial infarction, especially when compared with active treatment ( P = 0.06) ( Figure 2 ). Figure 1 Odds ratio for stroke. There was a significant reduction in the risk of stroke with …

Should we prefer different drugs to treat hypertension in older and younger adults? Practical implications of clinical trials: European perspective

Guidelines for the management of hypertension almost invariably include sections where the evidence for or against treatment or for certain types of treatment in certain types of patients is inconclusive. This is especially the case of older patients with hypertension. As a consequence, although a large number of randomized trials including hypertensive patients aged > or = 60 years showed that antihypertensive drugs reduce cardiovascular morbidity and mortality, health care professionals who take care of older adults have been often reluctant to provide adequate antihypertensive therapy. In a recent meta-analysis, the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) compared the effects of different drugs for reducing blood pressure (BP) in older and younger adults; the reduction in BP levels and the relative risk reduction of a cardiovascular event with various antihypertensive drugs occurred independently of the patients' ages, and the benefits of antihypertensive regimens based on different drug classes were widely comparable across age groups. The BPLTTC analysis strongly suggests an early and aggressive management of hypertension irrespectively of age; more myocardial infarctions, strokes, heart failures and deaths will be prevented by treating hypertensive patients aged > or = 65 years than by treating patients < or = 50 years with the same BP levels. Antihypertensive treatment should be embedded within the management of global cardiovascular risk, with the use of charts for stratifying risk based on additional risk factors, target organ damage or additional clinical conditions.

Is the jury out? Class specific differences on coronary outcomes with ACE-inhibitors and ARBs: insight from meta-analysis and The Blood Pressure Lowering Treatment Trialists' CollaborationThe opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.

This editorial refers to ‘Do angiotensin II receptor blockers increase the risk of myocardial infarction?’† by P. Verdecchia et al., on page 2381 Over the past year there has been fervent discussion and debate as to whether angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) offer similar coronary vascular protection.1–3 A widely held belief is that ARBs may be used interchangeably with ACE-Is, and that each regimen would offer a similar reduction in coronary vascular outcomes; a notion that argues against the concept of an ACE-I-specific, blood pressure-independent vascular protective effect relative to ARBs. The Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), recently presented at the European Society of Hypertension (ESH) and provides important insight into this matter.4 The BPLTTC is a prestigious group of clinical trialists' that is conducting prospectively planned meta-analysis of blood pressure lowering trials.5 At the 15th meeting of the ESH, Dr Turnbull presented the largest and most comprehensive meta-regression analysis of ACE-Is and ARBs.4 In this analysis, the reduction in systolic blood pressure was plotted against the relative risk of the pre-specified end-points of stroke, heart failure, and coronary heart disease. In this study of 21 large-scale randomized trials [16 trials with ACE-Is (AASK, ABCD (H), ABCD (N), ALLHAT, ANBP2, CAPPP, DIAB-HYCAR, EUROPA, HOPE, JMIC-B, PART-2, PEACE, PROGRESS, SCAT, STOP-2, UKPDS-HDS) and 5 trials with ARBs (IDNT-placebo and CCB, LIFE, RENAAL, SCOPE, VALUE)], involving 137 356 patients, the BPLTTC concluded that although there were no differences in risk reduction between ACE-Is and ARBs, with respect to the outcomes of stroke and heart failure, a highly statistically significant ( P =0.001) benefit of ACE-Is relative to ARBs on myocardial infarction (MI) and cardiovascular death was apparent. To our knowledge, this is the most robust data to support the notion that … *Corresponding authors. S.V. Tel: +1 416 782 0092; fax: +1 416 782 0096. M.H.S. Tel: +1 416 730 0938; fax +1 416 229 6162. E-mail addresses: subodh.verma@sympatico.ca or Dr.Marty@bellnet.ca

An Updated Meta-Analysis With a Few Surprises

The meta-regression analysis by Verdecchia et al in this issue of Hypertension 1 updates the 2003 analyses of Staessen et al2 and the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC).3 It includes the 5 trials published after those 2003 manuscripts were composed. All 5 of the additional studies were secondary prevention trials, all on patients with known coronary heart disease (CHD).4–8 In 4 of the 5, either an angiotensin-converting enzyme inhibitor (ACEI) or a calcium channel blocker (CCB) was compared with a placebo, providing an additional 3.0 to 6.1 mm Hg further reduction in the mean systolic blood pressure. In all of these 4 trials of ACEI or CCB versus placebo, patients were also receiving other antihypertensive drugs, mainly directly toward their coronary disease. The new analysis1 confirms …